Experimental And Theoretical Evaluation On The Conformational Behavior Of L-aspartic Acid Dimethyl Ester And Its N-acetylated Derivative

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)In this work the conformational preferences of L-aspartic acid dimethyl ester (AspOMe) and its N-acetylated derivative (AcAspOMe) were evaluated through spectroscopic data and theoretical calculations. Unlike amino acids, their corresponding amino ester derivatives do not exhibit a zwitterionic structure and are soluble in most organic solvents, enabling their studies in these media. Thus, the conformers of AspOMe and AcAspOMe were theoretically determined both in isolated phase and in solution (IEF-PCM model) at the omega B97X-D/aug-cc-pVTZ level. A joint analysis of the experimental and theoretical (3)J(HH) coupling constants in several aprotic solvents allowed assigning the most stable conformers, showing excellent agreement between these approaches. Also, IR spectroscopy allowed us to obtain quantitative data on AcAspOMe conformer populations in different solvents. Natural bond orbital (NBO) analysis indicated that both steric and hyperconjugative contributions count in determining the relative conformer stabilities of these compounds. Intramolecular hydrogen bonding, characterized by Quantum Theory of Atoms in Molecules (QTAIM) and Non-Covalent Interactions (NCI) methodologies, represents only a secondary factor to drive the stabilities of AspOMe and AcAspOMe conformers.5231801318024Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)FAPESP [2012/03933-5, 2012/18567-4