A search for C-H center dot center dot center dot O type hydrogen bonds inLamivudine (3TC). An exploratory conformational and electronic analysis

A conformational study of the molecule Lamivudine (3TC), or cis-1-[2 ' -hyd roxymethyl-5 '-(1,3-oxathiolanyl)] cytosine, was carried out. Rotation about the C-N bond (phi1) and about the C-CH2(OH) bond (phi2), whi ch connects the hydroxymethyl group to the five member ring, led to a confo rmational potential energy surface. The conformational potential energy 2D map, obtained at the HF/3-21G level of theory, had several minima. A topolo gical analysis of the electron density was carried out on four selected ab initio minimum energy conformations, using judiciously constructed hartree- fock (RHF) wave functions. In order to see all possible hydrogen bonding, t he DFT wave function was generated using a mixed basis set; a 6-311++G** ba sis was employed on atoms involved in hydrogen bonding interactions and a 3 -21G basis on all other atoms. For this analysis the theory of atoms in mol ecules, developed by Bader, was used. The stability of the intramolecular hydrogen bonding interactions was analy zed in terms of the results obtained. (C) 2001 Elsevier Science B.V. All ri ghts reserved.