Lowest-Lying Conformers of Alanine: Pushing Theory to Ascertain Precise Energetics and Semiexperimental R e Structures

The two lowest-energy gas-phase conformers, Ala-I and Ala-IIA, of the natural amino acid l-alanine (Ala) have been investigated by means of rigorous ab initio computations. Born−Oppenheimer (BO) equilibrium structures (r e BO) were fully optimized at the coupled-cluster [CCSD(T)/cc-pVTZ] level of electronic structure theory. Corresponding semiexperimental (SE) equilibrium structures (r e SE) of each conformer were determined for the first time by least-squares refinement of 11−15 structural parameters on modified, experimental rotational constant data from 10 isotopologues. The SE equilibrium rotational constants were obtained by, first, refitting Fourier transform microwave spectra using the method of predicate observations and, second, correcting the resulting effective rotational constants with theoretical vibration−rotation interaction constants (α i ). Careful analysis is made of the procedures to account for vibrational distortion, which proves essential to defining precise structures in flexible molecules such as Ala. Because Ala possesses no symmetry, has several large-amplitude nuclear motions, and exhibits conformers with different hydrogen bonding patterns, it is one of the most difficult cases where reliable equilibrium structures have now been determined. The relative energy of the alanine conformers was pinpointed using first-principles composite focal point analyses (FPA), which employed extrapolations using basis sets as large as aug-cc-pV5Z and electron correlation treatments as extensive as CCSD(T). The FPA computations place the Ala-IIA equilibrium structure higher in energy than that of Ala-I by a mere 0.45 kJ mol−1 (38 cm−1), showing that the two lowest-lying conformers of alanine are nearly isoenergetic; inclusion of zero-point vibrational energy increases the relative energy to 2.11 kJ mol−1 (176 cm−1). The yet unobserved Ala-IIB conformer is found to be separated from Ala-IIA by a vibrationally adiabatic isomerization barrier of only 16 cm−1.