Thiosemicarbazide-based iron(III) and manganese(III) complexes. Structural, electrochemical characterization and antioxidant activity

Polyhedron 173 (2019) 114130

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Thiosemicarbazide-based iron(III) and manganese(III) complexes. Structural, electrochemical characterization and antioxidant activity Büsßra Kaya a, Kerem Kaya b, Atıf Koca c, Bahri Ülküseven a,⇑ a

Department of Chemistry, Engineering Faculty, Istanbul University-Cerrahpasa, 34320 Avcilar, Istanbul, Turkey Department of Chemistry, Faculty of Science and Letters, Istanbul Technical University, 34469 Maslak, Istanbul, Turkey c Department of Chemical Engineering, Engineering Faculty, Marmara University, 34722 Göztepe, Istanbul, Turkey b

a r t i c l e

i n f o

Article history: Received 1 July 2019 Accepted 21 August 2019 Available online 27 August 2019 Keywords: Thiosemicarbazide Iron Manganese Electrochemistry Antioxidant

a b s t r a c t New iron(III) and manganese(III) complexes were synthesized by the condensation of 1-phenyl-1, 3-butanedione-S-propyl-thiosemicarbazone (1) with salicylaldehyde in the presence of iron(III) or manganese(II) ions. The complexes were characterised by analytical and spectroscopic methods. X-ray analysis displayed the square pyramidal environments of the iron and manganese ions. The electrochemical behaviors of the iron(III) (1a) and manganese(III) (1b) complexes were studied by cyclic voltammetry and square wave voltammetry in different solvents. Both complexes displayed metal-based electron transfer reactions in addition to ligand based irreversible reduction and oxidation processes, which were affected by the type of metal. Spectroelectrochemical methods were used to examine the electrogenerated species of the complexes and to define the redox processes. The total antioxidant capacity (as the TEAC value) and free radical scavenging activities (FRS%) of the compounds were determined. The TEAC values of 1 (2.78), 1a (1.63) and 1b (1.28) are higher than those of vitamin C (0.96). Ó 2019 Elsevier Ltd. All rights reserved.

1. Introduction Iron has an important role in the biological systems of mammals, as do many other transition metal ions. High iron levels in the body can cause some disease symptoms, as can iron deficiency, and free iron ions can catalyze the formation of reactive oxygen species which are damaging to cells. Excessive iron activity can be controlled using appropriate iron-binding molecules, preferably having antioxidant properties. Nitrogen-rich molecules which can easily bind to iron ions have been examined as potential drugs for various diseases, mostly cancers [1–4]. Manganese is functional in redox processes and a cofactor in enzymes that are essential in energy production. Manganese superoxide dismutase (MnSOD) is an antioxidant enzyme providing protection against damage arising from free radicals [5,6]. Since iron and manganese are compatible with mammalian biology, their complexes are an important option for research on human needs. In particular, chelate complexes with salen-type ligands have been one of the parent research topics. Many iron and manganese-centered complexes have been studied in detail to reveal their usefulness provided by redox properties [7–13].

⇑ Corresponding author. E-mail address: [email protected] (B. Ülküseven). https://doi.org/10.1016/j.poly.2019.114130 0277-5387/Ó 2019 Elsevier Ltd. All rights reserved.

The interest in thiosemicarbazide derivatives began after the discovery of compounds with specific therapeutic properties [14,15]. Research on thiosemicarbazones continued by the participation of various metal complexes whose useful biological effects have been defined [16–20]. Considering the reports published so far, organic and metal-organic compounds generated from thiosemicarbazide are useful chemicals with proven efficiencies against some diseases, especially cancers [4,21–26]. The S-alkyl thiosemicarbazidato (L2
) structures are homologous with salentype Schiff bases in the context of the donor atom set (N2O2). The structures and electrochemical features of nickel(II), copper (II) and zinc(II) complexes bearing an S-alkyl thiosemicarbazidato ligand have been investigated in detail by experimental and theoretical methods. The study describes how one-electron oxidized species of the complex molecules and the radical cation of the free ligand are formed [27]. Iron(III) and manganese(III) complexes of N2O2-donor thiosemicarbazones have exhibited in vitro cytotoxicity against myeloid leukemia (K562), cervical carcinoma (HeLa) and colorectal adenocarcinoma (HT-29) cells [20,28]. Some of these palladium-centric complexes, with strong xanthine oxidase inhibition, have been described as potent anticancer drug components on colorectal carcinoma (HCT116) and hepatocellular carcinomas cells (HepG2 and Hep3B) [29].

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B. Kaya et al. / Polyhedron 173 (2019) 114130

in 10 mL alcohol, then the reaction mixture was gently stirred for two hours at room temperature. The mixture was allowed to stand overnight to give a yellow solid product. Recrystallization of this matter was carried out using ethanol. The data defining compound 1 are given below. M.p.: 85 °C. Yield: 70%. Anal. Calc. for C14H19N3OS (277.38 g/mol): C, 60.62; H, 6.90; N, 15.15; S, 11.56. Found: C, 60.34; H, 6.79; N 15.05; S 11.09%. UV–Vis kmax (nm), log e (dm3 cm
1 mol
1): 246 (4.22), 315 (3.82), 386 (4.11). IR (cm
1): mas(NH2) 3381, ms(NH2) 3307, m(OH) 3205, d(NH2) 1650, m(C@N1), m(N2@C) 1619–1577. 1H NMR (d, ppm): 14.3, 14.01 (cis/trans ratio:1, s, 1H, OH), 8.01–7.81 (m, 5H, aromatic), 6.53, 6.45 (cis/trans ratio:2, s, 2H, NH2), 5.79 (s, 1H, @CH), 3.03–2.88 (m, 2H, S-C1H2), 2.16 (s, 3H, C-CH3), 1.67–1.61 (m, 2H, –C2H2), 0.99–0.91 (m, 3H, –C3H3).

Herein, we present new iron(III) (1a) and manganese(III) (1b) complexes, synthesized from a thiosemicarbazide, as shown in Fig. 1. Structural identification of the N2O2-chelate complexes was carried out by means of analytical, spectroscopic and also crystallographic analysis. The electrochemical and antioxidant properties of the compounds were studied to demonstrate their redox behaviors and thus to evaluate their possibility to act against oxidative stress-induced diseases. Moreover, the spectroelectrochemical features of 1a and 1b were revealed in order to determine the possibility of their use in various electrochemical technologies. 2. Experimental 2.1. Physical measurements

2.3. Synthesis of monochloro-N1-1-phenyl-1,3-butanedione-N4salicylidene-S-propyl-thiosemicarbazidato-iron(III) (1a)

Analytical data were obtained with a Thermo Finnigan analyzer. Agilent Carry 630 FTIR-ATR, Ocean Optics QE65000 diode array UV–Vis and Varian (500 MHz) NMR spectrometers were used to obtain the structural data. Magnetic moments were measured using a Sherwood Scientific device at room temperature. For X-ray analysis, the crystals were mounted on a micromount and attached to a goniometer head on a Bruker D8 VENTURE diffractometer equipped with PHOTON100 detector. Data collection was performed with graphite monochromated Mo Ka radiation (k = 0.71073 Å) using X rotation frames of 1.0 and 0.5° for 1a and 1b respectively at room temperature. The structures were solved by direct method using the SHELXS [30] program and refined by full-matrix least-squares methods with SHELXL-2014 [31]. All non-hydrogen atoms were refined anisotropically. All the hydrogen atoms were placed in their calculated positions and refined in the riding model. SADABS [32] was used to perform absorption corrections [33]. Molecular drawings were generated using OLEX2. Ver. 1.2-dev [34].

As described in reference [37], a 5 mL alcoholic solution of 1 mmol (0.27 g) FeCl3.6H2O was added to a mixture of the S-propyl-thiosemicarbazone (1) (1 mmol, 0.28 g) and salicylaldehyde (1 mmol, 0.1 mL). The mixture was gently brought to about 60 °C and allowed to stand at this temperature for 2 hours. After several days, the formed precipitate was filtered and the dark red crystals obtained were washed two times with 2 mL of ethanol. Analytical and spectroscopic data of 1a are: M.p.: 219 °C. Yield: 30%. leff: 5.84 BM. Anal. Calc. for C21H21N3O2SFeCl (470.77 g/mol): C, 53.58; H, 4.50; N, 8.93; S, 6.81. Found: C, 53.37; H, 4.31; N, 8.71; S, 6.05%. UV–Vis kmax (nm), log e (dm3 cm
1 mol
1): 240 (4.42), 300 (4.54), 400 (4.20), 435 (4.18), 470 (4.10), 500 (3.87). IR (cm
1): m(C@N1) 1606, m(N2@C) 1578, m(N4@C) 1559, m(CAO) 1163, 1142. 2.4. Synthesis of monochloro-N1-1-phenyl-1,3-butanedione-N4salicylidene-S-propyl-thiosemicarbazidato-manganese(III) (1b)

2.2. Synthesis of 1-phenyl-1,3-butanedione-S-propylthiosemicarbazone (1)

The reaction was performed as described above, but differently, MnCl2.4H2O was used and air was bubbled through the reaction mixture for 1 hour before heating. Characterization data of the dark red complex (1b) are: M.p.: >350 °C. Yield 25%. leff: 4.39 BM. Anal. Calc. for C21H21N3O2SMnCl (469.86 g/mol): C, 53.68; H, 4.50; N, 8.94; S, 6.82. Found: C, 53.39; H, 4.19; N, 8.61; S, 6.19%. UV–Vis kmax (nm), log e (dm3 cm
1 mol
1): 241 (4.16), 350 (3.82), 403 (3.56), 434 (3.45), 470 (3.34), 497 (3.29). IR (cm
1): m(C@N1) 1603, m(N2@C) 1574, m(N4@C) 1559, m(CAO) 1182, 1157.

To a 10 mL alcoholic solution of 1 mmol (0.91 g) thiosemicarbazide, was added 1.1 mmol (0.1 mL) 1-bromopropan, and the mixture was refluxed for 3 hours. After one day, the cream coloured precipitate that formed, S-propyl-thiosemicarbazide, was filtered and washed with ethanol; the yield was 0.1 g (75%) [35]. To prepare compound 1, a general method was applied with minor revisions [36]. 0.8 mmol (0.1 g) of the S-propyl derivative and 0.8 mmol (0.13 g) 1-phenyl-1,3-butanedione were dissolved

NH2

H2N

+

N

O

N H2N

Br

SH

CH3

NH2

CH3

S

CH3

(1)

+ HO

Thiosemicarbazide Cl OH

H3C

N

N

(1)

+ NH2 S

HO O CH3

+ FeCl 3 + MnCl 2 + air

O

(1a) (1b)

M

N H3C

N

O N S

M: Fe (1a), Mn (1b)

Fig. 1. Synthesis scheme for the iron(III) (1a) and manganese(III) (1b) complexes.

CH3

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B. Kaya et al. / Polyhedron 173 (2019) 114130

2.5. Electrochemistry For the electrochemical and spectroelectrochemical measurements, a Gamry Reference 600 potentiostat/galvanostat utilizing a three-electrode configuration was used at 25 °C. For cyclic voltammetry (CV) and square wave voltammetry (SWV) measurements, the working electrode was a Pt disc with a surface area of 0.071 cm2. In the experiments, where the internal reference was ferrocene, a Pt wire as the counter electrode and Ag/AgCl as the reference electrode were used. Tetrabutylammonium perchlorate (TBAP) in dichloromethane (DCM) was employed as the supporting electrolyte at a concentration of 0.10 mol dm
3. Prior to each measurement, high purity nitrogen was employed to remove dissolved oxygen and to maintain a nitrogen blanket during the measurements. In situ spectroelectrochemical measurements were carried out by utilizing a three-electrode configuration of a thin-layer quartz cell at 25 °C. The working electrode was semi-transparent Pt tulle. A Pt wire counter electrode and a SCE reference electrode separated from the bulk of the solution by a double bridge were used. 2.6. Antioxidant capacity and activity tests The total antioxidant capacity of the compounds was assessed according to the CUPRAC method [38]. To a test tube were added 1 mL of 10 mM CuCl22H2O, 1 mL of 7.5 mM neocuproine (Nc), 1 mL of 1.0 M pH 7 NH4Ac buffer solution, x mL antioxidant sample solution and (1.1
x) mL H2O, in this order. The mixture, in a total volume of 4.1 mL, was incubated for 30 min and the absorbance at 450 nm was recorded against a reagent blank. The TEAC coefficients (trolox equivalent antioxidant capacities) were calculated as the ratio of the molar absorptivity of each compound to that from the trolox method (Ɛtrolox: 1.67  104 L mol
1 cm
1). The scavenging activity of the compounds on DPPH (2,2-di(4tert-octylphenyl)-1-picrylhydrazy) radicals was measured according to the literature [39], with small modifications. A methanolic solution of the compounds (0.6 mL) was mixed with 1.4 mL of methanol and 2 mL of 0.1 mM DPPH solution in a test tube. The tubes were stoppered and after 30 min the absorbance at 515 nm was recorded against methanol. The free radical scavenging (FRS) activity was calculated as the percentage of DPPH decolorization using the equation, FRS activity (%) = [(ADPPH
AS)/ADPPH]  100. The assays were carried out in triplicate at room temperature and the results expressed as the mean value ± standard deviation. 3. Results and discussion 3.1. Synthesis and characterization

the OH and NH2 groups of compound 1 react by losing their protons, so their streching and bending bands disappear. The mas(NH2), ms(NH2), m(OH) and d(NH2) bands of the thiosemicarbazone (1) were not observed in the spectra of 1a and 1b. The C@N1, N2@C, and newly formed N4@C stretching bands overlap in the range 1606–1559 cm
1 and they appear as the peak ends of a broad band. In the electronic spectra of 1, the p–p* and n–p* bands arising from the aromatic and thioamide groups were recorded at 246, 315 and 386 nm. In the complex spectra, these bands were recorded in the range 300–435 nm. MLCT bands of the complexes are between 470 and 500 nm. The low band intensity of the d-d transitions made it impossible to observe the data for the square pyramidal geometry. 3.2. Crystallography Single crystals of complexes 1a (0.02  0.05  0.30 mm) and 1b (0.01  0.01  0.04 mm) were grown by slow evaporation of dichloromethane solutions. Crystal data and structure refinement parameters of the complexes are given in Table 1 and thermal ellipsoids are shown in Fig. 2 (1a) and 3 (1b). Table S1 shows selected bond lengths, bond and torsion angles for the complexes. Figs. S1 and S2 show the crystal packing for the complexes. In the square pyramidal structure of complex 1a, the O, N, N and O donor atoms of the thiosemicarbazidato structure (L2
) formed by the template reaction are at the corners of a square plane. The iron atom, bearing a chlorine atom at the fifth site of coordination, is 0.530 Å above this plane. The chlorine atom is weakly linked to the iron atom with a distance of 2.221 Å. According to Addison’s calculation, distortion in the square pyramid of 1a is equivalent to a s value of 0.04 [40]. The coordination bond lengths, 2.095 (Fe–N1), 2.051 (Fe–N3) and 1.891 Å (approx. value for Fe–O1 and

Table 1 Crystal data and structure refinement parameters for 1a and 1b.

Empirical formula Formula weight (g/mol) T (K) k (Å) Crystal system Space group Unit cell dimensions (Å, °) a b c V (Å3)

a b

c

S-propyl thiosemicarbazone (1) was readily identified by means of the characteristic cis-trans peak pattern of the NH2 protons (at d 6.53 and 6.45 ppm) as well as other aliphatic and aromatic proton signals. The template condensation of the thiosemicarbazone (1) with salicylaldehyde yielded the complexes, [Fe(L)Cl] (1a) and [Mn(L) Cl] (1b), as displayed in the synthesis scheme (Fig. 1). The aerial oxidation of manganese(II) to manganese(III) was conducted during the formation of complex 1b. The complexes are soluble in alcohols and chlorinated hydrocarbons, and very soluble in DMSO. The magnetic moment measurements indicated a high-spin state of both metal centers. The 5.84 BM (for 1a) and 4.39 BM (for 1b) values are equivalent to five and four unpaired electrons in the iron(III) and manganese(III) ions, respectively. Infrared spectroscopy is an important technique to monitor the formation of these template complexes. In the template reaction,

Z Absorption coefficient (mm
1) Dcalc (g/cm3) F(0 0 0) h range for data collection (°) Index ranges

Reflections collected Independent reflections Coverage of independent reflections (%) Data/parameters Max. and min. transmission Final R indices [I  2r(I)] R indices (all data) Goodness-of-fit (GOF) on F2

1a

1b

C21H21ClFeN3O2S 470.77 304(2) 0.71073 triclinic P1

C43H44Cl4Mn2N6O4S2 1024.64 303(2) 0.71073 monoclinic P 1 21/c 1

8.6668(19) 11.164(2) 11.981(3) 1062.4(4) 68.706(6) 79.670(7) 85.384(7) 2 0.956 1.472 486 2.39–25.00
10  h  10
13  k  13
14  l  14 19 674 3746 99.9

13.7065(6) 26.2211(11) 13.4885(6) 4612.9(3) 90 107.9070(10) 90 4 0.918 1.475 2104 2.20–25.00
16  h  16
31  k  31
16  l  16 129 823 8107 99.9

3746/264 1–0.867 R1 = 0.0414 wR2 = 0.0987 R1 = 0.0628 wR2 = 0.1102 1.080

8107/554 1–0.937 R1 = 0.0460 wR2 = 0.0856 R1 = 0.0926 wR2 = 0.1025 1.035




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B. Kaya et al. / Polyhedron 173 (2019) 114130

3.3. Electrochemical studies

Fig. 2. Thermal ellipsoids of complex 1a drawn at 50% probability. The clarity was provided by omitting all hydrogen atoms.

Fig. 3. Thermal ellipsoids of complex 1b drawn at 50% probability. The clarity was provided by omitting all hydrogen atoms.

Fe–O2), are in agreement with homologous iron(III) complexes [41–44]. 1a crystallized in the triclinic crystal system with the


P 1 space group. The crystal structure does not exhibit any intramolecular or intermolecular interactions. The molecules are packed in columns running along the b axis (Fig. S1). In the molecule of 1b, the square pyramidal environment of the manganese(III) ion consists of O, N, N, O and Cl atoms, and the pyramid is distorted (s = 0.06) to approximately the same extent as complex 1a. The manganese(III) ion bears a weakly bonded chlorine atom (the Mn-Cl bond length is 2.38 Å) and the manganese atom is 0.320 Å above the square plane. 1b crystallized in the monoclinic crystal system with the P 1 21/c 1 space group. Each unit cell contains two 1b molecules and one dichloromethane molecule, which does not come into contact with the 1b molecules. An interesting metal–p interaction is present between the C23–C28 phenyl ring for the Mn2 atom and the C16–C21 phenyl ring for the Mn1 atom, with metal-centroid distances of 3.77 and 3.84 Å and slippages of 0.71 and 1.40 Å, respectively. This interaction can be seen in Fig. S2.

The voltammetric responses of 1a and 1b were examined in DCM/TBAP and DMSO/TBAP electrolyte systems to illustrate their redox activities. Basic electrochemical parameters obtained from the voltammograms are listed in Table 2. The electron transfer characters of iron and manganese complexes differ depending on the ligand type and its substituents [7,8,12,45], and also on the coordination environment of the metal center [11,46]. The Fe(III) and Mn(III) centers of FeIII(salen)X and MnIII(salen)X type complexes give metal-based electron transfer reactions at small potentials. The salen ligands attached to the metal slightly alter the positions of these redox couples and the reversibility of the process [47–49]. For instance, a [MnIII(salen) (dca)]/[MnII(salen)(dca)]1
couple at around
0.27 V vs Ag/AgCl has been reported in a manganese(III) complex [47]. Similarly, the reversible reduction of Fe(III) into Fe(II) at
0.4 V vs Ag/AgCl has been described for an iron(III)-salen complex [48]. However, it is known that metal-based electron transfers occur at higher potentials. The reduction of a salen ligand in a copper(II) complex has been measured as
1.78 V vs Ag/AgCl [50]. As can be seen in many articles, salen complexes of the type of FeIII(salen)X and MnIII(salen)X exhibit similar metal-based electron transfer processes in addition to the ligand-based ones. Metal complexes of S-alkyl thiosemicarbazones are able to display metal- and ligand-based redox processes, like those complexes including salen ligands. Some copper(II) and cobalt(III) complexes having a S-methyl derivative showed reversible and quasi-reversible behaviors, depending on the ligand substituents [27,51]. Oxovanadium(IV) and dioxouranium(VI) complexes with this kind of N2O2 donor ligands gave irreversible reduction and oxidation processes at high potentials [52,53]. As shown in Figs. S3 and S4 (Supplementary data), complex 1a displays two metal-based and two ligand-based redox processes. The metal-based processes of complex 1a split into four couples. The observation of these couples may be due to the presence of 1a species where different ions are coordinated. Complex 1a is probably coordinated with the ClO
4 anion from the supporting electrolyte by removing the chloride anion from the [Fe(L)Cl] structure, and forms an equilibrium between the species bearing Cl
and ClO
4 anions. The different species of 1a illustrate redox processes at different potentials, and these redox processes might III be assigned to [Cl
-FeIIIL]/[Cl
-FeIIL]1
at 0.57 V, [ClO
4 -Fe L]/ II 1

II 1

I 2
[ClO
-Fe L] at 0.26 V, [Cl -Fe L] /[Cl -Fe L] at
0.08 V and 4 II 1
[ClO
/[FeIL]2
at
0.34 V, in addition to the ligand based 4 -Fe L] process at
1.32 V (Fig. S4). Repeated CV measurements indicate that a chemical reaction succeeding the ligand-based processes of complex 1a causes the decomposition of the reduced species at more negative potentials. The products formed by the decomposition reaction of the complex give a sharp and irreversible peak at
0.52 V (Fig. S4), when the vertex potential passes the ligand-based process (
1.60 V). Although metal-based electron transfer reactions of 1a are found as one-electron transfer processes, according to controlled potential coulometry measurements, their peak currents are different from each other due to the coordination equilibrium and chemical reactions succeeding the redox processes. In order to support these assignments regarding the coordination of the complex, CV measurements were performed in DCM and DMSO with different vertex potentials (Figs. S5 and S6). The vertex potentials of the CV measurements considerably influence the peak currents ratios of the redox processes of 1a and it is clearly shown that reduction of the complex alters the oxidation behaviors (Fig. S5). While the III II 1

peak currents of the couples for the [ClO
4 -Fe L]/[ClO4 -Fe L] and [Cl
-FeIIL]1
/[Cl
-FeIL]2
processes are small with respect to the reduction ones, when the potential is scanned towards positive

5

B. Kaya et al. / Polyhedron 173 (2019) 114130 Table 2 Voltammetric data of the complexes. Complexes 1a (in DCM)

1b (in DCM)

1b (in DMSO)

a b c d

Ligand oxd. a

E1/2 vs. SCE (V) Ip,a/Ip,cb DEp (mV)c E1/2 vs. SCE (V)a Ip,a/Ip,cb DEp (mV)c E1/2 vs. SCE (V)a Ip,a/Ip,cb DEp (mV)c

0.80 – – 1.43 0.55 154 1.45 0.55 200

Metal oxd.

Metal red. d

0.26 (0.57) 0.93 (0.24)d 93 (84)d 0.63 0.76 124 – – –


0.08 (
0.34) 1.00 (0.98)d 68 (77)d 0.14 0.95 110 0.11 1.03 60

Ligand red.’s d


1.32 0.34 84
1.57 0.48 94
1.36 0.63 63

– – – – – –
1.71 – –

E1/2 values are given for the processes having a reverse wave. Epc or Epa values are given for the completely irreversible processes. Ip,a/Ip,c values are given for cathodic couples and Ip,c/Ip,a values are given for anodic couples. DEp = | Epc
Epa |. Redox parameters of the coordinated species of 1a are given in parenthesis.

potentials, the peak currents of these couples increase after the reduction of the complex. This extraordinary behavior may be due to a change in the equilibrium between the species bearing Cl
and ClO4
anions as a result of reduction of complex 1a. As shown in Fig. S6, 1a also shows coordination behavior in the DMSO/TBAP electrolyte, however the peak current ratios are different than those observed in DCM/TBAP. The manganese complex (1b) gives well resolved [MnIIIL]/ [MnIIL]1
and [MnIIIL]/[MnIVL]1+ couples in DCM/TBAP, different from the iron complex (1a) (Fig. 4). The metal center of complex 1b undergoes metal-based electron transfer reactions at 0.14 V for [MnIIIL]/[MnIIL]1
and at 0.63 V for [MnIIIL]/[MnIVL]1+, in addition to irreversible ligand-based processes at
1.57 V (Figs. 4 and 5). The process observed at
1.57 V in DCM/TBAP splits into two peaks in DMSO/TBAP (at
1.36 and
1.71 V), while the metalbased processes shift to more negative potentials. In DMSO/TBAP

Fig. 5. CV and SWV responses of 1b at various scan rates on a Pt electrode in DMSO/ TBAP.

Fig. 4. CV and SWV responses of 1b at various scan rates on a Pt electrode in DCM/ TBAP.

medium, the metal-based oxidation process of complex 1b is not observed. While complex 1a only gives metal-based reduction processes from FeIII to FeII and then FeI oxidation states, complex 1b illustrated oxidation from MnIII to MnIV and also reduction from MnIII to MnII oxidation states. In situ spectroelectrochemical measurements were performed to support the peak assignments and to show the spectra of the electrogenerated species formed during the redox reactions. The iron and manganese complexes represent similar spectral changes during the redox reactions. Fig. S7 (Supplementary data) shows the spectroelectrochemical changes of complex 1a. The neutral form of the complex gives absorption bands for p ? p* transitions at 300 and 435 nm, having shoulders at 400, 470 and 500 nm [52–56]. Under
0.5 V applied potential, these bands decrease in intensity and a new band is observed at 541 nm, which indicate the metal-based nature of

6

B. Kaya et al. / Polyhedron 173 (2019) 114130

the reduction process (Fig. S7a). Although there are two redox peaks between 0 and
0.50 V in the CV of 1a, the spectral changes indicate formation of only one type of reduced species. These behaviors indicate that both of the peaks at
0.08 and
0.34 V are due to metal based reduction processes, and are assigned to II 1
[FeIIL]1
/[FeIL]2
and [ClO
/[FeIL]2
processes. The spec4 -Fe L] tral changes observed at
1.50 and 0.70 V show the decomposition of the dianionic, and monocationic species under the applied constant potentials (Figs. S7b and S7c). A distinct color change could not be observed during the redox reactions, as shown in the chromaticity diagram (Fig. S7d). Fig. 6 displays the spectroelectrochemical changes of complex 1b. Under an open circuit potential, complex 1b gives two intermolecular absorption bands at 350 and 434 nm, with small shoulders at 403, 470 and 497 nm. While the bands at 350, 403 and 434 nm are assigned to intra-ligand transition bands, the bands at 470 and 497 nm are assigned to MLCT. This spectrum is significantly changed when the neutral complex is reduced to its monoanionic and dianionic forms. As shown in Fig. 6a, while all the bands decrease in intensity, a new band increases at 613 nm under
0.50 V applied potential. These spectral changes are in harmony with a metal-based reduction reaction and support the [MnIIIL]/[MnIIL]1
reaction mechanism for the first reduction cou-

ple. During the second reduction reaction, all the bands decrease in intensity, which shows decomposition of the dianionic species under a more negative applied potential (Fig. 6b). These spectral changes, given in Fig. 6c, show the decomposition of the cationic species at 1.20 V applied potential. Fig. 6d shows that a slight color change from orange to yellow is observed during the reduction and oxidation processes. 3.4. Antioxidant capacity and free radical scavenging activity Trolox equivalent antioxidant capacity coefficients (TEAC) and free radical scavenging activities (FRS %) for 1, 1a and 1b are given in Table 3. The TEAC values of the metal complexes (1a and 1b) are lower than the starting material (compound 1) because of the absence of an hydroxyl group after coordination to the iron(III) or manganese(III) ions. However, the TEAC coefficients of all examples were found surprisingly to be higher than the value of 0.96 for ascorbic acid (see Table 3), and so these compounds can be considered as effective antioxidants. Hydroxyl groups increase the antioxidant property of a molecule because of electron donority. The electron-rich nitrogen atoms on the thiosemicarbazone backbone may have contributed through a similar mechanism to the total antioxidant capacity [57,58], and so the thiosemicarbazone

Fig. 6. In-situ UV–Vis spectral changes of 1b observed during the redox reactions in the DCM/TBAP electrolyte system, (a) Eapp =
0.50 V, (b) Eapp =
1.30 V, (c) Eapp = 1.30 V, and (d) Chromaticity diagram (each symbol represents the color of the electro-generated species; h:[MnIIIL]; 4: [MnIIL]1
; : [MnIVL]1+.

B. Kaya et al. / Polyhedron 173 (2019) 114130 Table 3 The TEAC coefficients and free radical scavenging activities. Compounds

TEAC

% FRS

1 1a 1b Ascorbic acid

2.78 1.63 1.28 0.96

49,62 ± 1,04 14,2 ± 3,31 11,52 ± 0,85 70,80 ± 0,38

structure is able to compete with the four hydroxyl groups of the ascorbic acid molecule. The thiosemicarbazone (1) was found to have moderate radical scavenging activity, but the complexes (1a and 1b) showed lower activities as compared to ascorbic acid. In previous studies, the antioxidant activity has been reported to be associated with the redox potential [59] and the number of phenolic-OH groups [60]. Also, steric hindrance is an important factor limiting the reaction between the test molecule and the DPPH radical [61]. For these reasons, the radical scavenging activities of the complexes are relatively low due to the three-dimensional large molecular structure and the absence of OH groups. In DPPH scavenging activity tests, 2,4-dihydroxybenzaldehyde-4-phenyl-3-thiosemicarbazone (a large molecule) and its palladium(II), copper(II) and nickel(II) complexes were not superior to ascorbic acid [62].

7

usable cytotoxicity [28,29,66] like their analogues obtained from salicylaldehydes [20,42]. It is understood that these metal complexes are promising ingredients for research related to oxidative stress-induced diseases and probably cancers. Acknowledgments This work was supported by the Scientific Research Projects Coordination Unit of Istanbul University-Cerrahpasa (Project number 22167). We thank TUBA, Turkey (The Turkish Academy of Sciences) for the financial support.

Appendix A. Supplementary data CCDC 1859072 and 1499370 contains the supplementary crystallographic data for1a and 1b. These data can be obtained free of charge via http://www.ccdc.cam.ac.uk/conts/retrieving.html, or from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: (+44) 1223-336-033; or e-mail: [email protected]. Supplementary data to this article can be found online at https://doi.org/10.1016/j.poly.2019.114130. References

4. Conclusion New square pyramidal metal complexes, which obtained by starting from a thiosemicarbazide compound, have been defined by using spectroscopic and crystallographic methods. In the first comparative study for the iron (1a) and manganese (1b) complexes, having the same N2O2-chelating thiosemicarbazone ligand, it was observed that the different electrochemical characteristics arise from the electronic configurations of the metal ions. The oxidation and reduction E1/2 values of the ligand system were altered depending on the metal center. In particular, the ligand-based oxidation process was more affected; while the oxidation potential of the iron complex was 0.8 V, it was measured as 1.43 V (in DCM) and 1.45 V (in DMSO) for the manganese complex. The metal effect is also evident in spectroelectrochemical experiments, giving reduced species under
0.5 V. The MLCT bands of the iron and manganese complexes were at the same wavelengths (470 and 500 nm for 1a; 470 and 497 nm for 1b), but the absorption bands of the reduced species were observed at quite different wavelengths, 541 nm for 1a and 631 nm for 1b. The possibility to adjust the electrochemical behavior of this type of thiosemicarbazide-based complex with metal cations suggests that these complexes could be developed for a variety of electrochemical technologies, such as electrochemical sensors and electrocatalysts. Compounds 1, 1a and 1b are able to compete with ascorbic acid, a popular antioxidant agent. The iron complex performed better than the manganese centric one in terms of both TEAC and FRS% values. Considering that the difference in antioxidant properties of 1a and 1b, having the same ligand system, is determined by the metal center, the redox potentials in Table 2 support the performance of 1a. Because a more powerful reducing agent will have a less positive oxidation potential, this performance of the iron complex may be explained by the fact that it is a better reducing agent. The concordance of the E1/2 and TEAC values also shows that the antioxidant capacity of thiosemicarbazone based chemicals can be determined by electrochemical methods, as in many compound classes [63–65]. Similar complexes of iron, manganese, nickel and palladium, synthesized using acetylacetone-S-alkyl-thiosemicarbazones, have

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