Two versatile salicylatocopper(II) complexes: Structure, spectral, magnetic, electrochemical properties and SOD mimetic activity

Accepted Manuscript Two versatile salicylatocopper(II) complexes: Structure, spectral, magnetic, electrochemical properties and SOD mimetic activity Miroslava Puchoňová, Simona Matejová, Vladimír Jorík, Ivan Šalitroš, Ľubomír Švorc, Milan Mazúr, Ján Moncoľ, Dušan Valigura PII: DOI: Reference:

S0277-5387(18)30274-2 https://doi.org/10.1016/j.poly.2018.05.036 POLY 13183

To appear in:

Polyhedron

Received Date: Accepted Date:

5 February 2018 17 May 2018

Please cite this article as: M. Puchoňová, S. Matejová, V. Jorík, I. Šalitroš, L. Švorc, M. Mazúr, J. Moncoľ, D. Valigura, Two versatile salicylatocopper(II) complexes: Structure, spectral, magnetic, electrochemical properties and SOD mimetic activity, Polyhedron (2018), doi: https://doi.org/10.1016/j.poly.2018.05.036

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Two versatile salicylatocopper(II) complexes: Structure, spectral, magnetic, electrochemical properties and SOD mimetic activity Miroslava Puchoňová1*, Simona Matejová1, Vladimír Jorík1, Ivan Šalitroš1, Ľubomír Švorc2, Milan Mazúr3, Ján Moncoľ1, Dušan Valigura4 1

Department of Inorganic Chemistry, Slovak University of Technology in Bratislava,

Radlinského 9, 812 37 Bratislava, Slovakia 2

Institute of Analytical Chemistry, Slovak University of Technology in Bratislava,

Radlinského 9, 812 37 Bratislava, Slovakia 3

Department of Physical Chemistry, Slovak University of Technology in Bratislava,

Radlinského 9, 812 37 Bratislava, Slovakia 4

Department of Chemistry, University of SS Cyril and Methodius in Trnava, J. Herdu 2,

917 01 Trnava, Slovakia *

Corresponding author: [email protected]

Abstract Two new salicylatocopper(II) complexes of formula [Cu(3-Mesal)2(inia)2]2 1 and [Cu(4-MeOsal)2(H2O)]·H2O 2, (where 3-Mesal = 3-methylsalicylate, inia = isonicotinamide, 4-MeOsal = 4-methoxylsalicylate) has been studied in solid state or in solutions. The coordination environment of compound 1 differs from complex 2, but both compounds build up 2-D supramolecular framework. The spectral and magnetic properties are in good agreement to their structure. Moreover, the cyclic voltammetric study, as well as the superoxide dismutase activity of prepared complexes has been studied in solution by NBT assay, and compared with the activity of the parent ligand, copper acetate and native SOD enzyme. SOD mimetic activity of the prepared compounds exhibited rather different IC50 values for compound 1 and 2. The SOD activity together with the redox stability is related to the composition and structure of the complexes.

Keywords:

copper(II)

complexes,

electrochemical behaviour, SOD activity.

salicylate,

spectral

and

magnetic

properties,

1. Introduction Metal complexes in presence of different ligands are frequently studied from different points of view e.g. supramolecular engineering [1,2,3], spectroscopic [4,5,6], electrochemical [6,7], magnetic [8,9,10] and biological behaviour [11-14]. The research of bioactive compounds is often focused on transition metal compounds such as platinum complexes [15], cobalt(II) complexes [16], manganese(II/III)[6,17], nickel(II) [18] and copper(II) complexes [19,20]. The interest in the last group of complexes is caused their long time known, rather significant and variable bioactivity [21,22,23]. In the last three decades, SOD mimetic activity has been frequently studied for many different types of compounds including copper(II) complexes [24,25,26]. For instance, copper complexes of the nicotinic acid have been found as substances exhibiting potent superoxide scavenging capacities and antioxidant properties [27]. It is well known that derivatives of nicotinamide (nia) and isonicotinamide (inia) have been studied in coordination chemistry [28-36] or biochemistry [37,38]. Our research has been focused on study of copper(II) compounds with nicotinamide derivatives in presence of salicylic acid derivatives, which have been used for many years as anti-inflammatory, antipyretic and analgesic drugs [39,40,41] or auxiliary ligands in some drugs [42,43]. Presented work is focused on the study of two salicylatocopper(II) complexes [Cu(3-Mesal)2(inia)2] 1, [Cu(4-MeOsal)2(H2O)]·H2O 2 (where 3-Mesal = 3-methylsalicylate, 4-MeOsal = 4-methoxysalicylate anionic ligand, inia = isonicotinamide) in solid state and in solution, their preparation, structural, spectral and magnetic properties together with electrochemical and SOD mimetic activity. 2. Experimental 2.1. Material and methods Analytical grade (Sigma, USA or Aldrich, USA) chemicals were used without further purification. Carbon, hydrogen and nitrogen analyses were carried out on a CHNSO FlashEATM 1112 Automatic Elemental Analyzer (Thermo Electron Flash, Italy). The infrared spectra (4000–200 cm–1) of the complexes were measured with a NICOLET 5700 FT-IR (Thermo Electron, USA) spectrophotometer at room temperature using ATR technique.

2

The electronic spectra (190–1100 nm) of compounds were measured in Nujol suspension and in DMSO solution with a SPECORD 250 Plus (Carl Zeiss Jena, Germany) spectrophotometer at room temperature in solid state and in solution. The EPR spectra of polycrystalline copper complexes 1 and 2 were recorded on EMX EPR spectrometer (Bruker, Germany) operating at X-band frequency (≈ 9.4 GHz) at room and low (98 K) temperature. The spin Hamiltonian parameter values, which were obtained from the experimental EPR spectra using WinEPR [44], were further refined by computer simulation using SimFonia [45]. All herein reported magnetic measurements were performed on a MPMS-XL7 SQUID magnetometer (Quantum Design). The temperature dependent magnetization was recorded at BDC = 1 T as an external magnetic field. The temperature sweeping rate was 1 K min -1 and it was the same for cooling and for heating modes. Every temperature data point was stabilized for 2 minutes before the measurement. Gelatine capsule was used as sample holders in the temperature range 1.8 ↔ 300 K. The very small diamagnetic contribution of the gelatine capsule had a negligible contribution to the overall magnetization which was dominated by the sample. The diamagnetic corrections of the molar magnetic susceptibilities were applied using Pascal’s constants [46]. The electrochemical experiments were undertaken using AUTOLAB PGSTAT 302N potentiostat (MetrohmAutolab B.V., The Netherlands). The redox potentials of the studied complexes were assessed by cyclic voltammetric technique using conventional three-electrode system consisting of Ag/AgCl/3 M KCl as reference electrode, a platinum wire as auxiliary electrode and boron-doped diamond electrode (BDD, Windsor Scientific Ltd., active surface area of 0.07 cm2, boron concentration of 1000 ppm) as working electrode, respectively. Cyclic voltammetry was executed in a potential window ranging from –1 to +1 V with a fixed scan rate value of 100 mV·s–1 by undergoing three scans. In regard to preparation of solutions, the studied complexes were firstly dissolved in 10 ml DMSO. Subsequently, they were diluted to the concentration of 1.10–3 M (stock complex solution) in 0.1 M NaCl which was considered to be supporting electrolyte. The working solutions (4.10 –4 M) were prepared by appropriate dilution of stock solution of the particular complex with 0.1 M NaCl. The measurement cell always contained 20 ml of the analysed solution of complex. Prior to launching the measurement, the respective studied solution was degassed by bubbling in N 2 atmosphere for 8 min to render an inert environment inside the cell. SOD activity of the studied complexes 1 and 2 were measured according to the literature [47,48] as the ability to inhibit the reduction of NBT by superoxide ions generated 3

by xanthin – xanthine oxidase system (X–XO). The NBT reduction was followed by measuring the absorbance at 560 nm on a SPECORD 250 Plus spectrophotometer. The reaction system contained 0.2 mM xanthine, 0.6 mM NBT in 0.1 M phosphate buffer, pH 7.8. The tested compounds were dissolved in DMSO. The measured concentrations of the compounds were 0.5, 2, 3, 4, 5, 7.5, 10 and 15 μM. Xanthine oxidase (0.07 U∙ml–1) was added to start the reaction. The reaction was started by the X–XO system of a concentration needed to yield the absorbance change ∆A/min, between 0.15 and 0.025. Each experiment was performed twice at the initial study, and now redone again twice. The SOD activity was quantified via the IC50 value, i.e. as the concentration of the tested compound needed for 50% inhibition of the NBT reduction by superoxide produced in the X– XO system. The value of inhibition concentration IC50 was calculated from linearized dependence of percentage inhibition upon the logarithm of molar concentration of the inhibitor. Both obtained results, initial and later repeated, gave nearly the same results and they are shown as average of four measurements. 2.2. Crystallography Intensity data for single-crystal structural analysis of 1 were collected by Oxford Diffraction Xcalibur S diffractometer at 293 K, and the multi-scan absorption correction was applied by SCALE3 ABSPACK algorithm in CRYSALIS-RED software package [49]. The structure was solved by charge-flipping method using the program SUPERFLIP [50], and refined by full-matrix least squares method on all F2 data using the program SHELXL [51] (ver. 2016/6). Geometric analyses were performed using SHELXL. The powder data of 2 were collected using a Rigaku Smart Lab transmission diffractometer, equipped with a rotating Cu anode generator and a silicon strip detector D/teX Ultra 250. The powder pattern of 2 was analysed using the multi-purpose program CMPR [52] and auto-indexing program DICVOL06 [53]. Le Bail pattern decomposition and Retvield refinement were performed in program JANA2006 [54]. The ab-initio structure solution was calculated using FOX [55]. The structures in both cases were drawn using OLEX2 software [56]. Crystal data and conditions of data collection and refinement are reported in Table 1.

4

Table 1 Crystallographic data for 1 and 2. 1 C56H52Cu2N8O16

Chemical formula Mr Cell setting, space group T (K) a (Å) b (Å) c (Å) α (°) β (°) γ (°) V (Å3) Z Radiation type Crystal size (mm) S R1, wR2 Data (points) / restrains −3 parameters Δρ max, Δρmin (e Å ) CCDC nos.

1220.13 Triclinic, P 1 293(1) 10.1043(5) 11.5598(2) 14.0550(7) 66.437(10) 74.693(4) 64.089(3) 1345.56(14) 1 Mo Kα 0.50 x 0.40 x 0.10 1.144 0.0437, 0.0937 / 5693/0/374 0.41, −0.41 1536492

2 C16H18CuO10 433.9 Triclinic, P 1 293(1) 7.29815(5) 8.46014(9) 15.13994(16) 96.5021(10) 94.7639(12) 112.3648(7) 850.784(15) 2 CuKα1 powder 4.52 0.0422, 0.0568 9701/56/115 0.53 −0.47 1536493

2.3. Synthesis Complex 1 Isonicotinamide (2 mmol) was added to aqueous solution of copper acetate (10 ml, 0.1 M). The 3-methylsalicylic acid (2 mmol) was washed down to the reaction mixture with small amount of solvent (water). The blue product precipitated within few minutes was filtered off and characterized by available methods (elemental analysis, infrared spectra) and powder X-ray diffraction. The mother liquid was left to crystallize at ambient temperature. Green crystals suitable for X-ray analysis were separated and dried at ambient temperature. [Cu(3-Mesal)2(inia)2]2Yield: 39% Anal Calc: C, 55.13; H, 4.30; N, 9.18. Found: C, 54.44; H, 4.17; N, 9.32. IR (ATR, cm–1): 3400(s), 3190 (w), 1698(w), 1602(m), 1560(ms), 1421(ms),1387(s),1298(s), 1194(m), 1056(ms), 763(s), 631(ms). UV-Vis (solid phase, λ/ nm): 620. UV-Vis (solution of dimethylsulphoxide, λ/ nm): 303 (ε = 10307 dm3mol–1cm–1), 422 (ε = 45.7 dm3 mol–1cm–-1), 783 (ε = 51.52 dm3 mol–1cm–1).

5

Complex 2 Copper acetate (1 mmol) was dissolved in water and after few minutes nitrogen donor ligand isonicotinamide was added (1 mmol) to reaction mixture and subsequently 4-methoxysalicylic acid (2 mmol) was washed down with water (about 50 ml). The mixture was intensively stirred. The blue-green precipitate was formed and filtered. The sample was characterized by powder X-ray diffraction. The solution was left to crystallize at laboratory temperature until the mixture crystals were obtained. Unfortunately, the particular crystals were not available for monocrystal X-ray analysis. [Cu(4-MeOsal)2(H2O)]·H2O: Yield: 87% Anal Calc: C, 44.30; H, 4.18; N, --. Found: C, 45.90; H, 4.40; N, --. IR (ATR, cm–1): 3461(w), 2932 (w), 1630 (m), 2527(w),1602(s), 1542(m), 1434(ms), 1358(ms), 1213(s), 1102(s), 985(ms), 823(s), 757(ms), 598(m). UV-Vis (solid phase, λ/ nm):400, 625. UV-Vis (solution of dimethylsulphoxide, λ/ nm): 296 (ε = 13439 dm3mol–1cm–1), 399 (ε = 45.41 dm3 mol–1cm–1), 780 (ε = 44.49 dm3 mol–1cm–1). 3. Results and discussion Two new compounds, the one with or the other one without nitrogen donor ligand, were obtained by similar synthesis. The different stoichiometric ratios of the reactants Cu : Me(O)salH : inia = 1 : 2 : 2 or 1 :2 : 1 and the various positional isomers of salicylic acid led to creation of four different products, but surprisingly only two of them were repeatedly characterized as substances and the other two products were the mixtures of at least two substances. Green crystals of dimeric complex [Cu(3-Mesal)2(inia)2]2 1 were prepared with 3methylsalicylic acid (ratio Cu : 3-MesalH : inia = 1 : 2 : 2) in water as solvent. The initial formation of the microcrystalline compound at the beginning of reaction exhibited the same composition as crystals and it was confirmed by elemental analysis and by comparing powder diffraction

pattern

to

that

one

of

crystals.

The

other

compound

[Cu(4-MeOsal)2(H2O)]·H2O 2 was acquired using the 4-methoxysalicylate anion by changing molar ratio Cu : 4-MeOsalH : inia = 1 : 2 : 1. The product 2 without nitrogen donor ligand was obtained in microcrystalline form thus the PXRD could be used for structure determination. Both complexes showed interesting molecular structure which gave rise to building up supramolecular interactions.

6

3.1. Crystal structures The centrosymmetric molecular structure of the dimeric complex 1 is drawn in Fig. 1. Selected bond distances and angles are given in Table 2. The complex 1 crystallizes in triclinic space group P-1, and its crystal structure consists of dinuclear units in which two heptacoordinated copper(II) ions are coordinated in distorted pentagonal-bipyramidal (4+1+2) geometry. Two copper atoms are bridged by two carboxylate oxygen atoms (O1) of two bridging 3-methylsalicylate ligands allowing intramolecular copper–copper distance of 3.5807(7) Å. Basal plane of the pentagonal-bipyramid is formed by two carboxylate oxygen atoms of chelating coordinated carboxylate group of bridging 3-methylsalicylate ligand [Cu1-O1 = 2.034(2) Å, Cu1–O2 = 2.612(2) Å], two carboxylate oxygen atoms of terminal chelating bonded 3-methylsalicylate ligand [Cu1–O4 = 1.972(2) Å, Cu1–O5 = 2.681(2) Å], and one carboxylate oxygen atom of second bridging 3-methylsalicylate ligand [Cu1–O1i = 2.562(2) Å]. Axial positions of the pentagonal-bipyramid are occupied by two pyridine nitrogen atoms of monodentate coordinated isonicotinamide ligands [Cu1–N1 = 2.008(2) Å, Cu1–N3 = 2.018(2) Å] in trans positions.

Fig. 1. Molecular structure of complex 1.

7

Table 2. Selected bond lengths (Å) for compounds 1 and 2 1 Cu1–O1

2.034(2)

Cu1–O2

2.612(2)

Cu1–O4

1.972(2)

Cu1–O5

2.681(2)

Cu1–N1

2.008(2)

Cu1–N3

2.018(2)

Cu1–O1i

2.562(2)

O4–Cu1–O1i

101.28(7)

O4–Cu1–O1

177.15(8)

O4–Cu1–O2

125.88(7)

O4–Cu1–O5

53.70(7)

O4–Cu1–N1

88.87(8)

O4–Cu1–N3

88.06(8) i

N1–Cu1–O1

93.95(8)

N1–Cu1–O1

92.51(7)

N1–Cu1–O2

90.26(8)

N1–Cu1–O5

89.50(8)

N1–Cu1–N3

176.69(9)

N3–Cu1–O1

89.10(8)

N3–Cu1–O1i

86.85(7)

N3–Cu1–O2

92.56(8)

N3–Cu1–O5

89.70(8)

Cu1–O1–Cu1i

101.73(7)

Cu–O11

1.889(8)

Cu–O21

1.931(8)

Cu–O13

1.899(4)

Cu–O23

1.878(4)

Cu–Ow1

2.524(4)

O11–Cu–O13

85.5(3)

O11–Cu–O21

176.8(4)

O11–Cu–O23

94.9(3)

O13–Cu–O21

92.1(3)

O13–Cu–O23

174.3(2)

O21–Cu–O23

87.3(3)

O11–Cu–Ow1

90.1(3)

O13–Cu–Ow1

93.31(18)

O21–Cu–Ow1

92.2(3)

O23–Cu–O23

92.36(18)

2

Symmetry code: (i) 1–x, 1–y, 1–z. The dimeric molecules of 1 are connected through N–H∙∙∙O hydrogen bonds between carboxamide groups [N2–H2A∙∙∙O8 (–1+x, 1+y, –1+z) and N4–H4A∙∙∙O7 (1+x, 1+y, 1+z) with d(N∙∙∙O) = 2.939(3) and 2.832(3) Å, respectively] into railway-like supramolecular chains (Fig. 2). The supramolecular chains are joined through multicentered N–H∙∙∙O hydrogen bonds between carboxamide groups and carboxylate oxygen atoms [N4–H4B∙∙∙O2 (2–x, 1–y, 1–z) and N4–H4B∙∙∙O5 (2–x, 1–y, 1–z) with d(N∙∙∙O) = 3.084(3) and 2.950(3) Å, respectively] 8

and between carboxamide groups and hydroxyl oxygen atoms [N2–H2B∙∙∙O6 (–1+x, y, z) with d(N∙∙∙O) = 3.177(3) Å] into 2D supramolecular framework (Fig. 2).

Fig. 2. Scheme of supramolecular hydrogen-bonded 2-D pattern of 1. Hydrogen atoms and 3-methylsalicylate group are omitted for clarity. The molecular structure of the centrosymmetric monomeric complex 2 is shown in Fig. 3. Complex 2 crystallizes in triclinic space group P-1. The crystal structure of 2 consists of complex molecules [Cu(4-MeOsal)2(H2O)] and uncoordinated water molecules. The coordination

environment

around

copper

atoms

of

complex

molecule

[Cu(4-MeOsal)2(H2O)] possesses square-pyramidal shape (Fig. 3, Table 2). The square-planes are formed by two carboxylate oxygen atoms of two 4-methoxysalicylate ligands [Cu–O11 = 1.889(8) Å, Cu–O21 = 1.931(8) Å] and two oxygen atoms of hydroxyl groups of two 4methoxysalicylate ligands [Cu–O13 = 1.899(4) Å, Cu–O23 = 1.878(4) Å] in trans positions.

9

The axial position of tetragonal-pyramid is occupied by coordinated water molecule [Cu–Ow1 = 2.524(4) Å].

Fig. 3. Molecular structure of complex 2. The complex molecules [Cu(4-MeOsal)2(H2O)] and uncoordinated water molecules are linked through O–H∙∙∙O hydrogen bonds and form 2D supramolecular framework. The coordinated water molecules (Ow1) are linked to uncoordinated (Ow2) and uncoordinated carboxylate oxygen atoms (O12) [Ow1–H1ow1∙∙∙Ow2 and Ow1–H2ow1∙∙∙O12 (1–x, 1–y, 1–z) with d(O∙∙∙O) = 2.729(9) and 2.534(9) Å, respectively]. The solvent water molecules (Ow2) are bonded to uncoordinated carboxylate oxygen atoms (O22) and phenolic oxygen atoms (O13) [Ow2–H1ow2∙∙∙O22 (1–x, 2–y, 1–z) and Ow2–H2ow2∙∙∙O13 (x, y, 1+z) with d(O∙∙∙O) = 2.524(11) and 2.858(7) Å, respectively]. The phenolic oxygen atoms (O13 and O23) are connected to coordinated water molecules (Ow1) and solvent water molecules (Ow2), respectively, [O13–H1o13∙∙∙Ow1 (1–x, 2–y, 1–z) and O23–H1o23∙∙∙Ow2 (1–x, 1–y, 1– z) with d(O∙∙∙O) = 2.869(6) and 2.813(8) Å, respectively].

Fig. 4. Molecular structure of complex 2. Hydrogen atoms are omitted for clarity. 10

3.2. Spectral properties The IR spectra are in good agreement with structural data. The spectrum of compound 1 comprises the bands confirming the presence of all characteristic functional groups. Spectrum of 1 is characteristic of two strong absorption bands assignable to asymmetric band υas(N–H) at 3390 cm–1and symmetric NH stretches bands υs(N–H) of NH2 group at 3167 cm– 1

. There is an absorption at about 1670 cm–1 attributable to C=O vibration of the carboxamide

group of isonicotinamide ligand. Another evidence of presence of N-donor ligand in copper(II) environment we could find in FAR IR spectra at 264 cm–1 [57]. The bands corresponding to as(COO–) and s(COO–) are at about 1601 cm–1 and 1422 cm–1, respectively. The difference between antisymmetric and symmetric stretch ( = as –

s) is comparable to  for the ionic form. The carboxylate group is bonded in bidentate bonding mode. On the other hand, the spectrum of complex 2 is characteristic of broad envelope of probably two or three overlapping medium intensity bands with maxima in the region from 3250 to 3456 cm–1 assignable to antisymmetric and symmetric OH stretches of water molecule. Weak but recognizable bands between 3000 and 2850 cm–1 could be assigned to the H-bond system. The bands corresponding to as(COO–) and s(COO–) are present at about 1620 cm–1 and 1437 cm–1, respectively. The difference between antisymmetric and symmetric stretch ( = as – s) is greater than  for the ionic form and it is in good agreement with monodentate bonding mode of carboxylate groups. It is in good accordance with structure motif. Both products showed broad asymmetric absorption bands at about 630 nm (maximum at 620 nm for complex 1 and about 640 nm for complex 2) with unresolved shoulders further on the lower energy side. Some intraligand charge transfer bands in the range 250 – 300 nm and 300 – 350 nm are present, too. The electronic spectra in DMSO solution revealed that electronic absorption bands are redshifted to the longer wavelength upon dissolution in the solvent. Observed broad absorption bands at 783 nm for complex 1 and 780 nm for complex 2 correspond to d→d transitions. Their observed λmax values are in the range expected for mononuclear Cu(II) complexes with distorted square planar geometry. In addition, the spectra exhibit also a clearly visible shoulder at 422 nm (complex 1) and 399 nm (complex 2) ascribed to a ligand-to-metal charge transition [40].

11

3.3. EPR spectroscopy Figure 5. illustrates solid state EPR spectra of powder copper (II) complexes 1 and 2 recorded at room temperature. The first derivative EPR spectrum of sample 1 shows axially symmetric line shape with not-resolved hyperfine splitting. The EPR spectrum of sample 2 apparently exhibits a broad „pseudosinglet“, however, in the computer simulation, the best fit to the experimental EPR spectrum was obtained using the axial symmetric model.

1

2000

2

2500

3000

3500

4000 -4

B [10 T]

4500

2000

2500

3000

3500

4000

4500

-4

B [10 T]

Fig. 5. Experimental EPR spectra of powdered copper (II) complexes 1 (left) and 2 (right) measured at room temperature (black line) paired with corresponding computer simulations (red line).

Hence, the spin Hamiltonian parameter values evaluated from the experimental EPR spectra were further refined by computer simulation. Following axial g-factor values were attained: for complex 1 g = 2.077 ± 0.005, g|| = 2.317 ± 0.005 and for the complex 2 g = 2.090 ± 0.005, g|| = 2.245 ± 0.005. The identical line shape was obtained in the case of EPR spectra of given complex recorded at 98 K (data not shown) and likewise the g-factor values for corresponding complex were identical (within experimental errors). The above presented g-factor values of 1 (with geometric factor, G = 4.1) indicate slightly elongated tetragonalbipyramidal geometry of coordination sphere [58,59] while the g-factor values of 2 and rather broad line are consistent with presence of quasi tetragonal CuO 4 moieties. Figure S2 shows the first derivative experimental EPR spectra of copper (II) complexes 1 and 2, which were measured in the liquid solution of DMSO at room temperature. The DMSO solution EPR spectra indicate distorted square planar rather than octahedral coordination environment.

12

3.4. Magnetic investigation Temperature dependency of effective magnetic moment as well as field dependent molar magnetisation of reported compounds are displayed on Fig. 6. The effective magnetic moment μeff is rather temperature invariant in the range 20-300 K for both compounds which agrees with Curie law (Fig. 6 left). The room temperature values 2.48 μB for 1 and 1.80 μB for 2 are close to the expected spin only values for two S=1/2 (2.45 μB) and one S=1/2 (1.732 μB) spin systems, respectively. The low temperature decrease of the μeff indicates the presence of weak antiferromagnetic interaction between the neighbouring molecules, which is confirmed by negative values of calculated Curie-Weiss constants Θ= -1.814 K for 1 and Θ= -1.760 K for 2, respectively (see ESI, Fig.S3). Most probably, the antiferromagnetic exchange coupling is mediated through hydrogen bonding networks present in the supramolecular structure of both compounds (vide supra). Field dependent molar magnetisation was recorded at 2 K as well as at 4.6 K (Fig. 6 right). At 2 K and at 7 T, both compounds show saturation of magnetisation close to the 2 μB for 1 and 1 μB for 2 as is expected for dinuclear and for mononuclear copper(II) paramagnetic complex, respectively. On the other hand, the subtle increase of the temperature from 2 K up to 4.6 K caused vanishing of the saturation.

Fig. 6 Temperature dependence of effective magnetic moment (left) and field dependency of molar magnetisation (right) for compound 1 (blue colour) and compound 2 (red colour).

3.5. Electrochemical behaviour study In order to investigate the electrochemical behaviour of the studied complexes, cyclic voltammetric technique was exploited. Figure 7 depicts the respective CV records for complexes 1 and 2 (both 4.10–4 M) in 0.1 M NaCl at BDD electrode. It is evident that the distinct reduction waves with peak potentials (Ep,red) at 0.135 V and 0.031 V for 1 and 2, 13

respectively, were recorded in the cathodic scan reflecting the redox reaction of Cu(II) to Cu(I) within the complexes. By application of reverse scan, the corresponding voltammetric waves with peak potentials (Ep,ox) at 0.157 V and 0.089 V for 1 and 2, respectively, were registered. These peaks may be attributed to the reoxidation of Cu(I) to Cu(II), thus revealing the quasi-reversible electrode reactions of both complexes at the particular working electrode. Moreover, the recorded oxidation peaks are characterized by the presence of oval “humps” with maximums at 0.026 V and 0.434 V 1 as well as at 0.041 V and 0.479 V 2. These humps are likely to be related to the electrochemical activity of the particular ligands within both complexes. 2

Current / A

0

-2

-4

0.1 M NaCl 1 2

-6

-8 -1.0

-0.5

0.0

0.5

1.0

Potential / V Fig. 7. CV records of studied complexes 1-2 (4.10−4 M) in 0.1 M NaCl at BDD electrode using the scan rate of 100 mV s -1. Summary of the basic redox parameters of studied complexes is given in Table 3. ΔE value describing the degree of electrochemical reversibility of studied complexes revealed that the compound 1 containing nitrogen donor ligand yielded the higher reversibility as this value (0.022 V) was lower than that obtained for 2 (0.058 V). This lower reversibility may be affected by the absence of nitrogen donor ligand in the structure, which hampers the mass transport during the redox reaction of copper at BDD electrode. Furthermore, the complex 1 provides the higher E1/2 value, thus confirming the stronger electron-withdrawing properties. In regards to peak currents (Ip,ox and Ip,red), the considerably higher value was noticed for compound 1 in comparison with 2. Overall, the results of electrochemical behaviour study of the complexes confirmed the similarity with those previously published in literature 14

[11,60,61]. In addition, the CV record of the supporting electrolyte (0.1 M NaCl) indicated the fact that the background current was appeared to be low at BDD electrode within the potential range. This phenomenon corroborates the benefits of this working electrode material for application of electrochemical study of miscellaneous structurally and biologically interesting compounds. Table 3. Redox parameters of studied complexes 1–2 evaluated by cyclic voltammetry Ep,ox

Ep,red

ΔE

E1/2

Ip,ox

Ip,red

Complex

Ip,ox/ Ip,red V

µA

1

0.135

0.157

0.146

0.022

0.827

-0.821

0.994

2

0.031

0.089

0.059

0.058

0.132

-0.547

0.243

3.6. SOD mimetic activity SOD activity was studied for two selected copper(II) compounds and their activities were compared with native enzyme SOD. The SOD like activity was investigated indirectly using standard NBT assay. The obtained data are presented as percentage of the inhibition of NBT reduction against the concentration of complexes 1-2 (Figs. S1) or against the logarithm of the concentration (insets in Figs. S1). The IC50 values for 1-2 along with some previously studied systems are summarized in Table 4. Out of the studied systems, compound 1 exhibited the SOD mimetic activity (IC50 = 10.8μM), while higher IC50 value was found for 2 (46.9 μM). The poor mimetic activity of 2 can be explained by absence of inia ligand. Both complexes are weaker inhibitors of NBT reduction than the copper(II) acetate (5.70 μM). Previously

studied

copper(II)

salicylate

type

complexes

[Cu(μ-menia)(3-

Mesal)2(menia)(H2O)]2, [Cu(3-Mesal)2(denia)2(H2O)2] were better scavengers of superoxide anion radical than compounds 1 and 2 [61]. This fact could be linked with its electrochemical behaviour, where the low degree of reversibility was observed. The different coordination environment of 1 and 2 could be the reason of its lower flexibility, which is important for interactions with the superoxide anion radical. In contrast to previously published SOD mimetics in literature [62,63,64] they can act as relatively good SOD mimetics despite their several hundred times lower activity than native Cu, Zn–SOD. The observed data allow to conclude, that the mechanism of SOD mimetic activity in presented series of complexes is probably of similar nature like that presented in literature [48]. 15

Table 4. SOD like activity of studied complexes Complex

IC50/μM

References

1

10.7

this work

2

46.5

this work

[Cu(3-Mesal)2(menia)2(H2O)]2

2.24

[61]

[Cu(3-Mesal)2(denia)2(H2O)2]

3.88

[61]

Copper acetate

5,7

[61]

SOD

0,016

[61]

4. Conclusion In conclusion we can summarize that two new compounds have been synthesized. These complexes in solid state have been characterized by elemental analysis, infrared, UVVIS, EPR spectra and X-ray analysis. The spectral properties are in good agreement with molecular structure. The X-ray analysis has shown that copper(II) complexes with different coordination environment build up 2D supramolecular framework through the hydrogen-bond system. The magnetic investigation has revealed paramagnetic behaviour and weak antiferromagnetic exchange coupling at very low temperature for both compounds. Electrochemical study has shown that the occurring redox processes are of quasireversible character for 1 in contrast with full reversibility for 2. This fact can be related to the composition of coordination spheres of central atom. Similarly, SOD mimetic activities of the prepared compounds have exhibited rather different IC50 values. While complex 1 shows mimetic activity comparable with literature, much poorer results are observed for compound 2. The lower redox reversibility and lower SOD activity of 2 could be related to the absence of inia ligand.

Acknowledgements. This work was supported by the Slovak Research and Development Agency under the contact Nos. APVV-15-0053, APVV-14-0073 and APVV14-0078 and by the Scientific Grant Agency of the Slovak Republic (Project VEGA 1/0489/16, VEGA 1/0639/18, VEGA 1/0125/18). One of authors is thankful to the Grant Scheme for Support of Excellent Teams of Young Researchers (BIOKA) for the financial support 16

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20

Supplementary material Table S1 Hydrogen bonds for 1 and 2 D-H∙∙∙A d(D–H)/Å d(H–A)/Å 1 O3–H3∙∙∙O2 0.82 1.83 O6–H6∙∙∙O5 0.82 1.80 N2–H2A∙∙∙O8ii 0.86 2.08 iii N2–H2B∙∙∙O6 0.86 2.33 N4–H4A∙∙∙O7iv 0.86 1.97 v N4–H4B∙∙∙O2 0.86 2.46 N4–H4B∙∙∙O5v 0.86 2.22 2 O13–H1o13–Ow1vi 0.82 2.06 i O23–H1o23∙∙∙Ow2 0.82 2.03 Ow1–H1ow1∙∙∙Ow2 0.82 1.92 Ow1–H1ow2∙∙∙O12i 0.82 1.74 vi Ow2–H2ow1∙∙∙O22 0.82 1.81 Ow2–H2ow2∙∙∙O13vii 0.82 2.17 Symmetry codes: (i) 1–x, 1–y, 1–z; (ii) –1+x, 1+y, (v) 2–x, 1–y, 1–z; (vi) 1–x, 2–y, 1–z; (vii) x, y, 1+z.

60

30

50

25

30

50

20

40

D–H–A/°

2.549(3) 2.528(3) 2.939(3) 3.177(3) 2.832(3) 3.084(3) 2.950(3)

146 148 173 168 175 130 143

2.869(6) 167 2.813(8) 159 2.729(9) 170 2.534(9) 161 2.524(11) 145 2.858(7) 142 –1+z; (iii) –1+x, y, z; (iv) 1+x, –1+y, 1+z;

20 30

15

25

Inhibition/%

Inhibition/ %

60

Inhibition/ %

Inhibition/ %

40

d(D–A)/Å

10

30 20

15

10

5

10 0.2

0.4

0

0.6

0.8

1.0

10

1.2

0.4

log c

0

0

20

4 8 12 Concetration of complex 1/ M

a)

16

0

2

4

0.6

0.8 log c

6 8 10 12 Concetration of complex 2/ M

1.0

1.2

14

16

b)

Fig. S1 Dependence of the inhibition of NBT reduction by superoxide on the concentration of complexes 1 (a) and 2 (b) and on the logarithm of the concentrations (inset); – experimental values.

21

1

2

2000

2500

3000

3500

4000

4500

-4

B [10 T]

Fig. S2. Experimental EPR spectra of copper (II) complexes 1 and 2 measured in the liquid solution of DMSO at room temperature.

22

Fig. S3 Analysis of the magnetic functions with respect to the Curie-Weiss law

23

24

Synopsis Dimeric salicylatocopper(II) complex with isonicotinamide and monomeric one without Ndonor ligand were synthesized. Different coordination environment led to different 2-D supramolecular networks through the hydrogen bond, but both compounds exhibit weak antiferomagnetic exchange at low temperature. Better SOD mimetic activity was found for complexes containing isonicotinamide.

25