Organometallic complexes with biological molecules. XI. Solid state and invivo 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 [= Hcyclo s]} 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 mon odentate ligand through the oxygen atom of the deprotonated secondary alcoh olic group, with formation of tetrahedral R2SnOCl and R2SnO2 environments. In R2Sn(IV)Clcyclos and R2Sn(IV)cyclos(2) derivatives, Mossbauer spectrosco py, and in particular the narrowness of the full width at half height of th e resonant peaks, Gamma(1) and Gamma(2), suggested the occurrence of two di fferent absorbing tin sites with different environments around the tin(IV) atoms. According to calculations performed by applying the point charge mod el formalism, one site was constituted by a tin(IV) tetrahedrically coordin ated by monoanionic monodentate cycloserinate groups, through the oxygen at om of the resonance stabilised hydroxamate anion, originating R2SnClO and R 2SnO2 polyhedrons both in R2Sn(IV)Clcyclos and R2Sn(IV)cyclos(2), respectiv ely. The second site would correspond to a tin(IV) in a polymeric octahedra l configuration with Me2SnCl2ON and Me2SnO2N2 environments, in Me2Sn(IV)Clc yclos 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) underwe nt total, (R = Me), or partial, (R = Ph), dissociation. As far as the organ otin(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 co ordinating properties of the solvent, octahedral and trigonal bipyramidal i somers were present in DMSO solution of Me2Sn(IV)Clcyclos and Me2Sn(IV)cycl os(2). Finally, the cytotoxic activity of the free chloramphenicol, D-cyclo serine and of their dimethyltin(IV) derivatives has been investigated towar ds Ciona intestinalis and Ascidia malaca fertilised eggs, at different deve loping stages. (C) 1998 Elsevier Science Inc. All rights reserved.