Towards new transition metal-based hypoxic selective agents for therapy and imaging

The greater lability of Co(II) relative to Co(III) can potentially be used to achieve selective delivery of nitrogen mustard type molecules to hypoxic cells. Attempts to improve the stability of the Co(II) state by utilising tripodal tetradentate ligands are described, together with the results of DF calculations. Rhenium has two beta -emitting isotopes Re-186 and Re-188 that have potential for use to treat cancer if the complexes can be targeted with sufficient specificity. We describe some new rapid low temperature routes using hydrazines to labile Re(V) and Re(III) species which provide potential convenient access to a wide range of oxo- and diazenido-complexes. The synthesis of new Re(V) and Re(III) thiosemicarbazone complexes is presented in the context of obtaining hypoxic selective species. Copper(TI) bis(thiosemicarbazone) complexes are known to be hypoxic selective and spectroscopic, cyclic voltammetric and computational studies of the mechanism are presented, together with the synthesis of new Cu(II) complexes directed towards the hypoxic selective delivery of nitrogen mustard type molecules. (C) 2001 Elsevier Science B.V. All rights reserved.