Theoretical Studies of Trans-Alkene Mycolic Acid

Abstract

Theoretical studies carried on trans-alkene mycolic acid (MA) that characterize (2R,3R,17R,39S,40S,E)-3-hydroxy-39-methoxy-17,40-dimethyl-2-tetra cosyl- octapentacont-18-enoic acid (1). The stereochemistry of MA was showed that the chiral centres in C(19), C(20), C(44), C(49) and C(51) were in (S), (S), (R), (R) and (R) configurations respectively and the double bond in C(42)-C(43) was described as E-isomer. The results of conformational energy for selected (85) conformers in the acid structure were showed that the torsion angles 15(?>>"> ) were in the range (±180) and this indicate the folding of MA a way same to that present in biomolecules. Theoretical studies of torsional strain (E) of each conformer were showed that the MA has eclipsed and staggered conformation. Internal coordinate mechanics (ICM) of MA was showed that the angle type in most of atoms was dihedral. The bond lengths, bond angles, torsion angles and dihedral angles were also studied, in order to study their effect in the molecule properties and their consequence in the molecular mechanics (MM2) and optimal minimization. Thus, the MM2 properties were envisioned, the results were showed that the torsion energy and the total energy were equal to 13.3334 and 255.0187 kcal/mol respectively. High Van der Waals (VDW) interactions of this MA were observed, due to the dipole/ dipole was not computed. Further, the results of MM2 minimization for MA were showed that the torsion energy and the total energy were equal to 8.8418 and 62.9851 kcal/mol respectively. Thus, the dipole/ dipole (0.2185) of acid was detected after minimization. The results after minimization were showed a significant increase in the actual close contact of atoms. Also, the results were displayed that the carboxylic O(47) atom was close contact with H(179) atom that bonded with alkane C(49) atom in mycolic motif. Further, the molecular mechanics force field (MMFF94) energy and gradient for MA were also calculated. The results were showed that the total energy and RMS gradients were equal to 228.561 kcal/mol and 17.735 respectively. The final energy of MMFF94 minimization and minimization/ sampling were equal to 11.2963 kcal/mol and 11.1221 kcal/mol respectively, which indicated that the minimization was attended successfully.

Keywords: Mycobacterium tuberculosis, Mycolic acid, Internal coordinates