Organometallic complexes with biological molecules. XI. Solid state and in vivo investigations of some diorganotin(IV)-chloramphenicol and cycloserine derivatives

Diorganotin(IV) derivatives of chloramphenicol, {= D-(-)threo-2,2-dichloro-N-[beta-hydroxy-alpha-(hydroxymethyl)-beta-(4-nitrophenyl)ethyl]acetamide (= Hchloramph)}, and D-cycloserine, {= (R)-4-amino-3-isoxazolidone [= Hcyclos]} have been prepared. The stoichiometries of the obtained compounds were R(2)SnClantib and R(2)Snantib(2) (antib(-1) = chloramph(-1), R = methyl and phenyl; antib(-1) = cyclos(-1), R = methyl). The solid state configuration of the complexes was investigated by I.R. and Mossbauer spectroscopy, from which structural hypotheses were inferred. In particular, the experimental data suggested monomer structures both for R2Sn(IV)Clchloramph and R2Sn(IV)chloramph(2), in which chloramphenicolate anion behaved as monoanionic monodentate ligand through the oxygen atom of the deprotonated secondary alcoholic group, with formation of tetrahedral R2SnOCl and R2SnO2 environments. In R2Sn(IV)Clcyclos and R2Sn(IV)cyclos(2) derivatives, Mossbauer spectroscopy, and in particular the narrowness of the full width at half height of the resonant peaks, Gamma(1) and Gamma(2), suggested the occurrence of two different absorbing tin sites with different environments around the tin(IV) atoms. According to calculations performed by applying the point charge model formalism, one site was constituted by a tin(IV) tetrahedrically coordinated by monoanionic monodentate cycloserinate groups, through the oxygen atom of the resonance stabilised hydroxamate anion, originating R2SnClO and R2SnO2 polyhedrons both in R2Sn(IV)Clcyclos and R2Sn(IV)cyclos(2), respectively. The second site would correspond to a tin(IV) in a polymeric octahedral configuration with Me2SnCl2ON and Me2SnO2N2 environments, in Me2Sn(IV)Clcyclos and Me2Sn(IV)cyclos(2) derivatives, respectively, in which the second donor atoms was the amino nitrogen atom. H-1 and C-13 NMR spectra, of both chloramphenicol and its diorganotin(IV) derivatives were carried in DMSO-d(6) solution, in which R2Sn(IV)Clchloramph and R2Sn(IV)chloramph(2) underwent total, (R = Me), or partial, (R = Ph), dissociation. As far as the organotin(IV)-D-cycloserine derivatives were concerned, H-1 and C-13 NMR spectra, also carried our for the free D-cycloserine, showed that, owing to the coordinating properties of the solvent, octahedral and trigonal bipyramidal isomers were present in DMSO solution of Me2Sn(IV)Clcyclos and Me2Sn(IV)cyclos(2). Finally, the cytotoxic activity of the free chloramphenicol, D-cycloserine and of their dimethyltin(IV) derivatives has been investigated towards Ciona intestinalis and Ascidia malaca fertilised eggs, at different developing stages