Ab initio MO study on model compounds of malonyl-CoA: Malonic acid and malonyl methyl sulfide

The conformational study on malonic acid, hydrogen malonate, malonate, malonyl methyl sulfide, and its anion is carried out at the HF/6-31G** and HF/6-31+G** levels in order to investigate the information on structures and energetics of the compounds when malonic acid, hydrogen malonate or malonate interacts with CoA and produces malonyl-CoA. In the preferred conformations of malonic acid and malonate at both levels, two carboxyl groups are nearly perpendicular to the plane formed by the central three C atoms, in spite of a different orientation of the two carboxyl groups themselves. On the other hand, two carboxyl groups of hydrogen malonate at both levels lie on the plane and form an intramolecular hydrogen bond, which appears to be responsible for the anomalous ratio of dissociation constants of malonic acid. The calculated results on the geometries and conformations of the three compounds at both levels are consistent with those of X-ray and spectroscopic experiments. From HF/6-31G** to HF/6-31+G**, the orderings of conformational energies of malonic acid, hydrogen malonate, malonate, and malonyl methyl sulfide are conserved, except for malonyl methyl sulfide anion. At both levels, the preferred conformations of the malonyl moiety of malonyl methyl sulfide are quite similar to that of malonic acid, whereas the preferred conformations of its anion are quite different from those of hydrogen malonate and malonate as well as malonyl methyl sulfide. The energy and free energy changes for the reactions involving the compounds studied here are calculated in the gas phase and in aqueous solution, which are reasonably consistent with available experimental data.