In Silico Studies of Potential Selective Inhibitors of Thymidylate Kinase from .

Continuing the work developed by our research group, in the present manuscript, we performed a theoretical study of 10 new structures derived from the antivirals cidofovir and ribavirin, as inhibitor prototypes for the enzyme thymidylate kinase from (TMPK). The proposed structures were subjected to docking calculations, molecular dynamics simulations, and free energy calculations, using the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) method, inside the active sites of TMPK and human TMPK (TMPK). The docking and molecular dynamic studies pointed to structures 2, 3, 4, 6, and 9 as more selective towards TMPK.

Conformational analysis of 1-chloro- and 1-bromo-2-propanol.

The conformational isomerism of 1-chloro- (1) and 1-bromo-2-propanol (2) was theoretically and spectroscopically (NMR) analyzed. Conformers with the X-C-C-O (X = Cl and Br) fragment in the gauche orientation were found to be strongly prevalent both in the gas phase and solution, as analyzed by means of coupling constants in the diastereotopic methylene hydrogens. The gauche effect was calculated to be due to hyperconjugation rather than intramolecular X···HO hydrogen bond, indicating the rule of the stereochemical control in compounds with motifs (halohydrins) widely found in pharmaceutical and agrochemical products and intermediates.