COORDINATION OF AQUATED CIS-PLATINUM(II) DIAMINES TO PURINE NUCLEOSIDES - KINETICS OF COMPLEX-FORMATION

Kinetics for the formation of 1:1 and 1:2 complexes between various aquated cis-Pt(II) diamines and the purine nucleosides adenosine, guanosine, 1-methylguanosine, inosine, 1-methylinosine, and 9-(β-D-ribofuranosyl)purine have been studied by LC in aqueous solution (pH 4) at 298.2 K. Substitution of the N–H protons in cis-PtII(NH3)2 with methyl groups gives the order CH3NH2 > NH3 > (CH3)2NH > tetramethylethylenediamine for the complexation rate of Pt compounds. Apart from steric hindrances exerted by the methyl groups, the reactivity of these Pt(II) ions can be influenced by other factors. The H-bonding ability of the amine ligands does not, however, significantly contribute to the kinetics under these conditions. The complexation rate of purine nucleosides follows the order Guo ≈ 1-MeGuo > Ino ≈ 1-MeIno > Puo > Ado with each Pt(II) compound. The minor reactivity difference between guanine and hypoxanthine derivatives is attributed to greater basicity of the N7 site of the former compounds. In contrast, the complexation rate is drastically influenced by the substituent at C6 of the purine ring. Formation of an H-bond from the coordinated water molecule to C(6)O plays an important role in the enhanced reactivity of 6-oxo-substituted purines, whereas the C(6)NH2 group sterically prevents the attack of Pt(II). © 1990, American Chemical Society. All rights reserved.