Revealing the Conformational Preferences of Proteinogenic Glutamic Acid Derivatives in Solution by ¹H NMR Spectroscopy and Theoretical Calculations

Abstract

The conformational preferences of proteinogenic glutamic acid esterified (GluOMe) and N-acetylated (AcGluOMe) derivatives have been determined in solution for the first time. Theoretical calculations at the ωB97X-D/aug-cc-pVTZ made possible the assignment of six and eight stable conformers for GluOMe and AcGluOMe, respectively. The conformational equilibrium of the studied compounds was evaluated in different organic solvents using a combination of the integral equation formalism polarizable continuum model (IEF-PCM) and H NMR spectroscopy data. The results showed that the conformational equilibrium of both derivatives change in the presence of solvent. According to the quantum theory of atoms in molecules (QTAIM), non-covalent interactions (NCI), and natural bond orbitals (NBO) analyses, the conformational preferences observed for GluOMe and AcGluOMe are not dictated by the presence of a specific interaction but are due to a combination of hyperconjugative and steric effects.

Dealing with Hydrogen Bonding on the Conformational Preference of 1,3-Aminopropanols: Experimental and Molecular Dynamics Approaches

“…This result is attributed to changes in the s-character of the oxygen sp n -hybridized lone pair (LP 1 O) orbital. 66,67 For the compounds herein, the data in Table 4 show that the s- character of the LPN orbital also decreases along with the decrease in the ε j − ε i energy gap and in the Kohn−Sham Fock matrix element for all conformers. Despite the reduction in scharacter and the increase in LPN p-character, the charge transfer from LPN to σ*OH slightly decreases in compounds 1−3 (Table 3).…”