Electrochemical Comparison on New (Z)-5-(Azulen-1-Ylmethylene)-2-Thioxo-Thiazolidin-4-Ones

S S symmetry

Article Electrochemical Comparison on New (Z)-5-(Azulen-1-Ylmethylene)-2-Thioxo-Thiazolidin-4-Ones

Eleonora-Mihaela Ungureanu 1, Mariana Popescu (Apostoiu) 1, Georgiana-Luiza Tatu (Arnold) 1, Liviu Birzan 2, Raluca Isopescu 1, Gabriela Stanciu 3 and George-Octavian Buica 1,*

1 Faculty of Applied Chemistry and Materials Science, University Politehnica of Bucharest, 1-7 Gh. Polizu Street, 011061 Bucharest, Romania; [email protected] (E.-M.U.); [email protected] (M.P.); [email protected] (G.-L.T.); [email protected] (R.I.) 2 Institut of Organic Chemistry “C. D. Nenitzescu” of the Romanian Academy, 202B Spl. Independentei, 71141 Bucharest, Romania; [email protected] 3 Department of Chemistry and Chemical Engineering, Ovidius University, 124 Mamaia Blvd., 900527 Constantza, Romania; [email protected] * Correspondence: [email protected]; Tel.: +40-21-402-3930

Abstract: Three (Z)-5-(azulen-1-ylmethylene)-2-thioxo-thiazolidin-4-ones are electrochemically char- acterized by cyclic voltammetry, differential pulse voltammetry, and rotating disk electrode voltammetry. The electrochemical investigations revealed that the redox potential is influenced by the number and position of the alkyl groups, and the possible oxidation mechanism is proposed. These compounds, after their immobilization on glassy carbon electrodes during oxidative electropolymerization, were examined as complexing ligands for heavy metal ions from aqueous solutions through Citation: Ungureanu, E.-M.; adsorptive stripping voltammetry. Popescu (Apostoiu), M.; Tatu (Arnold), G.-L.; Birzan, L.; Keywords: (Z)-5-(azulen-1-ylmethylene)-2-thioxo-thiazolidin-4-ones; electrochemical characteriza- Isopescu, R.; Stanciu, G.; Buica, G.-O. tion; modified electrodes; metal detection Electrochemical Comparison on New (Z)-5-(Azulen-1-Ylmethylene)-2- Thioxo-Thiazolidin-4-Ones. Symmetry 2021, 13, 588. https://doi.org/ 1. Introduction 10.3390/sym13040588 Azulene is an isomer of naphthalene, but they are essentially different. While naphtha- Academic Editor: Edwin lene has biaxial symmetry, azulene has single symmetry about the x-axis, which gives the Charles Constable azulene system an asymmetric charge distribution. This causes azulene to present important properties, such as a significant dipole moment and remarkable chemical, electronic Received: 10 March 2021 and optical behavior. As a result, such a system can have many technical applications Accepted: 29 March 2021 in optoelectronics [1,2], medicine [3], Li–S batteries [4], supercapacitors [5], photovoltaic Published: 2 April 2021 cells [6], sensing and imaging [7], etc. The ability of the electrons to move easily from the seven-member cycle to the five-member cycle [8] allows the azulene molecule to act as a Publisher’s Note: MDPI stays neutral donor and acceptor of electrons [9]. For the same reason, it is also possible to use azulenes with regard to jurisdictional claims in as building blocks for the development of new molecules [10–12]. Azulene can polymerize published maps and institutional affil- via electrochemistry resulting in polymers with high electrical conductivity [13]. If they are iations. properly substituted, they can complex specific targets. Moreover, if they are immobilized on an electrode surface, it could lead to materials that are able to enhance sensitivity and selectivity towards metal ions [14,15]. In line with our previous work [10–12,14,15], the results given in this paper are related Copyright: © 2021 by the authors. to the electrochemical characterization of new azulene compounds and highlight their Licensee MDPI, Basel, Switzerland. complexing properties towards metal ions [16]. The studied compounds are derivatives of This article is an open access article (Z)-5-(azulen-1-ylmethylene)-2-thioxo-thiazolidin-4-one (L1). Its structure contains the two distributed under the terms and essential elements of molecular recognition: a complexing part (2-thioxo-thiazolidin-4-one conditions of the Creative Commons ring) [17] and a polymerizable part—azulene moiety. Attribution (CC BY) license (https:// The 2-thioxo-thiazolidin-4-one (rhodanine) is a very important heterocyclic compound creativecommons.org/licenses/by/ used to synthesize different compounds because of its biological activity. The applications 4.0/).

Symmetry 2021, 13, 588. https://doi.org/10.3390/sym13040588 https://www.mdpi.com/journal/symmetry Symmetry 2021, 13, x FOR PEER REVIEW 2 of 12

The 2-thioxo-thiazolidin-4-one (rhodanine) is a very important heterocyclic com- Symmetry 2021, 13, 588 2 of 12 pound used to synthesize different compounds because of its biological activity. The applications of its antiviral, anticancer, and antimicrobial activity were recently reviewed of[18]. its It antiviral, is also known anticancer, for its and complexing antimicrobial prop activityerties towards were recently heavy metals reviewed [17]. [18 The]. It azulene is also knownderivative for itsof rhodanine complexing can properties be used towardsfor accurate heavy metal metals determination [17]. The azulene in the derivativesame way ofthat rhodanine the p-dimethylaminophenylidenrhodanine can be used for accurate metal determination was used to accurately in the same determine way that Cu, the Ni, p- dimethylaminophenylidenrhodanineFe, and Zn [19], or the way in which wastriarylamine used to accurately rhodanine determine derivatives Cu, were Ni, Fe,used and as Zncolorimetric [19], or the sensors way in to which detect triarylamine Ag and Hg rhodanineions [20]. derivatives were used as colorimetric sensorsElectrochemical to detect Ag and polymerization Hg ions [20]. of the ligand on the electrode results in a high density ofElectrochemical complexing groups, polymerization which allows of the accu ligandmulation on the electrodeof metal resultsions on in its a highsurface density [21– of24]. complexing groups, which allows accumulation of metal ions on its surface [21–24]. TheThe threethree (Z)-5-(azulen-1-ylmethylene)-2-thioxo-thiazolidin-4-ones(Z)-5-(azulen-1-ylmethylene)-2-thioxo-thiazolidin-4-ones (Figure 11)) were were comparedcompared byby thethe curvescurves obtainedobtained throughthrough electrochemicalelectrochemical methodsmethods (cyclic(cyclic voltammetryvoltammetry (CV),(CV), differential pulse pulse volta voltammetrymmetry (DPV), (DPV), and and rotating rotating disk disk electrode electrode (RDE) (RDE) voltamme- voltam- metry).try). This This comparison comparison allowed allowed the the establishm establishmentent of of the the main main characteristics for theirtheir polymerizationpolymerization processes. Then, they were used as ligands for the preparation of com- plexingplexing modiﬁedmodified electrodes.electrodes. The The obtained obtained modiﬁed modified electrodes electrodes were were compared compared in termsin terms of heavyof heavy metal metal sensing sensin propertiesg properties [25 [25].].

FigureFigure 1.1. Structure ofof (Z)-5-(azulen-1-ylmethylene)-2-thioxo-thiazolidin-4-ones;(Z)-5-(azulen-1-ylmethylene)-2-thioxo-thiazolidin-4-ones; R: R: H H ( L1(L1);); 4,6,8-Me 4,6,8- 3 (MeL2);3 ( 3,8-MeL2); 3,8-Me2-5-iPr2-5-iPr (L3). (L3).

2.2. Materials and Methods TheThe azulene derivatives derivatives were were synthesized synthesized according according to the to thepreviously previously published published pro- procedurecedure [26]. [26 The]. The electrochemical electrochemical experiments experiments were were performed performed either either in non-aqueous in non-aqueous sup- supportingporting electrolyte electrolyte (0.1 (0.1 M) M) (o (obtainedbtained from from acetonitrile acetonitrile (Sigma (Sigma Aldrich, Aldrich, electronic gradegrade 99.999%)99.999%) andand tetra-n-butylammoniumtetra-n-butylammonium perchlorateperchlorate (TBAP)(TBAP) (Fluka,(Fluka, puriss,puriss, electrochemicalelectrochemical gradegrade >>99%)) 99%)) or or in in 0.1 0.1 M acetate buffer solution (obtained from sodium acetateacetate (Roth,(Roth, 99.99%)99.99%) andand acetic acetic acid acid (Fluka, (Fluka, >99.0%, >99.0%, trace trace select)). select)). The The ionic ionic metal metal solution solution was obtainedwas ob- fromtained the from corresponding the corresponding metal salts. metal Puriﬁed salts. Purified water (18.2 water M (18.2Ωcm), M wasΩcm), obtained was obtained from a from Mil- liporea Millipore Direct-Q Direct-Q 3UV water3UV water puriﬁcation purification system system and used and to used prepare to prepare the aqueous the aqueous solutions. solutions.A PGSTAT 12 AUTOLAB potentiostat (Metrohm/Eco Chemie) was used to perform the electrochemicalA PGSTAT 12 experimentsAUTOLAB potentiostat by connecting (Metrohm/Eco it to a classical Chemie) 3-electrode was cell. used The to workingperform electrodethe electrochemical was a glassy experiments carbon disk by (3 connecting mm, from it Metrohm), to a classical and 3-electrode the counter cell. electrode The work- was aing Pt electrode wire. Ag/10 was mMa glassy AgNO carbon3 in 0.1 disk M (3 TBAP, mm, CHfrom3CN Metrohm), and Ag/AgCl, and the 3M counter KCl referenceelectrode electrodeswas a Pt wire. were Ag/10 used mM for experimentsAgNO3 in 0.1 performed M TBAP, CH in non-aqueous3CN and Ag/AgCl, and aqueous 3M KCl solutions, reference respectively.electrodes were For used the for electrochemical experiments perfor studiesmed performed in non-aqueous in the organic and aqueous solvent, solutions, all the potentialsrespectively. were For reported the electrochemical from the potential studies ofperformed the ferrocene/ferrocenium in the organic solvent, redox all couplethe po- + (Fc/Fctentials ),were which reported was +0.07 from V in the our conditions.potential of Before the ferrocene/ferrocenium each measurement, the redox surface couple of the working(Fc/Fc+), which electrode was was +0.07 cleaned V in our with conditions. diamond Before paste (0.25 eachµ measurement,m) and rinsed the with surface acetonitrile. of the workingThe electrode electrochemical was cleane experimentsd with diamond performed paste by CV,(0.25 DPV, μm) and rinsed RDE were with recorded acetonitrile. for millimolarThe electrochemical solutions of L1, 4(Z)-2-thioxo-5-((4,6,8-trimethylazulen-1-yl)methylene)thiazolidin-experiments performed by CV, DPV, and RDE were recorded4- onefor millimolar (L2), or (Z)-2-thioxo-5-((3,8-Me2-5-iPr-1-yl)methylene)thiazolidin-4-one solutions of L1, 4(Z)-2-thioxo-5-((4,6,8-trimethylazulen-1-yl)m (ethylene)thi-L3) in 0.1 M TBAP,azolidin-4-one CH3CN starting(L2), or from (Z)-2-thioxo-5-((3,8-Me2-5-iPr-1-yl)methylene)thiazolidin-4-one the stationary potential. CV was performed at different scan rates between 0.1 and 1.0 V s−1. DPV was conducted with a scan rate of 0.01 V s−1 with a (L3) in 0.1 M TBAP, CH3CN starting from the stationary potential. CV was performed at pulse height of 0.025 V and a step time of 0.2 s. RDE curves were recorded at 0.01 V s−1 for different rotation rates. The electrochemical behavior of the pattern of (Z)-5-((azulen-1-yl)methylene)-2-thioxo- thiazolidin-4-one ligand (L1) and (Z)-2-thioxo-5-((4,6,8-trimethylazulen-1-yl)methylene)thiazolidin- Symmetry 2021, 13, x FOR PEER REVIEW 4 of 12

At higher anodic and cathodic potentials, the electrochemical processes become non- selective and the whole molecule is destroyed. As expected, the alkyl groups induce a positive inductive effect and increase the electron densities of the molecules. Therefore, the alkyl-substituted compounds are easier to be oxidized and harder to be reduced than the pattern compound. However, the steric effect of these groups makes the reductions more difficult to anticipate, and the reduction potentials can sometimes even be reversed by this effect. Symmetry 2021, 13, 588 The azulene (Az) system is more stable when it is symmetrically substituted, but3 of 12it becomes very reactive by unsymmetrical substitution (the symmetry of the aromatic system is disrupted by the difference in the alkyl group's electronic influence). Therefore, the compounds4-one (L2) has containing previously three been symmetrically shown [17,27]. su Thebstituted redox characteristicsgroups (like 4,6,8-three of (Z)-2-thioxo-5- methyl azulene((3,8-Me2-5-iPr-1-yl)methylene)thiazolidin-4-one (TMA)) have higher activation energies than (L3 )those were unsymmetrically emphasized in a substituted, PhD thesis likeproduced guaiazulene by our group(Gu). Therefore, [25]. it is expected that guaiazulene will react faster than TMA,The despite immobilization its higher volume. of the ligands on the electrode surface was accomplished through controlledThe experimental potential electrolysis results show (CPE) that from the 0.1 redox mM potential TBAP, CH is3 CNinfluenced solutions by (1 the mM) number of L1, andL2, or positionL3. The of accumulation the alkyl groups, and detection as assumed of metal previously ions were (Figure performed S1 of the using Supplementary a previously Materials)described. procedureThe Gu-azulene [14,15 ].fragment Briefly, (3,8-Me the accumulation2-5-iPr -Az) of from metal L3 ionsis more was easily performed oxidized by thanchemical the TMA-azulene accumulation fragment in an open (4,6,8-Me circuit for3-Az) 15 from min. AfterL2, which careful is rinsingmore easily with oxidized purified thanwater the (to azulene remove fragment the unbound (Az) ions),from theL1. accumulatedThese compounds ions were present reduced a first to anodic metal zero-DPV peakvalent at ( −0.3731.2V) V, for 0.493 120 s,V, followed and 0.541 by V, the respec recordingtively. of In DPV reduction, stripping the curves. potential order is reversed,In order but the to remove differentiation the influence is less ofobviou the dissolveds because oxygen,the reductions all measurements occur specifically were inperformed the heterocyclic underan part argon (the atmosphere.first cathodic peaks of these compounds in DPV have the values of −1.529 V, −1.541 V, and −1.543 V for L1, L2, and L3, respectively). These curves also 3. Results and Discussions show an important variation in the peak current values for the same concentration of the 3.1. Studies by DPV ligands (Figure 2). The differences observed for the peak a1 current values can be at- tributedDPV to overlaid errors during curves the for allexperiment compounds due at to same the concentrationlow solubility areof these shown compounds. in Figure2. However,The oxidation the values and reduction for the height peaks of are a1 furtherand c1 peaks denoted agree in their with appearancetheir expected order solubility, during whichDPV scans varies (a1, in a2,the c1,order c2 .L3 . . ).> L1 > L2.

Figure 2. DifferentialDifferential pulse pulse voltammetry voltammetry (DPV) (DPV) (0.01 (0.01 V V s s−−1)1 anodic) anodic and and cathodic cathodic curves curves for for L1L1, L2, L2, , and L3 (at(at 0.5 0.5 mM). mM).

From the DPV curves, it can be observed that there are two main peaks for each ligand in the anodic domain. In the cathodic domain, there are different numbers of peaks: two for L2 (c1, c2), three peaks for L3 (c1–c3), and four peaks for L1 (c1–c4). Their potentials and the assessment of the peaks are given in Table1. The increase in DPV peak currents with concentration can be used to develop an analytical method for the evaluation of concentration for unknown samples. The π system of these compounds is identical, so the number of signals must be similar. The different numbers of observed peaks for each compound can be explained by the fact that the peaks can double by the protonation of ligands. The possible redox processes are illustrated in Scheme1. The two main DPV peaks correspond to the electron transfers formulated in Scheme1 for these compounds. The ﬁrst anodic step consists of the oxidation of azulene moiety (which is the electron-richest part of this structure), while the ﬁrst cathodic peak is due to the reduction of the rhodanine cycle (the most electronegative part of the compound). Symmetry 2021, 13, x FOR PEER REVIEW 3 of 12

different scan rates between 0.1 and 1.0 V s−1. DPV was conducted with a scan rate of 0.01 V s−1 with a pulse height of 0.025 V and a step time of 0.2 s. RDE curves were recorded at 0.01 V s−1 for different rotation rates. The electrochemical behavior of the pattern of (Z)-5-((azulen-1-yl)methylene)-2-thioxo-thiazolidin-4-one ligand (L1) and (Z)-2-thioxo-5-((4,6,8-trimethylazulen-1-yl)methylene)thiazolidin-4-one (L2) has previously been shown [17,27]. The redox characteristics of (Z)-2-thioxo-5-((3,8-Me2-5-iPr-1-yl)methylene)thiazolidin-4-one (L3) were emphasized in a PhD thesis produced by our group [25]. The immobilization of the ligands on the electrode surface was accomplished through controlled potential electrolysis (CPE) from 0.1 mM TBAP, CH3CN solutions (1 mM) of L1, L2, or L3. The accumulation and detection of metal ions were performed using a previously described procedure [14,15]. Briefly, the accumulation of metal ions was per- Symmetry 2021, 13, 588 formed by chemical accumulation in an open circuit for 15 min. After careful rinsing 4with of 12 purified water (to remove the unbound ions), the accumulated ions were reduced to metal zero-valent (−1.2V) for 120 s, followed by the recording of DPV stripping curves. Table 1. In Potentialsorder to (Vremove vs. Fc/Fc+) the influence of the peaks of andthetheir dissolved assessment. oxygen, all measurements were L1 [23]performed under L2 an [15 argon] atmosphere. L3 Peak Method Method Method Assessed Process 3. Results and Discussions DPV CV DPV CV DPV CV 3.1. Studies by DPV O /O .− −1.202 −1.316 (i) * - - - - Oxygen reduction 2 2 DPV overlaid curves for all compounds at same concentration are shown in Figure Low peak current process c1 −1.528 -2. The oxidation−1.541 and reduction - peaks−1.543 are further−1.610 denoted (i) * in(negligible) their appearance due to reduction order during of the DPV scans (a1, a2, c1, c2…). protonated ligand c2 −1.801 −1.842 (q) *From− the2.216 DPV curves,−2.112 (r) it *can be observed - − 1.991that there (q) * are twoReduction main peaks of C=C for bond each lig- and in the anodic domain. In the cathodic domain, there are differentLow peak numbers current process of peaks: (negligible) due to the reduction of c3 −2.431 −2.482two (q) for * L2 (c1,-- c2), three peaks for −L32.191 (c1–c3),− and2.430 four (q) * peaks for L1 (c1–c4). Their poten- a fragment (probably as a result of tials and the assessment of the peaks are given in Table 1. The increase in DPV peak cur- the decomposition of the azulene c4 −2.721 −2.794rents (q) * with concentration-- can be used−2.748 to develop−2.831 an (q) analytical * Reduction method for of the the C–S evaluation bond a1 0.541 0.578of (i) concentration * 0.473 for unknown 0.493 (i) * samples. 0.373 0.421 (i) * Radical cation formation a2 1.021 1.143 (i) *The π 0.942 system of 0.847these (i) compounds * 0.673 is identical, 0.721 (i)so * the number Oligomer of signals oxidation must be sim- a3 - -ilar. The different - numbers 1.571 (i) of * observed - peaks 1.490for each (i) * compound can be explained - by the a4 - -fact that the peaks - can double - by the protonation - 1.785 of (i) ligands. * The possible redox - processes are illustrated* q—quasi-reversible in Scheme 1. process; i—irreversible process.

R R R R R 2+ +

- 1e - 1e + 2e + 2e + 4e + + 2H -H2S O O O O O S S S S S NH NH NH NH NH S S S S Scheme 1.1. ElectrochemicalElectrochemical oxidation oxidation and and reduction reduction processes processes for (Z)-5-((azulen-1-l)methylene)-2-thioxo-thiazolidin-4-ones.for (Z)-5-((azulen-1-l)methylene)-2-thioxo-thiazolidin-4- ones. The small peaks in the cathodic region could be explained by the existence of a small concentrationThe two main of the DPV protonated peaks correspond compounds, to the which electron are more transfers easily formulated reduced due in Scheme to their 1positive for these charge, compounds. so each The peak first has anodic a pair at step lower consists potentials. of the oxidation of azulene moiety (whichAt is higher the electron-richest anodic and cathodic part of potentials, this structure), the electrochemical while the first processescathodic peak become is due nons- to theelective reduction and the of the whole rhodanine molecule cycle is destroyed. (the most electronegative part of the compound). TheAs expected,small peaks the in alkyl the cathodic groups region induce coul a positived be explained inductive by effectthe existence and increase of a small the concentrationelectron densities of the of theprotonated molecules. compounds, Therefore, which the alkyl-substituted are more easily compounds reduced due are to easier their positiveto be oxidized charge, and so each harder peak to behas reduced a pair at than lower the potentials. pattern compound. However, the steric effect of these groups makes the reductions more difﬁcult to anticipate, and the reduction potentials can sometimes even be reversed by this effect. The azulene (Az) system is more stable when it is symmetrically substituted, but it becomes very reactive by unsymmetrical substitution (the symmetry of the aromatic

system is disrupted by the difference in the alkyl group’s electronic influence). Therefore, the compounds containing three symmetrically substituted groups (like 4,6,8-three methyl azulene (TMA)) have higher activation energies than those unsymmetrically substituted, like guaiazulene (Gu). Therefore, it is expected that guaiazulene will react faster than TMA, despite its higher volume. The experimental results show that the redox potential is influenced by the number and position of the alkyl groups, as assumed previously (Figure S1 of the Supplementary Materials). The Gu-azulene fragment (3,8-Me2-5-iPr -Az) from L3 is more easily oxidized than the TMA-azulene fragment (4,6,8-Me3-Az) from L2, which is more easily oxidized than the azulene fragment (Az) from L1. These compounds present a first anodic DPV peak at 0.373 V, 0.493 V, and 0.541 V, respectively. In reduction, the potential order is reversed, but the differentiation is less obvious because the reductions occur specifically in Symmetry 2021, 13, x FOR PEER REVIEW 5 of 12

Table 1. Potentials (V vs. Fc/Fc+) of the peaks and their assessment.

L1 [23] L2 [15] L3 Peak Method Method Method Assessed Process DPV CV DPV CV DPV CV O2/O2.− −1.202 −1.316 (i) * - - - - Oxygen reduction Low peak current process (negligible) due to reduction of the c1 −1.528 - −1.541 - −1.543 −1.610 (i) * protonated ligand c2 −1.801 −1.842 (q) * −2.216 −2.112 (r) * - −1.991 (q) * Reduction of C=C bond Symmetry 2021, 13, 588 Low peak current process (negligible) due to the reduction5 of 12of c3 −2.431 −2.482 (q) * - - −2.191 −2.430 (q) * a fragment (probably as a result of the decomposition of the azulene c4 −2.721 −2.794 (q) * -the heterocyclic - − part2.748 (the −2.831 first (q) cathodic * peaks of these Reduction compounds of the C–S in DPV bond have the values a1 0.541 0.578 (i) * 0.473of −1.529 0.493 (i) V, *− 1.541 0.373 V, and 0.421− (i)1.543 * V for L1, L2, and RadicalL3, respectively). cation formation These curves also a2 1.021 1.143 (i) * 0.942show 0.847 an important (i) * 0.673 variation 0.721 (i) in * the peak current values Oligomer for the oxidation same concentration of the a3 - - -ligands 1.571 (Figure (i) * 2). -The differences 1.490 (i) * observed for the peak a1 current - values can be attributed a4 - - -to errors- during the - experiment 1.785 (i) * due to the low solubility of these - compounds. However, the values* q—quasi-reversible for the height process; of a1 and i—irreversible c1 peaks agree process. with their expected solubility, which varies in the order L3 > L1 > L2. 3.2. Studies by CV 3.2. StudiesFrom the by CVCV curves, it can be observed that in the oxidation domains for compounds L2 andFrom L3,the only CV two curves, peaks it are can significant be observed (a1 that and in a2). the The oxidation peaks situated domains at for more compounds positive L2potentialsand L3, (a3 only and two a4) peaks belong are to significant the supporting (a1 and electrolyte a2). The peaks(drawn situated with dotted at more line). positive In the potentialsreduction (a3domain, and a4) each belong compound to the supporting presents a electrolytedifferent number (drawn withof peaks: dotted compound line). In the L1 reductionhas three domain,reduction each peaks compound (c2–c4); presentscompound a different L2 has one number reduction of peaks: peak compound (c2); compoundL1 has threeL3 has reduction three reduction peaks (c2–c4); peaks compound(c1, c3, c4) L2(Figurhase one S2 reductionof the Supplementary peak (c2); compound Materials).L3 Thehas threepotentials reduction of the peaks CV peaks (c1, c3, are c4) given (Figure in S2 Table of the 1. Supplementary Like in the case Materials). of DPV curves, The potentials it is ob- ofserved the CV that peaks the areCV givenredox inpeak Table potentials1. Like in ar thee influenced case of DPV by curves, the number it is observed and position that the of CVthe redoxalkyl groups peak potentials (Table 1). are The influenced L1, L2, and by theL3 compounds number and present position their of the first alkyl anodic groups CV (Tablepeaks 1at). 0.578 The L1V,, 0.493L2, and V, L3andcompounds 0.421 V, respectively present their (Figure first anodic3). These CV potentials peaks at are 0.578 well V, 0.493correlated V, and with 0.421 the V, peak respectively potentials (Figure obtained3). These by DPV. potentials The reduction are well correlatedpotentials withare more the peakdifficult potentials to establish obtained in CV by be DPV.cause The the reductionpresence of potentials oxygen traces are more leads difficult to unwanted to establish over- inlaps. CV The because increase the presencein CV peak of currents oxygen traces with concentration leads to unwanted can be overlaps. used to develop The increase an ana- in CVlytical peak method currents for with the evaluation concentration of concentrat can be usedion to for develop unknown an analyticalsamples, as method in the forcase the of evaluationDPV. of concentration for unknown samples, as in the case of DPV.

Figure 3. Cyclic voltammetry (CV) (0.1 Vs−1) anodic and cathodic curves for L1, L2, L3 (at 0.5 mM).

Figure4 shows the anodic and cathodic voltammograms for L3 on different scan domains, and Table1 presents the potentials (V vs. Fc/Fc +) of the peaks and their assessment. It can be seen in the anodic domain that all the processes show an irreversible behavior, while in the cathodic one, they are quasi-reversible or irreversible, like in the case of the other two compounds (Figure S3 of the Supplementary Materials). Voltammograms were also recorded at different scan rates, as seen in Figure5, for the anodic and cathodic scans of compound L3. In the inset of Figure5, the linear dependences of the (a1) and (c1) processes on the square root of the scan rate are shown. The slopes vary in the following order: L3 > L1 > L2 (Table2). Their different slopes can be explained by Symmetry 2021, 13, x FOR PEER REVIEW 6 of 12

Figure 3. Cyclic voltammetry (CV) (0.1 Vs−1) anodic and cathodic curves for L1, L2, L3 (at 0.5 mM).

Symmetry 2021, 13, 588 Figure 3. Cyclic voltammetry (CV) (0.1 Vs−1) anodic and cathodic curves for L1, L2, L3 (at 0.5 6mM). of 12

Figure 4 shows the anodic and cathodic voltammograms for L3 on different scan domains,their solubility, and Table which 1 presents varies the in potentials the same order.(V vs. Fc/Fc As the+) of solubility the peaks of and these their compounds assessment. is quiteIt can low,be seen studies in the are anodic usually domain performed thatin all oversaturated the processes solutions show an fromirreversible which thebehavior, ligand whilesometimes in the precipitates; cathodic one, this they phenomenon are quasi-reversible is difﬁcult or toirreversible, control because like in thethe solutioncase of the is otherintensely two colored.compounds (Figure S3 of the Supplementary Materials).

Figure 4. Anodic and cathodic CV (0.1 V s−1) curves for L3 (0.5 mM in 0.1 M tetra-n-butylammonium perchlorate (TBAP), CH3CN) on different scan domains.

Voltammograms were also recorded at different scan rates, as seen in Figure 5, for the anodic and cathodic scans of compound L3. In the inset of Figure 5, the linear dependences of the (a1) and (c1) processes on the square root of the scan rate are shown. The slopes vary in the following order: L3 > L1 > L2 (Table 2). Their different slopes can be explained by their solubility, which varies in the same order. As the solubility of these Figurecompounds 4. Anodic is quite and cathodiccathodic low, studies CVCV (0.1(0.1 are V V s −s usually−11) curves performed forfor L3L3 (0.5(0.5 mMmM in inoversaturated in 0.1 0.1 M M tetra-n-butylammonium tetra-n-butylammo- solutions from niumwhich perchlorate the ligand (TBAP), sometimes CH3CN) precipitates; on different this scan phenomenon domains. is difficult to control because perchlorate (TBAP), CH3CN) on different scan domains. the solution is intensely colored. Voltammograms were also recorded at different scan rates, as seen in Figure 5, for the anodic and cathodic scans of compound L3. In the inset of Figure 5, the linear dependences of the (a1) and (c1) processes on the square root of the scan rate are shown. The slopes vary in the following order: L3 > L1 > L2 (Table 2). Their different slopes can be explained by their solubility, which varies in the same order. As the solubility of these compounds is quite low, studies are usually performed in oversaturated solutions from which the ligand sometimes precipitates; this phenomenon is difficult to control because the solution is intensely colored.

Figure 5. Anodic and cathodic voltammograms at different scan rates for L3 (0.5 mM); inset: linear dependences of the (a1) and (c1) processes on the square root of the scan rate.

Using the Randles-Sevcik equation for an irreversible process [28], the diffusion coeffi-

cients were calculated for one electron transfer (Table3). The diffusion coefficient (D) value varies in the same order as it is the solubility of the compounds (DL3 > DL1 > DL2). This result is probably due to their different structures, but it is also connected to their actual concentration in solution. There is a lack of precision in the evaluation of the actual concentration values of the working solutions due to the precipitation of compounds from the oversaturated solutions. Consequently, the results for D are inﬂuenced (the concentration is diminished due to uncontrolled precipitation), especially for the less soluble compounds L1 and L2. Therefore, D values for L1 and L2 are much lower than for L3. The linear

Symmetry 2021, 13, 588 7 of 12

dependence of the peak current as a function of the square root of the scan rate (Figure5, inset) also highlights a diffusion-controlled process [29,30].

Table 2. Equations obtained for the linear dependences of ﬁrst anodic (a1) and cathodic (c1) peak currents (in A) on the square root of the scan rate (in V s−1) for L1–L3.

ipa1 vs. v1/2 ipc1 vs. v1/2 ip = −3.80 × 10−6 + 44.67 × 10−6 × v1/2, L1 a1 Not recorded R2 = 0.998 ip = −6.58 × 10−6 + 40.2 × 10−6 × v1/2, ip = −1.25 × 10−6 − 24.6 × 10−6 × v1/2, L2 a1 c1 R2 = 0.935 R2 = 0.971 ip = −16.66 × 10−6 + 122.07 × 10−6 × v1/2 ip = 1.58 × 10−6 − 56.44 × 10−6 × v1/2, L3 a1 c1 R2 = 0.995 R2 = 0.998

Table 3. Estimated diffusion coefﬁcients of the ligands (for a concentration of 0.5 mM in each

compound in 0.1 M TBAP, CH3CN).

Compound L1 L2 L3 105 × D (cm2 s−1) 2.2 1.8 * 16.5 * Previously calculated value [15].

3.3. Studies by RDE Figure6 shows the RDE curves at different rotation rates for these compounds in 0.1 M TBAP, CH3CN. The processes are denoted with respect to the peak notation from the DPV curves. The studied compounds have regular behavior in the cathodic domain, where two main waves are seen for all compounds. For the investigated ligands, the behavior in the anodic domain is different in comparison with that in the cathodic domain. In the anodic domain, the currents drop suddenly after the a2 peak for all compounds. A similar drop has been seen in other azulene compounds [23,31]. This drop is connected to the oxidation of the ligands with the formation of insulating layers that cover the electrode. Isosbestic points appear only for L2 (at about 0.8 V) and for L3 (at 0.7 V). When the rotation rate increases from 500 rpm to 1000 rpm, for the pair of peaks a1 and a2, the increase in current for L3 is bigger than in the case of the other two ligands. This involves either weak polymerization in the case of L3 (as it will be shown further in the study of L3 polymerization) or a lower solubility for L2 than L3 (as discussed before, L3 > L1 > L2). The behavior in RDE at different concentrations is similar for all compounds (the current increases with concentration). Figure7A gives as examples the curves for L1 at 1000 rpm [26] and L3 at 500 rpm. The RDE waves from the oxidation domain change to peaks, as was shown for other azulenes [23,31]. This behavior is attributed to the formation of a compact film on the electrode surface. The film formation noticed by RDE occurs at the potential of the RDE peak a2: 0.686 V for L3, 0.785 V for L2 (Figure7B), and 0.927 V for L1 (Figure7C). These values agree with the potentials of the DPV peaks previously obtained. The values of the currents are consistent with the solubility of the compounds (the solubility of these compounds is different and quite low). Consequently, the electrochemical studies are performed usually in oversaturated solutions from which the ligand sometimes precipitates. This phenomenon is difficult to control because the solution is intensely colored. Better control of the concentration of the compounds L1, L2, and L3 could be obtained in more dilute solutions (where the precipitation can be avoided), but the results are not clearly seen as peaks in these conditions for CV, DPV, or RDE experiments. In the reduction domain, mainly two waves are seen for all compounds. Symmetry 2021, 13, x FOR PEER REVIEW 8 of 12

Symmetry 2021, 13, x FOR PEER REVIEW 8 of 12 Symmetry 2021, 13, 588 8 of 12

Figure 6. Rotating disk electrode (RDE) (0.01 V s−1) curves at different rotation rates for compounds L1, L2, and L3.

The behavior in RDE at different concentrations is similar for all compounds (the current increases with concentration). Figure 7A gives as examples the curves for L1 at 1000 rpm [26] and L3 at 500 rpm. The RDE waves from the oxidation domain change to peaks, as was shown for other azulenes [23,31]. This behavior is attributed to the formation of a compact film on the electrode surface. The film formation noticed by RDE occurs at the potential of the RDE peak a2: 0.686 V for L3, 0.785 V for L2 (Figure 7B), and 0.927 V for L1 (Figure 7C). These values agree with the potentials of the DPV peaks previously obtained. The values of the currents are consistent with the solubility of the compounds (the solubility of these compounds is different and quite low). Consequently, the electrochemical studies are performed usually in oversaturated solutions from which the ligand sometimes precipitates. This phenomenon is difficult to control because the solution is intensely colored. Better control of the concentration of the compounds L1, L2, and L3 could be obtained in more dilute solutions (where the precipitation can be avoided),

but the results are not clearly seen as peaks in these conditions for CV, DPV, or RDE ex- −−1 Figureperiments. 6. Rotating disk electrode (RDE)(RDE) (0.01(0.01 VV ss )) curves curves at at different different rotation rates forfor compoundscom- pounds L1, L2, and L3. L1, L2In, and theL3 reduction. domain, mainly two waves are seen for all compounds. The behavior in RDE at different concentrations is similar for all compounds (the current increases with concentration). Figure 7A gives as examples the curves for L1 at 1000 rpm [26] and L3 at 500 rpm. The RDE waves from the oxidation domain change to peaks, as was shown for other azulenes [23,31]. This behavior is attributed to the formation of a compact film on the electrode surface. The film formation noticed by RDE occurs at the potential of the RDE peak a2: 0.686 V for L3, 0.785 V for L2 (Figure 7B), and 0.927 V for L1 (Figure 7C). These values agree with the potentials of the DPV peaks previously obtained. The values of the currents are consistent with the solubility of the compounds (the solubility of these compounds is different and quite low). Consequently, the electrochemical studies are performed usually in oversaturated solutions from which the ligand sometimes precipitates. This phenomenon is difficult to control because the solu- Symmetry 2021, 13, x FOR PEER REVIEW 9 of 12 tion is intensely colored. Better control of the concentration of the compounds L1, L2, and L3 could be obtained in more dilute solutions (where the precipitation can be avoided), but the results are not clearly seen as peaks in these conditions for CV, DPV, or RDE experiments. In the reduction domain, mainly two waves are seen for all compounds.

FigureFigure 7.7. ((AA).). RDERDE (0.01(0.01 V s −1)1 )anodic anodic and and cathodic cathodic curves curves at atdifferent different concentrations concentrations for for L1L1 andand −1 −1 L3L3;(; (BB).). RDERDE (0.01(0.01 V V s s−1)) anodic anodic curves curves at at 500 500 rpm rpm and and 0.5 0.5 mM mM for for L2 and L3;;( (C)C).. RDE RDE (0.01 V s −)1 ) anodic curves at 500 rpm for L1 and L3 (0.2 mM). anodic curves at 500 rpm for L1 and L3 (0.2 mM).

3.4. Modified Electrodes Chemically modified electrodes were obtained either by potentiodynamic oxidation during 20 successive cycles or by CPE at different potentials and different amounts of electrical charges. The obtained electrodes were transferred in 1 mM ferrocene solution, and the signal was recorded. The voltammograms recorded with the modified electrodes were compared with those obtained on the bare electrode. The goal was a modified electrode that yielded positive results with L1 [27], both by CPE and by successive cycling. The ferrocene signal recorded on the modified electrode was diminished when compared with the signal obtained from the bare electrode. The electrode surface was covered by an insulating layer of polyL1, as was seen in electrochemical impedance spectroscopy and scanning electron microscopy studies [32]. The topography of atomic force microscopy (AFM) images exhibited the presence of columnar shape features. AFM results also revealed a dependence of surface roughness on the electropolymerization parameters (potential/charge) [33]. Similar behavior was observed for L2 after the transfer of the modified electrodes into ferrocene probe solution [17], showing the coverage of the electrode with polyL2 films. The behavior of L3 was different. The attempts to obtain polyL3 films either by 20 successive cycles (Figure 8) or by CPE led to very small changes in the ferrocene signal.

Figure 8. (A) Successive voltammograms (0.1 V s−1) in 0.5 mM solution of L3 (20 successive cycles) and (B) the corresponding CV (0.1 V s−1) curve recorded on the electrode obtained in Figure 8A in ferrocene solution (1 mM) in comparison with the bare electrode.

Symmetry 2021, 13, 588 9 of 12

3.4. Modified Electrodes Chemically modified electrodes were obtained either by potentiodynamic oxidation during 20 successive cycles or by CPE at different potentials and different amounts of electrical charges. The obtained electrodes were transferred in 1 mM ferrocene solution, and the signal was recorded. The voltammograms recorded with the modified electrodes were compared with those obtained on the bare electrode. The goal was a modified electrode that yielded positive results with L1 [27], both by CPE and by successive cycling. The ferrocene signal recorded on the modified electrode was diminished when compared with the signal obtained from the bare electrode. The electrode surface was covered by an insulating layer of polyL1, as was seen in electrochemical impedance spectroscopy and scanning electron microscopy studies [32]. The topography of atomic force microscopy (AFM) images exhibited the presence of columnar shape features. AFM results also revealed a dependence of surface roughness on the electropolymerization parameters (potential/charge) [33]. Similar behavior was observed for L2 after the transfer of the modified electrodes into ferrocene probe solution [17], showing the coverage of the electrode with polyL2 films. The behavior of L3 was different. The attempts to obtain polyL3 films either by 20 successive cycles (Figure8) or by CPE led to very small changes in the ferrocene signal. Different electropolymerization charges (0.2–0.8 mC) and potentials (0.59–2.12 V) in CPE did not lead to significant ferrocene signal changes compared to the bare electrode (Figure S4 of the Supplementary Materials). This behavior could be explained by a weak π- polymerization in the case of L3, since 3,8-Me2-5-iPr substituents are bulkier than 4,6,8-Me3 of L2 and H of L1. Other types of polymerization are not possible because these ligands have the most reactive position (3) blocked by substitution.

3.5. Metal Binding Properties The ability of modified electrodes with L1, L2, and L3 to coordinate and detect metal ions from aqueous probes was achieved through chemical accumulation in an open circuit, followed by anodic stripping [14]. Figure9 shows the anodic stripping curves obtained with modified electrodes after a 15 min accumulation time in a solution that contains heavy metal ions (Cd(II), Pb(II), Cu(II), and Hg(II)), each in a 10−6 M concentration. Not all ligands can complex the studied ions. For polyL1 and polyL2, lead stripping currents are higher than those for cadmium, copper, and mercury. The curves in Figure9 indicate a preferential recognition for lead out of all ligands, followed by cadmium and a specific detection of copper by polyL2. In the case of polyL3, a specific detection of cadmium and lead was noticed. For polyL1 and polyL3, no response for Cu and Hg was found. This shows a higher affinity of the ligands towards Pb(II) and Cd(II) ions. This selectivity can be explained by the fact that this type of compound can give substitution reactions in the free position three of the azulene fragment with the formation of organo- mercuric compounds. These compounds have different electrochemical properties, and the Hg peaks are considerably diminished [34]. The electrode modified with L2 detected all of the metal ions in the accumulation solutions but with different intensities varying in the following order: Pb > Cu > Cd >> Hg. The analytical properties of these modified electrodes towards metal ion detection are under consideration. Symmetry 2021, 13, x FOR PEER REVIEW 9 of 12

Figure 7. (A). RDE (0.01 V s−1) anodic and cathodic curves at different concentrations for L1 and L3; (B). RDE (0.01 V s−1) anodic curves at 500 rpm and 0.5 mM for L2 and L3; (C). RDE (0.01 V s−1) anodic curves at 500 rpm for L1 and L3 (0.2 mM).

3.4. Modified Electrodes Chemically modified electrodes were obtained either by potentiodynamic oxidation Symmetry 2021, 13, x FOR PEER REVIEWduring 20 successive cycles or by CPE at different potentials and different amounts10 of 12of electrical charges. The obtained electrodes were transferred in 1 mM ferrocene solution, and the signal was recorded. The voltammograms recorded with the modified electrodes were compared with those obtained on the bare electrode. Different electropolymerization charges (0.2–0.8 mC) and potentials (0.59–2.12 V) in The goal was a modified electrode that yielded positive results with L1 [27], both by CPE did not lead to significant ferrocene signal changes compared to the bare electrode CPE and by successive cycling. The ferrocene signal recorded on the modified electrode (Figure S4 of the Supplementary Materials). This behavior could be explained by a weak was diminished when compared with the signal obtained from the bare electrode. The π-polymerization in the case of L3, since 3,8-Me2-5-iPr substituents are bulkier than 4,6,8- electrode surface was covered by an insulating layer of polyL1, as was seen in electro- Me3 of L2 and H of L1. Other types of polymerization are not possible because these lig- chemical impedance spectroscopy and scanning electron microscopy studies [32]. The to- ands have the most reactive position (3) blocked by substitution. pography of atomic force microscopy (AFM) images exhibited the presence of columnar shape features. AFM results also revealed a dependence of surface roughness on the elec- 3.5. Metal Binding Properties tropolymerization parameters (potential/charge) [33]. Similar behavior was observed for L2 afterThe the ability transfer of modified of the modified electrodes electr withodes L1 ,into L2, ferroceneand L3 to probecoordinate solution and [17], detect showing metal ionsthe coveragefrom aqueous of the probes electrode was with achieved polyL2 thro films.ugh chemicalThe behavior accumulation of L3 was in different. an open Thecir- cuit,attempts followed to obtain by anodic polyL3 stri filmspping either [14]. by Figure 20 successive 9 shows cy thecles anodic (Figure stripping 8) or by curvesCPE led ob- to Symmetry 2021, 13, 588 10 of 12 tainedvery small with changes modified in electrodthe ferrocenees after signal. a 15 min accumulation time in a solution that contains heavy metal ions (Cd(II), Pb(II), Cu(II), and Hg(II)), each in a 10−6 M concentration. Not all ligands can complex the studied ions. For polyL1 and polyL2, lead stripping currents are higher than those for cadmium, copper, and mercury. The curves in Figure 9 indicate a preferential recognition for lead out of all ligands, followed by cadmium and a specific detection of copper by polyL2. In the case of polyL3, a specific detection of cadmium and lead was noticed. For polyL1 and polyL3, no response for Cu and Hg was found. This shows a higher affinity of the ligands towards Pb(II) and Cd(II) ions. This selectivity can be explained by the fact that this type of compound can give substitution reactions in the free position three of the azulene fragment with the formation of organo- mercuric compounds. These compounds have different electrochemical properties, and the Hg peaks are considerably diminished [34]. The electrode modified with L2 detected all of the metal ions in the accumulation solutions but with different intensities varying in the following order: Pb > Cu > Cd >> Hg. −1 FigureFigure 8. 8. (A(A) )Successive Successive voltammograms voltammograms (0.1 (0.1 V V s s−1) in) in0.5 0.5 mM mM solution solution of ofL3L3 (20(20 successive successive cycles) cycles) The analytical properties of these−1 modified electrodes towards metal ion detection andand (B (B) )the the corresponding corresponding CV CV (0.1 (0.1 V V s− s1) curve) curve recorded recorded on on the the electrod electrodee obtained obtained in inFigure Figure 8A8A in in areferroceneferrocene under solution solutionconsideration. (1 (1 mM) mM) in in comparison comparison with with the the bare bare electrode. electrode.

FigureFigure 9. 9. DPVDPV curves curves in inacetate acetate buffer buffer (pH (pH = 5.5) = 5.5)of modified of modiﬁed electrodes electrodes obtained obtained by controlled by controlled potentialpotential electrolysis electrolysis (CPE) (CPE) with with different different ligands ligands (L1 (,L1 L2,,L2 L3,) L3after) after 15 min 15 minof accumulation of accumulation in a in a solutionsolution containing containing a a concentration concentration of of 10 10−−6 M6 M from from all all of of the the following following cations: cations: Cd(II), Cd(II), Pb(II), Pb(II), Cu(II), Cu(II),and Hg(II). and Hg(II).

4.4. Conclusions Conclusions TheThe electrochemical electrochemical characterization ofof severalseveral (Z)-5-(azulen-1-ylmethylene)-2-thioxo- (Z)-5-(azulen-1-ylmethylene)-2-thioxo-thiazolidin-4-onesthiazolidin-4-ones was was performed performed using using CV, CV, DPV, DPV, and and RDE. RDE. Modiﬁed Modified electrodes electrodes were obtained by successive cycling of the potential or by controlled potential electrolysis at different potentials or amounts of electric charges. The responses of the modiﬁed electrodes for heavy metal ion recognition were evaluated. The best results in the recognition of heavy

metal ions were obtained for Pb(II) with polyL1. The stripping curves indicate a preferential recognition for lead by all ligands, followed by cadmium, and a specific detection of copper by polyL2. In the case of polyL3, a specific detection of cadmium and lead was observed. The lack of response from polyL1 and polyL3 towards Cu and Hg indicates their potential use to build sensors based on modified electrodes for Pb(II) and Cd(II) ions. The detection intensities in relation to different heavy metals using these ligands vary as follows: polyL1 > polyL2 ~ polyL3 (for Cd), polyL2 > polyL1 > polyL3 (for Pb), while polyL2 is selective for Cu. The investigated azulene derivatives of rhodanine can be used for very accurate metal determination of Pb, Cd, and Cu. The sensing properties towards heavy metal ions are in progress. Symmetry 2021, 13, 588 11 of 12

Supplementary Materials: The following are available online at https://www.mdpi.com/article/ 10.3390/sym13040588/s1: Figure S1: DPV (10 mV s−1) anodic and cathodic curves at different concentrations for L1, L2, L3; Figure S2: CV (0.1 V s−1) anodic and cathodic curves at different −1 concentrations for L1, L2, L3 in 0.1 M TBAP, CH3CN; Figure S3: Anodic and cathodic CV (0.1 V s ) curves for all compounds (0.5 mM in 0.1 M TBAP, CH3CN) on different scan domains; insets: details −1 of cathodic domains; Figure S4: CV (0.1 V s ) curves (1 mM, in 0.1 M TBAP, CH3CN) obtained after the transfer of the modified polyL3 electrodes in ferrocene solution for modified electrodes prepared by CPE: A—at different electropolymerization charges (0.2 mC; 0.4 mC; 0.6 mC; 0.8 mC) at 0.95 V; and B—at different electropolymerization potentials (0.59 V; 0.95 V; 1.71 V; 2.12 V) at 0.8 mC in comparison with the bare electrode (dotted line). Author Contributions: E.-M.U. and G.-O.B. designed the study and methodology, supervised, and wrote the main manuscript text. L.B. performed the organic synthesis, and G.S. and R.I. oversaw the characterization of the ligands. M.P. and G.-L.T. performed the electrochemical experiments and wrote the corresponding part of the manuscript. All authors have read and agreed to the published version of the manuscript. Funding: This research was funded by Romanian National Authority for Scientific Research, UEFIS- CDI, under grant PN-III-P2-2.1-PED-2019-0730, contract no. 293PED/2020. Institutional Review Board Statement: Not applicable. Informed Consent Statement: Not applicable. Acknowledgments: The authors gratefully acknowledge the financial support of the Romanian National Authority for Scientific Research, UEFISCDI, under grant PN-III-P2-2.1-PED-2019-0730, contract no. 293PED/2020. Conflicts of Interest: The authors declare no conflict of interest.

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