Platinum carboxylato-pendant-arm macrocycles: structure, redox properties and anti-cancer potential

In an attempt to generate new platinum compounds that may be effective in t he treatment of cancer, as well as having a lower toxicity than traditional platins and being orally viable, we are studing the synthesis and reactivi ty of platinum complexes of tetraazamacrocycles bearing carboxylato pendant arms. We have synthesized adducts of meso- and rac-5,5,7,12,12, 14-hexamet hyl-1,4,8,11-tetraazacyclotetradecane-1,7-diacetic acid ((LH2)-H-1). The me so-(PtL1)-L-II complex is unstable with respect to disproportionation, form ing platinum metal and [meso-(PtL1)-L-IV](2+). The rac-isomer shows less te ndency to disproportionate. Cyclic voltammetry suggests that the rac-(PtL1) -L-II complex undergoes two one-electron oxidations. Using bis-triazacyclon onanenickel(III), [Ni-III(tacn)(2)](3+) as an outer-sphere oxidant, the sel f-exchange rate for the [Pt-II/L-III](0/+) couple has been estimated at 0.0 34 M-1 s(-1). (C) 2001 Elsevier Science B.V. All rights reserved.