NMR study of interaction of nucleic acid bases in DMSO

Abstract

The mechanism of the interaction of DNA bases, with DMSO, or with other solutes in DMSO is not clear. It was suggested that this interaction might be through the formation of hydrogen bonding or through charge transfer complex [1]. The aim of this work is to study the interaction of those bases with different acceptors such as nitromethane, nitrobenzene, acetyl acetone, nicotine and acridon, using NMR techniques, in hope of shedding some light on the nature of the above mentioned interaction. Uracil At low concentrations (0.06 M) N 1H signal did not separate from N 3H, this is a good indication that uracil association is stronger than uracil–DMSO. However when a fixed concentration of uracil is mixed with varying concentration of acetyl acetone, acridon, nicotine and nitromethane, N 1H separates from N 3H and proton 5 splits into a doublet of doublets with 4J N 3H,H 5 = 1.5 Hz [2]. This indicates that N 3H freezed before N 1H due to the formation of hydrogen bonding between the more acidic proton (N 3H) and the above mentioned acceptors. All these acceptors seem to form similar types of hydrogen bonds with uracil. Thymine Dilution of thymine with DMSO will cause N 1H signal to separate from N 3H, this prove that thymine- thymine interaction is weaker than thymine-DMSO interaction. Addition of a small amount of the acceptors to thymine cause N 1H to separate from N 3H, once could conclude that uracil–uracil association is much stronger that thymine–thymine. Cytosine This study did not obtain any indication of the formation of tautomer in DMSO as reported before [3]. All acceptors didn't cause any effect on cytosine except for nitromethane, such that when the ratio of nitromethane:cytosine was 5:1, a broad band appears at about 10–11 ppm and protons 5 and 6 split to a doublet of doublets with J = 2.0 Hz. This could be explained that cytosine exists in the tautomer form [4], which might be stable in nitromethane medium, one could conclude that the coupling observed is between N 3H and protons 5 and 6 [5]/ Purine It was suggested that with increasing concentration purine associates through stack formation [6]. Hewson et al. [7], concluded that purine associates through hydrogen bonding. In this work we noticed that there is no change in the chemical shift of proton 2, 6 and 8, but N 9H moves to higher field with increasing concentration. It seems that purine associates in a manner similar to that in pyrrol [8]. No change was observed with all acceptors except with acetyl acetone and acridon where N 9H shifted to low field upon the mixing of purine with those two acceptors, this is strong evidence for the formation of hydrogen bonding between purine and each of acetyl acetone and acridon.