Synthesis and Optical Properties of Free Base Versus Protonated Species

molecules

Article Ethyne Functionalized Meso-Phenothiazinyl-Phenyl- Porphyrins: Synthesis and Optical Properties of Free Base Versus Protonated Species

Eva Molnar, Emese Gál *, Luiza Găină , Castelia Cristea * and Luminit, a Silaghi-Dumitrescu Faculty of Chemistry and Chemical Engineering, Babe¸s-BolyaiUniversity, 11 Arany Janos street, RO-400028 Cluj-Napoca, Romania; [email protected] (E.M.); [email protected] (L.G.); [email protected] (L.S.-D.) * Correspondence: [email protected] (E.G.); [email protected] (C.C.); Tel.: +40-264-593833 (C.C.)

Academic Editor: Narciso M. Garrido Received: 31 August 2020; Accepted: 2 October 2020; Published: 4 October 2020

Abstract: Synthesis, structural characterization and photophysical properties for a series of new trans-A2B2- and A3B-type ethynyl functionalized meso-phenothiazinyl-phenyl porphyrin derivatives are described. The new compounds displayed the characteristic porphyrin absorption spectra slightly modified by weak auxochromic effects of the substituents and fluorescence emission in the range of 651–659 nm with 11–25% quantum yields. The changes recorded in the UV-vis absorption spectra in the presence of trifluoroacetic acid (TFA) are consistent with the protonation of the two internal nitrogen atoms of the free-base porphyrin (19 nm bathochromic shift of the strong Soret band and one long wave absorption maxima situated in the range of 665–695 nm). Protonation of the phenothiazine substituents required increased amounts of TFA and produced a distinct hypsochromic shift of the long wave absorption maxima. The density functional theory (DFT) calculations of a porphyrin dication pointed out a saddle-distorted porphyrin ring as the ground-state geometry.

Keywords: phenothiazine; porphyrin; photophysical properties

1. Introduction A large variety of scientific articles describing tetrapyrrolic compounds and their metal derivatives were stated in the literature, most of them documenting synthetic procedures [1,2], chemical, photophysical properties and applications as photosensitizers in photodynamic therapy [3,4] including two-photon excitation [5], active materials for organic solar cells [6,7] or light emitting diodes [8–10], chemical/biosensors [11–13] and biologically active compounds [14,15]. The UV-Vis absorption spectroscopy was widely applied as a suitable analytical procedure for the investigation of the electronic structure of the porphyrins characterized by typical absorption and fluorescence emission bands situated in the visible region (Soret-band positioned at about 350–500 nm generally with molar absorptivity of 5 1 1 10 M− cm− , and up to four Q-bands at 500–750 nm with lower intensities) closely associated with electronic transitions influenced by the aromatic core electronic distribution [14,16]. The chemical and sensing properties could be tuned by introducing different acceptor/donor moieties on meso and/or β positions of the porphyrin or by core complexation with transition metals. Disturbances were reported for the characteristic absorption spectra of porphyrin derivatives as a result of different factors such as: conjugation pathway and symmetry [17]. Ethynyl groups were attached to the porphyrin core as a linker capable for inducing an extensive conjugation through π π orbital interactions − favourable to charge delocalization between the macrocycle and (hetero)aromatic units with the goal of achieving subsequent tailored electronic properties of porphyrin-based materials. The ethynyl bridges were grafted in the β [18] but mainly in the meso positions of the porphyrine core [19–22].

Molecules 2020, 25, 4546; doi:10.3390/molecules25194546 www.mdpi.com/journal/molecules Molecules 2020, 25, 4546 2 of 14

Substituents attached at the level of the peripheral porphyrin ring often caused minor structural changes without modifying the planar geometry of the porphyrin core, which instead could be affected by bulky aromatic substituents on meso or β positions and also by introducing substituents at the inner pyrrole nitrogen atom. It was documented that under acidic conditions, such as trifluoroacetic acid (TFA) [23] or methanesulfonic acid (MSA) [24] in homogeneous organic solvent solutions, the porphyrin core (H2Por) may undergo protonation at one or both nitrogen atoms of the pyrrole units, thus resulting in either + 2+ monocationic (H3Por ) or dicationic (H4Por ) species [25–27] displaying perturbed photophysical properties compared to their neutral parent compounds, including altered electronic absorption spectra, substantially lowered quantum yield of triplet-state formation, and increased Stokes-shifts in fluorescence spectra [12,13]. The core protonation of porphyrin contributes to an out-of-plane tilting of the individual pyrrole rings, as the four hydrogen atoms do not fit into the central cavity of the macrocycle and thus generate the so-called hyperporphyrin spectra, which are characterized by a broadened and/or split Soret band along with an intense new red-shifted absorption replacing the typical Q band situated in the visible spectral region. Electron-donating functional groups situated in the meso positions of the porphyrin core considerably increased the protonation tendency at the level of pyrrole rings and the chemical stability of the resulted cationic species [28]. Insights on the protonation behaviour of porphyrin macrocycle, molecular geometries, electronic structures, vibrational spectra, etc., were also brought by theoretical molecular modelling (DFT). It was found that the angles between the planes of aryl substituents and the porphyrin core substantially decrease upon protonation of the inner nitrogen atoms, leading to enhanced resonance interactions between π-systems of porphyrin and aryl substituents. The second protonation is particularly facilitated in case of tertraphenylporphyrin (TPP) by the large out-of-plane flexibility of the diprotonated species as unraveled by ab initio molecular dynamics [29]. The results of molecular modeling studies using the density functional theory described 2+ the ground-state structure of porphyrin diacid (H4Por ) as a stable saddle-distorted porphyrin ring (D2d symmetry) with the four pyrrole rings tilted up and down alternately with respect to the porphyrin mean plane and time-dependent DFT (TD-DFT) computations’ predicted excitation energies and oscillator strengths, at least for the first and second excited states, which are in good agreement with the experimental electronic absorption spectrum [30]. Encompassing our study on the topic of synthesis, metal complexation and optical properties of meso-phenothiazinyl-phenyl porphyrin (MPP) dyes previously reported by our research group [31,32], in this work we introduce a series of additional new MPP derivatives with extended-conjugation π-electron systems brought by peripheral/bridging ethyne auxochrome units capable of inducing favorable steric orientation of the aromatic rings. Their synthesis based on direct one-pot Adler–Longo mixt. condensation reaction of pyrrole with ethyne functionalized (hetero)aryl-carbaldehydes was considered as a more advantageous alternative to Sonogashira cross coupling reaction of an alkyne with halogen substituted MPP due to the low solubility of the porphyrin substrate. The variation of optical UV-Vis absorption/emission properties in the state of free bases and protonated species are discussed.

2. Results and Discussions

2.1. Chemical Synthesis A series of new MPP comprising peripheral ethynyl units (ethynyl-MPP) was successfully prepared by one-pot Adler–Longo mixt. mixed condensation reaction of pyrrole with ethynyl functionalized (hetero)aryl-carbaldehydes (7-ethynyl-10-methyl-10H-phenothiazin-3-carbaldehyde [33] or 4-ethynyl-benzaldehyde) and (hetero)aryl-carbaldehydes (7-bromo-10-methyl-10H-phenothiazin-3- carbaldehyde [34] or 4-bromo-benzaldehyde); mixtures of A3B- (2a, 2b, 2c, 2d) and trans-A2B2-type (3a, 3b, 3c, 3d) ethynyl-MPP dyes were thus obtained in a 2:1 molar ratio (Scheme1). Trans disubstituted isomers were selectively obtained as major rection products pointing towards a steric control induced by the folded structure of phenothiazine-carbaldehyde [31]. Molecules 2020, 25, x FOR PEER REVIEW 3 of 13

Trans disubstituted isomers were selectively obtained as major rection products pointing towards a stericMolecules control 2020 ,induced 25, x FOR PEERby the REVIEW folded structure of phenothiazine-carbaldehyde [31]. 3 of 13

TransMolecules disubstituted2020, 25, 4546 isomers were selectively obtained as major rection products pointing towards3 of 14 a steric control induced by the folded structure of phenothiazine-carbaldehyde [31].

Scheme 1. Synthesis of ethynyl-MPP. Scheme 1. Synthesis of ethynyl-MPP. Taking advantage of the efficacyScheme of the 1. porphyriSynthesis ofn synthesisethynyl-MPP. by direct one-pot Adler–Longo mixt. mixed condensationTaking advantage reaction, of the a e ﬃconvergentcacy of the porphyrinsynthetic synthesisstrategy bywas direct designed one-pot for Adler–Longo the preparation mixt. of Taking advantage of the efficacy of the porphyrin synthesis by direct one-pot Adler–Longo mixt. new mixedporphyrin condensation derivatives reaction, with aextended convergent conjugated synthetic strategyπ-electron was systems designed pending for the preparation to the porphyrin of mixed condensation reaction, a convergent synthetic strategy was designed for the preparation of core.new Thus, porphyrin ethynylene derivatives linked with (hetero)aryl extended conjugatedcarbaldehydesπ-electron 6 or systems7 prepared pending by toSonogashira the porphyrin cross- newcore. porphyrin Thus, derivatives ethynylene wi linkedth extended (hetero)aryl conjugated carbaldehydes π-electron6 systemsor 7 prepared pending by to Sonogashirathe porphyrin coupling reaction (Scheme 2) were further used as starting materials for porphyrin synthesis. TPP- core.cross-coupling Thus, ethynylene reaction linked (Scheme (hetero)aryl2) were further carbaldehydes used as starting 6 or materials7 prepared for porphyrinby Sonogashira synthesis. cross- ethynylene-phenothiazine conjugates (4a, 5a) were obtained using phenothiazine-ethynylene- couplingTPP-ethynylene-phenothiazine reaction (Scheme 2) were conjugates further used (4a, 5a as) werestarting obtained materials using for phenothiazine-ethynylene- porphyrin synthesis. TPP- benzaldehydeethynylene-phenothiabenzaldehyde conjugate conjugatezine 66 as conjugatesas a startinga starting carbaldehyde(4a, carbaldehyde5a) were and MPP-ethynylene-dibromobenzeneobtained and usingMPP-ethynylene-dibromobenzene phenothiazine-ethynylene- conjugates conjugatesbenzaldehyde(4b, 5b )(4b were, conjugate5b obtained) were starting6 obtainedas a withstarting starting dibromobenzene-ethynylene-phenothiazine carbaldehyde with dibr andomobenzene-ethynylene-phenothiazine MPP-ethynylene-dibromobenzene carbaldehyde carbaldehydeconjugatesconjugate conjugate7(4brespectively, 5b) 7were respectively (Scheme obtained3). (Scheme The starting puriﬁcation 3). withThe purification ofdibr theomobenzene-ethynylene-phenothiazine target porphyrinsof the target from porphyrins the complex from the complexcarbaldehydereaction reaction mixture conjugate mixture was achieved 7 wasrespectively afterachieved repeated (Scheme after column repeated 3). The chromatography purification column chromatography of separations the target (A porphyrins3B- separations and A2B from2-type (Athe3B- andcomplex Aporphyrins2B2-type reaction porphyrins were mixture eluted aswere was the eluted secondachieved as and theafter the second thirdrepeated fraction, and column the respectively). third chromatography fraction, respectively). separations (A3B- and A2B2-type porphyrins were eluted as the second and the third fraction, respectively).

SchemeScheme 2. Synthesis 2. Synthesis of of ethynylene ethynylene linked (hetero)aryl(hetero)aryl carbaldehydes. carbaldehydes. Scheme 2. Synthesis of ethynylene linked (hetero)aryl carbaldehydes.

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O H H N O + S NH N 6 NH N Molecules 2020, 25, 4546 N N 4 of 14 N N HN N HN Molecules 2020, 25, x FOR PEER REVIEW S S 4 of 13S

H N propanoic acid O H 4a 5a acetic anhydride H 16% 14% reflux,4h N O + S NH N 6 NH N Br N N Br N N N HN N HN O H S S S H S Br O + H 7 NH N NH N N propanoic acid Br Br 4a 5a acetic anhydride N N N Br 16% 14% reflux,4h N HN N HN S S S Br Br N O H H S Br Br Br Br O + Br Br 7 NH N NH N Br Br Br Br Br 4b 5b Br N N N 18% 16% N HN N HN S S S

Scheme 3. Synthesis of ethyne bridged TPP-phenothiazine (4a, 5a) and MPP-dibromobenzene (4b, 5b) Br Br Br Br Br conjugates. Br Br Br 4b 5b 18% 16% Scheme 3. Synthesis of ethyne bridged TPP-phenothiazine (4a, 5a) and MPP-dibromobenzene (4b, 2.2. UV-VisScheme Absorption 3. Synthesis and ofEmi ethynession bridged Properties TPP-phenothiazine of Ethynyl Functi (4a, 5aonalized) and MPP-dibromobenzene MPP Derivatives (4b 2A–L, 5b) 5b) conjugates. The conjugates.UV-Vis absorption spectra of the dark purple ethynyl-MPP 2a–d, 3a–d displayed a high intensity2.2. UV-Vis absorption Absorption band and with Emission maxima Properties in the of Ethynyl UV spectral Functionalized range MPP (250–253 Derivatives nm) 2A–L assigned to the 2.2. UV-Vis Absorption and Emission Properties of Ethynyl Functionalized MPP Derivatives 2A–L presence Theof the UV-Vis phenothiazine absorption chromophore spectra of the darkfollow purpleed by ethynyl-MPP a strong near-UV2a–d, 3a–dSoretdisplayed band (419–424 a high nm) accompaniedintensityThe UV-Vis absorptionby four absorption low band intensity with spectra maximaetio of-type the in darkQ the bands UVpurple spectralsituated ethynyl-MPP range in the (250–253 vi2a–dsible, 3a–d spectral nm) displayed assigned region a to high(514–659 the nm) presenceintensityrepresentative ofabsorption the phenothiazinefor the band porphyrin with chromophore maxima chromophore, in followedthe UV as spectral by exemplified a strong range near-UV in(250–253 Figure Soret nm) 1. band A assigned close (419–424 inspection to nm)the of presence of the phenothiazine chromophore followed by a strong near-UV Soret band (419–424 nm) the recordedaccompanied absorption by four low maxima intensity summarizedetio-type Q bands in Tabl situatede 1 disclosed in the visible a minor spectral bathochromic region (514–659 shift nm) of the accompaniedrepresentative by for four the low porphyrin intensity chromophore, etio-type Q bands as exempliﬁed situated in in the Figure visible1. A spectral close inspection region (514–659 of the Soret band (up to 4 nm) upon peripheral functionalization of parent MPP (λabs 420 nm [31]) with nm)recorded representative absorption for maxima the porphyrin summarized chromophore, in Table as1 disclosed exemplified a minor in Figure bathochromic 1. A close inspection shift of the of ethynylthe recordedunits, best absorption represented maxima by transsummarized-A2B2-type in Tabl ethynyl-MPPe 1 disclosed 3a a minorwith peripheral bathochromic functionalization shift of the Soret band (up to 4 nm) upon peripheral functionalization of parent MPP (λabs 420 nm [31]) with abs of theSoret phenyl band units (up withto 4 nm) electron upon dono peripherr trimethylsilyl-ethynylal functionalization of substituents parent MPP (λabs 424420 nm).nm [31]) Very with similar ethynyl units, best represented by trans-A2B2-type ethynyl-MPP 3a with peripheral functionalization absorptionethynyl spectra units, best were represented recorded by upon trans extending-A2B2-type theethynyl-MPP TPP/MPP 3a chromophore with peripheral system functionalization via ethynylene of the phenyl units with electron donor trimethylsilyl-ethynyl substituents (λabs 424 nm). Very similar bridgesofabsorption the with phenyl electron-rich spectra units werewith electron recordedphenothiazine dono uponr trimethylsilyl-ethynyl extending (4a, 5a) or the dibromophenylene TPP/MPP substituents chromophore ( λauxochromeabs system 424 nm). via Very ethynyleneunits similar (4b, 5b). Theseabsorptionbridges spectral with spectrafeatures electron-rich were indicate recorded phenothiazine that upon the extending UV-Vis (4a, 5a) absorptionthe or dibromophenyleneTPP/MPP spectra chromophore were auxochrome producedsystem via units ethynylenemainly (4b, 5b by). the porphyrinThesebridges spectral withchromophore electron-rich features indicatesystem, phenothiazine that the the substituents UV-Vis(4a, 5a) absorptionor dibromophenylene participating spectra were withauxochrome produced feeble mainlyunitselectronic/steric (4b by, 5b the). auxochromeporphyrinThese spectral effects. chromophore features Higher indicate system, molar the thatabsorptivity substituents the UV-Vis values participating absorption were withspectraexhibited feeble were electronicby producedA3B- as/steric compared mainly auxochrome by tothe A 2B2- porphyrin chromophore system, the substituents participating with feeble electronic/steric type eporphyrinsﬀects. Higher due molar to absorptivitytheir less symmetrical values were exhibitedstructure. by A3B- as compared to A2B2-type porphyrins auxochromedue to their less effects. symmetrical Higher molar structure. absorptivity values were exhibited by A3B- as compared to A2B2- type porphyrins due to their less symmetrical structure.

5 Figure 1. Normalized visible absorption spectra of 2a, 3a, 2c, 3c and 4a (10− M in DCM). FigureFigure 1. Normalized 1. Normalized visible visible absorption absorption spectraspectra ofof 2a 2a, ,3a 3a, 2c, 2c, 3c, 3c and and 4a 4a(10 (10−5 M−5 in M DCM). in DCM).

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Upon excitation with the Soret band maxima in dichloromethane solution, each MPP derivative displayedUpon red-orange excitation daylight with thefluorescence Soret band (Figure maxima 2) characterized in dichloromethane by large solution, Stokes shift each (8410–8691 MPP derivative displayed red-orange daylight ﬂuorescence (Figure2) characterized by large Stokes shift cm−1) and noticeable quantum yields (ΦF 0.11–0.25 against TPP standard) (Table 1), thus identifying (8410–8691 cm 1) and noticeable quantum yields (Φ 0.11–0.25 against TPP standard) (Table1), them as good candidates− for red-emitting materials. F thus identifying them as good candidates for red-emitting materials.

6 Figure 2. Normalized ﬂuorescence emission spectra of 2a, 3a, 2c, 3c and 4a (10− M in DCM). Figure 2. Normalized fluorescence emission spectra of 2a, 3a, 2c, 3c and 4a (10−6 M in DCM). Table 1. Optical properties of ethynyl-MPP derivatives.

Table 1. Opticalλabs [nm] properties of ethynyl-MPP derivatives. Stokes Shift a λ b Cpd Soret em [nm] 1 ΦF λabs [nm] [cm ] Ptz 1 1 Q4 Q3 Q2 Q1 − ε [mol− cm− ] Stokes Shift Cpd Soret a λem [nm] ΦF b Ptz Q4 Q3 Q2 Q1 [cm−1] 2a 251ε [mol 422−1 cm (239167−1] ) 519 556 593 650 658 8499 0.23 2b 252 419 (172178) 518 555 591 649 655 8485 0.21 2a2b 251252 422 ( 424239167 (165464) ) 519 520556 558593 594 650 651 658 659 8499 8410 0.210.23 2b3b 252253 419 (172178) 421 (79531 ) 518 520555 557591 591 649 651 655 658 8485 8443 0.200.21 2b2c 252252 424 ( 421165464 (283687) ) 520 518558 554594 591 651 651 659 659 8410 8691 0.220.21 3b2d 253252 421 420(79531 (248390) ) 520 519557 553591 589 651 648 658 655 8443 8542 0.210.20 3c 189598 2c 252252 421 ( 423283687 ( ) ) 518 520554 559591 590 651 650 659 658 8691 8555 0.210.22 3d 252 421 (111910) 519 556 591 650 657 8532 0.20 2d4a 252252 420 (248390 420 (95878) ) 519 514553 553589 591 648 648 655 651 8542 8448 0.230.21 3c5a 252252 423 ( 422189598 (173379) ) 520 518559 554590 591 650 649 658 656 8555 8452 0.250.21 3d4b 252253 421 ( 419111910 (184003) ) 519 517556 555591 592 650 649 657 655 8532 8599 0.210.20 4a5b 252251 420 421(95878 (173811)) 514 519553 557591 593 648 651 651 654 8448 8462 0.110.23 5a 252a employed 422 for(173379 excitation) in 518 fluorescence 554 experiments;591 b649quantum yields 656 against TPP 8452 standard. 0.25 4b 253 419 (184003) 517 555 592 649 655 8599 0.21 5bThe phenothiazine251 421 (173811) fluorophore 519 displayed 557 greenish593 daylight651 fluorescence 654 characterized 8462 by 0.11 large Stokesa employed shifts but for low excitation fluorescence in fluorescence quantum yields experiments; (e.g., phenothiazine-carbaldehyde b quantum yields against acetals TPP standard.λem 506 nm, Φfl < 0.01) [35], while meso-tetraphenothiazinyl-porphyrin exhibited electronic spectral characteristics The phenothiazine fluorophore displayed greenish daylight fluorescence characterized by large typical to the porphyrin fluorophore with a red shift of the emission maxima (λem = 669 nm, Φfl = Stokes shifts but low fluorescence quantum yields (e.g., phenothiazine-carbaldehyde acetals λem 506 0.05 [34]) comparative to TPP (λem 652 nm Φfl = 0.11). Functionalization of the meso positions of the nm, porphyrinΦfl < 0.01) with ethynyl[35], while groups meso- resultedtetraphenothiazinyl-porphyrin in a significant bathochromic shiftexhibited of the fluorescence electronic peakspectral characteristicsmaxima and typical higher fluorescenceto the porphyrin quantum fluoroph yields (e.g.,ore 5,15-with bis(arylethynyl)-10,20-diphenyl-porphyrine a red shift of the emission maxima (λem = 669 nm,λem =Φ695fl = nm,0.05Φ [34])fl = 0.20comparative [23]). In the to caseTPP of (λ theem 652 newly nm reported Φfl = 0.11). compounds, Functionalization by joiningthe of TPPthe meso positionssystem of via the ethynylene porphyrin bridges with with ethynyl phenothiazine groups units,resulted the positionin a significant of the emission bathochromic maxima appeared shift of the fluorescencecomparable peak to TPP maxima but the and fluorescence higher fluorescence quantum yield’s quantum value becameyields (e.g significantly., 5,15- bis(arylethynyl)-10,20- higher (e.g., for 5a λ = 656 nm, Φ > 0.25 Table1), situated among the highest values observed for porphyrin derivatives. diphenyl-porphyrineem fl λem = 695 nm, Φfl = 0.20 [23]). In the case of the newly reported compounds, by joining the TPP system via ethynylene bridges with phenothiazine units, the position of the emission maxima appeared comparable to TPP but the fluorescence quantum yield’s value became significantly higher (e.g., for 5a λem = 656 nm, Φfl > 0.25 Table 1), situated among the highest values observed for porphyrin derivatives.

Molecules 2020, 25, x FOR PEER REVIEW 6 of 13 Molecules 2020, 25, 4546 6 of 14 2.3. Optical Properties of the Protonated Ethynyl-MPP Derivatives

2.3. OpticalThe potential Properties changes of the Protonated of the photophysical Ethynyl-MPP proper Derivativesties of the novel ethynyl-MPP derivatives in the presence of strong acids were investigated. Protonation of ethynyl-MPP free bases with trifluoroaceticThe potential acid changes (TFA) of thewere photophysical carried out properties in DCM of thesolution novel ethynyl-MPPand monitored derivatives by UV-vis in the presenceabsorption/emission of strong acids spectroscopy. were investigated. Upon Protonationstepwise addition of ethynyl-MPP of increasing free bases amounts with trifluoroacetic of TFA, the acidmodifications (TFA) were that carried occurred out in in DCM the solutionUV-vis absorption and monitored spectra by UV-vis are consistent absorption with/emission the spectral spectroscopy. features Uponexhibited stepwise by hyperporphyrins addition of increasing [25], suggesting amounts ofthe TFA, formation the modifications of a dication that caused occurred by attaching in the UV-vis two absorption spectra are consistent with the spectral features exhibited by hyperporphyrins [25], protons to the inner nitrogen atoms of the macrocycle (H2MPP2+); thus, the Soret band appeared suggestingintensified theand formation red-shifted of with a dication 19 nm, caused while bythe attaching multiple twoQ bands protons collapsed to the inner and a nitrogen broad Q atoms band 2+ ofwas the displayed macrocycle above (H2MPP 680 nm.); thus, In theeach Soret case, band a dist appearedinct color intensified change andfrom red-shifted brown to with green 19 nm,was whileobservable the multiple with the Q bandsnaked collapsedeye. As exemplified and a broad in Q Figure band was3, showing displayed the above modifications 680 nm.In recorded each case, in a distinct color change from brown to green was observable with the naked eye. As exemplified in the UV-Vis spectra of the free-bases A3B-type 2a with peripheral ethynyl functionalization (Figure Figure3, showing the modifications recorded in the UV-Vis spectra of the free-bases A B-type 2a with 3a) and A2B2-type TPP-ethynyl-phenothazine conjugate 5a (Figure 3b), respectively,3 upon peripheralprotonation ethynyl with increasing functionalization amounts (Figure of TFA3a) (from and A 102B 2μ-typeL up TPP-ethynyl-phenothazineto 100 μL), the Soret band conjugateappeared µ 5amore(Figure intense3b), and respectively, red-shifted upon with protonation19 nm with the with occurrence increasing of an amounts isosbestic of TFApoint, (from while 10 the positionL up to µ 100of theL), red the hyperporphyrin Soret band appeared absorbance more situated intense ab andove red-shifted680 nm appeared with 19 to nmbe influenced with the occurrence by the degree of anof protonation. isosbestic point, We whileassumed the that position the addition of the red of hyperporphyrin10μL TFA ensured absorbance the protonation situated at abovethe porphyrin 680 nm appeared to be influenced by the degree of protonation. We assumed that the addition of 10 µL core and facilitated the formation of dications H22a2+ (λmax = 682 nm) and H25a2+ (λmax = 688 nm), 2+ TFArespectively, ensured thecharacterized protonation by at a the D–A porphyrin charge tran coresfer and between facilitated the the donor formation phenothiazine of dications peripheralH22a λ 2+ λ (unit(s)max = and682 nm)the andacceptorH25a protonated( max = 688 porphyri nm), respectively,n core. Further characterized addition byof amore D–A than charge 30μ transferL TFA betweenproduced the a noticeable donor phenothiazine hypsochromic peripheral shift of the unit(s) red absorption and the acceptor band and protonated this could porphyrin be the effect core. of µ Furtherthe protonation addition ofat morethe nitrogen than 30 Latom TFA producedin the phen a noticeableothiazine hypsochromicunit(s), which shiftsuppressed of the red the absorption electron band and this could be the effect of the protonation at the nitrogen atom in the phenothiazine unit(s), donor effect of the phenothiazine moiety in H32a3+ (λmax = 679 nm) and H45a4+ (λmax = 649 nm), 3+ λ whichrespectively. suppressed This theassumption electron donor designates effect ofphenot the phenothiazinehiazine as a moietyweaker in baseH32a in ( comparisonmax = 679 nm) to 4+ λ andporphyrin.H45a ( max = 649 nm), respectively. This assumption designates phenothiazine as a weaker base in comparison to porphyrin.

(a)

(b) −5 Figure 3. UV-Vis spectral changes following the addition of 10μL TFA for ethynyl-MPP (105 M in Figure 3. UV-Vis spectral changes following the addition of 10µL TFA for ethynyl-MPP (10− M in DCM): (a) protonation of 2a, (b) protonation of 5a. DCM): (a) protonation of 2a,(b) protonation of 5a.

Molecules 2020, 25, x FOR PEER REVIEW 7 of 13

Molecules 2020, 25, x FOR PEER REVIEW 7 of 13 In Figure 4 are shown the hyperporphyrin spectra of H2TPP2+ and H2MPP2+ obtained from TPP and MoleculesA3B-type2020 porphyrins, 25, 4546 2a, 2c, 4a, 4c respectively, upon protonation with TFA in DCM solution.7 of 14 A In Figure 4 are shown the hyperporphyrin spectra of H2TPP2+ and H2MPP2+ obtained from TPP comparison of the position of the Soret and Q4 absorption bands displayed in the spectra of the free and A3B-type porphyrins 2a, 2c, 4a, 4c respectively, upon protonation with TFA in DCM solution. A bases 2a, 2c, 4a, 4c (Table 1) with those of the corresponding protonated2+ species2+ (Figure 4) indicate comparisonIn Figureof the4 positiare shownon of the the hyperporphyrin Soret and Q4 spectraabsorption of H 2bandsTPP displayedand H2MPP in theobtained spectra from of TPPthe free bathochromic shifts of the Soret band (19–26 nm) and significant red shifts of the corresponding Q basesand 2a, A2c3B-type, 4a, 4c porphyrins (Table 1) with2a, 2c those, 4a, 4c ofrespectively, the corresponding upon protonation protonated with species TFA in (Figure DCM solution. 4) indicate band (151–176 nm) as a consequence of the core protonation of the porphyrin, in agreement with bathochromicA comparison shifts of theof the position Soret of band the Soret (19–26 and nm) Q4 absorption and significant bands displayed red shifts in of the the spectra corresponding of the free Q literaturebases 2adata, 2c ,mentioning4a, 4c (Table 1these) with distinctive those of the electronic corresponding characteristics protonated upon species protonation (Figure4) indicate of TPP and band (151–176 nm) as a consequence of the core protonation of the porphyrin, in agreement with porphyrinbathochromic functionalized shifts of thein Soretmeso bandpositions (19–26 with nm) ethy andnyl signiﬁcant linkages red [25]. shifts Almost of the correspondingsuperimposed Q Soret literature data mentioning these distinctive electronic characteristics upon protonation of TPP and bandsband are (151–176 observable nm) for as asimilar consequence H22a2+ ofand the H core22c2+ protonation (448 nm) but of the the porphyrin, long wave in maxima agreement displayed with a porphyrin functionalized in meso positions with ethynyl linkages [25]. Almost superimposed Soret 32 nmliterature bathochromic data mentioning shift for these H22a distinctive2+ containing electronic the electron characteristics dono uponr trimethylsilyl protonation substituents. of TPP and A bands are observable for similar H22a2+ and H22c2+ (448 nm) but the long wave maxima displayed a bathochromicporphyrin functionalizedshift of the Soret in meso bandpositions was observ with ethynyled for linkagesthe protonated [25]. Almost TPP-ethynyl-phenothiazine superimposed Soret 32 nmbands bathochromic are observable shift for for similar H22aH2+ 2acontaining2+ and H 2c the2+ (448 electron nm) but dono ther long trimethylsilyl wave maxima substituents. displayed A conjugate (H24a2+) as compared to H22TPP2+, indicative2 of an elongation of the conjugated π-electron bathochromic shift of the Soret band was2+ observed for the protonated TPP-ethynyl-phenothiazine systema 32 by nm the bathochromic electron donor shift phenothiazin for H22a containinge unit. The the extension electron donorof the trimethylsilylconjugated π-electron substituents. system conjugateA bathochromic (H24a2+) as shift compared of the Soret to H band2TPP was2+, indicative observed for of thean protonatedelongationTPP-ethynyl-phenothiazine of the conjugated π-electron at the level of the pending2+ phenothiazine 2substitu+ ent did not produce notable modifications in the systemconjugate by the (electronH24a ) asdonor compared phenothiazin to H2TPPe unit., indicative The extension of an elongation of the conjugated of the conjugated π-electronπ-electron system absorption spectrum of H24b2+ as compared to H2TPP2+. at thesystem level byof the electronpending donor phenothiazine phenothiazine substitu unit. Theent extensiondid not produce of the conjugated notable modificationsπ-electron system in the at the level of the pending phenothiazine substituent did not produce notable modiﬁcations in the absorption spectrum of H24b2+ as compared to H2TPP2+. 2+ 2+ absorption spectrum of H24b as compared to H2TPP .

Figure 4. UV-Vis spectral changes following protonation of ethynyl-MPP with 10μL TFA. Figure 4. UV-Vis spectral changes following protonation of ethynyl-MPP with 10 µL TFA.

Figure 4. UV-Vis spectral changes following protonation2+ of ethynyl-MPP with 10μL TFA. The fluorescence emission spectra of H2MPP2+ presented red-shifted and broadened emission The ﬂuorescence emission spectra of H2MPP presented red-shifted and broadened emission bandsbands with with reduced reduced intensity intensity (Figure (Figure 5a),5a), except forfor the the case case of of2c 2c(Figure (Figure5b), 5b), which which provided provided clear clear The fluorescence emission spectra of H2MPP2+ presented red-shifted and broadened emission evidenceevidence of efficient of eﬃcient energy energy transfer transfer processes processes byby peripheralperipheral substitution substitution with with ethynyl ethynyl groups. groups. bands with reduced intensity (Figure 5a), except for the case of 2c (Figure 5b), which provided clear evidence of efficient energy transfer processes by peripheral substitution with ethynyl groups.

(a) (b) 2+ FigureFigure 5. Fluorescence 5. Fluorescence emission emission(a) spectra spectra of protonated species: species: (a )H(a)2 HMPP2MPP(b) and2+ and (b) ( freeb) free base base versus versus 6 protonatedprotonated 2c (102c (10−6 M− inM DCM). in DCM). Figure 5. Fluorescence emission spectra of protonated species: (a) H2MPP2+ and (b) free base versus protonatedBased 2c on (10 the−6premise M in DCM). that electronic spectra of porphyrin compounds are routinely interpreted withBased the on four-orbital the premise model that of Goutermanelectronic [spectra36], assuming of porphyrin that the Soret compounds (B-) andQ- are bands routinely are generated interpreted with the four-orbital model of Gouterman [36], assuming that the Soret (B-) and Q- bands are Basedby one-electron on the premise excitations that from electronic HOMO/HOMO-1 spectra of (nearly porphyrin degenerate) compounds to the LUMO are (strictlyroutinely degenerate interpreted generatedorbitals), by an one-electron insight of the excitations electronic features from HOMO/HOMO-1 of the frontier molecular (nearly orbitals degenerate) of the symmetrical to the LUMO with the four-orbital model of Gouterman [36], assuming that the Soret (B-) and Q- bands are (strictlyTPP-ethynyl-phenothiazine degenerate orbitals), an conjugate insight of5a theas free electronic base and features corresponding of the frontier mono- andmolecular diprotonated orbitals of generated by one-electron excitations from HOMO/HOMO-1 (nearly degenerate) to the LUMO the symmetrical TPP-ethynyl-phenothiazine conjugate 5a as free base and corresponding mono- and (strictly degenerate orbitals), an insight of the electronic features of the frontier molecular orbitals of diprotonated species was achieved by the DFT method. The results of our B3LYP-DFT calculations the symmetrical TPP-ethynyl-phenothiazine conjugate 5a as free base and corresponding mono- and diprotonated species was achieved by the DFT method. The results of our B3LYP-DFT calculations

Molecules 2020, 25, 4546 8 of 14 Molecules 2020, 25, x FOR PEER REVIEW 8 of 13 pointedspecies out wasthe achievedground-state by the of DFT the method. most stable The results conformer of our B3LYP-DFTof H25a2+ containing calculations a pointed saddle-distorted out the 2+ porphyringround-state ring ( ofD2d the symmetry) most stable conformerwith the offourH2 5apyrrolecontaining rings atilted saddle-distorted up and down porphyrin alternately ring (D2d with respectsymmetry) to the porphyrin with the four mean pyrrole plane, rings similar tilted to up H and2TPP down2+ [24]. alternately As it canwith be seen respect in Figure to the porphyrin6, presenting 2+ the plotsmean of plane, the similarFMO toofH H2TPP25a2+, the[24]. spin As it density can be seen in inHOMO/HOMO-1 Figure6, presenting (separated the plots of theby FMO0.0043 of eV) 2+ appearedH25a delocalized, the spin density mainly in on HOMO the electron/HOMO-1 do (separatednor phenothiazine by 0.0043 eV)units, appeared while delocalizedthe LUMO/LUMO+1 mainly on the electron donor phenothiazine units, while the LUMO/LUMO+1 (separated by only 0.0013 eV) (separated by only 0.0013 eV) are mainly centered on the porphyrin core. are mainly centered on the porphyrin core.

Figure 6. Frontier molecular orbital plots of protonated TPP-ethynyl-phenothiazine conjugate 5a. Figure 6. Frontier molecular orbital plots of protonated TPP-ethynyl-phenothiazine conjugate 5a. 3. Materials and Methods 3. MaterialsThe and reagents Methods and solvents were purchased from commercial sources, and pyrrole was redistilled Thebefore reagents use. All and reactions solvents were were followed purchased by thin from layer commercial chromatography sources, (TLC) and analysis pyrrole using was redistilled Merck pre-coated silica gel 60 F aluminum sheets. Column chromatography was performed on silica (60 Å, before use. All reactions were254 followed by thin layer chromatography (TLC) analysis using Merck particle size 0.063-0.2 mm). pre-coated silica gel 60 F254 aluminum sheets. Column chromatography was performed on silica (60 One-dimensional, 2D-COSY, 2D-HMQC and 2D-HMBC NMR spectra were recorded on Bruker Å, particle size 0.063‒0.2 mm). Avance instruments (400 and 600 MHz) using deuterated solvents (CDCl3 and DMSO) at room One-dimensional,temperature (NMR 2D-COSY, spectra of compounds 2D-HMQC2a and, 3a ,2D-HMBC2c, 3c, 4a are NMR shown spectra in Supplementary were recorded Materials on Bruker AvanceFigures instruments S1–S14), chemical (400 and shifts 600 are MHz) quoted using in parts deuterated per million (ppm) solvents relative (CDCl to tetramethylsilane3 and DMSO) (TMS)at room temperatureand J values (NMR are spectra given in of Hz. compounds Mass spectra 2a were, 3a, measured2c, 3c, 4a on are a HRMSshown spectrometer in supplementary LTQ-Orbitrap materials figuresXL-Thermo-Scientific S1-S14), chemical usingshifts APCI are quoted or ESI ionization in parts techniquesper million (HRMS (ppm) spectra relative of compoundsto tetramethylsilane3a, 2c, (TMS)3c and, 5a areJ values shown are in Supplementarygiven in Hz. Mass Materials spectra Figures were S15–S18). measured UV-Vis on a spectraHRMS werespectrometer recorded inLTQ- Orbitrapdichloromethane XL-Thermo-Scientific with a Perkin Elmerusing LambdaAPCI 35or spectrophotometer, ESI ionization fluorescencetechniques spectra (HRMS measured spectra in of compoundsdichloromethane 3a, 2c, 3c using, 5a aare Perkin shown Elmer in 55supplementary PL spectrophotometer. material Thes figures fluorescence S15-S18). quantum UV-Vis yield wasspectra calculated using tetraphenylporphyrin (TPP) standard (Φ = 0.13 CH Cl solution). were recorded in dichloromethane with a Perkin Elmer Lambda 35 2spectrophotometer,2 fluorescence DFT Calculation Geometries were fully optimized using the density functional theory (DFT). spectra measured in dichloromethane using a Perkin Elmer 55 PL spectrophotometer. The The functional and basis set used in the DFT calculations were the Becke’s three-parameter hybrid fluorescencefunctional quantum combined yield with thewas Lee–Yang–Parr calculated us correlationing tetraphenylporphyrin functional (B3LYP) and(TPP) the standard 6-31G(d,p) (Ф basis = 0.13 CH2Clset,2 solution). respectively. Equilibrium geometries were verified via frequency calculations, where no imaginary DFTfrequency Calculation was found. Geometries All the calculations were fully wereoptimized carried using out using the density the Gaussian function 09 programal theory suite. (DFT). The functional7-Ethynyl-10-methyl-10H-phenothiazin-3-carbaldehyde and basis set used in the DFT calculations were the Becke’s6 was prepared three-parameter according hybrid to previously functional combinedreported with procedures the Lee–Yang–Parr [33]. correlation functional (B3LYP) and the 6-31G(d,p) basis set, respectively.7-Bromo-10-methyl-10H-phenothiazin-3-carbaldehyde Equilibrium geometries were verified via frequency7 was preparedcalculations, according where to previouslyno imaginary frequencyreported was procedures found. All [ 34the]. calculations were carried out using the Gaussian 09 program suite. 7-Ethynyl-10-methyl-10H-phenothiazin-3-carbaldehyde 6 was prepared according to previously reported procedures [33]

7-Bromo-10-methyl-10H-phenothiazin-3-carbaldehyde 7 was prepared according to previously reported procedures [34]

General Procedure for the Synthesis of 2A–L

Molecules 2020, 25, 4546 9 of 14

General Procedure for the Synthesis of 2A–L

Propanoic acid and acetic anhydride were stirred and heated at 110 ◦C for 1 h. After cooling at room temperature, aryl-aldehyde (2eq), 10-methyl-10H-phenothiazinyl-carbaldehyde derivative (2eq) and pyrrole (4eq) were added and the mixture was heated at 110 ◦C for 4 h. After completion, the obtained purple crystals were collected by ﬁltration and washed with methanol to remove the traces of propionic acid. In the case when the product did not precipitate, the solvent was removed by reduced pressure distillation and the residue was washed with methanol. The further puriﬁcation and separation by column chromatography on silica using dichloromethane/petrol ether (1:2) gave the corresponding A3B- and A2B2-type compounds. Due to the fact that the retention factors of the A3B-type compounds (Rf = 0.4) and A2B2-type (Rf = 0.3) are pretty close, 3–4 successive column chromatography separations are required in order to achieve high purity products. 5,10,15-tri(trimethylsilylethynyl-phenyl)-20-(7-bromo-10-methyl-10H-phenothiazin-3-yl)-21,23H- porphyrin (2a). Purple powder, yield 12% (0.2 g).1H-NMR (600 MHz, CDCl ) δppm 2.72 (s, 2H, NH), 3 − 0.46 (s, 27H), 3.54 (s, 3H), 6.78 (d, 1H, J = 8.7 Hz), 7.12 (d, 1H, J = 8.1 Hz), 7.37 (dd, 1H, J = 8.6 Hz, J = 2.1 Hz), 7.40 (s, 1H), 7.94 (d, 6H, J = 7.1 Hz), 7.98 (dd, 1H, J = 8.0 Hz, J = 1.8 Hz), 8.02 (s, 1H), 8.22 (d, 13 6H, J = 6.7 Hz), 8.88 (d, 6H, J = 4.5 Hz), 8.95 (d, J = 4.3 Hz); C-NMR (150 MHz, CDCl3) δppm 0.1 (9C), 35.6 (C), 95.7 (Cq), 105.0 (Cq), 112.5 (Cq), 114.9 (C), 115.1 (Cq), 115.2 (3C), 115.4 (Cq), 119.3 (Cq), 119.5 (Cq), 119.6 (C), 121.3 (Cq), 122.7 (C), 122.8 (Cq), 124.8 (2Cq), 125.5 (Cq), 129.4 (4C), 129.7 (2Cq), 130.3 (4C), 130.3 (2Cq), 130.4 (6C), 132.9 (Cq), 134.0 (Cq), 134.4 (6C), 136.6 (Cq), 142.3 (Cq), 142.3 (4Cq), + 144.5 (2Cq), 145.0 (2Cq), 145.2 (2Cq). HRMS-APCI Calcd for: C66H59BrN5SSi3 [M + H] 1116.29769, Found: 1116.29553. 5,15-di(trimethylsilylethynyl-phenyl)-10,20-di-(7-bromo-10-methyl-10H-phenothiazin-3-yl)-21,23H- porphyrin (3a). Purple powder, yield 12% (0.2 g).1H-NMR (600 MHz, CDCl ) δppm 2.70 (s, 2H, NH), 3 − 0.45 (s, 18H), 3.49 (s, 6H), 6.76 (d, 2H, J = 8.7 Hz), 7.03–7.07 (m, 2H), 7.34 (d, 2H, J = 2.1Hz), 7.39 (s, 2H), 7.93–7.95 (m, 4H), 7.95 (d, 2H, J = 7.7 Hz), 8.02 (s, 2H), 8.21 (d, 4H, J = 6.5Hz), 8.87–8.94 (m, 8H); 13 C-NMR (150 MHz, CDCl3) δppm 0.1 (6C), 35.6 (2C), 95.6 (2Cq), 105.0 (2Cq), 112.4 (2C), 115.0 (2C), 115.4 (4C), 119.1 (Cq), 119.2 (2Cq), 119.4 (2Cq), 119.5 (Cq), 121.3 (Cq), 122.7 (Cq), 122.7 (2C), 125.5 (2C), 129.7 (4C), 130.3 (4C), 130.4 (4C), 132.9 (2Cq), 132.9 (Cq), 134.0 (2Cq), 134.0 (Cq), 134.4 (4C), 136.6 (2Cq), 136.6 (Cq), 142.3 (2Cq), 142.4 (Cq), 144.9 (4Cq), 145.1 (2Cq), 145.1 (2Cq). HRMS-APCI Calcd for: + C68H55Br2N6S2Si2 [M + H] 1235.18090, Found: 1235.17603. 5,10,15-tri(4-bromophenyl)-20-(7-trimethylsilylethynyl-10-methyl-10H-phenothiazin-3-yl)-21,23H- porphyrin (2b). Purple powder, yield 18% (0.2 g).1H-NMR (600 MHz, CDCl ) δppm 2.81 (s, 2H, NH), 3 − 0.29 (s, 9H), 3.62 (s, 3H), 6.86 (d, 1H, J = 8.5 Hz), 7.21 (d, 1H, J = 7.0 Hz), 7.38–7.43 (m, 2H), 7.91 (d, 6H, J = 7.2 Hz), 7.98–7.99 (m, 2H), 8.08 (d, 6H, J = 6.6 Hz), 8.85 (s, 6H), 8.93 (d, J = 2.7 Hz); 13C-NMR (150 MHz, CDCl3) δppm 0.05 (3C), 35.7 (C), 90.0 (Cq), 94.2 (Cq), 104.3 (Cq), 112.5 (C), 113.9 (Cq), 115.1 (Cq), 115.5 (Cq), 118.7 (Cq), 118.8 (C), 119.4 (Cq), 121.4 (Cq), 121.5 (Cq), 122.6 (2C), 123.0 (Cq), 125.3 (2C), 125.4 (Cq), 128.2 (4C), 129.0 (4C), 129.9 (6C), 130.3 (Cq), 130.6 (Cq), 131.6 (Cq), 133.9 (Cq), 134.0 (Cq), 135.8 (6C), 136.5 (Cq), 136.5 (Cq), 137.8 (Cq), 140.9 (4Cq), 145.2 (Cq), 145.8 (Cq). HRMS-APCI Calcd for: + C56H41Br3N5SSi [M + H] 1082.03761, Found: 1082.03333. 5,15-di(4-bromophenyl)-10,20-di(7-trimethylsilylethynyl-10-methyl-10H-phenothiazin-3-yl)-21,23H- porphyrin (3b). Purple powder, yield 16% (0.2 g).1H-NMR (400 MHz, CDCl ) δppm 2.78 (s, 2H, NH), 3 − 0.31 (s, 18H), 3.55 (s, 6H), 6.80 (d, 2H, J = 9.2 Hz), 7.21 (d, 2H, J = 7.9 Hz), 7.36–7.38 (m, 4H), 7.89 (d, 4H, J = 7.4 Hz), 7.95–7.96 (m, 2H), 7.99 (s, 2H), 8.07 (d, 4H, J = 7.3 Hz), 8.83-8.93 (m, 8H); 13C-NMR (100 MHz, CDCl3) δppm 0.05 (6C), 35.6 (2C), 94.2 (2Cq), 104.2 (2Cq), 112.5 (2C), 115.1 (2C), 115.2 (2C), 118.6 (2Cq), 119.3 (2Cq), 122.5 (2C), 125.3 (2C), 125.4 (2C), 128.2 (4C), 129.0 (4C), 129.7 (4Cq), 129.9 (4C), 130.4 (4Cq), 130.6 (2Cq), 130.9 (2Cq), 131.6 (2Cq), 135.8 (4C), 136.5 (2Cq), 137.9 (2Cq), 140.9 (2Cq), 145.0 + (2Cq), 145.1 (2Cq).HRMS-APCI Calcd for: C68H55Br2N6S2Si2 [M+H] 1233.18294, Found: 1233.17751. Molecules 2020, 25, 4546 10 of 14

5,10,15-tri(ethynyl-phenyl)-20-(7-bromo-10-methyl-10H-phenothiazin-3-yl)-21,23H-porphyrin (2c). Purple powder, yield 14% (0.2 g).1H-NMR (600 MHz, CDCl ) δppm 2.79 (s, 2H, NH), 3.35 (s, 3H), 3 − 3.62 (s, 3H), 6.86 (d, 1H, J = 8.5 Hz), 7.18 (d, 1H, J = 8.6 Hz), 7.39–7.41 (m, 2H), 7.92 (d, 6H, J = 6.4 Hz), 8.00–8.01 (m, 2H), 8.20 (d, 6H, J = 8.8 Hz), 8.86 (d, 6H, J = 5.2 Hz), 8.93 (d, 2H, J = 4.0 Hz); 13C-NMR (150 MHz, CDCl3) δppm 35.7 (C), 78.4 (3C), 83.6 (3Cq), 112.5 (C), 115.1 (2Cq), 115.5 (C), 119.3 (Cq), 119.3 (Cq), 119.4 (C), 119.5 (C), 121.3 (2Cq), 121.7 (2C), 121.8 (2Cq), 125.4 (Cq), 128.2 (Cq), 129.0 (Cq), 129.7 (C), 130.3 (C), 130.5 (8C), 132.9 (C), 134.0 (C), 134.4 (8C), 136.5 (Cq), 142.5 (2Cq), 142.6 (2Cq), 142.6 (4Cq), + 145.0 (2Cq), 145.2 (2Cq). HRMS-APCI Calcd for: C57H35BrN5S [M + H] 900.17911, Found: 900.17433. 5,15-di(ethynyl-phenyl)-10,20-di-(7-bromo-10-methyl-10H-phenothiazin-3-yl)-21,23H-porphyrin (3c). Purple powder, yield 15% (0.2 g).1H-NMR (600 MHz, CDCl ) δppm 2.75 (s, 2H, NH), 3.35 (s, 2H), 3 − 3.55 (s, 6H), 6.80 (d, 2H, J = 8.7 Hz), 7.10–7.12 (m, 2H), 7.37 (d, 4H, J = 8.1 Hz), 7.91 (d, 4H, J = 6.7 Hz), 7.96 (d, 2H, J = 7.8 Hz), 8.00 (s, 2H), 8.19 (d, 4H, J = 6.7 Hz), 8.85–8.92 (m, 8H); 13C-NMR (150 MHz, CDCl3) δppm 35.6 (2C), 78.4 (2C), 83.6 (2Cq), 112.5 (2C), 115.0 (2C), 115.4 (2C), 119.2 (2Cq), 119.3 (2Cq), 121.3 (2Cq), 121.3 (2Cq), 121.7 (2C), 125.4 (2Cq), 129.7 (4C), 130.3 (4C), 130.5 (6C), 132.9 (2Cq), 132.9 (Cq), 134.0 (2Cq), 134.0 (Cq), 134.4 (6C), 136.6 (2Cq), 136.6 (Cq), 142.6 (2Cq), 145.0 (3Cq), 145.1 (Cq), 145.1 + (3Cq). HRMS-APCI Calcd for: C62H39Br2N6S2 [M + H] 1091.10184, Found: 1091.09713. 5,10,15-tri(4-bromophenyl)-20-(7-ethynyl-10-methyl-10H-phenothiazin-3-yl)-21,23H-porphyrin (2d). Purple powder, yield 14% (0.1 g).1H-NMR (600 MHz, CDCl ) δppm 2.79 (s, 2H, NH), 3.57 (s, 3 − 1H), 3.65 (s, 3H), 6.98 (dd, 1H, J = 8.6 Hz, J = 3.3 Hz),7.20 (d, 1H, J = 7.0 Hz), 7.37–7.38 (m, 2H), 7.83 (s, 1H), 7.89–7.91 (m, 6H), 7.99 (dd, 2H, J = 7.9 Hz, J = 2.0 Hz), 8.01 (d, 1H, J = 1.8 Hz), 8.07 (d, 4H, 13 J = 7.0 Hz), 8.85–8.93 (m, 8H); C-NMR (150 MHz, CDCl3) δppm 36.0 (C), 81.0 (C), 84.8 (Cq), 111.7 (Cq), 112.1 (Cq), 116.0 (C), 116.1 (C), 118.8 (Cq), 118.9 (2Cq), 119.2 (Cq), 121.3 (Cq), 121.4 (Cq), 122.5 (2Cq), 122.6 (C), 123.0 (C), 125.3 (C), 127.5 (C), 128.2 (2C), 128.2 (4C), 129.0 (4C), 129.7 (Cq), 131.7 (6C), 131.9 (Cq), 134.0 (Cq), 134.0 (Cq), 135.8 (4C), 139.1 (Cq), 139.8 (Cq), 140.9 (Cq), 145.1 (2Cq), 145.3 (Cq), 145.7 (Cq), + 146.0 (Cq), 148.8 (2Cq). HRMS-APCI Calcd for: C53H33Br3N5S [M+H] 1011.63168, Found: 1011.99146. 5,15-di(4-bromophenyl)-10,20-di(7-ethynyl-10-methyl-10H-phenothiazin-3-yl)-21,23H-porphyrin (3d). 1 Purple powder, yield 14% (0.1 g) H-NMR (400 MHz, CDCl3) δppm 2.79 (s, 2H, NH), 2.38 (s, 2H), 3.66 (s, 6H), 7.14–7.21 (m, 4H), 7.38 (d, 2H, J = 6.2 Hz), 7.83 (s, 2H), 7.90 (d, 4H, J = 6.4 Hz), 7.98–8.01 (m, 13 4H), 8.08 (d, 4H, J = 7.8 Hz), 8.85–8.94 (m, 8H); C-NMR (100 MHz, CDCl3) δppm 36.0 (2C), 112.5 (Cq), 112.9 (3C), 113.7 (3C), 115.5 (Cq), 118.8 (Cq), 118.9 (2Cq), 119.2 (Cq), 121.3 (Cq), 121.4 (Cq), 122.5 (2Cq), 122.6 (2C), 123.0 (2C), 125.3 (2C), 127.7 (2C), 128.2 (4C), 128.8 (Cq), 129.0 (4C), 129.7 (Cq), 130.0 (4C), 131.9 (Cq), 132.9 (2Cq), 132.9 (2Cq), 134.0 (Cq), 134.0 (Cq), 135.8 (4C), 137.1 (Cq), 137.9 (Cq), 140.9 (Cq), + 140.9 (2Cq), 144.2 (2Cq), 144.2 (2Cq), 149.8 (2Cq). HRMS-APCI Calcd for: C62H39Br2N6S2 [M + H] 1091.10184, Found: 1091.12134. 5,10,15-triphenyl-20-((10-methyl-10H-phenothiazin-3-yl)ethynylphenyl-4-yl)-21,23H-porphyrin (4a). Purple powder, yield 16% (0.06 g).1H-NMR (600 MHz, CDCl ) δppm 2.72 (s, 2H, NH), 3.45 (s, 3 − 3H), 6.85 (d, 1H, J = 8.2 Hz), 6.87 (d, 1H, J = 8.1 Hz), 7.01 (t, 1H, J = 7.5 Hz),7.20–7.24 (m, 2H), 7.48 (s, 1H), 7.50 (dd, 1H, J = 8.1 Hz, J = 1.8 Hz),7.77-7.82 (m, 9H), 7.92 (d, 2H, J = 7.9 Hz), 8.23 (d, 2H, 13 J = 7.9 Hz), 8.25 (d, 6H, J = 6.4 Hz), 8.90 (d, 8H, J = 8.1 Hz); C-NMR (150 MHz, CDCl3) δppm 35.4 (C), 89.3 (Cq), 90.1 (Cq), 113.9 (2C), 114.3 (2C), 117.2 (2Cq), 119.3 (Cq), 119.4 (Cq), 120.2 (2Cq), 120.3 (Cq), 120.4 (Cq), 122.9 (4C), 122.9 (2Cq), 122.9 (2Cq), 123.6 (2Cq), 126.7 (6C), 127.2 (2C), 127.6 (C), 127.7 (C), 129.8 (C), 130.3 (C), 131.2 (C), 134.5 (9C), 134.6 (4C), 141.9 (Cq), 142.0 (Cq), 142.1 (2Cq), 145.2 (2Cq), 146.0 + (2Cq). HRMS-APCI Calcd for: C59H40N5S [M + H] 850.29989, Found: 850.29675. 5,15-diphenyl-10,20-di((10-methyl-10H-phenothiazin-3-yl)ethynylphenyl-4-yl)-21,23H-porphyrin (5a). Purple powder, yield 14% (0.06 g).1H-NMR (600 MHz, CDCl ) δppm 2.75 (s, 2H, NH), 3.46 (s, 6H), 3 − 6.86–6.89 (m, 4H), 7.01 (t, 2H, J = 7.4 Hz), 7.20–7.25 (m, 4H), 7.48 (s, 2H), 7.50 (d, 2H, J = 8.1 Hz), 13 7.77–7.81 (m, 6H), 7.91-7.93 (m, 4H), 8.21–8.24 (m, 8H), 8.87-8.90 (m, 8H), C-NMR (150 MHz, CDCl3) δppm 36.0 (2C), 90.0 (2Cq), 96.1 (2Cq), 113.9 (Cq), 114.0 (2C), 114.1 (Cq), 114.5 (Cq), 114.6 (2C), 116.2 Molecules 2020, 25, 4546 11 of 14

(2C), 116.3 (Cq), 117.9 (Cq), 118.4 (Cq), 122.1 (Cq), 122.9 (Cq), 123.5 (2C), 123.5 (2C), 128.0 (4C), 128.0 (2C), 128.6 (Cq), 128.7 (Cq), 129.6 (4C), 129.7 (10C), 130.5 (Cq), 130.5 (2C), 131.8 (Cq), 132.3 (Cq), 133.7 (8C), 135.8 (Cq), 143.2 (Cq), 144.5 (Cq), 150.0 (2Cq), 150.3 (2Cq), 165.3 (8Cq). HRMS-APCI Calcd for: + C74H49N6S2 [M + H] 1085.34546 Found: 1085.64795. 5,10,15-tri(4-bromophenyl)-20-(7-((3,5-dibromophenyl)ethynyl)-10-methyl-10H-phenothiazin-3-yl)- 21,23H-porphyrin (4b). Purple powder, yield 18% (0.3 g).1H-NMR (600 MHz, CDCl ) δppm 2.81 (s, 3 − 2H, NH), 3.66 (s, 3H), 6.86 (d, 1H, J = 8.7 Hz), 6.96 (d, 1H, J = 8.5 Hz), 7.16–7.19 (m, 1H), 7.40 (dd, 1H, J = 7.59 Hz, J = 1.9 Hz),7.45–7.46 (m, 1H), 7.63 (d, 1H, J = 1.7 Hz), 7.64 (t, 1H, J = 1.7 Hz), 7.91 (d, 6H, 13 J = 7.9 Hz), 7.99–8.00 (m, 2H), 8.08 (d, 6H, J = 7.8 Hz), 8.86–8.95 (m, 8H), C-NMR (150 MHz, CDCl3) δppm 35.7 (C), 86.6 (Cq), 91.4 (Cq), 112.5 (Cq), 112.6 (C), 114.2 (C), 115.1 (Cq), 115.5 (Cq), 116.5 (Cq), 118.7 (Cq), 118.9 (2C), 119.4 (Cq), 121.3 (Cq), 121.4 (Cq), 122.6 (4C), 122.6 (2C), 123.4 (Cq), 125.4 (Cq), 126.8 (Cq), 129.7 (Cq), 129.9 (6C), 130.3 (C), 130.3 (Cq), 131.5 (Cq), 132.8 (4C), 132.9 (2C), 133.7 (Cq), 133.9 (Cq), 134.0 (Cq), 135.8 (6C), 136.7 (Cq), 140.8 (Cq), 140.9 (4Cq), 144.8 (Cq), 144.9 (Cq), 145.2 (Cq), + 146.3 (Cq). HRMS-APCI Calcd for: C59H35Br5N5S [M + H] 1245.84687, Found: 1245.84509. 5,15-di(4-bromophenyl)-10,20-di(7-((3,5-dibromophenyl)ethynyl)-10-methyl-10H-phenothiazin-3-yl)- 21,23H-porphyrin (5b). Purple powder, yield 16% (0.3 g), 1H-NMR (600 MHz, CDCl ) δppm 2.79 (s, 3 − 2H, NH), 3.60 (s, 3H) 3.65 (s, 3H), 6.85 (dd, 1H, J = 8.6 Hz, J = 1.3Hz), 6.95 (dd, 1H, J = 8.3 Hz, J = 1.6 Hz), 7.16–7.18 (m, 3H), 7.39–7.41 (m, 3H), 7.44–7.45 (m, 2H), 7.62 (s, 2H), 7.64 (s, 2H), 7.91 (d, 4H, J = 7.3 Hz), 13 8.00 (s, 4H), 8.09 (d, 4H, J = 6.7 Hz), 8.84–8.93 (m, 8H); C-NMR (150 MHz, CDCl3) δppm 35.8 (2C), 86.6 (2Cq), 91.4 (2Cq), 112.6 (Cq), 114.2 (2C), 115.1 (Cq), 115.5 (Cq), 116.5 (Cq), 118.6 (2Cq), 118.7 (Cq), 119.3 (Cq), 119.3 (Cq), 121.3 (Cq), 121.3 (Cq), 122.5 (2C), 122.6 (4C), 123.4 (2Cq), 125.4 (Cq), 126.8 (2C), 129.7 (2Cq), 129.9 (4C), 130.3 (2Cq), 130.3 (2Cq), 131.5 (2C), 132.8 (8C), 132.9 (2C), 133.0 (2Cq), 133.7 (2C), 134.0 (Cq), 134.0 (Cq), 135.8 (4C), 136.5 (Cq), 136.8 (Cq), 140.9 (2C), 144.8 (2Cq), 145.0 (2Cq), 145.2 (2Cq), + 146.3 (2Cq). HRMS-APCI Calcd for: C74H43Br6N6S2 [M + H] 1558.80240, Found: 1558.80615.

4. Conclusions This one-pot mixt. condensation of pyrrole with ethynyl functionalized (hetero)aryl-carbaldehydes is recommended as an advantageous synthetic strategy for the preparation of ethyne functionalized MPP in 12–16% yields. Feeble auxochromic effects were displayed in the UV-Vis absorption/emission spectra of the new ethynyl-MPP, which were shaped mainly by the porphyrin chromophore system characterized by intense Soret bands situated at 419–424 nm, four low intensity etio type Q bands situated in the range of 514–651 nm, and intensified fluorescence emission in the range of 651–659 nm with 11–25% quantum yields. These fluorescence emission properties open perspectives for staining biological tissues in the first NIR therapeutic window. Electron-donor phenothiazine units situated in the meso positions of the porphyrin core favoured the protonation at the level of pyrrole rings generating chemically stable dicationic species. Protonation of the phenothiazine substituents required increased amounts of TFA, indicating phenothiazine as a weaker base in comparison to porphyrin. The distinct color change from brown to green observable with naked eye qualify the described ethynyl-MPP for potential applications as acid indicators for analytical purposes.

Supplementary Materials: The following are available online. Figure S1. 1H-NMR spectrum of compound 2a, Figure S2. 13C-NMR spectrum of compound 2a, Figure S3. (1H-1H) COSY spectrum of compound 2a, Figure S4. (1H-13C) HMQC spectrum of compound 2a, Figure S5. 1H-NMR spectrum of compound 3a, Figure S6. 13C-NMR spectrum of compound 3a, Figure S7. 1H-NMR spectrum of compound 2c, Figure S8. 13C-NMR spectrum of compound 2c, Figure S9. 1H-NMR spectrum of compound 3c, Figure S10. 13C-NMR spectrum of compound 3c, Figure S11. (1H-1H) COSY spectrum of compound 3c, Figure S12. (1H-13C) HMQC spectrum of compound 3c, Figure S13. 1H-NMR spectrum of compound 4a, Figure S14. 13C-NMR spectrum of compound 4a, Figure S15. HRMS (APCI+) spectrum of compound 3a, Figure S16. HRMS (APCI+) spectrum of compound 2c, Figure S17. HRMS (APCI+) spectrum of compound 3c, Figure S18. HRMS (APCI+) spectrum of compound 5a. Molecules 2020, 25, 4546 12 of 14

Author Contributions: Conceptualization, L.S.-D.; methodology, L.G. and E.M.; validation, E.M.; formal analysis, E.G.; investigation, E.M.; resources L.S.-D.; data curation, C.C.; writing—original draft preparation, E.G.; writing—review and editing, C.C.; visualization, C.C.; supervision, L.S.-D.; project administration, L.G.; funding acquisition, L.S.-D. All authors have read and agreed to the published version of the manuscript. Funding: This research was funded by a grant of Romanian Ministry of Research and Innovation, CNCS-UEFISCDI, project number PN-III-P4-ID-PCCF-2016-0142, within PNCDI II. The APC was funded by PN-III-P4-ID-PCCF-2016-0142. Acknowledgments: Author Luiza Gainˇ aˇ greatly acknowledges The Romanian Academy for supporting the Joint Research Project: Romanian Academy and National Academy of Sciences of the Republic of Belarus AR-FRBCF-2020–2021. Conﬂicts of Interest: The authors declare no conﬂict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

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Sample Availability: Samples of the compounds 2a–l are available from the authors.

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