Hydrogen-bonded dimers in self-association of 5-substituted uracil derivatives and hetero-association with l-cysteine. A density functional theory study

Hydrogen-bonded dimers arising from self-association of 5-fluorouracil, 5-chlorouracil and 5-methyluracil (thymine) have been studied by density functional theory (DFT) at the B3LYP/6-311++G** level. Dimeric structures were optimized by counterpoise correction and confirmed by computation of harmonic normal vibrations. The most stable hydrogen-bonded dimers involve NH and CO groups, as in unsubstituted uracil. Binding energies are between −68.31 and −40.08 kJ mol−1, showing differences with relation to uracil which may reflect substituent effects. Vibrational analysis reveals band shifts and intensity charges characteristic of hydrogen bonding, and especially new intermolecular bands at low frequencies which are specific of each dimer. Hetero-association by hydrogen bonding of uracil derivatives with amino acid l-cysteine was studied at the same level of theory. The groups interacting are those active in the self-association of both partners and binding energies of dimerization are between −66.17 and −52.25 kJ mol−1. Favourable effects arising from fluorine and methyl substitution suggest an increase in basicity of the C2O group of uracil. In general, self-associated species predominate over hetero-complexes, but in the interactions involving N1H and C2O groups, both kinds of complexes could be present in similar proportion.