Novel platinum pyridinehydroxamic acid complexes:: Synthesis, characterisation, X-ray crystallographic study and nitric oxide related properties

Herein, we describe the synthesis and characterisation of a novel class of Pt-II and Pt-IV pyridinehydroxamic acid (pyhaH) complexes of general formula cis-[(PtCl2)-Cl-II(x-pyhaH)(2)] and cis-[(PtCl4)-Cl-IV(x-pyhaH)(2)], respectively (where x = 3 or 4) in which the pyridinehydroxamic acid is coordinated to the platinum ion via the pyridine nitrogen only leaving the hydroxamic acid free to potentially release cytotoxic nitric oxide (NO). The crystal structure of the Pt-IV derivative, cis-[PtCl4(4-pyhaH)(2)]center dot 2CH(3)OH is reported. To establish the biological effect of the uncoordinated hydroxamic acid moiety in the Pt-II compounds synthesised, the corresponding pyridinecarboxylic acid (pycaH) complexes of general formula cis-[(PtCl2)-Cl-II(x-pycaH)(2)] (where x = 3 or 4) and the Nil pyridine (py) complex, cis-[(PtCl2)-Cl-II(py)(2)] were synthesised and served as reference standards. The NO-releasing properties of each of the Pt-II compounds, the pyhaH and the pycaH ligands were studied. The Pt-II pyridinehydroxamic acid derivatives were found to induce potent in vitro effects attributable to either NO-release from the hydroxamic acid moiety and/or stimulation of inducible nitric oxide synthase of endothelial cells. (c) 2007 Elsevier Ltd. All rights reserved.