Comparative study of structure–activity relationship of di- and tri-organotin(IV) derivatives of amino acid and peptides

Novel non-electrolytic di- and tri-organotin(IV) derivatives of the general formula R2Sn(L/HL′) and Ph3Sn(HL/H2L′), where R is n-Bu and Ph, and L/HL is dianion/monoanion of d-penicillamine (H2L-1) and l-carnosine (H2L-2), and HL′/H2L′ is dianion/monoanion of triglycine (H3L-3) have been synthesized in 1:1 molar ratio either at pH 7.0 or pH<2.0. All n-Bu2Sn(IV) derivatives have been synthesized by the reaction of Bu2SnO with amino acid/peptides under azeotropic removal of water. Ph2Sn(IV)/Ph3Sn(IV) derivatives have been synthesized by either sodium chloride method or alkoxide method. The dibutyltin(IV) complexes synthesized at pH<2.0 possess chlorine in the coordination sphere (as revealed from molar conductance measurement in methanol) and a molecule of water in the crystal lattice. The structures of the complexes are discussed on the basis of IR, far-IR, multinuclear (1H-, 13C- and 119Sn-) NMR and 119Sn-Mössbauer spectroscopic studies. All the diorganotin(IV) derivatives possess a distorted trigonal bipyramidal structure in which D-penicillamine/peptides are tridentate coordinating through Namino, C(O)Ocarboxyl and Sthiol/Npeptide. The NH2 group bridging/hydrogen bonding may lead to the associated structure. Whereas a linear polymeric structure with a distorted trigonal bipyramidal environment around tin has been tentatively proposed for Ph3Sn(IV) derivatives in which the ligands may act as bidentate coordinating through Namino and C(O)Ocarboxyl. n-Bu2SnCl(HL-1)·H2O, synthesized at low pH, is dimeric. The anti-inflammatory activity, ALD50 and blood pressure lowering activity of the synthesized derivatives are reported. Some complexes exhibit good anti-inflammatory activities comparable to that of phenylbutazone (a comparative analysis is presented through plots). The triorganotin(IV) derivatives exhibit significantly better activities than the diorganotin(IV) derivatives.