CORRELATION BETWEEN THE ANTI-HIV ACTIVITY AND ELECTROSTATIC PROPERTIES OF 3'-SUBSTITUTED DEOXYTHYMIDINES

The molecular electrostatic potentials (MEPs) of conformers of thymidine, 3'-deoxythymidine and the 3'-N-3-, 3'-F-, 3'-CN- and 3'-NH2-derivatives of the latter were calculated, their minima were located, the MEP distributions of the deoxyderivatives were compared with those of the corresponding conformers of thymidine itself, and atomic charges and molecular dipole moments were calculated from the MEP distributions. The conformers studied were chosen among those found to be most stable in a previous AM1 study. MEPs were calculated from STO-3G eigenfunctions. The anti-HIV activities of the deoxythymidines (excluding the 3'-NH2 derivative) exhibit good qualitative correlation with their electrostatic properties; in particular, the distance of the MEP minimum associated with the 3'-OH group of thymidine from the corresponding minimum of the deoxyderivative qualitatively correlates with anti-HIV activity even when the 3'-NH2 derivative is included.