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z Inorganic Chemistry

Synthesis, Photophysical and Biological Properties of NewPhthalocyanines Bearing Peripherally 4-(Trifluoromethoxy)phenoxy GroupsNazli Farajzadeh,[a] Hande Pekbelgin Karaoğlu,[a] Mustafa Akin,[b] Neslihan Saki,[b] andMakbule Burkut Koçak*[a]

In this study, a novel phthalonitrile derivative namely 4-(4-(trifluoromethoxy)phenoxy) phthalonitrile (2) was introducedand characterized. A number of peripherally tetra-substitutedphthalocyanines (H2Pc, CuPc and PdPc) were obtained bycyclotetramerization of 2 in suitable high-boiling solvents.Characterization of the resulting phthalocyanines has beenperformed by diverse techniques such as NMR, FTIR and UV/Visspectroscopy. Organic solvents like acetone, N,N-Dimeth-ylformamide (DMF) and dichloromethane (DCM) were utilizedto investigate the influence of solvent nature on aggregationbehavior of CuPc. In addition, the aggregation properties of theCuPc were studied in tetrahydrofuran (THF) and DCM at

different concentrations ranging from 4×10 � 6 to 14×10 � 6 m.Fluorescence quantum yields of H2Pc and PdPc were deter-mined in DMF. Fluorescence lifetime for H2Pc was calculated2.07 ns, as well. The fluorescence quenching feature of H2Pcwas explored by adding different concentrations of benzoqui-none in DMF. The values of Ksv and kq for H2Pc were obtained59.01 m� 1 and 28.51 m� 1ns� 1, respectively. Moreover, tyrosinaseinhibition and antioxidant activities of the phthalocyanineswere studied by using TLC dot –blot technique and spectro-photometric assay. CuPc exhibited the highest inhibitoryactivity on tyrosinase enzyme. All tested molecules showedmoderate antioxidant activity.

Introduction

Phthalocyanines (Pcs) have planar aromatic 18π-electronstructures. Due to high electron transfer abilities, Pcs showparticular optical, physical and chemical properties. Despitetheir use in dyes and pigments industry for many years,[1–4]

possibility and advantage of their performance have beeninterested in vast range of various fields such as molecularphysics,[5] crystals,[6] thin films,[7] Langmuir-Blodgett films,[8]

electrochemical deposition techniques,[9] photodynamic ther-apy (PDT),[10] and nanotechnology.[11] As known, these applica-tions require special electronic, photochemical or photophys-ical properties and high solubility in various solvents.[1–4,12]

There are some ways for alteration of Pc ring to improve theseproperties. Metal insertion and/or substitution of differentfunctional groups such as long chain alkyl, bulky, alkylthio oralkoxy groups on axial, peripheral and/ or non-peripheralpositions of Pc ring can be appropriate approaches to obtainsuitable objects based on the usage purposes.[12–17]

Fluorinated Pcs show excellent thermal stability, chemicalresistance and high solubility. In addition, the presence offluorine atom as more powerful electron-withdrawing agent in

the macrocyclic molecules results in functional magnetic,electron transport and photosensitizing characteristics. Hence,the fluorine containing Pcs can become proper alternatives fordevelopment of the Pcs performance in the different applica-tions. Therefore, study of their synthesis and characterizationsounds useful.[18–25]

Generally substituted Pcs are synthesized by cyclotetrame-rization of phthalonitrile derivatives. Compared to symmetri-cally octasubstituted phthalocyanines, tetra-substituted phtha-locyanines containing the same groups are more soluble, sincethey are obtained as four structurally isomeric mixtures.[26] Afew literature has been reported for separation of the structuralisomers on small scale by applying chromatographictechniques.[27,28]

The biological activities of Pc molecules have been thesubject of many researches and photodynamic therapy,[16]

antimicrobial,[29] antioxidant,[30] and enzyme inhibition activitieswere investigated in details. Tyrosinase enzyme catalyses the o-hydroxylation of monophenol molecules to o-diphenols andthe oxidation of o-diphenols to produce o-quinones.[31] Brown-ing reactions in live beings is facilitated by tyrosinase enzymeand the degree of this browning reaction is affected by oxygen,metal ions, heat and phenolic compounds.[32] Tyrosinase activityis undesirable in some applications such as cosmetics and foodindustry and, thus, tyrosinase inhibitors have become veryimportant in these processes.

Recently, our group has been interested in synthesis,characterization and biological properties of the fluorinatedPcs.[33,34] This study presents the synthesis and characterizationof new tetra-substituted Pcs bearing 4-(trifluoromethoxy)

[a] N. Farajzadeh, Dr. H. P. Karaoğlu, Prof. Dr. M. B. KoçakDepartment of Chemistry, Istanbul Technical University, Maslak, Istanbul,34469 (TURKEY)E-mail: mkocak@itu.edu.tr

[b] M. Akin, Dr. N. SakiDepartment of Chemistry, Kocaeli University, Umuttepe, Kocaeli, 41380(TURKEY)

Supporting information for this article is available on the WWW underhttps://doi.org/10.1002/slct.201901509

Full PapersDOI: 10.1002/slct.201901509

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phenoxy groups peripherally. In addition, the aggregationbehavior of tetra-substituted metallophthalocyanine (CuPc)was investigated at different concentrations in THF and DCM.Spectrofluorometric properties of the compounds (H2Pc andPdPc) were studied in DMF. Fluorescence quenching propertyof H2Pc was examined by adding different concentrations ofbenzoquinone in DMF. Besides, antioxidant and tyrosinaseinhibition properties of synthesized compounds were alsodetermined by using TLC dot-blot and spectrophotometricassays.

Results and Discussion

Synthesis and characterization

The synthetic route of (2, H2Pc, CuPc and PdPc) is demonstratedin Scheme 1. As shown, the newly synthesized phthalonitrile

derivative namely 4-(4-(trifluoromethoxy)phenoxy)phthaloni-trile (2) was synthesized during the nucleophilic aromaticsubstitution of compound 1 with 4-(trifluoromethoxy)phenolcatalyzed by K2CO3 as the base.[35,36] After recrystallization fromethanol, a satisfactory yield (82.52%) was obtained for theresulting phthalonitrile derivative 2. According to the generalsynthetic procedure of phthalocyanines, compounds (H2Pc,CuPc and PdPc) resulted directly from cyclotetramerization ofcompound 2 without/ or with the anhydrous metal chlorides inappropriate high-boiling solvents at refluxed temperature for24 hours. DMAE was chosen as a suitable solvent for thesynthesis of H2Pc and CuPc. However, PdPc was synthesized in

n-penthanol having a higher boiling point. DBU as a strong N-base was utilized to create basic medium in n-penthanol. Thecrude products (H2Pc, CuPc and PdPc) were purified byapplying column chromatography (silica gel, chloroform / THF(50: 1) as the eluent). Purity and properties of the targetmacromolecules were investigated using various techniquesincluding 1HNMR, FTIR, UV–vis, Mass spectroscopy and elemen-tal analysis. The yields of the H2Pc, CuPc and PdPc weredetermined 46.51, 36.90 and 10.71%, respectively. The novelmacromolecular structures were highly soluble in a number oforganic solvents such as DCM, chloroform, THF, DMF anddimethyl sulfoxide (DMSO).

In the FTIR spectrum, displacement of the nitro of 4-nitrophthalonitrile with 4-(trifluoromethoxy)phenoxy group canbe verified by the absence of the NO2 band around 1550 cm� 1

and presence of Ar-O� Ar peak between 1000 and 1300 cm� 1.The characteristic FTIR peaks of compound 2 appeared at 3061,2235, 1313, and 1100 cm� 1 corresponding to Ar� H, CN, CF3,and Ar-O� Ar, respectively. In the 1HNMR spectrum of com-pound 2, the aromatic protons of the phthalonitrile structure(CN2-Ar-H) were observed at 7.77-7.76, 7.32 and 7.25 ppm asdoublet, singlet and doublet, respectively and those of thesubstituent (F3CO� Ar-H-O) appeared at 7.35-7.33 ppm asdoublet and 7.14 - 7.12 ppm as doublet. The related 13CNMRspectrum was assigned to the structure of the derivative 2. Inthe 13CNMR spectrum of compound 2, the aromatic carbonswere observed at a range between 161.23 and 109.50 ppm,while C� F carbons and C�N carbons appeared at 123.38 and115.18 ppm, respectively. 19FNMR spectroscopy is a properapproach to examine the fluorinated structures. In the 19FNMRspectrum of 2, the appearance of a single peak at – 57.08 ppmcorresponded to 3F. As expected, the mass spectrum ofcompound 2 exhibited the molecular ion peak at m/z=304.05[M]+.

Cyclotetramerization of the phthalonitrile derivative bearingonly one functional group on each benzo group results in amixture of four constitutional isomers. These structures differ insymmetry (D2h, C4h, C2v and Cs) and significantly hinder theaggregation of the tetra-substituted Pcs.[27,28] In the FTIR spectraof the newly synthesized H2Pc, CuPc and PdPc, the acuteabsorption peak of C�N group vanished owing to the cyclo-tetramerization of the compound 2. The IR spectra of the allPcs are very similar except the presence of weak N� H peak at3289 cm� 1 for compound H2Pc. For the macrocyclic molecules(H2Pc, CuPc and PdPc), the vibrations appearing at 1090, 1088and 1100 cm� 1 corresponded to aromatic ether groups (Ar-O� Ar) and distinctive substituted CF peaks were observed at1339, 1342 and 1329 cm� 1, respectively. The compound CuPccontainig a paramagnetic metal was not employed for 1HNMR.In the 1HNMR spectrum of H2Pc, each of broadening bandsobserved at 8.54, 8.24 and 7.55 ppm were attributed to 4H.Additionally, two bands appeared at 7.28-7.30 as doublet and7.11-7.12 as doublet per 8H. The inner core protons ascharacteristic of H2Pc was identified at � 0.11 ppm. The 1HNMRspectrum of PdPc showed the aromatic protons at 8 ppm assinglet, 7.6 ppm as singlet and 7.4-7.1 ppm as multipletcorresponded to 4H, 4H and 20H, respectively. In comparison

Scheme 1. Synthetic route for phthalonitrile (2) and phthalocyanines (H2Pc,CuPc and PdPc). a) DMF, K2CO3, 45 °C, 4 h. b) For H2Pc and CuPc, DMAE,135 °C, 24 h; for PdPc, n-Pentanol, DBU, 165 °C, 24 h.

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to 2, 1HNMR spectra of the resulting macromolecules H2Pc andPdPc are broader due to the presence of the isomeric mixture.Since each of the isomers displays slightly different chemicalshifts. In the MALDI-TOF mass spectra, synthesis of the highlypurified compounds H2Pc, CuPc and PdPc were confirmed byobservation of sharp peaks at 1218, 1279, 1322 m/z, respec-tively.

Electronic Absorption Spectra

The characteristic electronic absorption spectra of Pcs includetwo strong peaks denoted the B-band (Soret band, around300–400 nm) and the Q-band (around 650–700 nm). The darkblue/ blue-green color of Pcs results from the Q-bandattributed to the π - π* transition from the HOMO (highestoccupied molecular orbital) to the LUMO (lowest unoccupiedmolecular orbital) of the Pc ring. Due to lower symmetry ofmetal-free Pc (D2h) in comparison to the planar metal one (D4h),the Q-band of metal-free Pc splits approximately in half.However, addition of a strong base such as tetrabuthylammo-nium hydroxide causes to incorporate the Q-band owing to theformation of Pc2� anion with D4h structure. Generally substitu-tion, central metal ion and the media of the Pc ring can affectthe position and width of the Q-band. The B-band is related tothe π - π* transition from deeper π orbitals to the LUMO and isusually weaker than Q-band. Besides, extra bands can beobserved in UV/Vis spectra of some Pcs due to the chargetransfer between metal and ligand or exciton couplingbetween the π- systems of macrocyclic dimers.[1–4]

The UV/Vis spectra of the resulting Pcs determined at roomtemperature are displayed in Figure 1. Dilute solutions of the

all Pcs were prepared in THF. As shown, the Q-band ofcompound H2Pc split at 697 (Qx) and 662 (Qy) whereas, thoseof CuPc and PdPc were observed as single bands at 673 and661 nm, respectively. Additionally, the hypsochromic shift of12 nm for the compound PdPc can be attributed to palladium

ion, which is larger and heavier than copper one.[37] The B-bands of the target Pcs appeared between 324 and 344 nm, aswell. Log ε values of the stated bands are indicated in Table 1.

Moreover, the vibronic peaks of compounds H2Pc, CuPc andPdPc assigned to n - π* transitions were observed at 601, 605and 595 nm, respectively.[38,39]

Aggregation studies

Aggregation mostly arises from coplanar association of mono-meric Pc rings resulting in formation of dimers and higherorder macromolecules. Due to negative effect on singletoxygen production efficiency, bioavailability, optical and PDTproperties of Pcs, some efforts are carried out to minimize theaggregation. Generally, aggregation can be studied andmonitored by changing some factors such as temperature,concentration, nature of substituent or solvent type. Formationof higher order structures during the aggregation results incombination of the electronic states of the macrocyclic unitsand derangement of spectral properties. Therefore, the opticalabsorption spectra can be suitable means to study theaggregation behavior of Pcs.[1–4,12, 14–17]

In this study, the aggregation behaviour of CuPc wasexamined at different concentrations in THF and DCM (Fig-ure 2). In THF, as concentration of compound CuPc enhanced,intensity of the narrow Q-band increased and new bandsassigned to the aggregated structures were not identified(Figure 2A). However, increase in the concentration of thecompound CuPc in DCM followed by a slight increase in theshoulder of the related peaks (Figure 2C). Indeed, THF as acoordinating solvent diminishes π-π stacking of the rings byconnecting axially to the metal ion and results in narrow bandsof the dissolved Pcs. However, DCM does not have thecoordinating nature.[40] Moreover, the obedient of Lambert-Beerlaw for CuPc was studied at different concentrations in THF andDCM (Figure 2B and D).

The electronic absorption of compound CuPc were inves-tigated in a series of organic solvents including acetone, THF,toluene, DMF, ethylaceate (EtAc) and CHCl3 (Figure 3A). Theposition of the Q-band relies directly on the refractive index ofthe solvent. As the refractive index of the solvent increases, theQ band shifts to the red region. According to the solvent type,the shift of the Q-band to red region increased in the followingorder: toluene < CHCl3< DMF < THF< EtAc< acetone. Baylissmethod was applied to analyze the related spectra (Fig-ure 3B).[19,36, 41] The linearity of Q band frequency- refractiveindex plot confirms effect of solvation on the red shifts of theQ band.

Figure 1. UV/Vis spectra of H2Pc, CuPc and PdPc in THF (concentration; 6 ×10� 6 m ).

Table 1. UV/Vis data for H2Pc, CuPc and PdPc in THF.

Comp. B-Band λmax, (nm), log ε Q-Band λmax, (nm), log ε

H2Pc 341, 4.97 697, 5.28/ 662, 5.24CuPc 344, 4.71 673, 5.18PdPc 324, 4.79 661, 5.14

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Photopysical and photochemical properties

Fluorescence features of the compounds (H2Pc and PdPc) havebeen studied in DMF as described.[37,42, 43] The electronicabsoprtion, fluorescent emission and consequent excitationspectra of the compound H2Pc are depicted in Figure 4. Thefluorescence emission spectra of H2Pc and PdPc appeared at709 nm and 688 nm, respectively. Moreover, the Stokes’ shiftsof H2Pc and PdPc were obtained 11 nm and 23 nm, respec-tively. Due to the reliability of the comparative approach, thefluorescence quantum yields (ΦF) were calculated by using

unsubstituted ZnPc (ΦF=0.17) as the referance.[13,44] Thefluorescence quantum yields of H2Pc and PdPc were obtained0.343 and 0.0045, respectively. The metallophthalocyaninesincluding heavy metals have usually high intersystem crossingresulting in small fluorescence quantum yields.[37] As expected,PdPc has much smaller fluorescence quantum yield.

Fluorescence lifetime (τF) is introduced as the average timethat the molecule stays at the excited state before fluorescing.Internal conversion and intersystem crossing diminish thefluorescence lifetime. Additionally, the quantum yield as adirect dependent of the lifetime decreases, as the τF reduces. In

Figure 2. A) Electronic spectra of CuPc in THF at different concentrations from 4 × 10� 6 –14 × 10� 6 m, B) Plot of the absorbance of CuPc against toconcentration (THF), C) Electronic spectra of CuPc in DCM at different concentrations from 4 × 10� 6–14 × 10� 6 m, D) Plot of the absorbance of CuPc against toconcentration (DCM)

Figure 3. A) UV/Vis spectra of CuPc in different solvents (concentration; 6 × 10� 6 m), B) Plot of the Q-band frequency of CuPc against (n2 � 1)/(2n2 + 1).

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this study, the Strickler - Berg equation was used to determinethe fluorescence lifetimes (τF) of the compound (H2Pc).

[13,42, 43, 45]

Based on the equation 2, natural radiative lifetime (τ0) and thefluorescence lifetime (τF) of H2Pc were calculated as 6.05 and2.07 ns, respectively.

The fluorescence quenching of H2Pc was explored byadding different concentrations of benzoquinone (BQ) in DMF.The result follows the kinetics mechanism of the Stern - Volmerequation. The fluorescence spectra of H2Pc as fluorophore withdifferent values of benzoquinone as the quencher are demon-strated in Figure 5. The linearity of the I0/I - [BQ] curve confirmsthe obedient of the diffusion-control theory.

For H2Pc, Ksv and kq were evaluated 59.01 m� 1 and28.51 m� 1ns� 1, respectively. These values are higher than thoseof unsubstituted ZnPc (as the standard; Ksv=57.60 M � 1).

Tyrosinase inhibition

Copper containing tyrosinase enzyme (EC 1.14.18.1) catalysesthe oxidation of l-DOPA to dopaquinone using molecularoxygen[46] and it is a rate limiting step in the melaninsynthesis.[47]

TLC dot-blot technique is widely applied in antimicrobial[48]

and antioxidant activity[49] measurements of natural plantextracts. Because it is an easy and fast method, it is used tohave preliminary knowledge about the biological activities ofthe molecules. In recent years, the method has been also usedin enzyme inhibition studies of plant extracts[50,51] and reliableinformation about the inhibition ability of the molecules areobtained quickly and easily before the applications of thespectrophotometric method. In this technique, the plate isincubated at 37 °C for 20 min in a stove. As the enzymaticreaction proceeds, dyeing develops, and the initially colorlessTLC plate changes to brown because of the generation of o-quinones which is polymerized to generate brown coloredproducts. Inhibitors sorbed on the TLC plate are then visualizedas white spots under visible light.[52,53]

In this study, we determined the tyrosinase inhibitoryactivities of synthesized Pc molecules, ligand and standardinhibitor kojic acid by using TLC dot-blot and also spectropho-tometric assays.

First, kojic acid was loaded to the TLC plates at differentconcentrations and at all concentrations tyrosinase inhibitionwas detected as white spots against a brownish-purple back-ground (Figure 6A). When Pc molecules and 2 were loaded tothe TLC plate (2.5 μL at 500 μg/mL), all molecules except H2Pcformed the lighter parts against the purple background on theTLC plate indicating an inhibition against tyrosinase enzyme(Figure 6B). Since the H2Pc molecule did not show anyinhibitory activity, the resulting quinone molecules causedpurple color formation on TLC and detected by visually.

According to the spectrophotometric assay, the inhibitoryactivities of all the tested molecules increased with theincreasing of concentration and CuPc (82.09 � 0.03%) showedthe highest activity after the Kojic acid (91.34 � 0.10%). Theorder of inhibition activities of the tested molecules was 2(47.23 � 0.17%), PdPc (23.72 � 0.43) and H2Pc (16.05 � 1.14).IC50 values of the tested molecules and kojic acid are given inTable 2. In many studies, inhibition activity of standard inhibitorkojic acid has been determined[54] and the results were similar

Figure 4. Absorption (blue), excitation (red) and emission (green) spectra forcompound H2Pc in DMF.

Figure 5. A) Fluorescence emission spectral changes of H2Pc (4.00 × 10 � 6 moldm � 3) upon addition of different concentrations of BQ in DMF. [BQ]=0,0.008, 0.016, 0.024, … mol dm � 3. B) Stern–Volmer plots for benzoquinone(BQ) quenching of [H2Pc]=4.00 × 10 � 6 mol dm � 3 in DMF.

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to ours. Enzyme inhibition activities of phthalocyanines werealso investigated in a few studies.[55] Zhou et al., (2008)investigated the cationic Pc derivatives as potential inhibitorsof telomerase.[56] Barut et al., (2017), synthesized novel watersoluble morpholine substituted ZnII Pc and determined top-oisomerase I inhibition activities.[57]

DPPH radical scavenging activity

DPPH radical scavenging activities of Pc molecules, ligand andstandard molecule were investigated by using spectrophoto-metric and TLC-Dot blot assay. The preliminary informationabout the antioxidant activities of the molecules given by TLCDot-blot method was then confirmed by spectrophotometricmethod.

Synthesized compounds and standard molecule Troloxwere dropped on the TLC plates (2.5 μL) at different concen-trations. Molecule 2 did not show any activity at all testedconcentrations. H2Pc and trolox, on the other hand, appear toaffect at all tested concentrations (Figure 7).

Trolox showed the highest scavenging activity at all testedconcentrations in spectrophotometric method. Among thetested Pcs and ligand molecule; H2Pc exhibited 49.14 � 0.09%activity followed by CuPc 46.54 � 0.04%, PdPc 41.83 � 0.12%and compound 2 32.54 � 0.23% at 1500 μg/mL concentration(Figure 8).

Reducing power

The reducing capacity of a compound may serve as asignificant indicator of its potential antioxidant activity. Theresults of the reducing power assay of tested compounds aresummarized in Figure 9. High absorbance indicated highreducing power and BHA was used as the positive control.According to the results; at 1500 μg/mL concentration, thehighest activity was measured at 0.321 nm for H2Pc. Thehighest reducing power was obtained with BHA at allconcentrations.

Antioxidant activities of phthalocyanine molecules havebeen involved in many studies.[58,59] DPPH radical scavengingactivities of Pc molecules ranged from 71.83%[58] to 29.3%[60] at

Figure 6. Tyrosinase inhibition TLC bioautograms of Kojic acid at differentconcentrations (A) and synthesized molecules (2.5 μL at 500 μg/mL) (B).

Table 2. Inhibition activities of Pcs and compound 2 on the tyrosinase enzyme.

% Tyrosinase inhibition IC50μg/mLCompound 50 μg/mL 250 μg/mL 500 μg/mL 1000 μg/mL 1500 μg/mL

2 10.96 � 0.02 18.37 � 0.15 33.81 � 0.04 42.03 � 0.02 47.23 � 0.17 >1500CuPc 27.78 � 0.08 61.20 � 1.32 68.86 � 1.02 77.18 � 0.14 82.09 � 0.03 202�0.84PdPc ND 6.87 � 0.81 14.09 � 1.12 18.71 � 0.61 23.72 � 0.43 >1500H2Pc ND 3.71 � 1.25 10.33 � 0.09 13.14 � 1.02 16.05 � 1.14 >1500Kojic acid 39.56 � 0.03 84.29 � 0.13 92.57 � 1.22 90.76 � 0.03 91.34 � 0.10 56 � 1.23

Figure 7. TLC–direct bioautography bioautogram of DPPH radical scavengingactivities of synthesized molecules obtained by using the Dot-Blot technique.

Figure 8. DPPH free radical scavenging activities of synthesized Pcs andcompound 2 at different concentrations.

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highest studied concentrations. In the light of this information,it is possible to say that DPPH scavenging activities ofmolecules synthesized in our study were moderate with 49.14� 0.09% scavenging activity of H2Pc molecule at 1500 μg/mLconcentration.

Conclusions

In this study, a number of novel metal-free and metallatedph-thalocyanines (H2Pc, CuPc and PdPc) were prepared using thenewly synthesized phthalonitrile derivative bearing 4-(trifluor-omethoxy)phenoxy on 4- position. All the analyzed data wereachieved by performance of various spectroscopic methodsand confirmed the proposed structure. Moreover, acceptableresults were obtained for solubility of H2Pc, CuPc and PdPc incommon solvents. Aggregation behavior of CuPc were studiedin diverse solvents such as DCM, acetone, THF and etc.Obedient of Lambert–Beer law was examined for differentconcentration of the compound CuPc in THF and DCM.Antioxidant and tyrosinase enzyme inhibition activities werealso investigated. The antioxidant activity of the compounds ismoderate compared to the literature and CuPc showed thehighest activity on the tyrosinase enzyme among the synthe-sized molecules.

Supporting Information Summary

Experimental details, synthesis and spectroscopic data of thenewly synthesized compounds are given in supporting infor-mation file.

Acknowledgements

This work was supported financially by the TUBITAK (Project no.:115R030), the Research Fund of the Istanbul Technical University(Project no. TDK-2019-42066)and the Research Fund of the KocaeliUniversity (Project no. BAP-2018/026).

Conflict of Interest

The authors declare no conflict of interest.

Keywords: aggregation behavior · antioxidant activity ·phthalocyanine · 4-(trifluoromethoxy)phenoxy · tyrosinase

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Figure 9. Reducing power assay of synthesized complexes at 700 nm.

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Submitted: April 26, 2019Accepted: August 1, 2019

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