molecules

Review Immobilized Lignin Peroxidase-Like Metalloporphyrins as Reusable Catalysts in Oxidative Bleaching of Industrial Dyes

Paolo Zucca 1,2, Cláudia M. B. Neves 3, Mário M. Q. Simões 3, Maria da Graça P. M. S. Neves 3, Gianmarco Cocco 1 and Enrico Sanjust 1,*

1 Dipartimento di Scienze Biomediche, Università di Cagliari, Complesso Universitario, SP1 Km 0.700, Monserrato (CA) 09042, Italy; [email protected] or [email protected] (P.Z.); [email protected] (G.C.) 2 Consorzio UNO Oristano, via Carmine snc, Oristano 09170, Italy 3 Department of Chemistry and QOPNA, University of Aveiro, Aveiro 3810-193, Portugal; [email protected] (C.M.B.N.); [email protected] (M.M.Q.S.); [email protected] (M.G.P.M.S.N.) * Correspondence: [email protected]; Tel.: +39-70-675-4518; Fax: +39-70-675-4527

Academic Editor: Derek J. McPhee Received: 22 June 2016; Accepted: 19 July 2016; Published: 22 July 2016

Abstract: Synthetic and bioinspired metalloporphyrins are a class of redox-active catalysts able to emulate several enzymes such as cytochromes P450, ligninolytic peroxidases, and peroxygenases. Their ability to perform oxidation and degradation of recalcitrant compounds, including aliphatic hydrocarbons, phenolic and non-phenolic aromatic compounds, sulfides, and nitroso-compounds, has been deeply investigated. Such a broad substrate specificity has suggested their use also in the bleaching of textile plant wastewaters. In fact, industrial dyes belong to very different chemical classes, being their effective and inexpensive oxidation an important challenge from both economic and environmental perspective. Accordingly, we review here the most widespread synthetic metalloporphyrins, and the most promising formulations for large-scale applications. In particular, we focus on the most convenient approaches for immobilization to conceive economical affordable processes. Then, the molecular routes of catalysis and the reported substrate specificity on the treatment of the most diffused textile dyes are encompassed, including the use of redox mediators and the comparison with the most common biological and enzymatic alternative, in order to depict an updated picture of a very promising field for large-scale applications.

Keywords: metalloporphyrins; wastewaters; textile dyes; biomimetic; lignin peroxidase; immobilization

1. Introduction Textile industry is one of the largest water-consuming industrial sectors [1], releasing huge amounts of colored (absorbance up to 200), polluting (Chemical Oxygen Demand–COD, up to 60,000 ppm), and highly recalcitrant wastes in the environment. It has been estimated that every year more than 7 ˆ 105 tons of dyes are produced, and about 15% of the total amount used is released in the environment due to the low yields of textile processes [2,3]. In addition to the textile industry, dyes are also used by other sectors, such as food, cosmetic, paper, photographic, and plastic industries. The US Environmental Protection Agency (US-EPA) suggests dividing textile wastes into four principal categories: (i) dispersible; (ii) hard-to-treat; (iii) high-volume; (iv) hazardous and toxic wastes [4]. Their environmental impact is firstly evident from an aesthetical perspective (dyes absorb light in the visible range, being detectable even at a concentration of 1 ppm [5]).

Molecules 2016, 21, 964; doi:10.3390/molecules21070964 www.mdpi.com/journal/molecules Molecules 2016, 21, 964 2 of 40

Besides, only a half of the known dyes are regarded as biodegradable. The other half (about 53%–55%) is considered persistent in the environment [6], producing high amounts of textile dyes in water ecosystems with all the connected issues. Many textile dyes in fact are toxic, mutagenic, carcinogenic, being also able to lower light penetration in water bodies and therefore jeopardizing photosynthetic activity [7–9]. The legislators faced such issue since a long time. For instance, the European directive 2002/61/EC forbids the use of some derivatives from azo dyes [10]. More generally, a sustainable management is required by the European Water Framework Directive (2000/60/EC [11]). The textile industry, in addition to this, has one of the greatest water demands (up 200 L per kg of textiles fabricated [1,12]), usually met by high quality fresh water, whereas the re-use of wastewater is still not very common [1]. At the same time, all industrial sectors are increasing their water demands, and the water supplies are dwindling, resulting in higher water costs (up to almost 6 €/m3 in the European Community [1]) and stricter environmental policies and regulations [1,12]. Following these inputs, the scientific community is working hard to develop novel and economically sustainable methods for the detoxification of textile wastewaters, aiming to respect the prescribed quality criteria and thus close the water cycle. Many biological, physical, and chemical approaches have been proposed [5–7,12–14]. However, all these methods suffer from some drawbacks still preventing their wide and sustainable application. For instance, the common biological (both aerobic and anaerobic) activated sludge treatment is not very flexible when faced with the high variety in textile wastes composition (e.g., pH, conductibility, turbidity); the same chemical composition of dyes is usually very recalcitrant and can greatly differ among various industries, and in the same plant over different periods of time (Table1)[ 12,15,16]. Even if significantly less expensive than other approaches, biological treatment commonly requires large areas, and not always allows satisfactory bleaching efficiency [7]. Chemical oxidation is not usually very efficient, and some methods (e.g., ozonation) suffer from unaffordable costs [12,17]. Adsorption and coagulation techniques usually lead to the production of more secondary wastes, whose disposal poses even greater economic and environmental concerns [18]. Photocatalytic decolorization is costly and involves UV light [6,19].

Table 1. Typical Physical chemical composition of textile wastewaters [1,12,20–24].

Parameter Range pH 5–13 Temperature (˝C) 20–60 Conductivity (mS/cm) 0.1–120 Biological Oxygen Demand (ppm) 14–6000 Chemical Oxygen Demand (ppm) 150–90,000 Total Suspended Solids (ppm) 100–25,000 Total Dissolved Solids (ppm) 1800–30,000 Total Kjeldahl Nitrogen (ppm) 70–160 Turbidity (NTU) 0–200 Color (Pt-Co) 50–2500 Absorbance 0.9–200

An alternative methodology is based on metalloporphyrins as effective oxidation catalysts, whose ability to degrade a wide range of substrates under mild operational conditions is well known [25–34]. Accordingly, in this review, we describe their use as efficient, biomimetic and possibly environmentally friendly alternative for the treatment of textile wastes.

2. Synthetic Metalloporphyrins

2.1. Redox Metalloporphyrins: An Overview Tetrapyrrolic macrocycles such as porphyrins and analogs are widely distributed in Nature, playing essential roles in vital processes such as photosynthesis, respiration, oxygenation and electron transport [35–37]. The chemical and physical properties displayed by these macrocycles, including Molecules 2016, 21, 964 3 of 40

Molecules 2016, 21, 964 3 of 39 their syntheticMolecules 2016 analogs,, 21, 964 are responsible for their success in a wide range of fields such as supramolecular3 of 39 chemistry,their synthetic biomimetic analogs, models are responsibl for photosynthesis,e for their success in catalysis, a wide range electronic of fields such materials, as supramolecular sensors, and chemistry, biomimetic models for photosynthesis, catalysis, electronic materials, sensors, and medicinetheir synthetic [33,38–42 analogs,]. A particularly are responsibl attractivee for their success and successful in a wide range research of fields field such of as metalloporphyrinssupramolecular chemistry,medicine [33,38–42].biomimetic A particularlymodels for attractivephotosynthesis, and successful catalysis, research electronic field ofmaterials, metalloporphyrins sensors, and is is related with the possibility of mimicking biological oxidations involving heme proteins such as medicinerelated with [33,38–42]. the possibility A particularly of mimicking attractive biological and successful oxidations research involving field hemeof metalloporphyrins proteins such as is peroxidases,relatedperoxidases, with catalases thecatalases possibility and and cytochrome cytochrome of mimicking P450 P450enzymes biological enzymes (CYP450), (CYP450),oxidations and involving the the redox redox heme chemistry chemistry proteins of oxygen, ofsuch oxygen, as as summarizedperoxidases,as summarized in a catalases simplified in a simplified and form cytochrome form in Scheme in SchemeP4501 [enzymes43 1,44 [43,44].]. (CYP450), and the redox chemistry of oxygen, as summarized in a simplified form in Scheme 1 [43,44].

Scheme 1. Biological oxidations involving heme proteins. Adapted from references [43,44]. Scheme 1. Biological oxidations involving heme proteins. Adapted from references [43,44]. Scheme 1. Biological oxidations involving heme proteins. Adapted from references [43,44]. Catalases are responsible for the conversion of H2O2 into O2 and H2O through an intermediate of Catalasesthe type of are Compound responsible I (Cpd for I).the This conversion intermediate of and H2 CompoundO2 into O2 IIand (Cpd H II)2O are through the two intermediates an intermediate of Catalases are responsible for the conversion of H2O2 into O2 and H2O through an intermediate of the typeinvolved of Compound in the peroxidase I (Cpd I). action This intermediateresponsible by and the Compoundone-electron IIoxidation (Cpd II) of are a thelarge two number intermediates of the type of Compound I (Cpd I). This intermediate and Compound II (Cpd II) are the two intermediates involvedorganic in the substrates. peroxidase Cytochrome action responsible P450 enzymes by are the able one-electron to catalyze oxidationdifferent types of a of large reactions, number namely of organic involved in the peroxidase action responsible by the one-electron oxidation of a large number of the transfer of an oxygen atom into various organic substrates after reductive activation of dioxygen. substrates.organic Cytochromesubstrates. Cytochrome P450 enzymes P450 enzymes are able are to able catalyze to catalyze different different types types of of reactions, reactions, namely namely the In this last process, the two electrons needed for the reductive activation of molecular oxygen are transfer of an oxygen atom into various organic substrates after reductive activation of dioxygen. theusually transfer provided of an oxygen by NADPH atom orin toNADH various via organic a reductase substrates (Scheme after 2). reductive activation of dioxygen. In thisIn lastthis process,last process, the the two two electrons electrons needed needed forfor the reductive reductive activation activation of ofmolecular molecular oxygen oxygen are are usuallyusually provided provided by NADPHby NADPH or or NADH NADH via via a a reductasereductase (Scheme (Scheme 2).2).

Scheme 2. Cytochrome P450 reaction.

These monooxygenases areSchemeScheme largely 2. 2. distributedCytochrome Cytochrome in P450 P450 the reaction. reaction.majority of the living species and are particularly important in mammals for the oxidative metabolism of endogenous (e.g., steroids, prostaglandins)These monooxygenases and exogenous are colargelympounds distributed [45,46]. Thesein the enzymes majority possess of the theliving Fe(III) species complex and ofare These monooxygenases are largely distributed in the majority of the living species and are particularlyprotoporphyrin important IX as the in activemammals site, which for the is lioxidativenked to the metabolism protein by aof cysteinate endogenous residue (e.g., [47]. steroids, particularlyprostaglandins)The important versatility and of inexogenous these mammals heme-thiolate compounds for the enzymes, [45,46]. oxidative These which metabolism enzymes catalyze possessnot of only endogenous the oxidations Fe(III) complex (e.g.,but also steroids, of prostaglandins)protoporphyrinreductions, dehydrations and IX exogenous as the active and isomerizations, compounds site, which is [ li45arenked,46 asso]. to Theseciated the protein with enzymes the by ability a cysteinate possess of iron, the residue the Fe(III) metal [47]. complexion in of protoporphyrinthe Theinner versatility core IX asof thethe of activemacrocycle,these heme-thiolate site, whichto adopt is enzymes, linkeddifferent to oxidationwhich the protein catalyze states by not a[47]. cysteinate only These oxidations oxidation residue but states [47 also]. Thereductions,depend versatility on dehydrationsthe biological of these andenvironment, heme-thiolate isomerizations, the enzymes,presence are asso orciated whichabsence withcatalyze of thereductases ability not of and only iron, dioxygen, oxidationsthe metal and ion buton in also reductions,thethe innerintrinsic dehydrations core reactivity of the macrocycle,of and the isomerizations,substrate to adopt[47]. different are associated oxidation with states the [47]. ability These of oxidation iron, the states metal ion in thedepend innerSome on core thereactions of biological the catalyzed macrocycle, environment, by the to CYP450 adopt the presence differentenzymes or involving absence oxidation ofthe reductases states insertion [47 of ].and an These dioxygen,oxygen oxidation atom and are on states thesummarized intrinsic reactivity in Scheme of 3.the These substrate reactions [47]. can occur without bond cleavage (e.g., epoxidation, N- or depend on the biological environment, the presence or absence of reductases and dioxygen, and on the S-oxidation)Some reactions or with catalyzed the cleavage by the of CYP450different enzymes type of bondsinvolving such the as insertion C–H, N–H, of an C–O oxygen or C–N. atom The are intrinsic reactivity of the substrate [47]. summarizedcleavage of a in carbon-heteroatom Scheme 3. These linreactionskage can can also occur happen without when bond the C–H cleavage bond hydroxylation(e.g., epoxidation, occurs N -at or SomeSthe-oxidation) α-position reactions or relatively with catalyzed the to cleavage the by heteroatom, the of CYP450different such enzymestype as in ofethers, bonds involving amines, such amidesas theC–H, insertion an N–H,d thioethers, C–O of anor leading C–N. oxygen The to atom are summarizedcleavageO-, N- or of S a-oxidative incarbon-heteroatom Scheme dealkylations3. These lin reactionskage [47–50]. can alsoHowever, can happen occur this withoutwhen type the of bond C–Henzymes bond cleavage can hydroxylation also (e.g., be involved epoxidation, occurs in at N- or S-oxidation)theother α-position oxidation or relatively with processes, the to cleavage the although heteroatom, of without different such oxygen as type in ethers,transfer, of bonds amines, such such as amides in as the C–H, couplingand N–H,thioethers, of C–Ophenols leading or C–N.and to The cleavageOdehydrogenation-, N of- or a carbon-heteroatomS-oxidative reactions dealkylations [47]. linkage [47–50]. can also However, happen this when type theof enzymes C–H bond can hydroxylation also be involved occurs in at the αother-position oxidation relatively processes, to the although heteroatom, without such oxygen as in transfer, ethers, such amines, as in amidesthe coupling and thioethers,of phenols and leading to O-,dehydrogenationN- or S-oxidative reactions dealkylations [47]. [47–50]. However, this type of enzymes can also be involved in other oxidation processes, although without oxygen transfer, such as in the coupling of phenols and dehydrogenation reactions [47]. Molecules 2016, 21, 964 4 of 40 Molecules 2016, 21, 964 4 of 39

Molecules 2016, 21, 964 4 of 39

SchemeScheme 3. Main 3. Main oxidation oxidation reaction reaction pathways pathways catalyzed catalyzed by CYP450 by enzymes. CYP450 Adapted enzymes. from Adaptedreferences from [44,47–50]. references [44,47–50]. Scheme 3. Main oxidation reaction pathways catalyzed by CYP450 enzymes. Adapted from references As[44,47–50]. already mentioned above, the transfer of one oxygen atom into an organic substrate by AsCYP450 already enzymes mentioned requires above, the thereductive transfer activation of one oxygen of dioxygen, atom intothe two an organicelectrons substrate needed being by CYP450 enzymesprovided requiresAs inalready general the mentioned reductive by NADPH above, activation or NADH. the transfer of The dioxygen, most of one accepted oxygen the two mechanism atom electrons into foran needed organicthis activation substrate being process provided by in CYP450 enzymes requires the reductive activation of dioxygen, the two electrons needed being generalis bysummarized NADPH orin Scheme NADH. 4, The and most starts accepted with the heme mechanism group in for a six-coordinate this activation low process spin ferric is summarized state bearingprovided water in general as the exchangeableby NADPH or distal NADH. ligand The mosttrans acceptedto the proximal mechanism cysteinate for this residue. activation process in Schemeis summarized4, and starts in withScheme the 4, hemeand starts group with in the a six-coordinateheme group in a lowsix-coordinate spin ferric low state spin bearingferric state water as the exchangeablebearing water distal as the ligand exchangeabletrans to distal the proximalligand trans cysteinate to the proximal residue. cysteinate residue.

Scheme 4. The catalytic cycle of CYP450 including the shorter “peroxide shunt”, and the structure of Scheme 4. The catalytic cycle of CYP450 including the shorter “peroxide shunt”, and the structure of Schemethe 4. Fe(III)The complex catalytic of cycle protoporph of CYP450yrin IX. including Adapted thefrom shorter [38,47,51–54]. “peroxide shunt”, and the structure of the Fe(III) complex of protoporphyrin IX. Adapted from [38,47,51–54]. the Fe(III) complex of protoporphyrin IX. Adapted from [38,47,51–54].

The axial water in the enzyme resting form I is lost after the binding of the substrate (RH), generating the five coordinate high-spin ferric complex II. The conversion of the ferric iron ion from Molecules 2016, 21, 964 5 of 40 low to high spin induces a change in the redox potential of the iron center from ´330 to ´173 mV after substrate binding [50,51]. This modification in the coordination sphere facilitates the one-electron reduction of the pentacoordinated ferric center, by an associated reductase with NADPH, generating iron(II) complex III. The binding of molecular oxygen to this pentacoordinated iron(II) leads to the superoxo iron(III) complex IV. These two entities can be responsible for some reactions catalyzed by CYP450 involving nucleophilic oxidant intermediates, such as the oxidative decarboxylation of aldehydes [51]. A second electron reduction allows the formation of a ferric peroxide adduct V, which can be protonated giving the hydroperoxide complex VI. Further protonation of VI leads to the heterolytic cleavage of the O–O bond with the loss of a water molecule to form a reactive ferryl-oxo porphyrin π-cation radical intermediate VII, which is comparable to Compound I (Cpd I) of peroxidase or catalase (Scheme1). Finally, this intermediate VII transfers an oxygen atom to the substrate. Then, by product dissociation and coordination of water, complex I is regenerated [38,47,52–54]. More recently, another enzyme, structurally resembling both CYP450 and chloroperoxidase, has been found as a secreted glycoprotein in some fungi. The enzyme, which contains a ferriheme prosthetic group bound to the apoprotein by means of a thiolate from a specific cysteine residue, has been defined as peroxygenase (E.C. 1.11.2.1); it follows a catalytic cycle strictly paralleling the ”peroxide shunt” of CYP450 [55–60]. Therefore, no any external reducing agent (such as the expensive NAD(P)H) is required. Peroxygenases act on a wide substrate range, and therefore oxygenate (epoxidize and/or hydroxylate) aromatic rings, benzylic carbons, and even recalcitrant heterocycles such as pyridine. They can also act as bromoperoxidases, being on the contrary their chloroperoxidase activity quite negligible. The discovery that some oxygen atom donors such as alkyl hydroperoxides, H2O2, peracids, sodium hypochlorite, sodium periodate, or iodosylbenzene can replace molecular oxygen and the two electrons needed in the normal cycle (Scheme4), thus directly affording reactive intermediates VI or VII (“short circuit” or “peroxide shunt”; Scheme4), is responsible for the high success of synthetic metalloporphyrins as catalysts in different oxidative processes. Although nature has selected iron as the metal ion, extensive studies concerning the use of model systems to mimic the CYP450 role in biological systems showed that other metals, such as manganese, osmium, chromium, ruthenium, or cobalt are also able to generate very efficient catalytic systems [61–65]. These oxidation processes can have different practical aims, namely the possibility to: (i) obtain metabolites from drugs and other xenobiotics; (ii) lead from a drug to new potential drugs just in one step; (iii) obtain high-value compounds from readily available sources; (iv) obtain mutagens to in vitro studies; (v) degrade diverse pollutants released in the environment, such as drugs, pesticides, or textile dyes [61–68]. Most of the successful studies concerning the use of synthetic metalloporphyrins (also known as metalloporphines, to underline the lack of organic substituents at the beta positions) in CYP450 biomimetic studies are based on 5,10,15,20-tetraarylporphyrins (also called meso-tetraarylporphyrins) and started in 1979 when Groves and coworkers reported that the iron(III) complex of 5,10,15,20-tetraphenylporphyrin (TPP) (Figure1) was able to catalyze the oxidation of cyclohexane into cyclohexanol, and cyclohexene to the corresponding epoxide with iodosylbenzene as the oxygen donor [69]. In this landmark work, although the concept was proved, the macrocycle core was rapidly destroyed under the oxidative conditions of the reaction medium and affording also catalytically inactive µ-oxo complexes. The limitation of this so-called first generation of porphyrin catalysts was responsible for the appearance of the so-called second generation of porphyrin catalysts, bearing bulky groups with adequate electronic features in the aryl substituents, as exemplified in Figure1 with some of the most used and efficient metalloporphyrins based on the 5,10,15,20-tetrakis(2,6- dichlorophenyl)porphyrin (TDCPP) and the 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin (TPFPP) free-bases. Meanwhile, many groups all over the world decided to refine the structures of those catalysts by protecting also the β-pyrrolic positions of the macrocycle core, with halogens or nitro groups, in order to obtain even more robust and efficient catalysts, as shown in Figure1 for the general structure of the so-called third generation of porphyrin catalysts, exemplified here with the β-octachloro-5,10,15,20- Molecules 2016, 21, 964 6 of 40

Molecules 2016, 21, 964 6 of 39 β tetrakis(2,6-dichlorophenyl)porphyrinβ-octachloro-5,10,15,20-tetrakis(2,6-dichlorophenyl)porphyrin (TDCPCl8P) and -octafluoro-5,10,15,20- (TDCPCl8P) and β tetrakis(pentafluorophenyl)-octafluoro-5,10,15,20- Molecules 2016, 21, 964 6 of 39 porphyrintetrakis(pentafluorophenyl)porphyrin (TPFPF8P) free-bases [25]. (TPFPF8P) free-bases [25].

β-octachloro-5,10,15,20-tetrakis(2,6-dichlorophenyl)porphyrin (TDCPCl8P) and β-octafluoro-5,10,15,20- tetrakis(pentafluorophenyl)porphyrin (TPFPF8P) free-bases [25].

FigureFigure 1. Structures 1. Structures illustrating illustrating the the so-called so-called first,first, second second and and third third generation generation porphyrins porphyrins [25]. [25].

Most of the porphyrinic ligands used in heterogeneous catalysis are based on the 5,10,15,20- Mosttetraarylporphyrins ofFigure the 1. porphyrinic Structures of the illustrating first ligands and second the used so-called generati in heterogeneous first,on second bearing and the third catalysis adequate generation are functionalities porphyrins based on [25]. thethat 5,10,15,20-allow tetraarylporphyrinsits immobilization of on the the first support. and second In general, generation the access bearing to the thefirst adequate and second functionalities generation of thatthe free- allow its Most of the porphyrinic ligands used in heterogeneous catalysis are based on the 5,10,15,20- immobilizationbase 5,10,15,20-tetraarylporphyrins on the support. In general, is based the on access synthetic to the improvements first and second of the generation landmark Rothemund of the free-base tetraarylporphyrins of the first and second generation bearing the adequate functionalities that allow 5,10,15,20-tetraarylporphyrinsreaction. In 1936, Rothemund was is based able toon obtain, synthetic for the first improvements time, a series of of 5,10,15,20-tetrasubstituted the landmark Rothemund its immobilization on the support. In general, the access to the first and second generation of the free- porphyrins from the condensation of aliphatic, aromatic and heterocyclic aldehydes with pyrrole using reaction.base In5,10,15,20-tetraarylporphyrins 1936, Rothemund was able is tobased obtain, on sy fornthetic the first improvements time, a series of the of 5,10,15,20-tetrasubstitutedlandmark Rothemund a mixture of pyridine and methanol, at 145–155 °C in a sealed tube under anaerobic conditions (Scheme porphyrinsreaction. from In 1936, the Rothemund condensation was able ofaliphatic, to obtain, for aromatic the first time, and a heterocyclic series of 5,10,15,20-tetrasubstituted aldehydes with pyrrole 5) [70–72]. The low yields reported and the contamination˝ by the corresponding chlorin, identified by usingporphyrins a mixture from of pyridine the condensation and methanol, of aliphatic, at 145–155 aromatic andC in heterocyclic a sealed tube aldehydes under with anaerobic pyrrole conditionsusing Calvin and coworkers [73,74], were the major drawbacks which were partially solved by the aerobic (Schemea mixture5)[ 70 of– 72pyridine]. The and low methanol, yields reported at 145–155 and °C in the a sealed contamination tube under anaerobic by the corresponding conditions (Scheme chlorin, acidic conditions (propionic or acetic acid) described later by Adler and Longo [75]. Although under 5) [70–72]. The low yields reported and the contamination by the corresponding chlorin, identified by identifiedthese acidic by Calvin conditions and important coworkers improvements [73,74], were in thethe porphyrin major drawbacks yields were which reported, were the partially presence of solved Calvin and coworkers [73,74], were the major drawbacks which were partially solved by the aerobic by thechlorin aerobic was acidic still a limitation. conditions The (propionic elimination or of aceticthis contamination acid) described required later the by posterior Adler treatment and Longo of [75]. acidic conditions (propionic or acetic acid) described later by Adler and Longo [75]. Although under Althoughthe reaction under thesemixture acidic with conditions 2,3-dichloro-5,6-dicya important improvementsnobenzoquinone in (DDQ) the porphyrin [76] or, yieldsas reported were reported, by these acidic conditions important improvements in the porphyrin yields were reported, the presence of the presenceGonsalves of and chlorin coworkers was [77], still by a doing limitation. the condensati The eliminationon in a mixture of of this nitrobenzene contamination and acetic required acid. the chlorin was still a limitation. The elimination of this contamination required the posterior treatment of posteriorThe obtainment, treatment ofin thesome reaction cases, of mixture the porphyrin with 2,3-dichloro-5,6-dicyanobenzoquinone by simple crystallization directly from the (DDQ) reaction [76 ] or, the reaction mixture with 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) [76] or, as reported by medium is also a friendly advantage of the oxidative mixture reported by the Portuguese group. as reportedGonsalves by and Gonsalves coworkers and [77], coworkers by doing [the77 ],condensati by doingon the in condensationa mixture of nitrobenzene in a mixture and of acetic nitrobenzene acid. and aceticThe obtainment, acid. The obtainment, in some cases, in someof the cases,porphyrin of the by porphyrin simple crystallization by simple crystallization directly from the directly reaction from the reactionmedium medium is also is alsoa friendly a friendly advantage advantage of the oxid of theative oxidative mixture mixturereported reportedby the Portuguese by the Portuguese group. group.

Scheme 5. The synthetic methods usually employed to obtain 5,10,15,20-tetrasubstituted porphyrins from the condensation of different aldehydes with pyrrole.

SchemeScheme 5. The 5. The synthetic synthetic methods methods usually usually employed employed to ob obtaintain 5,10,15,20-tetrasubstituted 5,10,15,20-tetrasubstituted porphyrins porphyrins from the condensation of different aldehydes with pyrrole. from the condensation of different aldehydes with pyrrole.

Molecules 2016, 21, 964 7 of 40 Molecules 2016, 21, 964 7 of 39

AnAn important important contribution, contribution, allowing allowing obtaining obtaining porphyrins porphyrins from aldehydes from aldehydes that could that not could support not thesupport Adler the refluxing Adler refluxingacidic conditions, acidic conditions, was reported was by reported Gonsalves by and Gonsalves Lindsey and in the Lindsey late eighties, in the late by usingMolecules a 2016two-step, 21, 964 synthetic strategy (Scheme 5). The tetramerization of the monomeric7 of units 39 using eighties,Molecules 2016 by, 21 using, 964 a two-step synthetic strategy (Scheme5). The tetramerization of the7 of monomeric 39 chlorinatedunitsMolecules using 2016, 21solvents chlorinated, 964 was solventsperformed was in performed the presence in theof trifluoroacetic presence of trifluoroacetic acid (TFA) or acid7 ofBF 393 (TFA)at room or temperature,MoleculesAn 2016 important, 21 in, 964 the contribution, absence of oxygen allowing and obtaining light in po orderrphyrins to maximize from aldehydes the formation that could of not the support porphyrinogen,7 of 39 BF3 atAn room important temperature, contribution, in allowing the absence obtaining of oxygen porphyrins and from light aldehydes in order that to could maximize not support the formation the AdlerAn important refluxing contribution, acidic conditions, allowing was obtaining reported pobyrphyrins Gonsalves from and aldehydes Lindsey thatin the could late noteighties, support by followedofthe the AdlerAn porphyrinogen, important byrefluxing the oxidative contribution, acidic followedconditions, step allowing with by was DDQ theobtaining reported oxidativeor p-chloranil. po byrphyrins Gonsalves step Gonsalvesfrom with and aldehydes DDQ Lindsey and or thatin pPereira-chloranil. the could late used noteighties, support Gonsalvesthis by strategy and to usingthe Adler a two-step refluxing synthetic acidic conditions, strategy (Scheme was reported 5). Th bye tetramerization Gonsalves and ofLindsey the monomeric in the late unitseighties, using by preparePereiratheusing Adler a usedtwo-step5,10,15,20-tetraalkylporphyrins refluxing this synthetic strategyacidic conditions, strategy to prepare (Scheme was 5,10,15,20-tetraalkylporphyrinsreported [78], 5). Thand bye tetramerization GonsalvesLindsey to and prepare Lindseyof the monomeric5,10,15,20-tetraarylporphyrins [in78 the], and late eighties,units Lindsey using by to prepare chlorinated solvents was performed in the presence of trifluoroacetic acid (TFA) or BF3 at room withchlorinatedusing yields a two-step solventsbetween synthetic was 30% performed strategyand 40% (Scheme in[79,80]. the presence5). More The tetramerization recently,of trifluoroacetic Sharghi of theacid and monomeric (TFA) Nejad or reportedBF units3 at usingroom an efficient 5,10,15,20-tetraarylporphyrinsusingtemperature, a two-step in the synthetic absence of strategy oxygen with and(Scheme yields light in5). between order The totetramerization maximize 30% and the 40% formationof [the79, 80monomeric]. of More the porphyrinogen, recently, units using Sharghi and temperature,chlorinated solvents in the absence was performedof oxygen and in lightthe presencein order to of maximize trifluoroacetic the formation acid (TFA) of the orporphyrinogen, BF3 at room syntheticNejadchlorinatedfollowed reported byaccess solventsthe oxidative anto efficientseveral was stepperformed 5,10,15,20-tetraarylporphyrins synthetic with DDQ in accessthe or ppresence-chloranil. to several of Gonsalves trifluoroacetic 5,10,15,20-tetraarylporphyrins (yields and ranging Pereiraacid (TFA) used between or this BF strategy 320% at(yields room and to 65%) ranging by followedtemperature, by thein the oxidative absence stepof oxygen with DDQand light or p in-chloranil. order to maximize Gonsalves the and formation Pereira of used the porphyrinogen,this strategy to condensationbetweentemperature,prepare 5,10,15,20-tetraalkylporphyrins 20% in and ofthe pyrrole absence 65%) by ofand condensationoxygen aryl and aldehydes [78],light of inand pyrrole order atLindsey room to and maximize totemperature aryl prepare aldehydes the formation 5,10,15,20-tetraarylporphyrins and at usingof room the porphyrinogen, temperatureequimolar amount and using of preparefollowed 5,10,15,20-tetraalkylporphyrins by the oxidative step with DDQ [78], or pand-chloranil. Lindsey Gonsalves to prepare and 5,10,15,20-tetraarylporphyrins Pereira used this strategy to PClfollowed5 or CF by3SO the2Cl oxidative in the presence step with ofDDQ air oras pan-chloranil. oxidant Gonsalves [81,82]. and Pereira used this strategy to equimolarwithprepare yields 5,10,15,20-tetraalkylporphyrins amountbetween of30% PCl and5 or 40% CF 3[79,80].SO2 [78],Cl inMore and the recently,Lindsey presence toSharghi ofprepare air asand 5,10,15,20-tetraarylporphyrins an Nejad oxidant reported [81,82 an]. efficient preparewith yields 5,10,15,20-tetraalkylporphyrins between 30% and 40% [79,80]. [78], More and Lindseyrecently, toSharghi prepare and 5,10,15,20-tetraarylporphyrins Nejad reported an efficient syntheticwithTheThe yields possibilityaccess possibility between to several 30%to to apply and5,10,15,20-tetraarylporphyrins apply 40% microwave [79,80]. microwave More irradiation recently, irradiation (yields Sharghiin the ranging in preparationand the Nejad between preparation reported of20% a andseries an 65%) ofefficient of a by5,10,15,20- series of withsynthetic yields access between to several 30% and5,10,15,20-tetraarylporphyrins 40% [79,80]. More recently, (yields Sharghi ranging and Nejad between reported 20% and an efficient65%) by tetraarylporphyrinscondensationsynthetic access of topyrrole several is beingand 5,10,15,20-tetraarylporphyrins aryl consid aldehydesered atby room different temperature (yields authors ranging and and, using between in equimolar most 20% of and amountthese 65%) studies, byof the 5,10,15,20-tetraarylporphyrinssyntheticcondensation access of topyrrole several and 5,10,15,20-tetraarylporphyrins aryl isaldehydes being considered at room temperature by (yields different ranging and authors using between and,equimolar 20% in mostand amount 65%) of these byof studies, PCl5 or CF3SO2Cl in the presence of air as an oxidant [81,82]. presencethePClcondensation presence5 or CF of3SO an of2ofCl acid anpyrrole in acidthe was presence wasand considered consideredaryl of aldehydes air asessential an essential oxidant at room [83– [ 83[81,82]. 87].temperature–87 Interestingly,]. Interestingly, and using Pereira Pereira equimolar and and coworkers coworkersamount of reported reported condensationThe possibility of pyrrole to apply and aryl microwave aldehydes irradiation at room temperaturein the preparation and using of aequimolar series of amount5,10,15,20- of thatPCl 5the Theor CF5,10,15,20-tetraaryl possibility3SO2Cl in theto presenceapply and microwave of 5,10,15,20-tetraalkylporphyrins air as an irradiation oxidant [81,82]. in the preparation can be of obtaineda series ofin 5,10,15,20-good yields under thatPCl5 theor CF 5,10,15,20-tetraaryl3SO2Cl in the presence and of 5,10,15,20-tetraalkylporphyrins air as an oxidant [81,82]. can be obtained in good yields under tetraarylporphyrinsThe possibility isto beingapply considmicrowaveered byirradiation different inauthors the preparation and, in most of aof series these of studies, 5,10,15,20- the microwavemicrowavetetraarylporphyrinsThe possibility irradiation isto being applyusing consid microwavewater, ered which byirradiation different acts simultaneouslysimu inauthors ltaneouslythe preparation and, asin solventmost of aof series andand these acid acidof studies, 5,10,15,20- catalystcatalyst the [[88]. 88]. presencetetraarylporphyrins of an acid wasis being considered consid essentialered by [83–different87]. Interestingly, authors and, Pereira in most and of coworkers these studies, reported the tetraarylporphyrinspresenceInIn some some of an cases, cases,acid was isthe the being considered starting starting consid aldehyde aldehyde essentialered by [83–differenthas has87]. not not Interestingly, thauthors thee adequate and, Pereira in functionality functionality most and of coworkers these to to studies, be be reported grafted grafted the into into the the thatpresence the 5,10,15,20-tetraaryl of an acid was considered and 5,10,15,20-tetraalkylporphyrins essential [83–87]. Interestingly, can be Pereira obtained and in coworkers good yields reported under support,presencethat the 5,10,15,20-tetraaryl requiringof an acid wasextra considered functionalization and 5,10,15,20-tetraalkylporphyrins essential [83– such87]. as Interestingly, the introduction can bePereira obtained of, and e.g., in coworkers good sulfonic yields reported or under nitro groups support,microwavethat the 5,10,15,20-tetraaryl requiring irradiation extra using functionalizationand water, 5,10,15,20-tetraalkylporphyrins which acts suchsimultaneously as the introduction ascan solvent be obtained and of, acid e.g., in good catalyst sulfonic yields [88]. or under nitro groups thatthatmicrowave can the 5,10,15,20-tetraarylbe furtherirradiation reduced using and water,to 5,10,15,20-tetraalkylporphyrinsamino which groups. acts simu Theltaneously access to ascanthe solvent bethird obtained generationand acid in good catalyst of yields porphyrin [88]. under catalysts thatmicrowave canIn some be furtherirradiation cases, reducedthe using starting water, to aminoaldehyde which groups. hasacts notsimu The thltaneouslye accessadequate to as thefunctionality solvent third and generation acidto be catalyst grafted of porphyrin [88]. into the catalysts microwaveIn some irradiation cases, the using starting water, aldehyde which hasacts notsimu thltaneouslye adequate as functionality solvent and acidto be catalyst grafted [88]. into the requiresrequiressupport,In some also alsorequiring cases,posterior posterior extra the starting functionalizationhalogenation halogenation aldehyde or or hassuch nitration nitration not as the by byintroductionadequate using using fumingfunctionality fuming of, e.g., nitric nitric sulfonic to acid acidbe graftedor or or nitro a a mixture mixtureinto groups the of of acetic support,In some requiring cases, extra the starting functionalization aldehyde hassuch not as the adequateintroduction functionality of, e.g., sulfonic to be graftedor nitro into groups the anhydrideanhydridethatsupport, can be requiring furtherand and zinc zinc reducedextra nitrate nitrate functionalization to [89–91]. [amino89–91 groups.]. The The suchmost most The as awidespread widespreadccess the introduction to the third metalloporphyrins metalloporphyrins generation of, e.g., sulfonic of porphyrin citedor cited nitro in incatalysts groupsthis this paper, paper, and and support,that can be requiring further reducedextra functionalization to amino groups. such The as access the introduction to the third generation of, e.g., sulfonic of porphyrin or nitro catalysts groups theirrequiresthat canrespective bealso further posterior acronyms reduced halogenation to are amino listed groups.or in nitration Table The 2. abyccess using to the fuming third generationnitric acid orof porphyrina mixture catalystsof acetic theirthatrequires can respective bealso further posterior acronyms reduced halogenation to are amino listed groups. or in nitration Table The2 a .byccess using to the fuming third generationnitric acid ofor porphyrina mixture catalystsof acetic anhydriderequires also and posterior zinc nitrate halogenation [89–91]. The or mostnitration widespread by using metalloporphyrins fuming nitric acid cited or a inmixture this paper, of acetic and requiresanhydride also and posterior zinc nitrate halogenation [89–91]. The or mostnitration widespread by using metalloporphyrins fuming nitric acid cited or a inmixture this paper, of acetic and theiranhydride respectiveTable and zinc2.acronyms meso nitrate-Tetrasubstituted are [89–91]. listed Thein Table mostporphyrins 2. widespread with and metalloporphyrins without substituents cited in thisthe βpaper,-positions and anhydridetheir respectiveTable and zinc 2.acronymsmeso nitrate-Tetrasubstituted are [89–91]. listed The in Table most porphyrins 2. widespread with and metalloporphyrins without substituents cited in thethisβ paper,-positions. and their respective acronyms are listed in Table 2. their respectiveTable 2. acronyms meso-Tetrasubstituted are listed in porphyrins Table 2. with and without substituents in the β-positions Table 2. meso-Tetrasubstituted porphyrins with and without substituents in the β-positions Table 2. meso-Tetrasubstituted porphyrins with and without substituents in the β-positions Table 2. meso-Tetrasubstituted porphyrins with and without substituents in the β-positions

Acronyms Designations Ar R AcronymsAcronyms Designations Designations Ar R R Acronyms Designations Ar R TPP 5,10,15,20-tetraphenylporphyrin 8 H AcronymsTPPTPP 5,10,15,20-tetraphenylporphyrin 5,10,15,20-tetraphenylporphyrinDesignations Ar 8R H 8 H AcronymsTPP 5,10,15,20-tetraphenylporphyrinDesignations Ar R8 H TPP 5,10,15,20-tetraphenylporphyrin 8 H TPP 5,10,15,20-tetraphenylporphyrin 8 H TDCPPTDCPP 5,10,15,20-tetrakis(2,6-dichlorophenyl)porphyrin5,10,15,20-tetrakis(2,6-dichlorophenyl)porphyrin 8 H 8 H TDCPPTDCPP 5,10,15,20-tetrakis(2,6-dichlorophenyl)porphyrin 5,10,15,20-tetrakis(2,6-dichlorophenyl)porphyrin 8 H 8 H TDCPP 5,10,15,20-tetrakis(2,6-dichlorophenyl)porphyrin 8 H TDCPP 5,10,15,20-tetrakis(2,6-dichlorophenyl)porphyrin 8 H

ββ-octachloro-5,10,15,20-tetrakis(2,6--octachloro-5,10,15,20-tetrakis(2,6- 8 8 TDCPClTDCPCl8P β-octachloro-5,10,15,20-tetrakis(2,6- 8 TDCPCl8P dichlorophenyl)porphyrindichlorophenyl)porphyrinβ-octachloro-5,10,15,20-tetrakis(2,6- Br Br TDCPCl8P dichlorophenyl)porphyrinβ-octachloro-5,10,15,20-tetrakis(2,6- Br8 8 Br TDCPCl8P β-octachloro-5,10,15,20-tetrakis(2,6-dichlorophenyl)porphyrin 8 TDCPCl8P dichlorophenyl)porphyrin Br dichlorophenyl)porphyrin Br

TPFPP 5,10,15,20-tetrakis(pentafluoro-phenyl)porphyrin 8 H TPFPPTPFPP 5,10,15,20-tetrakis(pentafluoro-phenyl)porphyrin5,10,15,20-tetrakis(pentafluoro-phenyl)porphyrin 8 H 8 H TPFPPTPFPP 5,10,15,20-tetrakis(pentafluoro-phenyl)porphyrin 5,10,15,20-tetrakis(pentafluoro-phenyl)porphyrin 8 H 8 H TPFPP 5,10,15,20-tetrakis(pentafluoro-phenyl)porphyrin 8 H β-octafluoro-5,10,15,20- 8 TPFPF8P β-octafluoro-5,10,15,20- 8 TPFPF8P tetrakis(pentafluorophenyl)porphyrinβ-octafluoro-5,10,15,20- Br 8 TPFPF8P tetrakis(pentafluorophenyl)porphyrinβ-octafluoro-5,10,15,20-β Br8 TPFPF8P βtetrakis(pentafluorophenyl)porphyrin-octafluoro-5,10,15,20--octafluoro-5,10,15,20- 8 Br TPFPFTPFPF8P8 P tetrakis(pentafluorophenyl)porphyrin Br 8 Br tetrakis(pentafluorophenyl)porphyrintetrakis(pentafluorophenyl)porphyrin Br TCPP 5,10,15,20-tetrakis(4-carboxy-phenyl)porphyrin 8 H TCPP 5,10,15,20-tetrakis(4-carboxy-phenyl)porphyrin 8 H TCPPTCPP 5,10,15,20-tetrakis(4-carboxy-phenyl)porphyrin5,10,15,20-tetrakis(4-carboxy-phenyl)porphyrin 8 H 8 H TMCPPTCPPTCPP 5,10,15,20-tetrakis(4-carboxy-phenyl)porphyrin5,10,15,20-tetrakis(4-meth 5,10,15,20-tetrakis(4-carboxy-phenyl)porphyrinoxy-carbonylphenyl)porphyrin 8 H 8 H TMCPP 5,10,15,20-tetrakis(4-methoxy-carbonylphenyl)porphyrin 8 H TMCPPTMCPP 5,10,15,20-tetrakis(4-meth5,10,15,20-tetrakis(4-methoxy-carbonylphenyl)porphyrinoxy-carbonylphenyl)porphyrin 8 H 8 H TMCPPTHPP 5,10,15,20-tetrakis(4-meth5,10,15,20-tetrakis(4-hydroxy-phenyl)porphyrinoxy-carbonylphenyl)porphyrin 88H H THPP 5,10,15,20-tetrakis(4-hydroxy-phenyl)porphyrin 8H THPPTHPP 5,10,15,20-tetrakis(4-hydroxy-phenyl)porphyrin5,10,15,20-tetrakis(4-hydroxy-phenyl)porphyrin 8H 8H THPP 5,10,15,20-tetrakis(4-hydroxy-phenyl)porphyrin 8H

Molecules 2016, 21, 964 7 of 39 Molecules 2016, 21, 964 7 of 39 An important contribution, allowing obtaining porphyrins from aldehydes that could not support An important contribution, allowing obtaining porphyrins from aldehydes that could not support the Adler refluxing acidic conditions, was reported by Gonsalves and Lindsey in the late eighties, by the Adler refluxing acidic conditions, was reported by Gonsalves and Lindsey in the late eighties, by using a two-step synthetic strategy (Scheme 5). The tetramerization of the monomeric units using using a two-step synthetic strategy (Scheme 5). The tetramerization of the monomeric units using chlorinated solvents was performed in the presence of trifluoroacetic acid (TFA) or BF3 at room chlorinated solvents was performed in the presence of trifluoroacetic acid (TFA) or BF3 at room temperature, in the absence of oxygen and light in order to maximize the formation of the porphyrinogen, temperature, in the absence of oxygen and light in order to maximize the formation of the porphyrinogen, followed by the oxidative step with DDQ or p-chloranil. Gonsalves and Pereira used this strategy to followed by the oxidative step with DDQ or p-chloranil. Gonsalves and Pereira used this strategy to prepare 5,10,15,20-tetraalkylporphyrins [78], and Lindsey to prepare 5,10,15,20-tetraarylporphyrins prepare 5,10,15,20-tetraalkylporphyrins [78], and Lindsey to prepare 5,10,15,20-tetraarylporphyrins with yields between 30% and 40% [79,80]. More recently, Sharghi and Nejad reported an efficient with yields between 30% and 40% [79,80]. More recently, Sharghi and Nejad reported an efficient synthetic access to several 5,10,15,20-tetraarylporphyrins (yields ranging between 20% and 65%) by synthetic access to several 5,10,15,20-tetraarylporphyrins (yields ranging between 20% and 65%) by condensation of pyrrole and aryl aldehydes at room temperature and using equimolar amount of condensation of pyrrole and aryl aldehydes at room temperature and using equimolar amount of PCl5 or CF3SO2Cl in the presence of air as an oxidant [81,82]. PCl5 or CF3SO2Cl in the presence of air as an oxidant [81,82]. The possibility to apply microwave irradiation in the preparation of a series of 5,10,15,20- The possibility to apply microwave irradiation in the preparation of a series of 5,10,15,20- tetraarylporphyrins is being considered by different authors and, in most of these studies, the tetraarylporphyrins is being considered by different authors and, in most of these studies, the presence of an acid was considered essential [83–87]. Interestingly, Pereira and coworkers reported presence of an acid was considered essential [83–87]. Interestingly, Pereira and coworkers reported that the 5,10,15,20-tetraaryl and 5,10,15,20-tetraalkylporphyrins can be obtained in good yields under that the 5,10,15,20-tetraaryl and 5,10,15,20-tetraalkylporphyrins can be obtained in good yields under microwave irradiation using water, which acts simultaneously as solvent and acid catalyst [88]. microwave irradiation using water, which acts simultaneously as solvent and acid catalyst [88]. In some cases, the starting aldehyde has not the adequate functionality to be grafted into the In some cases, the starting aldehyde has not the adequate functionality to be grafted into the support, requiring extra functionalization such as the introduction of, e.g., sulfonic or nitro groups support, requiring extra functionalization such as the introduction of, e.g., sulfonic or nitro groups that can be further reduced to amino groups. The access to the third generation of porphyrin catalysts that can be further reduced to amino groups. The access to the third generation of porphyrin catalysts requires also posterior halogenation or nitration by using fuming nitric acid or a mixture of acetic requires also posterior halogenation or nitration by using fuming nitric acid or a mixture of acetic anhydride and zinc nitrate [89–91]. The most widespread metalloporphyrins cited in this paper, and anhydride and zinc nitrate [89–91]. The most widespread metalloporphyrins cited in this paper, and their respective acronyms are listed in Table 2. their respective acronyms are listed in Table 2.

Table 2. meso-Tetrasubstituted porphyrins with and without substituents in the β-positions Table 2. meso-Tetrasubstituted porphyrins with and without substituents in the β-positions

Acronyms Designations Ar R Acronyms Designations Ar R TPP 5,10,15,20-tetraphenylporphyrin 8 H TPP 5,10,15,20-tetraphenylporphyrin 8 H

TDCPP 5,10,15,20-tetrakis(2,6-dichlorophenyl)porphyrin 8 H TDCPP 5,10,15,20-tetrakis(2,6-dichlorophenyl)porphyrin 8 H

β-octachloro-5,10,15,20-tetrakis(2,6- 8 TDCPCl8P β-octachloro-5,10,15,20-tetrakis(2,6- 8 TDCPCl8P dichlorophenyl)porphyrin Br dichlorophenyl)porphyrin Br

TPFPP 5,10,15,20-tetrakis(pentafluoro-phenyl)porphyrin 8 H TPFPP 5,10,15,20-tetrakis(pentafluoro-phenyl)porphyrin 8 H Molecules 2016, 21, 964 8 of 40

β-octafluoro-5,10,15,20- 8 TPFPF8P β-octafluoro-5,10,15,20- 8 TPFPF8P tetrakis(pentafluorophenyl)porphyrinTable 2. Cont. Br tetrakis(pentafluorophenyl)porphyrin Br

TCPPAcronyms 5,10,15,20-tetrakis(4-carboxy-phenyl)porphyrin Designations Ar8 H R TCPP 5,10,15,20-tetrakis(4-carboxy-phenyl)porphyrin 8 H

TMCPPTMCPP 5,10,15,20-tetrakis(4-meth 5,10,15,20-tetrakis(4-methoxy-carbonylphenyl)porphyrinoxy-carbonylphenyl)porphyrin 8 H 8 H TMCPP 5,10,15,20-tetrakis(4-methoxy-carbonylphenyl)porphyrin 8 H

MoleculesTHPP 2016 , 21, 9645,10,15,20-tetrakis(4-hydroxy-phenyl)porphyrin 88H of 39 MoleculesTHPPTHPP 2016 , 21, 9645,10,15,20-tetrakis(4-hydroxy-phenyl)porphyrin 5,10,15,20-tetrakis(4-hydroxy-phenyl)porphyrin 88H of 39 8H Molecules 2016, 21, 964 8 of 39 Molecules 2016, 21, 964 8 of 39 Molecules 2016, 21, 964 8 of 39 Molecules 2016, 21, 964 8 of 39 5,10,15,20-tetrakis(2,6-dichloro-3-5,10,15,20-tetrakis(2,6-dichloro-3- TDCSPPTDCSPP 5,10,15,20-tetrakis(2,6-dichloro-3- 8 H 8 H TDCSPP sulfonatophenyl)porphyrin5,10,15,20-tetrakis(2,6-dichloro-3-sulfonatophenyl)porphyrin 8 H TDCSPP 5,10,15,20-tetrakis(2,6-dichloro-3-sulfonatophenyl)porphyrin 8 H TDCSPP 5,10,15,20-tetrakis(2,6-dichloro-3-sulfonatophenyl)porphyrin 8 H TDCSPP sulfonatophenyl)porphyrin5,10,15,20-tetrakis(2,6-dichloro-3- 8 H TDCSPPT4MPyP sulfonatophenyl)porphyrin5,10,15,20-tetrakis(N-methyl-pyridinium-4-yl)porphyrin 8 H T4MPyPT4MPyP 5,10,15,20-tetrakis(sulfonatophenyl)porphyrin 5,10,15,20-tetrakis(N-methyl-pyridinium-4-yl)porphyrinN-methyl-pyridinium-4-yl)porphyrin 8 H 8 H T4MPyP 5,10,15,20-tetrakis(N-methyl-pyridinium-4-yl)porphyrin 8 H T4MPyP 5,10,15,20-tetrakis(N-methyl-pyridinium-4-yl)porphyrin 8 H T4MPyP 5,10,15,20-tetrakis(5,10,15,20-tetrakis(2,4,6-tribromo-3-N-methyl-pyridinium-4-yl)porphyrin 8 H TBr3MPP 5,10,15,20-tetrakis(2,4,6-tribromo-3- 8 H TBr3MPP methoxyphenyl)porphyrin5,10,15,20-tetrakis(2,4,6-tribromo-3-5,10,15,20-tetrakis(2,4,6-tribromo-3- 8 H TBrTBr3MPP3MPP 5,10,15,20-tetrakis(2,4,6-tribromo-3-methoxyphenyl)porphyrin 8 H 8 H TBr3MPP 5,10,15,20-tetrakis(2,4,6-tribromo-3-methoxyphenyl)porphyrinmethoxyphenyl)porphyrin 8 H TBr3MPP methoxyphenyl)porphyrin5,10,15,20-tetrakis(2,4,6-tribromo-3- 8 H TBr3MPP 8 H TSPP methoxyphenyl)porphyrin5,10,15,20-tetrakis(4-sulfonato-phenyl)porphyrin 8 H TSPP 5,10,15,20-tetrakis(4-sulfonato-phenyl)porphyrin 8 H TSPP 5,10,15,20-tetrakis(4-sulfonato-phenyl)porphyrin 8 H TSPPTSPP 5,10,15,20-tetrakis(4-sulfonato-phenyl)porphyrin 5,10,15,20-tetrakis(4-sulfonato-phenyl)porphyrin 8 H 8 H TSPP β5,10,15,20-tetrakis(4-sulfonato-phenyl)porphyrin-octabromo-5,10,15,20-tetrakis-(N-methylpyridinium-3- 8 H Br8T3MPyPTSPP β5,10,15,20-tetrakis(4-sulfonato-phenyl)porphyrin-octabromo-5,10,15,20-tetrakis-(N-methylpyridinium-3- 8 H Br8T3MPyP yl)porphyrinβ-octabromo-5,10,15,20-tetrakis-( N-methylpyridinium-3- Br8 Br8T3MPyP βyl)porphyrin-octabromo-5,10,15,20-tetrakis-( N-methylpyridinium-3- 8Br Br8T3MPyP βyl)porphyrin-octabromo-5,10,15,20-tetrakis-(β-octabromo-5,10,15,20-tetrakis- N-methylpyridinium-3- 8Br Br8BrT3MPyP8T3MPyP yl)porphyrinβ-octabromo-5,10,15,20-tetrakis-( N-methylpyridinium-3- Br8 8 Br Br8T3MPyP (N-methylpyridinium-3-yl)porphyrin yl)porphyrin5,10,15,20-tetrakis(1,3-dimethyl-imidazolium-2- Br TDMImP 5,10,15,20-tetrakis(1,3-dimethyl-imidazolium-2- 8 H TDMImP yl)porphyrin5,10,15,20-tetrakis(1,3-dimethyl-imidazolium-2- 8 H TDMImP 5,10,15,20-tetrakis(1,3-dimethyl-imidazolium-2-yl)porphyrin 8 H TDMImP 5,10,15,20-tetrakis(1,3-dimethyl-imidazolium-2-yl)porphyrin 8 H TDMImP yl)porphyrin5,10,15,20-tetrakis(1,3-dimethyl-imidazolium-2-5,10,15,20-tetrakis(1,3-dimethyl- 8 H TDMImPTDMImP yl)porphyrin 8 H 8 H yl)porphyrinimidazolium-2-yl)porphyrin 2.2. Substrate Specificity 2.2. Substrate Specificity 2.2. Substrate Specificity 2.2. SubstrateSince the Specificity confirmation that synthetic models based on porphyrins are able to mimic the action 2.2. SubstrateSince the Specificity confirmation that synthetic models based on porphyrins are able to mimic the action 2.2.of heme SubstrateSince thiolates, the Specificity confirmation the type thatand syntheticnumber of models substrates base dstudied on porphyrins are countless. are able One to mimicof the importantthe action 2.2.of heme SubstrateSince thiolates, the Specificityconfirmation the type thatand syntheticnumber of models substrates base dstudied on porphyrins are countless. are able One to mimicof the importantthe action goalsof hemeSince for developingthiolates, the confirmation the efficient type thatand biomimetic syntheticnumber modelsof models substrates is base related dstudied on to porphyrins the are necessity countless. are of able developing One to mimicof the sustainable, importantthe action ofgoals hemeSince for developingthiolates, the confirmation the efficient type thatand biomimetic syntheticnumber modelsof models substrates is base related dstudied on to porphyrins the are necessity countless. are of able developing One to ofmimic the sustainable, importantthe action environmentallyofgoals hemeSince for developingthiolates, the confirmation benign, the efficient type safe, and biomimetic that and number synthetic clean modelsof methodol substrates models is relatedogies based studied tofor the on synthetic are porphyrinsnecessity countless. orga of developingnic areOne ablechemistry of the to sustainable, mimicimportant [92–98]. the action of goalsenvironmentallyof heme for developingthiolates, benign, the efficient type safe, and biomimetic and number clean modelsof methodol substrates is relatedogies studied tofor the synthetic are necessity countless. orga of developingnic One chemistry of the sustainable, important [92–98]. hemeIngoalsenvironmentally particular, for thiolates, developing the theoxidationbenign, efficient type safe, andreactions biomimetic numberand neededclean ofmodels methodol substratesto co nvertis relatedogies bulk studied to forchemicals the synthetic necessity are countless.(e.g., orga offrom developingnic petroleum Onechemistry of sustainable, the products) [92–98]. important goals environmentallyIngoals particular, for developing the oxidationbenign, efficient safe, reactions biomimetic and neededclean models methodol to convert is relatedogies bulk to forchemicals the synthetic necessity (e.g., orga offrom developingnic petroleum chemistry sustainable, products) [92–98]. intoenvironmentallyIn particular, useful products the oxidationbenign, are amongst safe, reactions and the neededmostclean problematicmethodol to convertogies bulktransformations forchemicals synthetic (e.g., in orgaindustrial fromnic petroleum chemistry core technologies products) [92–98]. forInintoenvironmentally particular, developing useful products the oxidation efficientbenign, are amongst safe,reactions biomimetic and the neededmostclean models problematicmethodol to convert isogies related bulktransformations 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transformations research environmentally groups in industrial studying malignant core the technologiesoxidationconditions), of In(expensive,henceinto particular, useful justifying products not the selective,the oxidation arehuge amongst andinvestment reactions frequently the most made needed performedproblematic by diff to converterent under transformations research bulkenvironmentally chemicals groups in industrial studying (e.g.,malignant from core the oxidationtechnologiesconditions), petroleum of products) aliphatic(expensive,hence justifying (alkanes not selective,the and huge alkenes) andinvestment frequently and aromatic made performed byhydrocarbons different under research (e.g.,environmentally toluene, groups ethylbenzene, studying malignant the andoxidationconditions), styrene) of intohencealiphatic(expensive, useful justifying (alkanes productsnot selective,the and huge arealkenes) amongstandinvestment frequently and aromatic the made most performed byhydrocarbons problematic different under research (e.g., transformationsenvironmentally toluene, groups ethylbenzene, studying malignant in industrial the andoxidationconditions), corestyrene) technologies of orhencealiphatic phenolic justifying (alkanes derivatives the and huge alkenes) under investment homogeneous and aromatic made andbyhydrocarbons diff heteerentrogeneous research (e.g., conditions toluene, groups ethylbenzene, studying [61,62,64,65,99–104]. the andoxidation styrene) This of (expensive,aliphaticorhence phenolic justifying (alkanes derivatives not the selective, and huge alkenes) under investment and homogeneous and frequently aromatic made andbyhydrocarbons performed diff heteerentrogeneous research under (e.g., conditions toluene, environmentallygroups ethylbenzene, studying [61,62,64,65,99–104]. the malignant andoxidation styrene) This conditions),of isaliphaticor alsophenolic a challenging (alkanes derivatives and topic alkenes) under if considering homogeneous and aromatic the andpossibilityhydrocarbons heterogeneous to use (e.g., natural conditions toluene, and ethylbenzene, abundant [61,62,64,65,99–104]. substrates and styrene) suchThis orisaliphatic alsophenolic a challenging (alkanes derivatives and topic alkenes) under if considering homogeneous and aromatic the andpossibilityhydrocarbons heterogeneous to use (e.g., natural conditions toluene, and ethylbenzene, abundant [61,62,64,65,99–104]. substrates and styrene) suchThis henceasoris alsophenolicterpenes justifyinga challenging derivativesgiving the rise topic huge under to if high-value considering investment homogeneous compounds the made andpossibility hete by with differentrogeneous to organolepticuse natural research conditions and or groups pharmacologicalabundant [61,62,64,65,99–104]. studying substrates interest. the suchThis oxidation of isasor alsophenolicterpenes a challenging derivativesgiving rise topic under to if high-value considering homogeneous compounds the possibilityand hete withrogeneous to organolepticuse natural conditions and or pharmacologicalabundant [61,62,64,65,99–104]. substrates interest. suchThis aliphaticInisas alsoparticular,terpenes a challenging (alkanes giving Meunier andrise topic and alkenes)to if high-value coworkersconsidering and aromaticcompoundshad the an possibility import hydrocarbons withant to organolepticcontributionuse natural (e.g., and toluene,orto thispharmacologicalabundant field ethylbenzene, by substrates studying interest. such andthe styrene) asInis alsoparticular,terpenes a challenging giving Meunier rise topic and to if high-value coworkersconsidering compoundshad the an possibility import withant to organolepticcontributionuse natural and orto thispharmacologicalabundant field by substrates studying interest. such the orasIn phenolicparticular,terpenes derivativesgiving Meunier rise and to under high-valuecoworkers homogeneous compoundshad an import and with heterogeneousant organolepticcontribution conditionsorto thispharmacological field [ 61by, 62studying,64 interest.,65,99 the–104 ]. This Inasepoxidation particular,terpenes givingof Meunier 3-carene rise and towith high-valuecoworkers NaClO inhadcompounds the an presen import withceant of organolepticcontributionMn(III) porphyrins toor thispharmacological fieldand theby studyingoxidation interest. the of epoxidationIn particular, of Meunier 3-carene and with coworkers NaClO inhad the an presen importceant of contributionMn(III) porphyrins to this fieldand theby studyingoxidation the of isInαepoxidation-pinene alsoparticular, a and challenging of αMeunier -terpinene3-carene and topic with with coworkers ifNaClO the considering same inhad oxidant the an presen import the and possibilityce KHSOant of contributionMn(III)5 [105,106]. to porphyrins use Theto natural this possibility fieldand and theby to studying abundantoxidation use H2O 2the asof substrates epoxidationα-pinene and of α -terpinene3-carene with with NaClO the same in oxidant the presen andce KHSO of Mn(III)5 [105,106]. porphyrins The possibility and the to oxidation use H2O2 asof suchoxidantepoxidationα-pinene as terpenesand and of Mn(III)α -terpinene3-carene giving porphyrin with risewith toNaClO the high-valuecatalysts same in oxidant the of presen compoundsthe and secondce KHSO of andMn(III) with5 [105,106]. third organoleptic porphyrins generation The possibility and orwas pharmacologicalthe developedto oxidation use H2O 2 byasof interest. αoxidantepoxidation-pinene and and of Mn(III)α -terpinene3-carene porphyrin with with NaClOthe catalysts same in oxidant the of presenthe and secondce KHSO of andMn(III)5 [105,106]. third porphyrins generation The possibility and was the developedto oxidation use H2O 2 byasof Cavaleiroαoxidant-pinene and and and Mn(III)α coworkers-terpinene porphyrin inwith the the oxidation catalysts same oxidant ofof 3-carene the and second KHSO [107] and and5 [105,106]. third other generationterpenoids The possibility wassuch developedtoas use1,8-cineole, H2O 2 byas InoxidantCavaleiroα-pinene particular, and and and Mn(III)α coworkers Meunier-terpinene porphyrin and inwith the coworkers the oxidation catalysts same oxidant ofof had 3-carene the an and second important KHSO [107] and and5 [105,106]. third other contribution generationterpenoids The possibility to wassuch this developedtoas field use1,8-cineole, byH2O studying 2 byas the methyloxidantCavaleiro dehydroabietate and and Mn(III) coworkers porphyrin [108], in the carvacrol, oxidation catalysts thymol, ofof 3-carene the orsecond p-cymene [107] and and [109],third other as generationterpenoids revised recently wassuch developedas [33,65]. 1,8-cineole, by epoxidationCavaleiromethyloxidant dehydroabietate and and Mn(III) of coworkers 3-carene porphyrin [108], in with the carvacrol, oxidation catalysts NaClO thymol, of inof 3-carene thethe or presencesecond p-cymene [107] and and of [109],third other Mn(III) as generationterpenoids revised porphyrins recently suchwas developedas and[33,65]. 1,8-cineole, the oxidationby of CavaleiromethylConsidering dehydroabietate and coworkers the biological [108], in the carvacrol, andoxidation pharmacological thymol, of 3-carene or p -cymene importance[107] and [109], other of steroids,as terpenoids revised several recently such groups as [33,65]. 1,8-cineole, studied αmethyl-pineneConsidering dehydroabietate and α-terpinene the biological [108], with carvacrol, and the pharmacological same thymol, oxidant or p -cymeneimportance and KHSO [109], of5 steroids,as[105 revised,106 several]. recently The possibilitygroups [33,65]. studied to use H2O2 methylalso readilyConsidering dehydroabietate available the biologicalsteroids [108], carvacrol,aiming and pharmacological to obtainthymol, new or p bioactive -cymeneimportance [109],compounds of steroids,as revised using several recently simple groups [33,65]. biomimetic studied asalsomethyl oxidant readilyConsidering dehydroabietate andavailable Mn(III)the biologicalsteroids [108], porphyrin aimingcarvacrol, and pharmacological to catalysts obtainthymol, new ofor p thebioactive -cymeneimportance second [109],compounds andof steroids,as thirdrevised using generationseveral recently simple groups [33,65]. biomimetic was studied developed by oxidativealso readilyConsidering strategies. available the biologicalInsteroids fact, aaiming andconsiderable pharmacological to obtain nu newmber bioactive importance of studies compounds ofconcerni steroids, ngusing several the simple epoxidation groups biomimetic studied and alsooxidative readilyConsidering strategies. available the biologicalInsteroids fact, aaiming andconsiderable pharmacological to obtain nu newmber bioactive importance of studies compounds ofconcerni steroids, usingng several the simple epoxidation groups biomimetic studied and Cavaleiroalsooxidative readily strategies. and available coworkers Insteroids fact, in aaiming the considerable oxidation to obtain nu of newmber 3-carene bioactive of studies [107 compounds] and concerni other usingng terpenoids the simple epoxidation biomimetic such asand 1,8-cineole, oxidativealsohydroxylation readily strategies. available of readily Insteroids fact,available aaiming considerable steroid to obtain deri nuvatives newmber bioactive byof usingstudies compounds different concerni oxidants ngusing the simple suchepoxidation as biomimetic tert-butyl and methylhydroxylationoxidative dehydroabietate strategies. of readily In fact,available [108 a], considerable carvacrol, steroid deri thymol, nuvativesmber or byofp using-cymenestudies different concerni [109], oxidants asng revisedthe suchepoxidation recently as tert-butyl [and33,65 ]. oxidativehydroperoxidehydroxylation strategies. of(TBHP), readily In 2,6-dichloropyridine fact,available a considerable steroid deri Nnuvatives-oxide,mber byiodosylbenzeneof usingstudies different concerni or oxidantsHng2O 2the as oxygensuchepoxidation as donorstert-butyl and in hydroxylationhydroperoxide of (TBHP), readily 2,6-dichloropyridine available steroid deri Nvatives-oxide, byiodosylbenzene using different or oxidantsH2O2 as oxygensuch as donorstert-butyl in thehydroxylationhydroperoxide presenceConsidering of of Fe,(TBHP), readily theRu, Mn, biological 2,6-dichloropyridine available or Os porphyrins andsteroid pharmacological deri wereNvatives-oxide, reported byiodosylbenzene using importance [110–118]. different or of oxidantsH steroids,2O2 as oxygensuch several as donorstert groups-butyl in studied hydroperoxidethehydroxylation presence of of(TBHP),Fe, readily Ru, Mn, 2,6-dichloropyridine available or Os porphyrins steroid deri wereNvatives-oxide, reported byiodosylbenzene using [110–118]. different or oxidantsH2O2 as oxygensuch as donorstert-butyl in alsohydroperoxidethe presence readilyIn general, availableof (TBHP),Fe,the Ru,key Mn,route steroids2,6-dichloropyridine or for Os the aimingporphyrins elimination to obtain wereN-oxide, of xenoreported new iodosylbenzenebiotics, bioactive [110–118]. such as compounds drugs, or H2O after2 as theiroxygen using introduction simple donors biomimeticin thehydroperoxide presenceIn general, of Fe,(TBHP),the Ru,key Mn,route 2,6-dichloropyridine or for Os the porphyrins elimination wereN-oxide, of xenoreported iodosylbenzenebiotics, [110–118]. such as drugs, or H2O after2 as theiroxygen introduction donors in theinto presence theIn general, organism of Fe,the is Ru,key initiated Mn,route or for byOs the oxidationporphyrins elimination reactions were of xenoreported catalyzedbiotics, [110–118]. suchby enzymes as drugs, of after the theircytochrome introduction P450 oxidativeintothe presence theIn general, organism strategies. of Fe,the is Ru,key initiated Mn,route In fact,or for byOs the oxidation aporphyrins considerableelimination reactions were of xeno reported number catalyzedbiotics, [110–118]. of suchby studies enzymes as drugs, concerning of after the theircytochrome theintroduction epoxidation P450 and (CYP450)into theIn general, organism group. the Therefore, is key initiated route forthe by the possibilityoxidation elimination reactions to moduof xeno catalyzedlatebiotics, their suchbymetabolic enzymes as drugs, activation of after the theircytochrome by introduction biomimetic P450 hydroxylationinto(CYP450) theIn general, organism group. the of Therefore,is readilykey initiated route available thefor by theoxidationpossibility elimination steroid reactions to derivativesmodu of xeno catalyzedlatebiotics, their by such usingbymetabolic enzymes as differentdrugs, activation of after the oxidants theircytochrome by introduction biomimetic such P450 as tert -butyl syntheticinto(CYP450) the organism modelsgroup. has Therefore,is initiatedbeen also the by responsible oxidationpossibility toreactions to intens moduive catalyzedlate studies their allbymetabolic over enzymes the activationworld. of the Most cytochrome by of biomimetic the events P450 hydroperoxide(CYP450)syntheticinto the organism modelsgroup. (TBHP), hasTherefore, is initiatedbeen 2,6-dichloropyridinealso the by responsible possibilityoxidation toreactions to intens moduNive-oxide, catalyzedlate studies their iodosylbenzene allbymetabolic over enzymes the activationworld. of orthe HMost cytochrome2 Oby2 of asbiomimetic the oxygen events P450donors in catalyzed(CYP450)synthetic modelsgroup.by CYP450 hasTherefore, been enzymes, also the responsible possibility namely to aliphaticto intens moduive lateand studies their aromatic allmetabolic over hydroxylation, the activationworld. Most bydouble of biomimetic the eventsbond thesyntheticcatalyzed(CYP450) presence modelsgroup.by ofCYP450 Fe, hasTherefore, Ru, been enzymes, Mn, also the or responsible Ospossibility namely porphyrins to aliphaticto intens modu wereive lateand studies reported their aromatic allmetabolic [over110 hydroxylation, –the118 activationworld.]. Most bydouble of biomimetic the eventsbond epoxidation,syntheticcatalyzed modelsby N -oxidationCYP450 has been enzymes,, Nalso-dealkylation, responsible namely Sto-oxidationaliphatic intensive ,and studiesdecarboxylation aromatic all over hydroxylation, the can world. be efficiently Most double of thesimulated eventsbond catalyzedepoxidation,synthetic modelsby N -oxidationCYP450 has been enzymes,, Nalso-dealkylation, responsible namely Sto-oxidationaliphatic intensive ,and studiesdecarboxylation aromatic all over hydroxylation, the can world. be efficiently Most double of thesimulated eventsbond bycatalyzedepoxidation, biomimetic by N -oxidationCYP450models underenzymes,, N-dealkylation, proper namely conditions S -oxidationaliphatic [51,61,63,66,119]. ,and decarboxylation aromatic This hydroxylation, approachcan be efficiently can givedouble simulated access bond to epoxidation,bycatalyzed biomimetic by N -oxidationCYP450models underenzymes,, N-dealkylation, proper namely conditions S -oxidationaliphatic [51,61,63,66,119]. ,and decarboxylation aromatic This hydroxylation, approachcan be efficiently can givedouble simulated access bond to importantepoxidation,by biomimetic metabolites N -oxidationmodels inunder ,adequate N-dealkylation, proper amounts, conditions S-oxidation thus [51,61,63,66,119]. facilitating, decarboxylation the prediction This approachcan studies be efficiently can of theirgive simulated accessuseful orto byimportantepoxidation, biomimetic metabolites N -oxidationmodels inunder ,adequate N-dealkylation, proper amounts, conditions S-oxidation thus [51,61,63,66,119]. facilitating, decarboxylation the prediction This approach can studies be efficiently can of theirgive simulated accessuseful orto harmfulbyimportant biomimetic effects. metabolites models inunder adequate proper amounts, conditions thus [51,61,63,66,119]. facilitating the prediction This approach studies can of theirgive accessuseful orto importantharmfulby biomimetic effects. metabolites models inunder adequate proper amounts, conditions thus [51,61,63,66,119]. facilitating the prediction This approach studies can of theirgive usefulaccess orto importantharmful effects. metabolites in adequate amounts, thus facilitating the prediction studies of their useful or harmfulimportant effects. metabolites in adequate amounts, thus facilitating the prediction studies of their useful or harmful effects.

Molecules 2016, 21, 964 9 of 40

In general, the key route for the elimination of xenobiotics, such as drugs, after their introduction into the organism is initiated by oxidation reactions catalyzed by enzymes of the cytochrome P450 (CYP450) group. Therefore, the possibility to modulate their metabolic activation by biomimetic synthetic models has been also responsible to intensive studies all over the world. Most of the events catalyzed by CYP450 enzymes, namely aliphatic and aromatic hydroxylation, double bond epoxidation, N-oxidation, N-dealkylation, S-oxidation, decarboxylation can be efficiently simulated by biomimetic models under proper conditions [51,61,63,66,119]. This approach can give access to important metabolites in adequate amounts, thus facilitating the prediction studies of their useful or harmful effects. Nowadays, the negative impact caused by the presence of organosulfur compounds such as the recalcitrant benzothiophenes (BTs) and dibenzothiophenes (DBTs) in fuels is well established [120]. In fact, the combustion of organosulfur compounds is usually associated with the formation of acid rains, the poisoning of the catalysts and the corrosion of the internal parts of combustion engines [121]. Considering the restrictive regulations limiting the sulfur content on petroleum products, allied to the technical limitations of the common hydrodesulphurization procedures, synthetic metalloporphyrins are also being considered in the research studies concerning the so-called oxidative desulfurization (ODS) methodologies [122,123]. In some of those studies the authors selected H2O2 as oxidant and manganese(III) or iron(III) complexes of the second generation, affording the corresponding fully oxidized derivatives with high conversions at room temperature. So, the high potential of the metalloporphyrin complexes as catalysts for the sulfoxidation of the S-recalcitrant benzothiophenes and dibenzothiophenes by H2O2 was demonstrated [122,123]. Polluting phenolics and humic substances have been also suggested as substrates for synthetic metalloporphyrins, in an intriguing series of papers dealing with the development of processes for the treatment of polluted soils [124–128]. Dehalogenation of halogenated phenols, mimicking chloroperoxidases has been also described [129–133]. In recent years a particular attention was also given to the use of biomimetic models in the oxidative degradation of lignin [134]. This subject is also considered a hot topic since this renewable polymer can be an excellent source of aromatic compounds of low molecular weight. Additionally, the selective degradation of lignin and its removal from the carbohydrate component of wood is a key step in pulp and paper industry [29,135]. Another important field of research where the oxidative potential of these biomimetic models is being considered is related with the presence of drugs and its metabolites, pesticides, or dyes in natural waters, being a serious problem to aquatic and human life. In particular, textile dyes, due to their chemical inertness, toxicity, and high production, are of special environmental concern and the potential of metalloporphyrins to degrade different dyes will be the subject of a more profound discussion in the next section.

2.3. Immobilization and Emulation of Ligninolytic Enzymes A huge amount of papers reports the catalytic activity of metalloporphyrins in homogenous phase [33,127,136–139], even in the context of the treatment of textile dyes [140,141]. However, the heterogenization of the catalyst is a striking priority for the feasibility of a large scale process [29,142]. Several factors prompt such a requirement:

‚ The synthesis of metalloporphyrins is quite expensive, and at the same time, a significant part of their initial catalytic activity is retained at the end of the process [143,144]. Accordingly, their recovery is significantly cost-effective; ‚ Toxicology of metalloporphyrins is still almost unknown. So, a separation from reaction mixture is usually required, further increasing the cost of the process [29]; ‚ If performed correctly, i.e., emulating ligninolytic peroxidases active site [28,145], immobilization could increase stability and efficiency of the catalyst [25]; Molecules 2016, 21, 964 10 of 40

‚ Metalloporphyrins are intensely colored, as well as the dye substrates, frustrating the whole purpose of the process when used in free form to bleach dyes.

Immobilization, however, poses also some potential drawbacks in addition to all these positive effects. For instance, too strict confinement of catalysts inside a narrow 3D network of the support could lead to some mass transfer limitations, or at least sterical hindrance of immobilized catalysts. Especially, if the immobilization is not performed properly (i.e., not proper size of support pores, excessive crowding of catalysts onto the surface of the support). Several approaches for metalloporphyrins heterogenization have been proposed, somewhat resembling the methods used for protein immobilization [146–148]. The main methods are encompassed in Table3.

Table 3. Main features of the various immobilization approaches for metalloporphyrins [29].

Type of Method of Advantages Disadvantages Interaction Immobilization Leakage Physical Encapsulation/ Minimization of chemical modification of the inclusion entrapment catalyst No emulation of peroxidases active site Involvement of toxic and costly reagents Minimization of chemical modification of the Usually the interaction catalyst/support is weak catalyst Adsorption Leakage Weak chemical Easy method interaction No emulation of peroxidases active site Usually the interaction catalyst/support is weak Minimization of chemical modification of the Ion exchange catalyst Leakage No emulation of peroxidases active site Covalent The interaction catalyst/support is very strong Chemical modification of the catalyst is possible Strong chemical binding Minimal catalyst leakage No emulation of peroxidases active site interaction Real emulation of peroxidases active site Axial Axial bis-ligation of the catalysts coordination Increased stability and activity

Adsorption is the most common method for immobilization of metalloporphyrins, not involving any grafting of supports or elaborate coupling reactions. Adsorption relies on a combination of overlapping non-specific weak interactions [146], being not always easily distinguishable from other techniques, such as ion exchange. Physical inclusion (i.e., encapsulation, and entrapment) is also possible, involving any interaction between catalyst and support, but the first is simply included in the tridimensional frame of the later. Therefore, no chemical modification of catalyst occurs, allowing theoretically the retention of its whole catalytic activity. The strongest interaction possible can be achieved, on the contrary, through covalent bonds. Consequently, this approach tops the others about the minimization of leakage issues. Several reactions have been developed to perform the immobilization of the most diffused metalloporphyrins (particularly, the second generation ones, Figure1). Perfluorinated porphyrins, such as the Fe(III) and Mn(III) complexes of 5,10,15,20-tetrakis (pentafluorophenyl)porphyrin TPFP can be for instance immobilized by nucleophilic addition from aminofunctionalized support, yielding a stable secondary amine [68,103,149], as shown on the path (a) of Scheme6). Carboxyfunctionalized porphyrins, such as the Mn(III) complex of 5,10,15,20-tetrakis(4- carboxyphenyl)porphyrin, can be activated through a carbodiimide [146] to give amide bond with aminopropylated supports [150] (path (b) Scheme6). In the case of methoxylated analog porphyrins, such as the Mn(III) complex of 5,10,15,20-tetrakis(4-methoxycarbonylphenyl)porphyrin, a similar reaction occurs in the presence of NaH as the condensation activator [151]. Molecules 2016, 21, 964 11 of 40

Hydroxyl porphyrins, such as the Mn(III) complex of 5,10,15,20-tetrakis(4-hydroxyphenyl) porphyrin, can be easily immobilized on epoxyfunctionalized supports. The presence of suitable basic catalysts (such as triethylamine, NaOH, or Na2CO3) affords the formation of a stable alkyl-aryl-ether bond [152], as shown in the path (c) of Scheme6. Covalent immobilization of dichlorophenylporphyrins, such as the Mn(III) complex of 5,10,15,20-tetrakis(2,6-dichlorophenyl)porphyrin, TDCP, is not direct, usually requiring the insertion in the meso-aromatic ring of –NH2 functions. These aromatic amines can yield in turn amide bond with carboxyl-grafted supports, upon thionyl chloride activation [153], as depicted in the path (d) of Scheme6. Thionyl chloride (or other activating halides like PCl5 [29]) can be used as well to activate sulfonated porphyrins, such as the Mn(III) and Fe(III) complexes of 5,10,15,20-tetrakis(2,6-dichloro-3- sulfonatophenyl)porphyrin, yielding sulfonamide bonds with aminated supports [153] (path (e)

SchemeMolecules6). 2016, 21, 964 11 of 39

Scheme 6. Some of the most common methods for the covalent immobilization of metalloporphyrins. Scheme 6. Some of the most common methods for the covalent immobilization of metalloporphyrins. Each technique, however, shows some drawbacks, as summarized in Table 2. Physical inclusion, Eachadsorption, technique, and however, ion exchange shows immobilization, some drawbacks, in fact, as suffer summarized from too in weak Table linkage2. Physical between inclusion, adsorption,metalloporphyrin and ion exchange and support, immobilization, involving a possible in fact,leakage suffer of the from catalyst too during weak reaction. linkage This between metalloporphyrincircumstance andshould support, be avoided involving by all means, a possible since it leakageposes a double of the economical catalyst duringconcern. reaction.In fact, a This part of still active catalysts is relentlessly loss. On the other hand, reaction products could be seriously circumstancecontaminated should by be the avoided colored metalloporphyrin. by all means, since it poses a double economical concern. In fact, a part of still activeConversely, catalysts covalent is relentlessly immobilization loss. provides On the a other strong hand, interaction, reaction minimizing products leakage could issues. be seriously contaminatedBut during by the immobilization colored metalloporphyrin. reactions chemical modification of the catalyst is possible. All these Conversely,approaches covalent have found, immobilization in any case, extensive provides applications a strong interaction, for the immobilized minimizing metalloporphyrins leakage issues. But during the[32,152,154–157]. immobilization reactions chemical modification of the catalyst is possible. All these approaches have found,However, in any case, none extensive of these approaches applications strictly for the emulat immobilizedes ligninolytic metalloporphyrins peroxidase active [ 32site.,152 In, 154fact,– 157]. in lignin peroxidase (LiP), manganese peroxidase (MnP), and versatile peroxidase (VP), the imidazole However, none of these approaches strictly emulates ligninolytic peroxidase active site. In fact, in from a histidine side chain coordinates iron(III)-heme. Similarly, the thiolate function from a cysteine lignin peroxidaseresidue is responsible (LiP), manganese for immobi peroxidaselization of the (MnP), prosthetic and versatilegroup in peroxygenases peroxidase (VP), and thein some imidazole from a histidinecytochromes side [29]. chain Besides, coordinates the favorable iron(III)-heme. effect of axial Similarly, ligand on the metalloporphyrins thiolate function stability from and a cysteine efficiency has been clearly demonstrated [25,29,104,158,159]. Accordingly the immobilization through coordinative interaction onto imidazole coated supports has been also proposed [143,160–162] (Figure 2a), avoiding the need of adding imidazole as the co-catalyst to the reaction mixture [163–165]. Somewhat paralleling the emulation of ligninolytic peroxidases active site, also immobilization through coordinative bonds onto pyridine- [26,27,31] (Figure 2b), and thiol-grafted supports [30] (Figure 2c) has been reported with promising results both in terms of metalloporphyrin loading onto the supports and catalytic performance of the adduct. Besides, the effect of different ligands on specificity, selectivity, and promotion of different catalytic paths (in particular one-electron oxidations versus direct oxygenation [29]) has been clearly demonstrated [26,30,104].

Molecules 2016, 21, 964 12 of 40 residue is responsible for immobilization of the prosthetic group in peroxygenases and in some cytochromes [29]. Besides, the favorable effect of axial ligand on metalloporphyrins stability and efficiency has been clearly demonstrated [25,29,104,158,159]. Accordingly the immobilization through coordinative interaction onto imidazole coated supports has been also proposed [143,160–162] (Figure2a), avoiding the need of adding imidazole as the co-catalyst to the reaction mixture [163–165]. Somewhat paralleling the emulation of ligninolytic peroxidases active site, also immobilization through coordinative bonds onto pyridine- [26,27,31] (Figure2b), and thiol-grafted supports [ 30] (Figure2c) has been reported with promising results both in terms of metalloporphyrin loading onto the supports and catalytic performance of the adduct. Besides, the effect of different ligands on specificity, selectivity, and promotion of different catalytic paths (in particular one-electron oxidations versusMolecules direct 2016, 21 oxygenation, 964 [29]) has been clearly demonstrated [26,30,104]. 12 of 39

FigureFigure 2.2. ImmobilizationImmobilization of metalloporphyrins through through coordination coordination bond. bond. The The most most common common ligands ligands areare imidazoleimidazole ((aa)) toto emulateemulate thethe activeactive sitesite of ligninolyticligninolytic peroxidases peroxidases [28,143]; [28,143]; pyridine pyridine (b (b) )[[26,31];26,31]; and and mercaptomercapto functionfunction (c) to emulate emulate the the active active site site of of cytochrome cytochrome P450 P450 and and peroxygenase peroxygenase [30]. [30 ].

3.3. Textile Dyes Dyes are chemical compounds characterized by absorbing in the visible region of the Dyes are chemical compounds characterized by absorbing in the visible region of the electromagnetic spectrum (400 to 700 nm). Until the XIXth century, most dyes came from natural electromagnetic spectrum (400 to 700 nm). Until the XIXth century, most dyes came from natural sources such as leaves, roots, berries, insects, molluscs, or were mineral substances. sources such as leaves, roots, berries, insects, molluscs, or were mineral substances. The Perkin reaction opened the way to the development of a huge number of synthetic dyes, The Perkin reaction opened the way to the development of a huge number of synthetic dyes, belonging to different classes, according to the structural motifs representing the chromophoric belonging to different classes, according to the structural motifs representing the chromophoric moieties within their chemical structures [166]. moieties within their chemical structures [166]. Industrial dyes represent a large group of organic compounds that could have undesirable effects Industrial dyes represent a large group of organic compounds that could have undesirable effects on the environment [167] and, in addition, many of them can pose risks to human health [168–170]. By on the environment [167] and, in addition, many of them can pose risks to human health [168–170]. By definition, an industrially applicable dye should be a quite resistant compound, capable of surviving definition, an industrially applicable dye should be a quite resistant compound, capable of surviving against harsh conditions such as prolonged exposition to sunlight, and harsh washing and/or bleaching against harsh conditions such as prolonged exposition to sunlight, and harsh washing and/or bleaching treatments. Accordingly, they are very often recalcitrant with respect to chemical and biological treatments. Accordingly, they are very often recalcitrant with respect to chemical and biological degradation processes [169,171–173]. degradationUnfortunately, processes nowadays [169,171– the173 demand]. has led to the widespread use of synthetic colors. They representUnfortunately, the most economical nowadays solution the demand for industri has ledes, to for the both widespread the higher use performances of synthetic compared colors. They to representthe natural the ones, most and economical for considerably solution lower for industries, costs. for both the higher performances compared to the naturalThe synthetic ones, and dyes for have considerably to show lowerthe two costs. features of being absorbed by the fabrics to be dyed (affinity)The syntheticand of remaining dyes have fixed to show(solidity). the two features of being absorbed by the fabrics to be dyed (affinity)These and dyes of remaining are very often fixed aromatic (solidity). compounds with largely delocalized π electrons, responsible for theThese absorption dyes are of very visible often light. aromatic In particular, compounds the dye with moiety, largely primarily delocalized responsibleπ electrons, for the responsiblecoloration forof thethe absorptioncompound, of is visible defined light. as the In particular, chromophore. the dye Co moiety,lor intensity primarily is reinforced responsible by forthe thepresence coloration of ofsubstituents, the compound, capable is of defined participat as theing chromophore.to the electron delocalization, Color intensity and is called reinforced auxochromes. by the presence These are of substituents,often involved capable in other of participatingimportant properties, to the electron such as delocalization, the solubility andof the called dye in auxochromes. water (or sometimes These are oftenin non-aqueous involved in solvents) other important as well as properties, its affinity such and assolidity the solubility [166,174]. of the dye in water (or sometimes in non-aqueousFor the purposes solvents) of the as present well as re itsview, affinity industrial and solidity dyes could [166 be,174 co].nveniently classified by following a chemical/structural criterion [169], rather than a technical one. So, the main classes of industrial dyes, that have been the target of biomimetic oxidative degradation studies, under metalloporphyrin catalysis, are briefly described below: Azo Dyes. These synthetic dyes are typical for the presence of one or sometimes more chromophoric groups –N=N–. The azo bridge joins two aromatic rings, one of which bears electron-releasing, and the other electron-withdrawing substituents (Figure 3a. R1, R2, R3 represent hydrogen and/or electron- releasing substituents such as –OH, –OCH3, –NH2; X1, X2, X3 represent hydrogen and/or electron- withdrawing groups such as –NO2 and –SO3−).

Molecules 2016, 21, 964 13 of 40

For the purposes of the present review, industrial dyes could be conveniently classified by following a chemical/structural criterion [169], rather than a technical one. So, the main classes of industrial dyes, that have been the target of biomimetic oxidative degradation studies, under metalloporphyrin catalysis, are briefly described below: Azo Dyes. These synthetic dyes are typical for the presence of one or sometimes more chromophoric groups –N=N–. The azo bridge joins two aromatic rings, one of which bears electron-releasing, and the other electron-withdrawing substituents (Figure3a. R 1,R2,R3 represent hydrogen and/or electron-releasing substituents such as –OH, –OCH3, –NH2;X1,X2,X3 represent hydrogen and/or ´ electron-withdrawingMolecules 2016, 21, 964 groups such as –NO2 and –SO3 ). 13 of 39

FigureFigure 3. Core 3. Core structure structure of of some some of of the the most most usedused textile dyes. dyes. (a ()a azo;) azo; (b) ( banthraquinone;) anthraquinone; (c) indigo; (c) indigo; (d) cationic; (e) triphenylmethane; (f) other cationic dyes with condensed tricyclic systems derived (d) cationic; (e) triphenylmethane; (f) other cationic dyes with condensed tricyclic systems derived from acridine/phenazine/phenoxazine or similar structures, where one heteroatom bears a net from acridine/phenazine/phenoxazine or similar structures, where one heteroatom bears a net positive charge. positive charge. The aromatic rings could virtually derive from benzene, naphthalene, or also heteroaromatics. TheCommercially, aromatic azo rings dyes could represent virtually the most derive important from cl benzene,ass of synthetic naphthalene, dyes, as they or also show heteroaromatics. at the same Commercially,time facile azoproduction dyes represent at low cost, the bright most importantcolors with classa number of synthetic of beautiful dyes, different as they nuances, show at high the same timeaffinity facile production and solidity. atThe low –N=N– cost, moiety, bright placed colors betw witheen a the number two aromatic of beautiful portions, different is called nuances,azo group high affinityand and it is solidity. a strong The chromophore –N=N– moiety, conferring placed a bright between color, the usually two aromatic ranging from portions, yellow is calledto orange azo to group red [175]. An example of an azo dye is Methyl Orange, used for dyeing wool and silk, and perhaps and it is a strong chromophore conferring a bright color, usually ranging from yellow to orange to better-known by far as a popular pH indicator. red [175]. An example of an azo dye is Methyl Orange, used for dyeing wool and silk, and perhaps As a general feature, azo dyes are toxic to many forms of life. Many have been withdrawn from the better-knownmarket—in by particular far as a popularamong those pH used indicator. for coloring food—because of their carcinogenic properties. AsTheir a general toxicity feature,arises from azo their dyes in are vivo toxic reduction to many to formsaromatic of amines life. Many upon have enzymatic been withdrawn cleavage of fromthe the market—inazo group particular [170,176,177]. among Therefore, those used their formassive coloring presence food—because in wastewaters, of their released carcinogenic by textile plants, properties. Theirrepresents toxicity arises a major from concern their inin the vivo perspectivereduction of to so aromaticlving the aminessevere pollution upon enzymatic problems cleavagecaused by of the azo groupsuch plants. [170,176 ,177]. Therefore, their massive presence in wastewaters, released by textile plants, representsAnthraquinone a major concern dyes. These in the derive perspective from the ofalmost solving colorle thess severe9,10-anthraquinone. pollution problems The industrially caused by suchrelevant plants. derivatives contain powerful electron-donating groups such as amino or hydroxy substituents as auxochromes, in at least one of the four α positions (Figure 3b, X1, X2, X3, X4 represent electron- Anthraquinone dyes. These derive from the almost colorless 9,10-anthraquinone. The industrially releasing substituents such as –OH and –NH2, which can also form hydrogen bonds with the adjacent relevant derivatives contain powerful electron-donating groups such as amino or hydroxy substituents carbonyls. Up to three substituents could be hydrogen atoms; additional substituents could be as auxochromes,present at the in βat positions). least one Some of the hydroxyanthr four α positionsaquinones (Figure are3b, of X natural1,X2,X origin,3,X4 represent but can be electron-releasing industrially substituentssynthesized such with as –OHsharply and lower –NH costs,2, which whereas can many also ot formhers hydrogen(amino-, nitro-, bonds and/or with sulfo-derivatives) the adjacent carbonyls. are Up tosynthetic. three substituents Simple anthraquinone could be hydrogendyes include atoms; Alizarin additional (1,2-dihydroxy substituents-anthraquinone), could be once present obtained atthe β positions).from Rubia Some tinctorum hydroxyanthraquinones, and its non-natural derivative are of natural Alizarin origin, Red S but (1,2-dihydroxyanthraquinone-3- can be industrially synthesized with sharplysulfonic acid, lower ARS). costs, Whether whereas natural many or based others on (amino-,natural molecules, nitro-, and/or anthraquinone sulfo-derivatives) dyes show cumulative are synthetic. Simpletoxicity anthraquinone [178]. Anthraquinone dyes include dyes are Alizarin among the (1,2-dihydroxy-anthraquinone), most durable industrial dyes and therefore once obtained are used from Rubiawhen tinctorum high, resistance and its non-natural against sunlight derivative and/or Alizarin harsh environmental Red S (1,2-dihydroxyanthraquinone-3-sulfonic conditions is required. Such a feature could obviously be a significant problem for their degradation [144]. Unnatural, α-amino- acid, ARS). Whether natural or based on natural molecules, anthraquinone dyes show cumulative substituted hydroxyanthraquinones are valuable dyes whose colors range from green to blue to purple. Indigoid dyes. These are named after indigo (Figure 3c) obtained from the plant Indigofera tinctoria [179]. One or more positions on each benzene ring could bear different substituents in both natural and synthetic indigoids. Another prominent dye of this class is 6,6′-dibromoindigo, which is the Tyrian purple, produced as a colorless precursor by the shellfish Murex brandaris [180]. Natural indigoids are insoluble pigments rather than dyes, but can be transiently solubilized by reduction, and in turn

Molecules 2016, 21, 964 14 of 40 toxicity [178]. Anthraquinone dyes are among the most durable industrial dyes and therefore are used when high resistance against sunlight and/or harsh environmental conditions is required. Such a feature could obviously be a significant problem for their degradation [144]. Unnatural, α-amino-substituted hydroxyanthraquinones are valuable dyes whose colors range from green to blue to purple. Indigoid dyes. These are named after indigo (Figure3c) obtained from the plant Indigofera tinctoria [179]. One or more positions on each benzene ring could bear different substituents in both natural and synthetic indigoids. Another prominent dye of this class is 6,61-dibromoindigo, which is the Tyrian purple, produced as a colorless precursor by the shellfish Murex brandaris [180]. Natural indigoids are insoluble pigments rather than dyes, but can be transiently solubilized by reduction, and in turn directly fixed to the fibers upon re-oxidation by air (vat dyes). Indigoids are typical for their exceptional resistance to sunlight, durability and solidity. Cationic dyes. Cationic dyes should be defined as dyes whose positive charge(s) are an essential part of their chromophores [181]. They should not be confused with other dyes, whose positive charges are not involved in the chromophoric structures, but have the main function of conferring solubility in water and/or the ability of forming strong ionic interaction with negatively charged fibers. Several applications have been described for these dyes [182,183]. In a stricto sensu cationic dyes belong to the cyanine group (in turn a subclass of the polymethine family, Figure3d), showing a variable number of conjugated double bonds ending with two nitrogen atoms at the two termini of the unsaturated chain. The odd number of carbon atoms forming the unsaturated chain implies the presence of a net positive charge, delocalized between the two nitrogen atoms at the ends of the polyene bridge. Many dyes belong to the group, although many are conventionally classified as diphenylmethane, triphenylmethane, fuchsoneimine and benzophenoneimine derivatives (Figure3e, showing as an example the fundamental structure of fuchsoneimine, where R1 and R2 represent generic amine substituents) and moreover their condensed and/or internally bridged derivatives [184]. Other cationic dyes contain condensed tricyclic systems derived from acridine, phenazine, phenoxazine, phenothiazine, xanthene, where one heteroatom bears a net positive charge (Figure3f, showing a generic azine); the X atom can be O, S, N. The positive charge on the ring heteroatom is partially delocalized on the two amino substituents). Such systems could be regarded as azomethine isologs where the nitrogen atom could be eventually changed in an oxygen or sulfur atom, in the form of an oxonium or sulfonium cation, respectively.

4. Application of Metalloporphyrins in the Decolorization of Textile Dyes

4.1. Biomimetic Bleaching of Industrial Dyes As previously underlined (Section3), industrial (more particularly, textile) dyes are organic molecules, almost invariably containing heteroatoms such as oxygen, nitrogen, sulfur, and combinations of these. As such, they are potentially oxidizable by a variety of different oxidizing agents, ranging from molecular oxygen to more active and efficient compounds such as hydrogen peroxide, some alkyl- or acyl-peroxides, peroxyacids, possibly in the presence of suitable catalysts. Sadly, the most active oxidizing agents are very often unstable species, could in turn release exhaust products causing environmental and toxicological concerns, and are unacceptably expensive. In this sense, hydrogen peroxide represents a good compromise between cost and effectiveness [28,185]:

‚ It is reasonably stable and safe for production, transport, storage, delivery, and usage. ‚ Its relatively low price has allowed a more and more wide use in many technological applications. ‚ Last but not least, side products arising from its action are only water and molecular oxygen, causing no environmental and toxicological concern.

Hydrogen peroxide is much more reactive than molecular oxygen, due to its substantially lower activation energy. Although the redox potential for H2O2 reduction is higher at acidic pH values, Molecules 2016, 21, 964 15 of 40 where it acts as a weak electrophile toward electron-rich substrates, as a rule it is generally much more effective as an oxidant for organic compounds in alkaline environment. Under such conditions, the concentration of the hydroperoxide ion HOO´ becomes important, which explains the reactivity towards electrophilic positions of the oxidizable substrates. In the pH range 10–12, hydroperoxide anion can react with non-dissociated peroxide [186], giving rise to the very strong oxidizer hydroxyl radical, and superoxide anion. The latter acts as a relatively weak oxidizer [187], preferentially attacking electrophilic places (when present) in the oxidizable organic molecules, or can also react further with each other releasing molecular oxygen. Moreover, two superoxide anions can produce the very aggressive singlet oxygen. Therefore, within that pH range hydrogen peroxide can indirectly oxidize and bleach substances, which are quite resistant to the same oxidizer when pH is lower than 10. However, a substantial peroxide fraction is wasted as molecular oxygen, so the overall efficiency of the oxidation process can be noticeably lowered. The above described picture can dramatically change in the presence of a number of catalysts, such as polyoxometalates (POMs), which have been very recently reviewed [188]. Many POMs are effective oxidation catalysts, and some can profitably use hydrogen peroxide as the oxidizer. However, despite of their efficiency and stability, that allow catalyst recycling, their solubility in the (aqueous) media poses a serious concern for their recovery, to avoid unwanted losses and dispersion of heavy metal compounds in treated wastewaters. As noted in Section 2.3, redox-active metalloporphyrins usually behave as more or less efficient oxidation catalysts. For the particular purpose of textile plant wastewater bleaching, they have to be immobilized, to allow their retention within the reactor, so determining substantial savings (they are rather expensive compounds) and preventing pollution and toxicological concerns. However, a number of studies have been carried out also with metalloporphyrins in solution, that have brought a substantial contribute in elucidating degradation/bleaching mechanism(s) for some classes of industrial dyes. To a certain extent, metalloporphyrin catalysts could be compared to high-redox- potential peroxidases [189], which are on the whole much more active, but also substantially costlier. Somewhat surprisingly, no degradation studies are reported on indigoid dyes, under metalloporphyrin catalysis, although water-soluble indigo carmine is a good substrate for peroxidases (vide infra). Therefore, the efficient, biomimetic oxidative bleaching of indigoids by means of redox-active metalloporphyrins looks highly likely. The applications to azo, anthraquinone and cationic dyes are reported in Sections 4.1.1–4.1.3, respectively. Finally, applications of the same catalysts to dyes of different classes are reported in Section 4.1.4.

4.1.1. Azo Dyes Some synthetic iron porphyrins have been tested as catalysts for azo dye bleaching. Hodges and colleagues [190,191] have prepared the relatively stable Cpd II analog of a sterically hindered, anionic, water-soluble iron(III) complex of 5,10,15,20-tetrakis(2,6-dichloro-3-sulfonatophenyl)porphyrin, and assessed its effectiveness in bleaching some azo dyes under different working conditions. The chosen dyes were all phenylazo derivatives of substituted 1- or 2-naphthols (Figure4). As such, these azo dyes exist in tautomeric equilibrium with the corresponding hydrazones. The studied pH range was between 6.93 and 12.68, which influenced the protonation state of the 2-naphthol derived dyes, where a strong internal hydrogen bridge exists between the phenolic hydroxyl and the distal nitrogen of the azo group. Therefore, the acidity of the phenolic function is reduced, and under neutral conditions each dye effectively exists as a mixture of the azo and hydrazone forms (each with its own reactivity towards the oxidizing agent, and with a prevalence of the hydrazone form over the conventional azo form), whereas at alkaline pH values such tautomerism is abolished as the dyes largely exist as the corresponding delocalized anions. On the whole, the Cpd II analog of the studied iron porphyrin behaved as an efficient oxidant towards this series of azo dyes. Molecules 2016, 21, 964 15 of 39

The above described picture can dramatically change in the presence of a number of catalysts, such as polyoxometalates (POMs), which have been very recently reviewed [188]. Many POMs are effective oxidation catalysts, and some can profitably use hydrogen peroxide as the oxidizer. However, despite of their efficiency and stability, that allow catalyst recycling, their solubility in the (aqueous) media poses a serious concern for their recovery, to avoid unwanted losses and dispersion of heavy metal compounds in treated wastewaters. As noted in Section 2.3, redox-active metalloporphyrins usually behave as more or less efficient oxidation catalysts. For the particular purpose of textile plant wastewater bleaching, they have to be immobilized, to allow their retention within the reactor, so determining substantial savings (they are rather expensive compounds) and preventing pollution and toxicological concerns. However, a number of studies have been carried out also with metalloporphyrins in solution, that have brought a substantial contribute in elucidating degradation/bleaching mechanism(s) for some classes of industrial dyes. To a certain extent, metalloporphyrin catalysts could be compared to high-redox- potential peroxidases [189], which are on the whole much more active, but also substantially costlier. Somewhat surprisingly, no degradation studies are reported on indigoid dyes, under metalloporphyrin catalysis, although water-soluble indigo carmine is a good substrate for peroxidases (vide infra). Therefore, the efficient, biomimetic oxidative bleaching of indigoids by means of redox- active metalloporphyrins looks highly likely. The applications to azo, anthraquinone and cationic dyes are reported in Sections 4.1.1–4.1.3., respectively. Finally, applications of the same catalysts to dyes of different classes are reported in Section 4.1.4.

4.1.1. Azo Dyes Some synthetic iron porphyrins have been tested as catalysts for azo dye bleaching. Hodges and colleagues [190,191] have prepared the relatively stable Cpd II analog of a sterically hindered, anionic, water-soluble iron(III) complex of 5,10,15,20-tetrakis(2,6-dichloro-3-sulfonatophenyl)porphyrin, and assessed its effectiveness in bleaching some azo dyes under different working conditions. The chosen dyes were all phenylazo derivatives of substituted 1- or 2-naphthols (Figure 4). As such, these azo dyes exist in tautomeric equilibrium with the corresponding hydrazones. The studied pH range was between 6.93 and 12.68, which influenced the protonation state of the 2-naphthol derived dyes, where a strong internal hydrogen bridge exists between the phenolic hydroxyl and the distal nitrogen of the azo group. Therefore, the acidity of the phenolic function is reduced, and under neutral conditions each dye effectively exists as a mixture of the azo and hydrazone forms (each with its own reactivity towards the oxidizing agent, and with a prevalence of the hydrazone form over the conventional azo form), whereas at alkaline pH values such tautomerism is abolished as the dyes largely exist as the Moleculescorresponding2016, 21, 964 delocalized anions. On the whole, the Cpd II analog of the studied iron porphyrin16 of 40 behaved as an efficient oxidant towards this series of azo dyes.

FigureFigure 4. Substituted 4. Substituted phenylazo phenylazo derivatives derivatives of substituted 1- 1- or or 2-naphthols 2-naphthols studied studied as substrates as substrates of of the iron(III) complex of 5,10,15,20-tetrakis(2,6-dichloro-3-sulfonatophenyl)porphyrin (TDCSP). the iron(III) complex of 5,10,15,20-tetrakis(2,6-dichloro-3-sulfonatophenyl)porphyrin (TDCSP).

Molecules 2016, 21, 964 16 of 39 In principle, three different mechanisms can operate in oxidation by the Cpd II analog, the studied iron porphyrin:In principle, (i) oxygen three different transfer mechanis (OT); (ii)ms can electron operate transfer in oxidation (ET); by and the (iii)Cpd hydrogenII analog, the atom studied transfer (HAT).iron The porphyrin: general (i) mechanisms oxygen transfer are (OT); encompassed (ii) electron in transfer Scheme (ET);7. Of and these, (iii) thehydrogen OT has atom been transfer ruled out (HAT). The general mechanisms are encompassed in Scheme 7. Of these, the OT has been ruled out for for that iron porphyrin in aqueous environment. ET was the only possible mechanism under alkaline that iron porphyrin in aqueous environment. ET was the only possible mechanism under alkaline conditions,conditions, where where the the studied studied dyes dyes exist exist as as thethe correspondingcorresponding anions. anions. Also Also the theHAT HAT mechanism mechanism seems seems to beto unlikely, be unlikely, as the as the authors authors noted noted that that when when methoxylmethoxyl group group was was substituted substituted for hydroxyl for hydroxyl group group in in positionposition 2 of 2 the of the naphthalene naphthalene ring, ring, onlyonly a marginal difference difference in the inthe reaction reaction rate was rate observed. was observed.

SchemeScheme 7. The 7. The reductions reductions of of metalloporphyrin metalloporphyrin Cpd II II analoganalog can can follow follow three three main main pathways: pathways: oxygen oxygen transfertransfer (OT), (OT), hydrogen hydrogen atom atom transfer transfer (HAT), (HAT), andand electron transfer transfer (E (ET)T) (S (S= substrate). = substrate). OT path OT pathunder under thesethese conditions conditions was was not not observed. observed.

When the same ferriporphyrin was treated with a stoichiometric excess of peroxyacids such as metaWhen-chloroperoxybenzoic the same ferriporphyrin acid or magnesium was treated monoperoxyphthalate, with a stoichiometric the Cpd excessI analog ofis the peroxyacids first suchreaction as meta product.-chloroperoxybenzoic This can quickly acid attack or magnesiumthe azo dye with monoperoxyphthalate, a two-electron mechanism, the Cpd therefore I analog is the firstrestoring reaction the product.resting ferriporphyrin, This can quickly or alternatively attack the can azo comproportionate dye with a two-electron with the mechanism,resting thereforeferriporphyrin, restoring thus the restinggiving rise ferriporphyrin, to two molecules or alternativelyof Cpd II analog. can comproportionate with the resting ferriporphyrin,The latter thus slowly giving reacts rise with to two the moleculesdye, following of Cpd a one-electron II analog. oxidation mechanism that again leadsThe latter to the slowlyresting ferriporphyrin. reacts with the Interestingly, dye, following when a the one-electron peroxyacid oxidation concentration mechanism is increased that far again beyond the stoichiometric requirements, the overall oxidant accountability tends to decline. This has leads to the resting ferriporphyrin. Interestingly, when the peroxyacid concentration is increased far been attributed to the competing comproportionation reaction, consuming the very active Cpd I beyond the stoichiometric requirements, the overall oxidant accountability tends to decline. This has analog and therefore slowing the dye bleaching. At sharply alkaline pH (11.88) 1-phenylazo-2- beennaphthol attributed dyes to themainly competing exist as the comproportionation corresponding anions, reaction, which consumingare attacked theby the very Cpd active I analogCpd by I analoga and thereforedirect oxygen slowing transfer the (or dye by bleaching. an oxygen Atrebound sharply mech alkalineanism [192]), pH (11.88) giving 1-phenylazo-2-naphthol rise to 1-carbinols. Upon dyes mainlyhydrolysis, exist as such the corresponding carbinols are cleaved anions, unsymmetrically, which are attacked giving byrise theto oCpd-naphthoquinone I analog by aderivatives direct oxygen transfer(and (or their by degradation an oxygen products) rebound and mechanism phenylazenes [192 (and]), giving their degradation rise to 1-carbinols. products), Scheme Upon hydrolysis,8. At pH 9.30, the same dyes are largely un-ionized, with the hydrazone tautomers prevailing. Under these conditions, transient β-azoxycompounds arise, which in turn undergo a nucleophilic attack of a hydroxide ion at the position 4 of the naphthol ring, whereas the original azo moiety is restored as it happens along the Wallach rearrangement, Scheme 9. Finally, when pH was fixed at 6.93 and the oxygen donor was tert-butylhydroperoxide, Cpd II analog directly arose together with tBu–O∙. Both are unable to perform direct (or rebound) oxygen transfer, and act by a HAT mechanism on the 2-naphthol function of the dye. The arising free radical can react with molecular oxygen, and further transformations afforded the same product obtained at pH 11.88 with peroxyacids, Scheme 10.

Molecules 2016, 21, 964 17 of 40 such carbinols are cleaved unsymmetrically, giving rise to o-naphthoquinone derivatives (and their degradationMolecules products) 2016, 21, 964 and phenylazenes (and their degradation products), Scheme8. 17 of 39

Molecules 2016, 21, 964 17 of 39

Scheme 8. At alkaline pH (almost 12) Cpd I analog converts 1-phenylazo-2-naphthol dyes in 1-carbinols. Scheme 8. At alkaline pH (almost 12) Cpd I analog converts 1-phenylazo-2-naphthol dyes in 1-carbinols. These in turn can be cleaved unsymmetrically by Cpd II (X = –NO2 or –OCH3). These in turn can be cleaved unsymmetrically by Cpd II (X = –NO2 or –OCH3).

At pH 9.30, the same dyes are largely un-ionized, with the hydrazone tautomers prevailing. Under these conditions, transient β-azoxycompounds arise, which in turn undergo a nucleophilic attack of a hydroxideScheme 8. At alkaline ion at pH the (almost position 12) Cpd 4 Iof analog the converts naphthol 1-phenylazo-2-naphthol ring, whereas dyes the in original 1-carbinols. azo moiety is restored as itThese happens in turn alongcan be cleaved the Wallach unsymmetrically rearrangement, by Cpd II (X = Scheme –NO2 or 9–OCH. 3).

Scheme 9. At pH 9.30 a nucleophilic attack of a hydroxide ion at position 4 of the naphthol ring takes place after the reaction with Cpd I analog. No cleavage of azo moiety was detected, whereas Wallach rearrangement occurs.

SchemeScheme 9. At pH 9. At 9.30 pHa 9.30 nucleophilic a nucleophilic attack attack of ofa a hydroxidehydroxide ion ion at atposition position 4 of the 4 of naphthol the naphthol ring takes ring takes place afterplace the after reaction the reaction with withCpd Cpd I analog. I analog. No Nocleavage cleavage of of azo azo moiety moiety waswas detected, detected, whereas whereas Wallach Wallach rearrangementrearrangement occurs. occurs.

Molecules 2016, 21, 964 18 of 40

Finally, when pH was fixed at 6.93 and the oxygen donor was tert-butylhydroperoxide, Cpd II analog directly arose together with tBu–O¨. Both are unable to perform direct (or rebound) oxygen transfer, and act by a HAT mechanism on the 2-naphthol function of the dye. The arising free radical can react with molecular oxygen, and further transformations afforded the same product obtained at pH 11.88 withMolecules peroxyacids, 2016, 21, 964 Scheme 10. 18 of 39

Molecules 2016, 21, 964 18 of 39

Scheme 10. At neutral pH, the oxidizing species was Cpd II analog through HAT transfer. The arising Scheme 10.radicalAt neutral from the pH, azo thedye can oxidizing in turn react species with molecular was Cpd oxygen, II analog yielding through the same HATproduct transfer. observed The arising radical fromat the alkaline azo pH. dye can in turn react with molecular oxygen, yielding the same product observed at alkaline pH. With concern to the 4-hydroxy isomers, in these compounds any intramolecular H-bonding between the naphthol hydroxyl and the azo moiety cannot take place, and therefore these compounds With concernare distinctly to more the 4-hydroxyacidic than their isomers, 2-isomers inare. these Therefore, compounds they largely exist any as intramolecular the corresponding H-bonding between theanions naphthol also at hydroxyllower pH values, and theand azoshow moiety lower oxidation cannot potentials take place, for the and same therefore reason [190]. these The compounds observation that the 1-naphthol dyes are more readily bleached in the presence of the studied are distinctly moreScheme acidic 10. Atthan neutral their pH, the 2-isomers oxidizing species are. was Therefore, Cpd II analog through they largelyHAT transfer. exist The asarising the corresponding ferriporphyrin catalyst in comparison with their 2-naphthol counterparts, when both the isomeric anions also at lowerradical from pH the values, azo dye can and in turn show react with lower molecular oxidation oxygen, yielding potentials the same product for the observed same reason [190]. series atare alkaline in their pH. unionized state, strongly speaks in favor of a HAT mechanism under those The observationexperimental that theconditions. 1-naphthol Such behavior dyes arestrictly more parallels readily that observed bleached for the in thesame presence dyes, oxidized of the studied ferriporphyrinby hydrogen catalystWith concern peroxide in comparison to inthe the 4-hydroxy presence with isomers,of their horseradish 2-naphtholin these peroxidase compounds counterparts, or fungalany intramolecular ligninase when [193]. both H-bonding the isomeric series betweenThe action the naphthol of H2O hydroxyl2 on Acid and Orange the azo 7moiety in the cannot presence take ofplace, the andMn(III) therefore complex these of compounds 5,10,15,20- are in their unionizedtetrakis(4-carboxyphenyl)porphyrin,are distinctlystate, more acidic strongly than their speaks 2-isomers covalently infavor are. immobilized Therefore, of a HAT theyonto mechanismlargelyFe3O4 magnetic exist as the undernanoparticles corresponding those was experimental conditions.studied Suchanions behavior[194].also at Although lower strictly pH novalues, mechanisms parallels and show for thatlower dye observed degradationoxidation potentials forwere the presented, for same the same dyes,the reasonstudy oxidized underlined[190]. The by hydrogen peroxide inthe theobservation high presence catalytic that of performancesthe horseradish 1-naphthol of dyesthe peroxidase immobilized are more re ormetalloporphyrinadily fungal bleached ligninase in andthe itspresence [ 193stability]. of after the repeatedstudied oxidationferriporphyrin cycles. catalyst in comparison with their 2-naphthol counterparts, when both the isomeric The actionseriesIn of anotherare H 2inO 2their studyon Acidunionized some Orangeamino-substituted state, strongly 7 in the speaksazo presence dyes in werefavor of studied theof a Mn(III)HAT to assess mechanism complex their degradation under of5,10,15,20-tetrakis those by (4-carboxyphenyl)porphyrin,metaexperimental-chloroperoxybenzoic conditions. covalently Suchacid behavior(MCPBA) immobilizedstrictly and iodosylbenzene, parallels that onto observed in Fethe3 Oforpresence4 themagnetic same of thedyes, commercial nanoparticlesoxidized was studied [194Fe(TDCCP)Cl].by Althoughhydrogen peroxideand no Fe(TPFPP)Cl mechanisms in the presence [195]. forofIn hors particul dyeeradish degradationar, peroxidasethe Fe(TDCPP)Cl/MCPBA or were fungal presented, ligninase system [193]. the oxidized study a underlined varietyThe of substitutedaction of H azobenzenes2O2 on Acid Orangesuch as 7Sudan in the II, presence 4-phenylazophenol, of the Mn(III) Methyl complex Yellow, of 5,10,15,20- N-methyl- the high catalytic performances of the immobilized metalloporphyrin and its stability after repeated 4-phenylazoanilinetetrakis(4-carboxyphenyl)porphyrin, and 4-phenylazoaniline covalently (Figure immobilized 5). onto Fe3O4 magnetic nanoparticles was oxidation cycles.studied [194]. Although no mechanisms for dye degradation were presented, the study underlined In anotherthe high study catalytic some performances amino-substituted of the immobilized azo metalloporphyrin dyes were studied and its stability to assess after repeated their degradation oxidation cycles. by meta-chloroperoxybenzoicIn another study some acid amino-substituted (MCPBA) and azo iodosylbenzene, dyes were studied to in assess the their presence degradation of the by commercial Fe(TDCCP)Clmeta and-chloroperoxybenzoic Fe(TPFPP)Cl acid [195 (MCPBA)]. In particular, and iodosylbenzene, the Fe(TDCPP)Cl/MCPBA in the presence of the commercial system oxidized a variety of substitutedFe(TDCCP)Cl azobenzenes and Fe(TPFPP)Cl such [195]. as In Sudan particul II,ar, 4-phenylazophenol,the Fe(TDCPP)Cl/MCPBA Methylsystem oxidized Yellow, a N-methyl-4- variety of substituted azobenzenes such as Sudan II, 4-phenylazophenol, Methyl Yellow, N-methyl- phenylazoaniline4-phenylazoaniline and 4-phenylazoaniline and 4-phenylazoaniline (Figure (Figure5). 5).

Figure 5. Several substituted azobenzenes have been proved to be substrates of Fe(TDCPP)Cl/MCPBA system.

On the contrary, azobenzene, 4-nitroazobenzene, and 4-phenylazo-benzoic acid did not react. Instead, a noticeable catalyst autodestruction was observed. Preliminary work on Sudan II showed that

Figure 5. Several substituted azobenzenes have been proved to be substrates of Fe(TDCPP)Cl/MCPBA system. Figure 5. Several substituted azobenzenes have been proved to be substrates of Fe(TDCPP)Cl/MCPBA system. On the contrary, azobenzene, 4-nitroazobenzene, and 4-phenylazo-benzoic acid did not react. Instead, a noticeable catalyst autodestruction was observed. Preliminary work on Sudan II showed that

Molecules 2016, 21, 964 19 of 40

On the contrary, azobenzene, 4-nitroazobenzene, and 4-phenylazo-benzoic acid did not react. Molecules 2016, 21, 964 19 of 39 Instead, a noticeable catalyst autodestruction was observed. Preliminary work on Sudan II showed that thisthis dye dye was was bleached bleached upon upon oxidative oxidative unsymmetrical unsymmetrical azo azo linkage linkage cleavage cleavage leading leading to a to phenylazene a phenylazene andand 1,2-naphthoquinone 1,2-naphthoquinone and and their their further further degradation degradation products products (Scheme (Scheme 11). 11 ). Molecules 2016, 21, 964 19 of 39 O O this dye was bleached upon oxidative unsymmetrical azo linkage cleavage leading to a phenylazene Sudan II + and 1,2-naphthoquinone and their further degradation products (Scheme 11). N O HN O

Sudan II + further further degradation degradationN HN SchemeScheme 11. 11.Sudan Sudan II wasII was bleached bleached in in the thepresence presence of the the Fe(TDCPP)Cl/MCPBA Fe(TDCPP)Cl/MCPBA system system with with oxidative oxidative unsymmetricalunsymmetrical cleavage cleavage of of the the azo azo linkage. linkage. further further degradation degradation In the case of amino-containing azo dyes, to a certain extent such a pathway is still operating In theScheme case of 11. amino-containing Sudan II was bleached azoin thedyes, presence to of a the certain Fe(TDCPP)Cl/MCPBA extent such system a pathway with oxidative is still operating (with theunsymmetrical obvious difference cleavage ofthat the a azo quinoneimine linkage. rather than a quinone is the primary product of the (withcleavage the obvious reaction). difference However, that the a main quinoneimine pathway passe rathers through than a a quinone direct attack is the of primarythe oxidizing product system of the cleavageto the reaction).amineIn the nitrogen case However, of amino-containing of the thedyes. main In the pathway azo case dyes, of Methyl passesto a certain Yellow, through extent which a such direct contains a pathway attack a ofN is,N the still-dimethylamino oxidizing operating system to thesubstituent, amine(with the nitrogen obviousthis was of difference thegradually dyes. that Indemethylated a thequinoneimine case of Methyland rather oxidized, than Yellow, a quinone giving which isrise contains the to primary a complex a N product,N-dimethylamino mixture of the of substituent,differentcleavage products, this reaction). was as gradually However, shown in the demethylatedScheme main pathway 12. By th passe andis pathways oxidized, through the a directazo giving linkage attack rise ofremains tothe a oxidizing complex untouched, system mixture and of differentfurtherto the products, azo amine linkages nitrogen as shown are offormed the in dyes. Scheme through In the 12 casewell-known. By of this Methyl pathway condensation Yellow, the which azo reactions contains linkage a[196–199], N remains,N-dimethylamino giving untouched, rise to and substituent, this was gradually demethylated and oxidized, giving rise to a complex mixture of furtherpolyazo, azo linkages quite recalcitrant are formed dyes. through Interestingly, well-known iron(III) condensation porphyrin promoted reactions oxidation [196–199 of], amino giving azo rise to dyesdifferent can lead products, to nitro asazo shown dyes, in representing Scheme 12. By dead this end pathway products the azo of the linkage reaction remains and untouched,posing additional and polyazo,further quite azo recalcitrant linkages are dyes. formed Interestingly, through well-known iron(III) condensation porphyrin reactions promoted [196–199], oxidation giving of rise amino to azo toxicological and environmental concerns. As a point of fact, peroxyacid action towards dialkylamino dyes canpolyazo, lead to quite nitro recalcitrant azo dyes, dyes. representing Interestingly, dead iron(III) end productsporphyrin ofpromoted the reaction oxidation and of posing amino additionalazo azo dyes (such as Methyl Yellow and Methyl Orange) in the absence of iron(III) porphyrin catalysts toxicologicaldyes can and lead environmental to nitro azo dyes, concerns. representing As dead a point end ofproducts fact, peroxyacid of the reaction action and posing towards additional dialkylamino affords the corresponding N-oxides. These lack the extensive electron conjugation of the parent azo azo dyestoxicological (such as Methyland environmental Yellow and concerns. Methyl As Orange)a point of fact, in the peroxyacid absence action of iron(III) towards porphyrin dialkylamino catalysts dyes, and so appear deceptively pale-colored in comparison to their azo counterparts. This is an affordsazo the dyes corresponding (such as MethylN-oxides. Yellow and These Methyl lack Orange the extensive) in the absence electron of iron(III) conjugation porphyrin of catalysts the parent azo outstandingaffords the example corresponding of how N the-oxides. simple These decolorization lack the extensive criterion electron could conjugation be unsatisfactory of the parent to assess azo the dyes, and so appear deceptively pale-colored in comparison to their azo counterparts. This is an bleachingdyes, and of aso given appear azo deceptively dye. pale-colored in comparison to their azo counterparts. This is an outstandingoutstanding example example of how of how the the simple simple decolorization decolorization criterion criterion could could be unsatisfactory be unsatisfactory to assess to the assess the bleachingbleaching of a given of a given azo dye.azo dye.

Scheme 12. Fe(TDCPP)Cl/MCPBA system in the case of azo dyes with N,N-dimethylamino substituent Scheme 12. Fe(TDCPP)Cl/MCPBA system in the case of azo dyes with N,N-dimethylamino substituent Schemegives 12. riseFe(TDCPP)Cl/MCPBA to gradual demethylation, system followed in the by caseoxidation, of azo leading dyes with to a Ncomplex,N-dimethylamino mixture of products. substituent gives rise to gradual demethylation, followed by oxidation, leading to a complex mixture of products. gives rise to gradual demethylation, followed by oxidation, leading to a complex mixture of products.

Molecules 2016, 21, 964 20 of 40

Another cationic porphyrin, the iron(III) complex of 5,10,15,20-tetrakis(N-methylpyridinium-4-yl) porphyrin, immobilized by ionic exchange on montmorillonite K10, was applied as a catalyst in Disperse Orange 3 (4-(41-nitrophenylazo)aniline) oxidation by hydrogen peroxide [141,200]. In that study, pH 3 was optimal for dye degradation, which mainly gives 4-nitroaniline as the oxidation product. In particular, 4-nitroaniline became almost the sole product when tert-butylhydroperoxide was substituted for hydrogen peroxide as the oxidant. However, when iodosylbenzene was used, no asymmetrical cleavage of the azo linkage was observed, and the main product was 4-(41-nitrophenylazo)nitrobenzene. Somewhat surprisingly, iodosylbenzene, which is an oxygen donor capable of directly generating the Cpd I analog, proved to be incapable of cleaving the azo linkage. On the whole, the catalytic system–which strictly resembles the action of hydrogen peroxide in the presence of high-redox-potential peroxidases [201]—is not able to transform the toxic dye Disperse Orange 3 in less dangerous compounds. In fact, 4-nitroaniline and in particular 4-(41-nitrophenylazo)nitrobenzene are very toxic and recalcitrant aromatic compounds. In conclusion, amino azo dyes, although attacked by oxidants in the presence of iron(III) porphyrin catalysts, give rise to major amounts of oxidation and/or condensation products, where the azo moiety is kept intact, and showing both increased recalcitrancy and toxicity in comparison with their parent dyes. Mn(III) porphyrins have been the focus for a number of studies where some have proven to be very effective bleaching catalysts as discussed in Section2. Pioneering experiments [ 202] dealing with the Mn(III) complex of 5,10,15,20-tetraphenylporphyrin, complexed with imidazole, as a catalyst in industrial wastewaters containing both azo dyes and detergents, as well as perborate bleach, showed that the system was poorly effective. Bleaching effectiveness was still decreased by detergents, masking dye molecules within micelles, therefore preventing the approach of the high-valent metalloporphyrin intermediates, responsible for dye oxidation. Sulfonation of the porphyrin has only a marginal effect towards catalyst effectiveness. Moreover, perborate showed an irreversible, destructive action against the catalyst itself, when dye substrates were absent. The authors concluded that at least the Mn(III) porphyrin they studied is not promising as an activator for azo dye bleaching in industrial wastewaters also containing—as is usual—detergents. The first study on azo dye bleaching by H2O2 in the presence Mn(III) porphyrins was conducted by using the catalysts covalently bound to a PEG chain to ensure solubility in water under mild experimental conditions (25 ˝C, pH 7 or 8) [203]. Three azo dyes (Acid Orange 7, Acid Orange 52, and Basic Orange 33, Figure6) were tested as substrates for decolorization experiments. At first, catalysts stability was tested in the presence of hydrogen peroxide and in the absence of dye substrates: the Mn(III) porphyrins, where the eight β positions had been substituted with bromine, proved to be quite resistant against destruction by the oxidant, whereas unsubstituted porphyrins were largely destroyed within a few hours. However, such a resistance against bleaching by hydrogen peroxide did not correlate with catalytic efficiency, as the Mn(III) β-octabromoporphyrins were poorer catalysts than their unsubstituted counterparts. This is in agreement with previous studies, where the adverse effect of bulky substituents (such as bromine) at the β positions has been underlined. On the whole, the MnTDCP series was more effective as decolorization catalyst than MnTPFPP. The catalytic performances of the studied Mn(III) porphyrins was significantly enhanced in the presence of imidazole: this favored the heterolytic cleavage of the Cpd 0 and thus the formation of the very effective Cpd I analog over the milder oxidant Cpd II analog. The bleaching kinetics of the decolorization was also studied, and a noticeable resemblance of the catalysts behavior with that of their enzymatic counterpart was pointed out, therefore allowing the use of the same format, comprising KM and kcat. More recently, the action of similar PEG-bearing Mn(III) porphyrins was studied on the water-insoluble dye Solvent Yellow 14 in non-aqueous solvents such as benzene, chloroform, dichloromethane, pyridine, dimethylsulfoxide, tetrahydrofuran, and methanol [204]. Interestingly, in the presence of imidazole the bleaching efficiency decreased, opposite to that observed in an aqueous Molecules 2016, 21, 964 21 of 40 environment. Such a surprising behavior perhaps depends on a bis-coordination of the Mn(III) ion within the porphyrin ring, favored by water absence. Molecules 2016, 21, 964 21 of 39

Molecules 2016, 21, 964 21 of 39

Figure 6. Three azo dyes (Acid Orange 7, Acid Orange 52, and Basic Orange 33) were used as the Figure 6. Three azo dyes (Acid Orange 7, Acid Orange 52, and Basic Orange 33) were used as the substrates in the first study about bleaching by Mn(III) porphyrins. substrates in the first study about bleaching by Mn(III) porphyrins. In another study, two manganese(III) porphyrins, namely the Mn(III) complexes of 5,10,15,20- tetrakis(4-carboxyphenyl)porphyrin and 5,10,15,20-tetrakis(N-methylpyridinium-4-yl)porphyrin, In another study, two manganese(III) porphyrins, namely the Mn(III) complexes of 5,10,15,20- were used to catalyze the bleaching of the azo dyes Acid Orange 7 and Basic Orange 33 by hydrogen tetrakis(4-carboxyphenyl)porphyrin and 5,10,15,20-tetrakis(N-methylpyridinium-4-yl)porphyrin, were peroxide,Figure under 6. Three very azo mild dyes conditions (Acid Orange (25 7,°C Acid and Orange pH 8) [205].52, and Imidazole Basic Orange addition 33) were caused used substantial as the used to catalyzeincreasesubstrates in the the in bleaching catalyticthe first study efficiency, of about the bleaching most azo dyesprobably by Mn(III) Acid because porphyrins. Orange it favors 7 and the Basicformation Orange of high-valent 33 by hydrogen peroxide,manganese under very intermediates mild conditions such as PorphMn(IV)=O (25 ˝C and pH or PorphMn(V)=O, 8) [205]. Imidazole which are addition the causal caused agents substantialof increasedye in theInbleaching. another catalytic study,No significant efficiency, two manganese(III) differences most probably inporphyrins the bleaching because, namely rates itthe were favors Mn(III) observed the complexes formation with bothof 5,10,15,20- the of Mn high-valent porphyrins when the anionic and the cationic dyes were exchanged. This observation suggests that manganesetetrakis(4-carboxyphenyl)porphyrin intermediates such as PorphMn(IV)=O and 5,10,15,20-tetrakis( or PorphMn(V)=O,N-methylpyridinium-4-yl)porphyrin, which are the causal agents wereunder used the toexperimental catalyze the bleachingconditions of adopted, the azo dyes no noteworthyAcid Orange importance 7 and Basic shouldOrange be33 byassigned hydrogen to of dye bleaching. No significant differences in the bleaching rates were observed with both the peroxide,electrostatic under attractive very mild or repulsive conditions effe (25ct with °C and respect pH 8) to [205]. bleaching Imidazole mechanism. addition caused substantial Mn porphyrinsincreaseAcid in when Red the 27catalytic the (amaranth, anionic efficiency, Scheme and themost 13), cationic probablyonce used dyes because as a werefood it dyefavors exchanged. but thewithdrawn formation This for observationof its high-valent noticeable suggests that undermanganesetoxicity, the experimentalhas intermediates been recentlyconditions studiedsuch as [140] PorphMn(IV)=O as adopted, the substrate noor forPorphMn(V)=O, noteworthy oxidation by importanceH which2O2 in aqueousare the shouldcausal solution, agents be in assignedthe of to presence of the Mn(III) complex of 5,10,15,20-tetrakis(1-methylpyridinium-4-yl) porphyrin MnT4MPyP. electrostaticdye bleaching. attractive No or significant repulsive differences effect with in respectthe bleaching to bleaching rates were mechanism. observed with both the Mn First, the mechanism of hydrogen peroxide with this cationic Mn porphyrin was studied. The Cpd 0 Acidporphyrins Red 27 (amaranth,when the anionic Scheme and the 13 cationic), once dyes used were as aexchanged. food dye This but observation withdrawn suggests for its that noticeable underanalog therapidly experimental changed into conditions a trans-dioxo-Mn(V) adopted, noderivative noteworthy (a Cpd importanceI analog), which should in turn be slowly assigned fades, to toxicity, haselectrostaticaffording been a recently transattractive-dioxo-Mn(IV) studiedor repulsive derivative [140 effe] asct with the(a Cpd substraterespect II analog). to bleaching for When oxidation Amaranthmechanism. by was H 2 Opresent,2 in aqueous the Cpd I solution, in the presenceanalogAcid was ofRed rapidly the 27 Mn(III)(amaranth, reduced complexto Scheme its Cpd II13), ofanalog once 5,10,15,20-tetrakis(1-methylpyridinium-4-yl) counterpart, used as a food whereas dye butthe dyewithdrawn was bleached. for its Thenoticeable Cpd porphyrinII analog is strong enough as an oxidizing agent to oxidize another dye molecule. Various cleavage MnT4MPyP.toxicity, First, has thebeenmechanism recently studied of [140] hydrogen as the substrate peroxide for oxidation with this by cationic H2O2 in aqueous Mn porphyrin solution, in was the studied. products were found, such as naphthalene-1-sulfonic acid, 1-naphthol-4-sulfonic acid, and 2-hydroxy- The Cpdpresence 0 analog of rapidlythe Mn(III) changed complex intoof 5,10,15,20-tetr a trans-dioxo-Mn(V)akis(1-methylpyridinium-4- derivativeyl) (a Cpdporphyrin I analog), MnT4MPyP. which in turn First,1,4-naphthoquinone the mechanism (lawsone).of hydrogen The peroxide optimum with pH this for cationicthe bleaching Mn porphyrin reaction was foundstudied. at The10.4. Cpd The 0 slowly fades,formation affording of an ainactivetrans-dioxo-Mn(IV) complex between derivative the deprotonated (a Cpd dye II analog). and the Whencatalyst Amaranthunder stronger was present, analog rapidly changed into a trans-dioxo-Mn(V) derivative (a Cpd I analog), which in turn slowly fades, alkalinity was suggested. the Cpd Iaffordinganalog wasa trans rapidly-dioxo-Mn(IV) reduced derivative to its Cpd(a Cpd II IIanalog analog). counterpart, When Amaranth whereas was present, the dye the wasCpd I bleached. The Cpdanalog II analog was rapidly is strong reduced enough to its Cpd as an II analog oxidizing counterpart, agent whereas to oxidize the dye another was bleached. dye molecule. The Cpd II Various cleavageanalog products is strong were enough found, as suchan oxidizing as naphthalene-1-sulfonic agent to oxidize another acid, dye 1-naphthol-4-sulfonicmolecule. Various cleavage acid, and 2-hydroxy-1,4-naphthoquinoneproducts were found, such as (lawsone).naphthalene-1-sulfon The optimumic acid, 1-naphthol-4-sulfonic pH for the bleaching acid, and reaction 2-hydroxy- was found at 10.4. The1,4-naphthoquinone formation of an(lawsone). inactive The complex optimum between pH for the the bleaching deprotonated reaction was dye found and at the 10.4. catalyst The under formation of an inactive complex between the deprotonated dye and the catalyst under stronger strongeralkalinity alkalinity was was suggested. suggested.

Scheme 13. Acid Red 27 (amaranth) is cleaved by Mn porphyrins in various products, such as the salts of naphthalene-1-sulfonic acid, 1-naphthol-4-sulfonic acid, and 2-hydroxy-1,4-naphthoquinone (lawsone), concomitantly to the formation of a dimer.

Scheme 13. Acid Red 27 (amaranth) is cleaved by Mn porphyrins in various products, such as the Scheme 13. Acid Red 27 (amaranth) is cleaved by Mn porphyrins in various products, such as the salts of naphthalene-1-sulfonic acid, 1-naphthol-4-sulfonic acid, and 2-hydroxy-1,4-naphthoquinone salts of naphthalene-1-sulfonic(lawsone), concomitantly to acid,the formation 1-naphthol-4-sulfonic of a dimer. acid, and 2-hydroxy-1,4-naphthoquinone (lawsone), concomitantly to the formation of a dimer.

Molecules 2016, 21, 964 22 of 40 Molecules 2016, 21, 964 22 of 39

In Inanother another study study some some Mn Mn porphyrins porphyrins were were tested tested as ascatalysts catalysts for for azo azo dye dye oxidation oxidation (Sudan(Sudan IV IVand and Methyl Methyl Orange, Orange, Figure Figure 7) [206].7)[ 206 Su].dan Sudan IV bleaching IV bleaching experiments experiments were were carried carried out in out dichloromethanein dichloromethane solution, solution, whereas whereas Methyl Methyl Orange Orange was wastested tested in aqueous in aqueous solution. solution. The The chosen chosen porphyrinsporphyrins were were the the Mn(III) Mn(III) complexes complexes of TDCPP, of TDCPP, 5,10,15,20-tetrakis(2,4,6-tribromophenyl)porphyrin, 5,10,15,20-tetrakis(2,4,6-tribromophenyl)porphyrin, 5,10,15,20-tetrakis(2,4,6-tribromo-3-methoxyphenyl)porphyrin,5,10,15,20-tetrakis(2,4,6-tribromo-3-methoxyphenyl)porphyrin, 5,10,15,20-tetrakis(2,4,6-tribromo-3-5,10,15,20-tetrakis(2,4,6-tribromo-3-N,N- N,Ndiethylsulfonamidophenyl)porphyrin,-diethylsulfonamidophenyl)porphyrin, andand 5,10,15,20-tetrakis(2,4,6-tribromo-3-5,10,15,20-tetrakis(2,4,6-tribromo-3-p-toluene-sulfonyl-p-toluene-sulfonyl- oxyphenyl)porphyrin.oxyphenyl)porphyrin.

FigureFigure 7. Methyl 7. Methyl Orange Orange (please, (please, refer refer to Figure to Figure 6) 6and) and Sudan Sudan IV IVhave have been been the the subject subject of ofa comparative a comparative bleachingbleaching study study by bydichloro- dichloro- or ordibromophenyl dibromophenyl mesomeso-substituted-substituted Mn Mn porphyrins. porphyrins.

A Adeep deep comparative comparative study study was was planned, planned, where where some some parameters parameters were were varied varied to tofind find the the best best conditionsconditions for for Methyl Methyl Orange Orange bleaching bleaching (Sudan (Sudan IV IVwas was judged judged as asless less interesting interesting owing owing to toits its insolubilityinsolubility in inwater). water). Halogen Halogen substitution substitution at the at the mesomeso-phenyls-phenyls proved proved to tobe beadvantageous, advantageous, as asshown shown byby the the observation observation that that simple simple Mn complexcomplex ofofmeso meso-tetraphenylporphyrin-tetraphenylporphyrin was was the the worst worst catalyst catalyst when whencompared compared to its to halogenated its halogenated derivatives. derivatives. The bestThe catalystbest catalyst was thewas dichlorosubstituted the dichlorosubstituted one, bearing one, bearingan additional an additional diethylsulfonamide diethylsulfonamide moiety moiety at the at 3the1 position. 3′ position. The The addition addition of oftert tert-butylpyridine-butylpyridine as a as co-catalysta co-catalyst was was found found to to be be sharply sharply favorable favorable to to catalyst catalyst efficiency. efficiency. OnOn the the other other hand, hand, azo azo dyes dyes could could successfully successfully resist resist against against bleaching, bleaching, mediated mediated by byMn Mn porphyrins,porphyrins, as shown as shown by an by interesting an interesting study study where where aromatic aromatic amines amines were oxidized were oxidized with high with yields high to yieldsthe corresponding to the corresponding azo dyes (through azo dyes oxidative (through coup oxidativeling) by periodate, coupling) in by the periodate, presence inof the Mn(III) presence complexof the Mn(III)of meso-tetraphenylporphyrin complex of meso-tetraphenylporphyrin and some imidazole and someand pyridine imidazole axial and ligands pyridine for axialthe metal ligands centerfor the[207]. metal However, center under [207]. proper However, experimental under proper conditions, experimental some Mn conditions, porphyrins some efficiently Mn porphyrins oxidize andefficiently bleach azo oxidize dyes, andas reported bleach above. azo dyes, In particular, as reported in above.a biphasic, In particular,micellar system in a biphasic,[208] the micellarwater insolublesystem azo [208 ]dye the Sudan water insolubleIV was bleached azo dye Sudanby hydrogen IV was peroxide bleached byin the hydrogen presence peroxide of two in manganese the presence porphyrinof two manganese complexes, porphyrinnamely 5,10, complexes,15,20-tetrakis(dichlorophe namely 5,10,15,20-tetrakis(dichlorophenyl)porphyrinnyl)porphyrin and 5,10,15,20-tetrakis(2,4,6- and tribromo-3-methoxyphenyl)porphyrin,5,10,15,20-tetrakis(2,4,6-tribromo-3-methoxyphenyl)porphyrin, in the presence of the activators in the presence tert-butylpyridine of the activators and benzoictert-butylpyridine acid. More recently, and benzoic the same acid. Mn More porphyri recently,ns the and same two Mnother porphyrins catalysts andcontaining two other sulfonate catalysts moietiescontaining at the sulfonate four peripheral moieties phenyl at the four rings peripheral in addition phenyl to the rings two inchlorine addition and to the twothree chlorine bromine and substituents,the three bromine were tested substituents, to assess were their tested cataly totic assess activity their in catalytic Methyl activityOrange inbleaching Methyl Orangeby H2O bleaching2 [206]. Additionally, these four catalysts were compared with the manganese complex of 5,10,15,20- by H2O2 [206]. Additionally, these four catalysts were compared with the manganese complex of tetraphenylporphyrin,5,10,15,20-tetraphenylporphyrin, which was by which far the was worst, by as far expected. the worst, The as experiments expected. The were experiments carried out werein a dichloromethane/watercarried out in a dichloromethane/water biphasic system, biphasic and show system,ed the and high showed catalytic the high efficiency catalytic of efficiency the Mn of porphyrinsthe Mn porphyrins tested, although tested, althoughthey stayed they in stayed the organic in the organicphase, whereas phase, whereas Methyl MethylOrange Orange was in wasthe in aqueousthe aqueous phase. phase. Unfortunately, Unfortunately, the authors the authors gave gave no data no data about about the thedegradation degradation products products of Methyl of Methyl OrangeOrange under under the the experimental experimental conditions conditions tested. tested. In Inconclusion, conclusion, azo azo dyes dyes bearingbearing aromatic aromatic amine amine functions functions could could be oxidized be oxidized by hydrogen by hydrogen peroxide peroxideor other or suitable other suitable oxidants oxidants in the presence in the presen of Fe orce Mnof Fe porphyrins. or Mn porphyrins. However, However, noticeable noticeable amounts of amountscomplex of products,complex products, still containing still containing the azo moiety the azo and moiety carrying and thecarrying nitro functionthe nitro arise,function being arise, more beingtoxic more and toxic recalcitrant and recalcitrant than the startingthan the dyes.starting This dyes. drawback This drawback is not observed is not observed with phenolic with phenolic azo dyes azothat dyes undergo that undergo oxidative oxidative cleavage cleavage at the azo at function, the azo thereforefunction, givingtherefore elemental giving nitrogenelemental together nitrogen with togetherquinones with and quinones other hydroxylated and other hydroxylated aromatic fragments. aromatic fragments.

Molecules 2016, 21, 964 23 of 40

4.1.2. Anthraquinone Dyes Although anthraquinone dyes are widespread for several applications, in-depth studies about their oxidative degradation, possibly by enzymatic or chemical catalysis are rare. In particular a detailed report has been published [209] dealing with alizarin (1,2-dihydroxyanthraquinone) degradation by H2O2 under strongly alkaline conditions. The transient formation of an epoxy intermediateMolecules along 2016 the, 21, degradation964 process was suggested. On the other hand, anthraquinone23 of 39 dye degradation has been the target of several studies, usually focused on the use of titania as the photocatalytic4.1.2. agent Anthraquinone [210–212 ].Dyes Also electrochemical methods have been described [213,214]. A detailed Although anthraquinone dyes are widespread for several applications, in-depth studies about study was conducted on Alizarin Red S (ARS) degradation by H2O2 in the presence of the manganese their oxidative degradation, possibly by enzymatic or chemical catalysis are rare. In particular a detailed complex of 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrinreport has been published [209] dealing with alizarin (1,2-dihydroxyanthraquinone) (TSPP), coordinatively degradation immobilized by on a silica matrix,H functionalized2O2 under strongly alkaline with covalentlyconditions. The bound transienNt formation-propylimidazole of an epoxy intermediate moieties along [144 the]. The catalyst was optimallydegradation effective process at pH was 7. suggested. Decolorization On the other was hand, more anthraquinone than 50% dye degradation after 2 h, has whereas been the the dye was target of several studies, usually focused on the use of titania as the photocatalytic agent [210–212]. totally bleachedAlso electrochemical within 3 h. methods have been described [213,214]. A detailed study was conducted on Alizarin In principle,Red S (ARS) two alternativedegradation by mechanisms H2O2 in the presence could of the be manganes suggestede complex to describe of 5,10,15,20-tetrakis(4- the oxidative bleaching of the dye: (a)sulfonatophenyl)porphyrin oxygen transfer (direct (TSPP), or coordinatively through a reboundimmobilized mechanism) on a silica matrix, from functionalized the Cpd with I analog to ARS, covalently bound N-propylimidazole moieties [144]. The catalyst was optimally effective at pH 7. targeted to theDecolorization double bond was more shared than between50% after 2 h, the wh sulfocatecholereas the dye was andtotally the bleached quinone within rings; 3 h. and (b) an HAT (or ET, dependingIn principle, on pH) two mechanism, alternative mechanisms passing throughcould be suggested a Cpd II to analog.describe the A oxidative third alternative, bleaching involving hydroxyl radicalof the intermediacy,dye: (a) oxygen transfer was ruled (direct out or through thanks a torebound two findings:mechanism) ARS from successfullythe Cpd I analog resisted to against ARS, targeted to the double bond shared between the sulfocatechol and the quinone rings; and (b) an heating in theHAT presence (or ET, depending of the well-known on pH) mechanism,¨OH passing generator through azo- a Cpdbis II-propionamidine analog. A third alternative, dihydrochloride (APH), and theinvolving degradation hydroxyl radical was unaffected intermediacy, by was the rule additiond out thanks of mannitol,to two findings: a well-known ARS successfully¨OH scavenger. The oxygen transferresisted against would heating lead in to the a presence transient, of the very well-known reactive ∙OH epoxide, generator so azo- parallelingbis-propionamidine that described for dihydrochloride (APH), and the degradation was unaffected by the addition of mannitol, a well-known alizarin bleaching∙OH scavenger. by hydrogen The oxygen peroxide transfer would under lead stronglyto a transient, alkaline very reactive conditions epoxide, so [ 209paralleling]. However, that the close similarity ofdescribed the UV/Vis for alizarin bleaching bleaching pattern by hydrogen between peroxide the described under strongly bleaching alkaline conditions and the laccase-catalyzed[209]. one (vide infraHowever,Section the 4.3close) stronglysimilarity of speaks the UV/Vis in blea favorching of pattern a HAT between mechanism, the described which bleaching has and been detailed the laccase-catalyzed one (vide infra Section 4.3) strongly speaks in favor of a HAT mechanism, which (Scheme 14).has The been degradation detailed (Scheme of the14). dyeThe degradation is not a complete of the dye mineralization,is not a complete mineralization, as the unsubstituted as the ring of the original moleculeunsubstituted was ring found of the original after molecule bleaching was completionfound after bleaching as o-phthalic completion acid. as o-phthalic acid.

Scheme 14. Alizarin Red S is bleached by a Mn porphyrin complex through a HAT mechanism Scheme 14. Alizarinleading to incomplete Red S is bleachedmineralization. by a Mn porphyrin complex through a HAT mechanism leading to incomplete mineralization. Hematin, a naturally occurring Fe(III) porphyrin known to mimic peroxidases, has been proposed as a catalyst for ARS and Orange II bleaching by H2O2 [215]. Hematin was used as an Hematin,immobilized a naturally preparation occurring on to glutaraldehyde-activated Fe(III) porphyrin chitosan known beads, to mimicalso in the peroxidases, presence of has been proposed asaminopropyltriethoxysilane. a catalyst for ARS and The Orangeauthors hypothesiz II bleachinged the formation by H2O of2 covalent[215]. linkages Hematin between was used as an immobilizedglutaraldehyde preparation and on hematin, to glutaraldehyde-activated eventually with aminopropyltriethoxysilane chitosan intermediacy. beads, also In inanother the presence of study [216], hemin (ferriheme) was used in combination with hydrogen peroxide to bleach some aminopropyltriethoxysilane.synthetic azo dyes such The as Reactive authors Red hypothesized 195 (Figure 8). Activity the formation and stability of of covalent the catalyst linkages were between glutaraldehydesubstantially and hematin, improved eventuallyupon adsorption with on to aminopropyltriethoxysilane carbon fibers. intermediacy. In another study [216], heminAlthough (ferriheme) poorly used, wasphenosafrani usedne in (Scheme combination 15) is a toxic, with polluting, hydrogen and recalcitrant peroxide dye, whose to bleach some inexpensive and “green” degradation could be of interest. Accordingly, in a recent study it was tested synthetic azoas dyesa substrate such for asa bleaching Reactive oxidation Red 195by H2 (FigureO2, under8 catalysis). Activity by silica-supported and stability MnTSPP of the [143]. catalyst were substantially improved upon adsorption on to carbon fibers. Although poorly used, phenosafranine (Scheme 15) is a toxic, polluting, and recalcitrant dye, whose inexpensive and “green” degradation could be of interest. Accordingly, in a recent study it was tested as a substrate for a bleaching oxidation by H2O2, under catalysis by silica-supported MnTSPP [143]. Molecules 2016, 21, 964 24 of 40 Molecules 2016, 21, 964 24 of 39

Molecules 2016, 21, 964 24 of 39

Molecules 2016, 21, 964 24 of 39

Figure 8. Reactive Red 195 structure. Figure 8. Reactive Red 195 structure. Figure 8. Reactive Red 195 structure.

Scheme 15. Phenosafranine structure. Figure 8. Reactive Red 195 structure. Scheme 15. Phenosafranine structure. 4.1.3. Cationic Dyes Scheme 15. Phenosafranine structure. 4.1.3.Phenosafranine Cationic Dyes belongs to cationic dyes, showing an N-phenylphenazinium delocalized cation 4.1.3. Cationicalso bearing Dyes two peripheral amino groups. Therefore, the compound is an electron-deficient Phenosafranine belongs to cationic dyes, showing an N-phenylphenazinium delocalized cation heteroaromatic, quite resistant to attack by electrophilic agents. Consequently, the only described also bearing two peripheral amino groups. Therefore, the compound is an electron-deficient Phenosafraninechemical bleaching belongs procedure to cationic for phenosafranine dyes, showing uses an 0.5N -phenylphenaziniumM potassium peroxodisulfate delocalized under cation heteroaromatic, quite resistant to attack by electrophilic agents. Consequently, the only described also bearingstrongly two acidic peripheral conditions and amino leads groups.to dye polyme Therefore,rization and the precipitation compound rather is anthan electron-deficientbleaching. chemical bleaching procedure foSchemer phenosafranine 15. Phenosafranine uses structure.0.5 M po tassium peroxodisulfate under The reaction goes through a two consecutive one electron oxidation, producing a radical dication and heteroaromatic,strongly acidic quite conditions resistant and to leads attack to bydye electrophilicpolymerization agents.and precipitation Consequently, rather than the bleaching. only described a4.1.3. nitrenium Cationic dication, Dyes respectively [217]. The latter is an extremely powerful electrophile, triggering a chemicalThe bleaching reaction proceduregoes through for a two phenosafranine consecutive one useselectron 0.5 oxidation, M potassium producing peroxodisulfate a radical dication under and strongly polymerization process at the expenses of the still unreacted phenosafranine molecules. Obviously, acidic conditionsa nitreniumPhenosafranine and dication, leads belongsrespectively to dye to cationic polymerization[217]. Thedyes, latter showing is an and extremelyan N precipitation-phenylphenazinium powerful electrophile, rather delocalized than triggering bleaching. cation a The such a treatment is not applicable for wastewater remediation, and a milder procedure is of potential polymerizationalso bearing two process peripheral at the expensesamino groups. of the stilTherefl unreactedore, the phenosafranine compound is molecules.an electron-deficient Obviously, reactionusefulness. goes through The study a two showed consecutive that in the one presence electron of the oxidation, above catalyst, producing H2O2 at a concentration radical dication as and a suchheteroaromatic, a treatment quiteis not resistantapplicable to forattack wastewater by electrophilic remediation, agents. and Consequently, a milder procedure the only is of described potential nitreniumlow dication, as 8.8 mM respectively efficiently and [217 completely]. The latterbleached is anthe extremelydye (starting powerful concentration electrophile, 0.3 mM) within triggering a usefulness.chemical bleaching The study procedure showed that for inphenosafranine the presence of uses the above0.5 M catalyst,potassium H2 Operoxodisulfate2 at a concentration under as polymerization3lowstrongly h. As as a8.8 processpointacidic mM of conditionsefficiently fact, at the8.8 mM expensesandand peroxodisulfate completelyleads to of dye the bleached polyme still was unreactedquiterization the dye inert and (starting towards phenosafranineprecipitation concentration 0.2 mM rather phenosafranine, molecules.0.3than mM) bleaching. within and Obviously, such a treatmentthe3The h. same Asreaction a waspoint is notgoes observed of applicable fact,through 8.8 when mM a two forworkingperoxodisulfate consecutive wastewater with one8.8 was mMelec remediation, quitetron H2O oxidation,inert2 in the towards andabsence producing a 0.2 milder ofmM MnTSPP a phenosafranine, radical procedure catalyst. dication is With and of potential concern to the reaction mechanism, the H2O2/catalyst system most probably acts differently from usefulness.thea nitrenium Thesamestudy was dication, observed showed respectively when that working in [217]. the withThe presence latter8.8 mM isof an H the2extremelyO2 in above the absencepowerful catalyst, of electrophile, MnTSPP H O atcatalyst. triggering a concentration With a as peroxodisulfate, as revealed by the different UV/Vis spectroscopic patterns observed2 2 for the two low as 8.8concernpolymerization mM efficientlyto the reactionprocess and atmechanism, completelythe expenses the of bleachedH the2O2 /catalyststill unreacted the system dye phenosafranine (startingmost probably concentration molecules. acts differently Obviously, 0.3 from mM) within oxidants.peroxodisulfate,such a treatment Perhaps isas an not revealed OT applicable mechanism by the for operates,differentwastewater UV/Vispossibly remediation, spectroscopic together and with a milder patternsan ET/HAT procedure observed one, isprovided forof potential the twothat 3 h. As athe point Mn-based of fact, Cpd 8.8 I analog mM peroxodisulfateis stable enough to wassignificantl quitey inertoxygenate towards susceptible 0.2 mM substrates phenosafranine, prior to and oxidants.usefulness. Perhaps The study an OT showed mechanism that in operates, the presence possibly of the together above withcatalyst, an ET/HAT H2O2 at one,a concentration provided that as the samefadethelow was Mn-based byas observed 8.8ET/HAT mM Cpd efficiently to whenI the analog less workingand isreactive stable completely enoughCpd with II analog.bleached 8.8to significantl mM the H 2dyeOy 2oxygenate (startingin the absence concentrationsusceptible of substrates MnTSPP 0.3 mM) prior within catalyst. to With Another cationic triphenylmethane dye, Brilliant Green (as the hydrogen sulfate, Figure 9) has concern tofade3 h. the As by reactionaET/HAT point of to fact, mechanism, the 8.8 less mM reactive peroxodisulfate the Cpd H II2 Oanalog.2/catalyst was quite inert system towards most 0.2 probably mM phenosafranine, acts differently and from been extensively studied [218] as a substrate for bleaching by hydrogen peroxide in water, under peroxodisulfate,the sameAnother was as revealed cationicobserved triphenylmethane when by the working different with dye, 8.8 UV/VisBrilliant mM H Green2O spectroscopic2 in (asthe the absence hydrogen patternsof MnTSPP sulfate, observed catalyst. Figure 9) With has for the two catalysisbeenconcern extensively byto twothe reactionsimilar studied metalloporphyrins, mechanism, [218] as a substratethe H 2Mn(III)T4MPyP,O 2/catalystfor bleaching system andby mosthydrogen the Mn(II)probably peroxide complex acts differently inof water,β-octabromo- under from oxidants. Perhaps an OT mechanism operates, possibly together with an ET/HAT one, provided that 5,10,15,20-tetrakis-(catalysisperoxodisulfate, by two similar asN revealed-methylpyridinium-3-yl)porphyrin metalloporphyrins, by the different Mn(III)T4MPyP, UV/Vis spectroscopic (Br8 andT3MPyP). the Mn(II) patterns complex observed of β -octabromo-for the two the Mn-based5,10,15,20-tetrakis-(oxidants.Cpd Perhaps I analog anN -methylpyridinium-3-yl)porphyrinOT is stablemechanism enough operates, to significantly possibly together (Br8T3MPyP). oxygenate with an ET/HAT susceptible one, provided substrates that prior to fade by ET/HATthe Mn-based to the Cpd lessI analog reactive is stableCpd enough II analog. to significantly oxygenate susceptible substrates prior to Anotherfade by cationic ET/HAT triphenylmethaneto the less reactive Cpd II dye, analog. Brilliant Green (as the hydrogen sulfate, Figure9) has been extensivelyAnother cationic studied triphenylmethane [218] as a substratedye, Brilliant for Green bleaching (as the hydrogen by hydrogen sulfate, Figure peroxide 9) has in water, been extensively studied [218] as a substrate for bleaching by hydrogen peroxide in water, under under catalysiscatalysis by by two two similar similar metalloporphyrins, metalloporphyrins, Mn(III)T4MPyP, Mn(III)T4MPyP, and the Mn(II) complex and the of β Mn(II)-octabromo- complex of β-octabromo-5,10,15,20-tetrakis-(5,10,15,20-tetrakis-(N-methylpyridinium-3-yl)porphyrinN-methylpyridinium-3-yl)porphyrin (Br8T3MPyP). (Br8T3MPyP).

Figure 9. Brilliant Green (a triphenylmethane) and Rhodamine B (a tricyclic immonium/oxonium cation) structures. Figure 9. Brilliant Green (a triphenylmethane) and Rhodamine B (a tricyclic immonium/oxonium cation) structures.

Figure 9. Brilliant Green (a triphenylmethane) and Rhodamine B (a tricyclic immonium/oxonium cation) structures. Figure 9. Brilliant Green (a triphenylmethane) and Rhodamine B (a tricyclic immonium/oxonium cation) structures. Molecules 2016, 21, 964 25 of 40

The latter is an uncommon example of a low-spin Mn(II) complex, favored by the electron-withdrawing features of both bromine and pyridinium substituents on to the porphyrin ring. The catalysts were immobilized by ion exchange onto two different supports: halloysite nanotubes and silica-coated magnetite nanoparticles. As a general result, Mn(III)T4MPyP performed better than the other metalloporphyrin, owing to the presence of eight bulky bromine substituents on the latter, which prevent the optimal approach of the substrate to the metal center. Moreover, magnetite-based solid support seems to be more promising since it allows catalyst reuse (whereas halloysite caused a rapid drop in catalyst activity after the first use) and recovery by means of an external magnetic field.

4.1.4. Applications of Metalloporphyrins as Generic Decolorizing Catalysts A number of published studies are devoted to the assessment of the usefulness of redox-active metalloporphyrins as “generic” decolorizing catalysts rather than to the study of bleaching mechanisms of selected dyes. Among these, a comparative study involving two metalloporphyrin catalysts, namely the manganese and iron complexes of 5,10,15,20-tetrakis(4-carboxyphenyl)porphyrin (TCPP), acting as promoters of oxidative bleaching of four dyes by H2O2 has been reported [185]. The tested dyes were Methyl Orange, Crystal Violet, Methylene Blue, and Congo Red: azo, triphenylmethane, and thiazine dye classes were therefore represented. The catalysts were covalently immobilized on multi-walled carbon nanotubes (MWCNTs). Both catalysts showed their best performances at slightly acidic pH values (around 5), being the Fe-based catalyst more active towards Methyl Orange than its Mn-based counterpart. By contrast, the Mn-porphyrin is more active towards the other dyes. The presence of imidazole cocatalyst was compulsory to observe significant catalytic activity in the case of the Mn-porphyrin, whereas it completely inhibited the Fe-porphyrin activity. In another comparative study, six textile dyes, namely Alizarin Red S, Phenosafranine, Xylenol Orange, Methylene Blue, Methyl Green, and Methyl Orange, were tested as substrates for oxidative bleaching in the presence of two catalysts [162]: MnTSPP immobilized on imidazole-functionalized crosslinked polyvinyl alcohol, and FeTPFPP immobilized on pyridine-functionalized silica gel. Such organic functions behaved as ligating agents for Mn(III) and Fe(III) within the porphyrin macrocycles. Bleaching was studied at pH 7, in aqueous environment, without any added organic cosolvent, and the bleaching agent was H2O2. The results showed that the Mn-based catalyst was sharply more effective, whereas the Fe-based catalyst needed a redox mediator such as Mn2+ ion complexed with malonate to prevent disproportionation of the active species, Mn(III). The same preparation FeTPFPP immobilized on crosslinked pyridine-functionalized PVA was used to oxidatively bleach a number of organic compounds with H2O2 [31]; in particular, the decolorization of the thiazine dye Azure B was studied under different experimental conditions. This dye was chosen because it is an ideal substrate for LiP, but not for MnP [219]. However, a positive effect of Mn(II)/malonate addition to the reaction mixtures has been reported for that study. Another synthetic catalyst, iron(II) tetrakis(5,6-dichloro-1,4-dithiin)porphyrazine (Figure 10), strictly resembling in its structure the “normal” metalloporphyrins, has been studied [220] to assess its ability in catalyzing the degradation of the cationic dye Rhodamine B (a tricyclic oxonium cation) by hydrogen peroxide (Figure9). Formic, acetic, benzoic, and o-phthalic acids were detected among the degradation products of the dye. The reaction mechanism was different at pH 2 (formation of a Cpd I analog) and pH 7 (homolytic fission of the O–O bond of the Cpd 0 analog, with concomitant ¨OH production, as assessed by means of EPR analysis). Although not directly related to industrial dye bleaching an outstanding study must be cited here. It is the case of the Mn(III) complex of 5,10,15,20-tetrakis(1,3-dimethylimidazolium-2-yl)porphyrin (TDMImP) which proved to be capable of evolving chlorine dioxide from chlorite in aqueous solution at slightly acidic pH values and at about room temperature [221]. Somewhat surprisingly, the apparently similar Mn(III)TMPyP [both (N-methylpyridinium-2-yl) and (N-methylpyridinium-4-yl) isomeric forms) were quite inactive, perhaps owing to their too high redox potentials (Mn(V)/Mn(III) ´ couples) [222] to be oxidized by ClO2 . The authors have proposed a reaction cycle that satisfactorily Molecules 2016, 21, 964 26 of 40

explains the ClO2 production. The reaction was studied both in solution and with the catalyst adsorbed ontoMolecules montmorillonite; 2016, 21, 964 in both cases a transient O=Mn(V)=O trans-dioxo species was found.26 of 39 If not removed, the formed ClO2 slowly reduced the Mn(V)porphyrin to its Mn(IV) counterpart, while it If not removed, the formed ClO´ 2 slowly reduced the Mn(V)porphyrin to its Mn(IV) counterpart, while is changed into chlorate ClO3 . The obtained ClO2 could be easily stripped from the solution by it is changed into chlorate ClO3−. The obtained ClO2 could be easily stripped from the solution by sparging it with air, and then bubbled within the to-be-bleached solution. Chlorine dioxide is poorly sparging it with air, and then bubbled within the to-be-bleached solution. Chlorine dioxide is poorly studied as a dye-bleaching agent [223] due to its very unstable nature: it can explode and has to studied as a dye-bleaching agent [223] due to its very unstable nature: it can explode and has to be be generatedgenerated closeclose toto thethe plantplant where has has to to be be used. used. However, However, taking taking into into account account its very its verystrong strong oxidizingoxidizing properties properties and and its its noticeable noticeable tendency tendency to oxidize organics organics with with no noconcomitant concomitant chlorination, chlorination, its potentialits potential as a as very a very effective effective bleaching bleaching agent agent shouldshould be be considered. considered.

FigureFigure 10. Iron(II) 10. Iron(II) tetrakis(5,6-dichloro-1,4-dithiin)porphyrazine tetrakis(5,6-dichloro-1,4-dithiin)porphyrazine is isa catalyst a catalyst strictly strictly resembling resembling the the structure of “normal” metalloporphyrins. structure of “normal” metalloporphyrins. 4.2. Effect of Redox Mediators 4.2. Effect of Redox Mediators In the case of redox-active enzymes, and in particular for fungal laccases, the use of redox Inmediators the case (RMs) of redox-activeto widen the application enzymes, field and of in these particular enzymes fortowards fungal compounds laccases, that the are use not of per redox mediatorsse laccase (RMs) substrates, to widen is thewell-known application [224] field and ofhas these been enzymesrecently reviewed towards [169]. compounds Therefore, that it areseems not per se laccaseobvious substrates, to extend isthe well-known use of such [compounds224] and has to beenother recentlyoxidative reviewedenzymes and [169 to]. their Therefore, emulators, it seems obviousredox-active to extend metalloporphyrins. the use of such Somewhat compounds unexpectedly, to other oxidative only a few enzymes articles have and been to their published emulators, redox-activeabout the metalloporphyrins. use of RMs together with Somewhat such catalysts, unexpectedly, and the reports only a underline few articles the substantial have been lack published of activity of these putative co-catalysts. What are the reasons for these disappointing results? First of about the use of RMs together with such catalysts, and the reports underline the substantial lack of all, one should note that the redox potentials of the commonly used metalloporphyrins are, as a rule, activity of these putative co-catalysts. What are the reasons for these disappointing results? First of higher than those observed for fungal laccases (that are the most powerful oxidizing agents among all, onethe shouldlaccases note in general) that the [225]. redox Therefore, potentials added of theRMs commonly cannot help used redox-active metalloporphyrins metalloporphyrins are, as to a rule, higherexpand than their those substrate observed inventory for fungal on the laccases sole basis (that of electrochemical are the most powerful considerations: oxidizing on the agents contrary, among the laccasesan adverse in general)effect could [225 be]. anticipated, Therefore, addedas a superfluous RMs cannot additional help redox-active step is interposed metalloporphyrins between the to expandhigh-valent their substrate oxometal inventory center of the on themetalloporphyrin sole basis of electrochemicaland the to-be-oxidized considerations: substrate. On on the the other contrary, an adversehand, some effect RMs could could be be anticipated, helpful when as the a superfluousshape and/or the additional bulky nature step of is the interposed substrates betweenhinders the high-valentor also totally oxometal preclude center the of proper the metalloporphyrin approach of the substrate and the to to-be-oxidized the catalytic center. substrate. This could On the be other hand,most some probably RMs could the case be helpfulof the industrial when the dye shape Methyl and/or Green thewhen bulky bleached nature by ofH2 theO2 under substrates catalysis hinders by MnTSPP immobilized on imidazole functionalized silica gel [162]. Regardless to the particular or also totally preclude the proper approach of the substrate to the catalytic center. This could be RMs used (TEMPO, N-hydroxysuccinimide, N-hydroxy-phthalimide, N-hydroxybenzotriazole) the mostactivity probably of thethe casecatalyst of the was industrial about tripled, dye Methyl whereas Green other when dyes bleachedunder the by same H2O conditions2 under catalysis gave by MnTSPPcontrasting immobilized results: onfor imidazoleexample, in functionalizedthe case of Methyl silica Orange gel [ 162the]. addition Regardless of TEMPO to the produced particular a RMs useddramatic (TEMPO, dropN-hydroxysuccinimide, in catalyst activity, and inN -hydroxy-phthalimide,the case of phenosafranineN the-hydroxybenzotriazole) catalyst activity was invariably the activity of theworsened catalyst by was the aboutfour RMs tripled, tested whereas[143]. In this other last case, dyes the under electrochemical the same explanation conditions as gave above contrasting is the results:most for likely. example, In the in case the of case Alizarin of Methyl Red S Orangeunder th thee same addition experimental of TEMPO conditions produced [144] athe dramatic same RMs drop in catalystwere activity, ineffective and (TEMPO in the case and of N phenosafranine-hydroxyphthalimide) the catalyst or produced activity a moderate was invariably increase worsenedin bleaching by the four RMseffectiveness tested [(143N-hydroxysuccinimide]. In this last case, theand electrochemicalN-hydroxybenzotriazole). explanation The asreasons above of is such the mostbehaviors likely. In the caseare ofunknown. Alizarin Red S under the same experimental conditions [144] the same RMs were ineffective Starting from the well-known occurrence of hemoenzymes specifically featured by Nature to (TEMPO and N-hydroxyphthalimide) or produced a moderate increase in bleaching effectiveness oxidize Mn(II) to Mn(III) chelates (fungal manganese peroxidases, MnPs), Mn(II) salts in the presence (N-hydroxysuccinimideof a sodium malonate and bufferN-hydroxybenzotriazole). (as a chelating and stabilizing The reasons agent for of the such putative behaviors Mn(III) are species unknown. Startingarising from from oxidation) the well-known have been sometimes occurrence tested of hemoenzymesto assess the putative specifically MnP emulating featured ability by Natureof to oxidize Mn(II) to Mn(III) chelates (fungal manganese peroxidases, MnPs), Mn(II) salts in the

Molecules 2016, 21, 964 27 of 40 presence of a sodium malonate buffer (as a chelating and stabilizing agent for the putative Mn(III) species arising from oxidation) have been sometimes tested to assess the putative MnP emulating ability of some redox-active metalloporphyrin preparations. When FeTPFPP was immobilized on pyridine-functionalized cross-linked PVA [30], Mn(II) addition slightly enhanced catalyst performances above pH 6, whereas the opposite was observed at lower pH values. The reasons for this behavior are unknown. As a point of fact, when veratryl alcohol (a widely accepted simple model compounds to evaluate ligninolytic activity) was used as the substrate, its influence was invariably favorable. However, it should be noted that the catalytic activity was evaluated in terms of veratraldehyde production, whereas it was found that the studied FeTPFPP produced mainly 2-hydroxymethyl-5-methoxy-1,4-benzoquinone as the oxidation product of veratryl alcohol [31]. Therefore, the observed increased production of veratraldehyde is not necessarily to be ascribed to a true activity enhancement. In other words, the presence of the manganese salt could drive the reaction to the aldehyde at the expenses of substituted benzoquinone formation. In conclusion, also the RMs couple Mn(II)/Mn(III) has found no significant application in the field of technological use of biomimetic or bioinspired redox-active metalloporphyrins.

4.3. Comparison with Enzymatic Decolorization Several enzymes have been also used in the bleaching of textile dyes [226–230], including in particular laccases and peroxidases. Their comparison is crucial to encompass the catalytic potential of immobilized metalloporphyrins since usually enzymatic catalysts stand out about efficiency [146,231–234] and specificity [29,231]. In particular, the use of high-potential fungal laccases has been recently discussed [169,235], being this enzyme able to oxidize a wide range of natural and synthetic phenolics and aromatic amines [236–240]. Several studies have shown the ability of microbial laccases to specifically bleach industrial azo dyes [241,242]. Laccases cannot produce any direct oxygenation of the substrates, but only oxidize them by ET/HAT mechanisms, depending on pH, substrate structure, and other operational conditions. In this sense, they somewhat resemble “classical” peroxidases. Therefore, in the presence of some electron-withdrawing substituents in the azo dye structure, a noticeable recalcitrancy towards oxidative degradation could be easily anticipated, and such a forecast is met by the experimental work. Laccases could bleach many dyes, not belonging to the azo dye class [243–246], possibly in the presence of suitable redox mediators [247,248]. Owing to its relatively low redox potential, horseradish peroxidase is not the tool of choice to build a versatile bleaching system for industrial dyes. However, in some selected cases it represents an inexpensive and effective alternative to more complex and costly procedures [227,249,250]. Only seldom can horseradish peroxidase act as an oxygen donor towards some substrates [251]. As a point of fact, horseradish peroxidase was inactive towards ARS, whereas a moderate activity was found when using Pleurotus pulmonarius (formerly referred to as P. sajor-caju) laccase. However, bleaching with laccase was incomplete, perhaps because of the formation of a 1,2,9,10-anthradiquinone-3-sulfonic acid as an intermediate, which slowly fades and probably has an adverse effect on the enzyme. Anyway, the spectrophotometric patterns of the two processes (H2O2 and MnTSPP versus laccase) are qualitatively similar, which suggests a similar degradation pathway passing through the diquinone intermediate. Only in the case of the artificial catalyst the reaction goes forward leading to o-phthalic acid as the main degradation product. Not surprisingly, H2O2 addition to laccase enhances the bleaching process, although it becomes not as efficient as observed with the system hydrogen peroxide plus metalloporphyrin. The things go differently in the case of high-potential peroxidases such as LiP, MnP, and haloperoxidases: the two azo dyes Orange G and Sunset yellow were efficiently bleached by hydrogen peroxide in the presence of very low concentrations of chloroperoxidase [189]. Two alternative cleavage mechanisms were identified by studying the product pattern with LC-MS (ESI): a symmetrical one (the double bond of the azo chromophore is cleaved) and two variants of unsymmetrical breaking, each Molecules 2016, 21, 964 28 of 40 involving one linkage between the azo chromophore and one of the two aromatic moieties. Similar conclusions were reached (coexistence of symmetrical and unsymmetrical cleavage mechanisms) in the case of MnP acting on Orange II [252]. However, also high-potential peroxidases sometimes fail in bleaching recalcitrant dyes. This is the case of phenosafranine: the dye was at first partially bleached by H2O2 in the presence of LiP, but the enzyme was rapidly and irreversibly inactivated along the bleaching process [143]. Perhaps a very reactive intermediate (the same hypothesized for the metalloporphyrin-catalyzed bleaching?) attacks the enzyme leading to permanent modification and therefore loss of catalytic activity.

5. Conclusions Redox-active metalloporphyrins are very promising bleaching catalysts for synthetic textile dyes when the ecofriendly and not too costly hydrogen peroxide is used as the oxidizing agent. However, they also show some limitations and drawbacks to be kept in mind when envisaging a specific bleaching process. First of all, metalloporphyrins are quite expensive compounds, which have to be recovered and recycled to build any economically sustainable process. This goal can be achieved by immobilization on proper supports, recoverable by means of decantation, filtration, or by means of applied magnetic fields. Metalloporphyrin toxicology is largely unknown, and therefore efficient recovery of the catalysts is even more compulsory. Adverse effects can be easily forecast, owing to their resemblance to physiological metalloporphyrins such as heme; the topic is quite complex and is far from being deeply explored [253–255]. Another limitation has been discussed above, and is related to amino azo dyes, which when attacked by metalloporphyrins produce compounds that are often more toxic and recalcitrant than the original dyes. On the other hand, the lack of specificity and the high redox potentials of the metalloporphyrins allow the efficient bleaching of a wide range of different dyes, almost regardless to the specific chemical classes. This is a very useful feature when working on dyes, whose bleaching by means of oxidative enzymes is not possible, as well as depicted by the example of phenosafranine. In conclusion, some guidelines can be proposed to enhance the usefulness of redox-active metalloporphyrins to remediate textile wastewaters: (i) exploring the (inexpensive) synthesis of more and more active and stable catalysts; (ii) envisaging new supports and new procedures to obtain robust and effective immobilized catalysts; (iii) optimizing the operative conditions to balance higher bleaching rates, and lower oxidant consumption with minimal catalyst degradation.

Acknowledgments: Acknowledgements are due to FCT/MEC for the financial support to QOPNA (PEst-C/QUI/UI0062/2013; FCOMP-01-0124-FEDER-037296) through national funds and, where applicable, co-financed by the FEDER, within the PT2020 Partnership Agreement. C.M.B. Neves thanks FCT for her Ph.D. Grant (SFRH/BD/52531/2014). Author Contributions: C.M.B.N., M.M.Q.S., and M.G.P.M.S.N. have contributed mainly for Sections 2.1 and 2.2 and in the preparation of some schemes and figures. G.C. has contributed mainly for Section3. P.Z. has written Section1 and has cooperated with E.S. to contribute for Sections4 and5. E.S. had the original idea, has contributed to Sections4 and5 together with P.Z. and coordinated all the coauthors to prepare the final version. Conflicts of Interest: The authors declare no conflict of interest.

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