CALORIMETRIC AND PT-195 NMR-STUDIES ON AROMATIC RING STACKING BETWEEN NUCLEOTIDES AND PLATINUM DNA INTERCALATORS

Calorimetric and spectroscopic investigations have been carried out on the stacking interactions between nucleosides or nucleotides (NMP) and platinum DNA intercalators and other planar platinum(II) complexes with heteroaromatic ligands (L). Pt(L)(diamine) (L=1,10-phenathroline (phen), its methyl and nitro derivatives, 2,2'-bipyridine; diamine=ethylenediamine (en), L-2,3-diaminopropionate) reacts with NMP (=adenosine 5'-monophosphate (AMP), guanosine 5'-monophosphate (GMP), inosine 5'-monophosphate (LMP), cytidine 5'-monophosphate (CMP); nicotinamide adenine dinucleotide (NAD), adenosine, cytidine) to give the Pt(L) (diamine)-(NMP)(n) adducts (n=1, 2) with log K-1=1.63-3.00 and log K-2=1.47-2.51 at 25 degrees C at ionic strength=0.1 mol dm(-3) (NaCl). The 1:1 adduct formation mainly depends on the enthalpy change Delta H-1 degrees=-6.5-26.2 kJ mol(-1), and the entropy change (Delta S-1 degrees=-38-20 J mol(-1) K-1) makes a negative or small contribution. H-1 NMR upheld shires observed for the Pt(phen)(en)-NMP systems have substantiated the presence of stacked adducts in dilute aqueous solution, whereas diquat, a dicationic organic molecule, did not cause appreciable shifts, and hence the adduct formation was negligible. NAD was found to interact with Pt(phen)(en) through the adenine moiety. (195)ptNMR signals of Pt(phen)(en) in water suffered downfield shifts upon addition of NMP, the Delta delta(1) values being in the order NAD greater than or equal to AMP approximate to GMP>IMP. This indicates that stacking causes an electron density decrease of the Pt(Il) center. Linear relationships have been detected between the Sigma Delta H-n degrees values and the absorption coefficients epsilon(n) Of the difference spectra in the charge transfer region and between Sigma Delta H-n degrees and (195)ptNMR shift differences Delta delta(n). These observations serve as evidence for the electronic effects of stacking interactions on the stacked rings and the central Pt(II) ion.