Synthesis, X-ray crystallographic structures of thio substituted N-acetyl N'-methylamide alanine and evaluation of sp sulfur parameters of the CFF91 force field.

Abstract

Acetyl thioalanine N-methyl (Ac-Alat-NHMe) and thioacetyl alanine N-methyl (Act-Ala-NHMe) were synthesized, crystallized and their X-ray diffraction structures determined for the first time. Both molecules adopted beta-sheet conformations and showed similar hydrogen bonding patterns with one molecular surface forming two oxo hydrogen bonds and the other forming two thio hydrogen bonds. The crystal structure data for the two thioamides provided a validation of the thioamide parameters for the newly derived CFF91 force field because the observed crystal (phi, psi) angles were situated in the global minimum regions of the theoretical (phi, psi) map predicted using the parameters. In addition, the parameters were further validated because conformational energy minimization of the crystal structure produced low deviations in unit cell dimensions, bond lengths, bond angles and torsional angles, and a 120-ps molecular dynamics simulation also gave a low deviation for the most probable N-H...S=C bond distance.