IMPORTANCE OF CORRELATION-GRADIENT GEOMETRY OPTIMIZATION FOR MOLECULAR CONFORMATIONAL-ANALYSES

The geometries of three conformations of glycine {Gly, forms 1 to 3} and of two conformations of the diamide, N-formylalanineamide {Ala, forms C5 and C7eq}, were determined by MP2 gradient optimization at the MP2/6-311G** level in order to study the effects of correlation-gradient geometry refinement on the results of molecular conformational analyses. The MP2/6-311G** energy difference (AE) between 1 and 2 is 3.5 kJ/mol for MP2/6-311G** optimized geometries. This value increases by 1.9 kJ/mol to 5.4 kJ/mol when the MP2 calculations are performed with HF/6-311G** optimized geometries. The MP2/6-311G** DELTA-E for 1 and 3 is 2.9 kJ/mol for MP2/6-311G** optimized geometries, and increases to 4.8 kJ/mol for MP2/6-311G** calculations at HF/6-311G** geometries. In Ala, geometry optimization has the opposite effect; that is, DELTA-E for C5 and C7eq is smaller (by 1.4 kJ/mol) for the unoptimized structures. Thus, the effects of MP2 geometry optimization on MP2 energies are unpredictable and cannot be neglected, and single-point MP2 energies calculated at HF-optimized (MP2-unoptimized) geometries are not reliable. Similarly, RHF calculations performed at various levels (3-21G,4-21G,4-31G, 6-31G, 6-31G**, 6-311G**) demonstrate the difficulty of obtaining reliable estimates of the DELTA-E values and torsional angles of the most stable conformations of Gly and Ala. In the case of Gly, different levels of theory do not agree on the symmetry of the second minimum, the planar 2 or nonplanar 3; the scatter in AE between 2 and 1 is 6 kJ/mol, and, most disturbingly, the most advanced HF calculations compare the worst with experimental results. The exact locations of the two most stable energy minima in the phi,psi-torsional space of the diamide are significantly affected by MP2 geometry optimization (changes of >4-degrees between MP2/6-311G** and HF/6-311G**, and changes of >15-degrees between MP2/6-311G** and HF/3-21G). Concomitant with these effects, considerable shrinkage by electron correlation is observed for H...X nonbonded interactions. Conformational changes in bond distances and angles also display significant variances with computational method, but the fluctuations do not preclude the identification of some clear and useful structural trends. Thus, even at simple levels of theory, such as HF/4-21G, conformational geometry maps of diamides capture essential structural trends which are not falsified by more advanced calculations. In contrast to this, RHF conformational energy maps are intrinsically inaccurate: the nonbonded interactions are incorrectly evaluated not only because dispersion effects are neglected but also because nonbonded distances are wrong due to errors in torsions.