Synthesis of Coordination Complexes with [O, O] and [S, S] Donor ligands: Physicochemical Characterization, Theoretical studies and Biological Activities

Abstract

In the present study, various series of organotin(IV) [R4-nSnLn where R = CH3, C4H9, C6H5 and n = 1 or 2] and transition metal [ ML2 where M = Zn2+, Cd2+, Hg2+] carboxylates and thiocarboxylates have been synthesized by the reaction of tri- and diorganotin(IV) chlorides/transition metal chlorides with ligands in anhydrous toluene / methanol. The carboxylates used were 4-oxo-4-(thiazol-2-ylamino)but-2-enoic acid (HL1), 4-oxo-4-(thiazol-2-ylamino) butanoic acid (HL2), 4-oxo-4-(3-(trifluoromethyl) phenylamino)butanoic acid (HL3) and 4-oxo-4-(3-(trifluoromethyl)phenylamino)but-2-enoic acid (HL4) whereas thiocarboxylates used were potassium salts of oxo-methyl, oxo-ethyl, oxo-propyl, oxo-isopropyl, oxo-butyl and oxo-isobutyl carbonodithioate (HL5-HL10. The coordination behavior of the donor groups and structural assignments assignment were made by using different analytical techniques such as elemental analysis, FT-IR, multinuclear (1H and 13C) NMR, TGA, X-ray single crystal analysis, semiempirical and DFT. Based on these results, it is observed that the ligands (carboxylates and thiocarboxylates) coordinate to metals (Zn, Cd, Hg and Sn) through [O, O] or [S, S] donor sites. Triorganotin(IV) demonstrate mostly trigonal bipyramidal geometry in the solid and sometimes in solution whereas diorganotin derivatives are hexacoordinated in the solid (skew-trapezoidal geometry) and have an equilibrium between hexa- and penta-coordination in non-coordinating solvent. The interaction of the synthesized complexes with DNA was investigated by UV-visible spectroscopy. A hypochromic effect along with obvious hypsochromic (blue shift) and in some cases bathochromic (red shift) was observed. These are the signs of intercalative mode of interaction. The negative values of ΔG assign the spontaneity of complex-DNA adduct formation. The binding constants K were also calculated from from the intercept-to-slope ratios of A0/(A-A0) vs. 1/[DNA] plots by using the Benesi-Hildebrand equation. The synthesized complexes were screened for their antibacterial and antifungal activities against various strains of bacteria and fungi. The triorganotin(IV) derivatives have more bactericidal and fungicidal activity than diorganotin(IV) complexes. Most of the compounds were found to have biologically active comparable to the reference drugs and some were found even more active. These observations suggest that these compounds may be used as bactericides and iii fungicides in future. The cytotoxic activities of these complexes present a new line of antitumor agents and could also serve as a potential source of chemoprotective agent(s) which is the major challenge for the chemists/pharmacists at the present time. The compounds were screened for the antileishmanial activity and observed that they have high activity even more than the standard drug, amphotericin B. Some representative compounds were also found to be effective antioxidant of the 2,2-diphenyl-1-picrylhydrazyl radical (DPPH). All series were screened for protein kinease inhibition activity and some of these compounds showed excellent activity of kinease inhibition. Semiempirical and DFT studies demonstrate that a large HOMO-LUMO gap indicates a stable molecule with low chemical reactivity, while a small EHOMO is associated with an unstable molecule with high chemical reactivity. The bond angles and bond lengths calculated from theoretical studies were comparable with bond angles and bond lengths observed in the crystal structure. The compounds were subjected to thermal decomposition by thermogravimetry analysis (TGA). Decomposition kinetics i.e., order of reaction, activation energy, enthalpy and entropy were calculated for each step of decomposition. The synthesized complexes have positive values of activation energy and enthalpy.