PLATINUM DNA INTERCALATOR MONONUCLEOTIDE ADDUCT FORMATION - COOPERATIVITY BETWEEN AROMATIC RING STACKING AND ELECTROSTATIC INTERACTIONS

Adduct formation by aromatic ring stacking and electrostatic interactions has been investigated for solutions containing platinum DNA intercalators Pt(L)(en)2+ (L = 2,2'-bipyridine (bpy), 1,10-phenanthroline (phen), 5-nitro-1,10-phenanthroline (nphen), 3,4,7,8-tetramethyl-1,10-phenanthroline (Me4phen); en = ethylenediamine) and mononucleotides NMP2- (= AMP, GMP, CMP, UMP) or adenosine by spectroscopic methods. Difference absorption spectra of the Pt(L)(en)2+-NMP2- systems revealed spectral changes in the region 290-350 nm probably due to the stacking interaction between Pt(L)(en)2+ and NMP2-, which was supported by the induced circular dichroism (CD) peaks observed in this region. The stacking has been substantiated by H-1 NMR spectra, which exhibited upfield shifts (DELTA-delta) of the proton signals of the purine and pyrimidine rings and the H-1' signal of the D-ribose moiety due to the ring current effect of coordinated L. The DELTA-delta values were largest for Pt(Me4phen)(en)2+ (0.39-0.91 ppm for purine H-2 and H-8, 0.39-0.55 ppm for pyrimidine H-5 and H-6, and 0.49-0.71 ppm for ribose H-1'), implying that a large hydrophobic area is most effective for stacking. The stability constants log K were determined for the adducts Pt(L)(en)2+-NMP2-, where NMP2- = AMP (L = bpy), GMP (L = bpy, Me4phen), and CMP (L = bpy), and Pt(bpy)(en)2+(-)adenosine from the absorption and CD spectra at pH 7-8 and 25-degrees-C (I = variable, 0.1 M). The spectral data and the stability constants indicated cooperativity between the aromatic ring stacking and electrostatic interactions in adduct formation. Modes of interactions within the adducts in solution are discussed and compared with those in the solid state.