ORGANOTIN(IV) COMPLEXES WITH OXYGEN DONOR LIGANDS: SYNTHESIS, CHARACTERIZATION AND BIOLOGICAL ACTIVITY

Abstract

Eleven series of tri- and diorganotin(IV) carboxylates were synthesized by using stoichiometric amounts of various carboxylic acids with R2SnCl2, R2SnO, R3SnCl and R3SnOH in dry toluene. The carboxylic acids having different functional groups were used in order to study their effect on the biological assay and their role for the delivery of these compounds. Elemental analysis, FT-IR, multinuclear (1H, 13 C and 119 Sn) NMR, mass spectrometry and X-ray single crystal analysis were used for the structural assignment of the synthesized complexes, and for the determination the coordination mode of the ligands. Based on results, the ligands appear to coordinate to the Sn atom through the COO moiety. The results obtained from different analytical techniques ascertain the tetrahedral environment around the tin atom in solution while penta coordination is found in the solid state for triorganotin(IV) carboxylates. In diorganotin(IV) dicarboxylates, a skew trapezoidal geometry was observed both in solid and solution form. Single crystal analysis shows that bulky phenyl groups present in the complexes hinder the carbonyl oxygen of the neighboring ligand from interacting with the Sn atom for further coordination. The ORTEP diagrams for compounds 18, 26 and 33 show that the triphenyltin(IV) species coordinate to only one ligand and exist in monomeric form. Small sized groups do not show any hindrance to the carbonyl oxygen of the neighboring ligands. Therefore, in complexes 19, 28, 31, 46, 56 and 67 a polymeric behavior is observed. Diorganotin(IV) carboxylates mostly show a distorted octahedral geometry, with four strong and two weaker bonds in the solid state which is also called as skew trapezoidal geometry. The interaction of four But3SnL compounds (where L= 3-[(2′- flurophenylamido)]propanoic acid, 3-[(3′,5′-dimethylphenylamido)]propenoic acid, 3- [(3′,4′-dichlorophenylamido)]propanoic acid, 3-[(3′,5′-dimethylphenylamido)]propanoic acid) with cetyl N,N,N-trimethyl ammonium bromide (CTAB), a cationic surfactant, was studied as a model of organotin(IV) carboxylate-cell membrane interaction using conductometry, UV-Vis and steady state fluorescence spectroscopy. All the four complexes and CTAB showed interaction in the pre and post micellar region of CTAB. The higher partition constant value between the bulk water and the micelles of CTAB, Kx and the negative values of the standard free energy change of partition ΔG iii designate the spontaneity of the complex - CTAB binding. The partition constant and the free energy change of the partition values obtained from all three techniques showed the following increasing order of binding strength: 21> 17> 32> 9. The complex containing more electronegative atoms showed higher interaction which decreases the permeability. Selected complexes were tested for their antiviral studies. Compounds 1, 5 and 18 showed high potential against HCV and reduced the viral load up to 80%, at low concentrations. The tributyl compounds with more electronegative atoms showed lower HCV potential. All the synthesized complexes were screened for antibacterial and antifungal activities, against various medically important bacteria and fungi. In general, the triorganotin(IV) derivatives showed higher potential against bacteria and fungi than the diorganotin(IV) derivatives. The bioassay results of the synthesized complexes suggest that these compounds may be used for chemotherapy in the treatment for HCV, bacterial infection and fungal action in future. Selected organotin(IV) complexes were subjected to thermal decomposition by means of thermogravimetry analysis (TGA). Decomposition kinetics like order of reaction, activation energy, enthalpy and entropy were calculated for each step of decomposition.