A theoretical and experimental¹H NMR spectroscopy study of the stereoelectronic interactions that rule the conformational energies of alanine and valine methyl ester

Abstract

Amino acids exhibit a bipolar zwitterionic structure ( + H 3 N-CHR-COO À ) in solution; hence, conformational studies of these compounds have been limited to the gas phase. The conformational preferences of amino acids have been widely attributed to intramolecular hydrogen bonding, despite steric and hyperconjugative effects. In this work, we propose the conformational study of alanine and valine methyl esters, which do not show zwitterionic structures in solution, by 1 H NMR and theoretical calculations. The 3 J HH spin-spin coupling constants and theoretical calculations were found to be in agreement, showing that the interplay between steric hindrance and hyperconjugation is the forces that are responsible for determining the conformational preferences of alanine and valine methyl esters.

Conformational study of L-methionine and L-cysteine derivatives through quantum chemical calculations and 3JHH coupling constant analyses

“…The starting conformer geometries for 1 and 2 were constructed from the six most stable optimized conformers of L-alanine methyl ester (Ala-OMe), reported by a previous study [ 33 ], which have the less energetic arrangement of the backbone [CH 3 −O−C(O)−CH(NH 2 )−], as follows. A methyl hydrogen atom (side chain) of Ala-OMe was substituted by CH 2 −S−CH 3 and S−H, giving rise to six new geometries for the compounds 1 and 2 , respectively.…”

Experimental and theoretical evaluation on the conformational behavior of l-aspartic acid dimethyl ester and its N-acetylated derivative

“…The conformational investigation to nd the possible energy minima of AspOMe was performed starting from the six conformers (I, III, IV1, IV2, V1 and V2) previously obtained for alanine methyl ester (AlaOMe), 9 which have the less energetic arrangement of the backbone [CH 3 -O-C(O)-CH(NH 2 )-]. To this end, a methyl hydrogen atom (side chain) of AlaOMe was replaced by the C(O)-O-CH 3 group, giving rise to the side chain of aspartic acid.…”

“…The conformational investigation to nd the possible energy minima of AspOMe was performed starting from the six conformers (I, III, IV1, IV2, V1 and V2) previously obtained for alanine methyl ester (AlaOMe), 9 The 34 minima resulting from the PES were subsequently fully reoptimized using DFT different functionals (B3LYP, 16 CAM-B3LYP, 17 M05-2X, 18 M06-2X, 19 B97-D 20 and uB97X-D 21 ) with the aug-cc-pVTZ basis set, and their harmonic frequencies were calculated and also zero-point energy (ZPE) correction. The obtained data were referenced to the single point calculations at the MP2/aug-cc-pVTZ level of theory.…”

“…In order to overcome the aforementioned difficulties, an alternative approach proposed by our group is to analyze their esteried and N-acetylated derivatives, [9][10][11] which, unlike amino acids, are soluble in most organic solvents. Moreover, these compounds properly simulate the amino acid residue in a polypeptide chain or protein.…”

Conformational Analysis and Intramolecular Interactions of l-Proline Methyl Ester and Its N-Acetylated Derivative through Spectroscopic and Theoretical Studies

“…12,13 These compounds do not exist as zwitterions in solution and are soluble in a majority of organic solvents, making possible their studies in solution by properly simulating the amino acid residues in biological media, better than amino acids in the gas phase.…”