DNA DRUG-INTERACTION - THE EFFECTS OF VITAMIN-C ON THE SOLUTION STRUCTURE OF CALF-THYMUS DNA STUDIED BY FTIR AND LASER RAMAN DIFFERENCE SPECTROSCOPY

The interaction of calf-thymus DNA with L-ascorbic acid was investigat ed in aqueous solution at pH = 7-6 with drug/DNA(P)(P = phosphate) mol ar ratios (r) of 1/40, 1/20, 1/10, 1/5, 1/2, 1 and 2. Fourier Transfor m infrared (FTIR) and laser Raman difference spectroscopic techniques were used to establish correlations between spectral modifications and drug binding mode, sequence specificity, DNA melting and conformation al changes, as well as structural variations of drug-DNA complexes in aqueous solution. Infrared and Raman spectroscopic results showed that at low drug concentration (r = 1/40), a B to A-type conformational co nversion occurs with minor drug-DNA interaction through AT bases. At r = 1/20, drug-PO2 binding was also observed with reduced intensity of DNA inplane vibrational frequencies, due to the increased base-stackin g interaction and duplex stability. At r > 1/20, major perturbations o f DNA bases were observed for both A-T and G-C base pairs in the major and minor grooves of the duplex. Evidence for this comes from the shi ft of the infrared and Raman vibrations of the A-T and G-C bases on dr ug interaction. At r > 1/5, a minor helix destabilization occurred wit h participation of several DNA donor sites in drug complexation. The a scorbate anion interaction occurred mainly through H-bonding of the ac id OH and C-O groups with DNA phosphate, bases and deoxyribose donor a toms.