SEMIEMPIRICAL MO STUDY ON MALONYL-COA .1. MALONIC-ACID AND MALONYL METHYL SULFIDE

The conformational study on malonic acid, hydrogen malonate, malonate, malonyl methyl sulfide, and malonyl methyl sulfide anion, as the mode l compounds of malonyl-CoA, was carried out using the semiempirical MO methods (MNDO, AM1, and PM3) and hydration shell model. On the whole, the feasible conformations of malonic acid, hydrogen malonate, and ma lonate seem to be similar to each other. In malonic acid and malonate, two carboxyl groups are nearly perpendicular to the plane of the carb on skeleton, despite of different orientation of two carboxyl groups t hemselves. In particular, two carboxyl groups of hydrogen malonate are on the plane formed by carbon atoms with an intramolecular hydrogen b ond. The calculated results on the geometry and conformation of three compounds are reasonably consistent with those of X-ray and spectrosco pic experiments as well as the previous calculations, The orientation of two carbonyl groups of malonyl methyl sulfide is quite similar to t hat of malonic acid, but different from that of its anion. Especially, the computed probable conformations of the sulfide anion by the three methods are different from each other. The role of hydration seems no t to be crucial in stabilizing the overall conformations of malonic ac id, hydrogen malonate, malonate, and malonyl methyl sulfide. However, the probable conformations of the unhydrated sulfide anion obtained by the MNDO and AM1 methods become less stabilized by including hydratio n. The AM1 method seems to be appropriate for conformational study of malonyl-CoA and its model compounds because it does not result in the formation of too strong hydrogen bonds and significant change in confo rmational energy from one compound to another.