Substitution and Reduction of Platinum(IV) Complexes by a Nucleotide, Guanosine 5'-Monophosphate.

A series of PtIV anticancer complexes with different reduction potentials has been investigated for their reactivity toward 5‘-guanosine monophosphate (5‘-GMP). The PtIV complexes studied were PtIV(trans-d,l)(1,2-(NH2)2C6H10)Cl4 (tetraplatin, PtIV(dach)Cl4; dach = diaminocyclohexane), cis,trans,cis-[PtIV((CH3)2CHNH2)2(OH)2Cl2] (iproplatin, PtIV(ipa)2(OH)2Cl2; ipa = isopropylamine), cis,trans,cis-[PtIV(en)(OH)2Cl2] (PtIV(en)(OH)2Cl2; en = ethylenediamine), PtIV(en)Cl4, and cis,trans,cis-[PtIV(en)(OCOCH3)2Cl2] (PtIV(en)(OCOCH3)2Cl2). The reactivity was monitored by the decreased 1H NMR peak intensity at 8.2 ppm due to H8 of free 5‘-GMP and the increased intensity of a new peak around 8.6 ppm due to H8 of 5‘-GMP bound to PtII. The reactivity followed the order of cathodic reduction potentials of the PtIV complexes:  PtIV(dach)Cl4 (−90 mV) ≫ PtIV(en)Cl4 (−160 mV) > PtIV(en)(OCOCH3)2Cl2 (−546 mV) > PtIV(ipa)2(OH)2Cl2 (−730 mV). The most reactive complex, PtIV(dach)Cl4, showed an additional weak peak at 9.2 ppm...