|
Conformational free energy calculations using an empirical potential function (ECEPP/2) and hydration shell model were carried out on the four 4-aminodiphenyl sulfone analogues of 4, 4’’-diamino-2’’-methyldiphenyl sulfone, 4, 2’’, 4’’-triaminodiphenyl sulfone, 4, 4’’-diaminodiphenyl sulfone, and 4-aminodiphenyl sulfone as antibacterial agents on Mycobacterium lufu. The conformational energy was minimized from starting conformations which included possible combinations of torsion angles in the molecule. The conformational entropy change of each conformation was computed using a harmonic approximation. To understand the hydration effect on the conformation of the molecule in aqueous solution, the contributions of water-accessible volume and the hydration free energy of each group or atom in the lowest-free-energy conformation was calculated and compared each other. From comparison of the computed lowest-free-energy conformations of four analogues with their antibacterial activities, it is known that the conformation and the hydrophobicity of sulfonyl group and its adjacent carbon atom in each compound are the essential factors to show the strong antibacterial activity.
|