Bis(2-aminobutanol)dichloroplatinum(II) complexes and their singly and doubly ring-closed butanolato species - Novel prodrugs for platinum-based antitumour chemotherapy?

Cytotoxic hydroxyethyl-substituted (amine)platinum(II) and -(IV) complexes have recently attracted attention because of the ability of their hydroxyethyl groups to coordinate through the oxygen atom to the platinum centre during oxidation with hydrogen peroxide or through intramolecular ligand exchange reactions in dichloroplatinum(II) complexes. The last point in particular is of great interest, because the intramolecular attack of the hydroxy group dramatically influences the mode of action of platinum(II) compounds. On the other hand, there is also the chance to use such reactions specifically for the synthesis of novel anticancer platinum-based drugs for chemotherapy. We have therefore focused our chemistry program on the synthesis of dichloroplatinum(II) complexes that are in a position to form singly and, especially, doubly ring-closed alcoholato species and on investigation of their structures by X-ray crystallography. It was possible to determine the crystal structures of [Pt{(R)-(-)-HL}2Cl2], [Pt{(S)-(+)-HL}2Cl2], [Pt{(R)-(-)-HL}{(S)-(+)-HL}Cl2], [Pt{(S)-(+)-HL}{(S)-(+)-L}Cl], [Pt{(R)-(-)-L}2] and [Pt{(S)-(+)-L}2] (HL = 2-aminobutanol-?N, L = 2-aminobutanolato-?2N,O). The results obtained may represent the first step towards novel prodrugs for platinum-based antitumour chemotherapy. ΠWiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.