title: Conformational preferences of proline analogues with a fused benzene ring.
abstract: The intrinsic conformational preferences of indoline-2-carboxylic acid (Inc) and its α-methylated derivative (αMeInc) have been investigated using quantum mechanical calculations. Specifically, the behavior of their N-acetyl-N'-methylamide derivatives, Ac-L-Inc-NHMe and Ac-L-αMeInc-NHMe, has been explored at the B3LYP/6-31+G(d,p) level. Such amino acids are analogues of proline and (α-methyl)proline, respectively, bearing a benzene ring fused to the C(γ)-C(δ) bond of the five-membered pyrrolidine ring. The additional aromatic group has been shown to significantly restrict the conformational space available to these residues by reducing the flexibility of both the five-membered cycle and the peptide backbone. The fused benzene ring also plays a critical role in determining the cis-trans arrangement of the amide bond involving the pyrrolidine nitrogen, which is also modulated by the presence of the α-methyl group in the αMeInc derivative. Furthermore, the influence of the environment on the conformational propensities of these compounds has been evaluated by using both a self-consistent reaction field model and a recently developed interface in a hybrid QM/MM scheme, in which the solvent molecules are treated explicitly with classical mechanics while the solute is described by quantum mechanics at the density functional theory level.
authors: Departamento de Química Orgánica, Instituto de Ciencia de Materiales de Aragón, Universidad de Zaragoza-CSIC, 50009 Zaragoza, Spain.
authors: Javier G
authors: JG
authors: Warren
authors: Guillem
authors: G
authors: Revilla-López
authors: Carlos
authors: C
authors: Alemán
authors: Ana I
authors: AI
authors: Jiménez
authors: Carlos
authors: C
authors: Cativiela
authors: Juan
authors: J
authors: Torras
mesh_terms: D001554:Benzene / Q000737:chemistry*; D002264:Carboxylic Acids / Q000737:chemistry; D015394:Molecular Structure; D011392:Proline / Q000031:analogs & derivatives*; D011789:Quantum Theory; D012997:Solvents / Q000737:chemistry; D013816:Thermodynamics
chemical_list: D002264:Carboxylic Acids; D012997:Solvents; D011392:Proline; D001554:Benzene