6533b7dcfe1ef96bd1271682

RESEARCH PRODUCT

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

subject

description

Abstract Diorganotin(IV) derivatives of chloramphenicol, {=D-(-)threo-2,2-dichloro-N-[ β -hydroxy- α -(hydroxymethyl)- β -(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 R 2 Sn(IV)Clchloramph and R 2 Sn(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 R 2 SnOCl and R 2 SnO 2 environments. In R 2 Sn(IV)Clcyclos and R 2 Sn(IV)cyclos 2 derivatives, Mossbauer spectroscopy, and in particular the narrowness of the full width at half height of the resonant peaks, Γ 1 and Γ 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 R 2 SnClO and R 2 SnO 2 polyhedrons both in R 2 Sn(IV)Clcyclos and R 2 Sn(IV)cyclos 2 , respectively. The second site would correspond to a tin(IV) in a polymeric octahedral configuration with Me 2 SnCl 2 ON and Me 2 SnO 2 N 2 environments, in Me 2 Sn(IV)Clcyclos and Me 2 Sn(IV)cyclos 2 derivatives, respectively, in which the second donor atoms was the amino nitrogen atom. 1 H and 13 C NMR spectra, of both chloramphenicol and its diorganotin(IV) derivatives were carried in DMSO-d 6 solution, in which R 2 Sn(IV)Clchloramph and R 2 Sn(IV)chloramph 2 underwent total, (R=Me), or partial, (R=Ph), dissociation. As far as the organotin(IV)-D-cycloserine derivatives were concerned, 1 H and 13 C NMR spectra, also carried out 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 Me 2 Sn(IV)Clcyclos and Me 2 Sn(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.