Organometallic complexes with biological molecules. XVIII. Alkyltin(IV) cephalexinate complexes: synthesis, solid state and solution phase investigations

Abstract

Dialkyltin(IV) and trialkyltin(IV) complexes of the deacetoxycephalo-sporin-antibiotic cephalexin [7-( d-2-amino-2-phenylacetamido)-3-methyl-3-cephem-4-carboxylic acid] (Hceph) have been synthesized and investigated both in solid and solution phase. Analytical and thermogravimetric data supported the general formula Alk 2SnOHceph · H 2O and Alk 3Snceph · H 2O (Alk=Me, n-Bu), while structural information has been gained by FT-IR, 119Sn Mössbauer and 1H, 13C, 119Sn NMR data. In particular, IR results suggested polymeric structures both for Alk 2SnOHceph · H 2O and Alk 3Snceph · H 2O. Moreover, cephalexin appears to behave as monoanionic tridentate ligand coordinating the tin(IV) atom through ester-type carboxylate, as well as through β-lactam carbonyl oxygen atoms and the amino nitrogen donor atoms in Alk 2SnOHceph · H 2O complexes. On the basis of 119Sn Mössbauer spectroscopy it could be inferred that tin(IV) was hexacoordinated in such complexes in the solid state, showing skew trapezoidal configuration. As far as Alk 3Sn(IV)ceph · H 2O derivatives are concerned, cephalexin coordinated the Alk 3Sn moiety through the carboxylate acting as a bridging bidentate monoanionic group. Again, 119Sn Mössbauer spectroscopy led us to propose a trigonal configuration around the tin(IV) atom, with R 3Sn equatorial disposition and bridging carboxylate oxygen atoms in the axial positions. The nature of the complexes in solution state was investigated by using 1H, 13C and 119Sn NMR spectroscopy. Finally, the cytotoxic activity of organotin(IV) cephalexinate derivatives has been tested using two different chromosome-staining techniques Giemsa and CMA 3, towards spermatocyte chromosomes of the mussel Brachidontes pharaonis (Mollusca: Bivalvia). Colchicinized-like mitoses (c-mitoses) on slides obtained from animals exposed to organotin(IV) cephalexinate compounds, demonstrated the high mitotic spindle-inhibiting potentiality of these chemicals. Moreover, structural damages such as ‘chromosome achromatic lesions’, ‘chromosome breakages’ and ‘chromosome fragments’ have been identified through a comparative analysis of spermatocyte chromosomes from untreated specimens (negative controls) and specimens treated with the organotin(IV) complexes.