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RESEARCH PRODUCT

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

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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 2 SnOHceph · H 2 O and Alk 3 Snceph · H 2 O (Alk=Me, n -Bu), while structural information has been gained by FT-IR, 119 Sn Mossbauer and 1 H, 13 C, 119 Sn NMR data. In particular, IR results suggested polymeric structures both for Alk 2 SnOHceph · H 2 O and Alk 3 Snceph · H 2 O. 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 2 SnOHceph · H 2 O complexes. On the basis of 119 Sn Mossbauer 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 3 Sn(IV)ceph · H 2 O derivatives are concerned, cephalexin coordinated the Alk 3 Sn moiety through the carboxylate acting as a bridging bidentate monoanionic group. Again, 119 Sn Mossbauer spectroscopy led us to propose a trigonal configuration around the tin(IV) atom, with R 3 Sn equatorial disposition and bridging carboxylate oxygen atoms in the axial positions. The nature of the complexes in solution state was investigated by using 1 H, 13 C and 119 Sn 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.