Conformational analysis of carbonic anhydrase inhibitors using ab initio molecular orbital methods. 1. Rotational isomerism in methane sulfonamide anion, CH3-SO2-NH−

Ab initio calculations have been performed on methane sulfonamide anion. Geometries have been optimized using Hartree-Fock basis sets up to 6-31+G*, and single-point calculations employing those Hartree-Fock geometries have been performed at levels up to MP2/6-311++G**. In addition, geometry optimizations for the 0°, 90°, 150°, and 180° conformers have been carried out at the MP2/6-31G*, MP2/6-31+G*, and MP2/6-311++G** levels. Vibrational frequencies have been calculated using the HF/4-31G*, MP2/6-31G*, and MP2/6-31+G* geometries. All calculations at or above the 4-31G* level agree that H—N—S—C ˜90° is the global minimum. The H—N—S—C = 180° conformer is clearly higher in energy although the relative energy of this conformer varies from 0.36 to 1.03 kcal/mol for the post-HF calculations depending on basis set. The H—N—S—C = 180° conformer appears to be a very shallow local minimum. However, the potential energy surface is quite flat in this region, and the highest-level calculations, including MP2 optimizations and vibrational frequency analysis, are ambiguous on this point. The conformer with an H—N—S—C torsion of 0° is a transition state with a relative energy ˜8 kcal/mol. Received: 3 December 1996 / Accepted: 2 January 1997