Abstract
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-[Pt IICl 2( x-pyhaH) 2] and cis-[Pt IVCl 4( 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-[PtCl 4(4-pyhaH) 2] · 2CH 3OH 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-[Pt IICl 2( x-pycaH) 2] (where x = 3 or 4) and the Pt II pyridine (py) complex, cis-[Pt IICl 2(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.
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