Conformational isomerism

About: Conformational isomerism is a research topic. Over the lifetime, 11563 publications have been published within this topic receiving 199312 citations.

Photoelectron Spectroscopy and Circular Dichroism in Chiral Biomolecules: l-Alanine

Abstract: A theoretical treatment of the photoionization of the chiral amino acid l-alanine is presented. Particular attention is paid to a previously unobserved circular dichroism which should be detectable in the photoelectron angular distribution (CDAD) from randomly oriented molecules. Numerical estimates of this difference in the differential cross-sections for left- and right-circularly polarized light range as large as 40% of the mean cross-section. Three different low-energy conformational structures are considered. Further comparisons with the experimental photoelectron spectrum suggest, however, that only one dominates in the gas phase. This concurs with other experimental data but disagrees with conclusions drawn from previous molecular orbital calculations. The magnitude of the predicted CDAD effect, especially when ionizing skeletal bonding orbitals, is sufficient to suggest that it may provide an experimental means for successfully distinguishing optical and conformational isomers.

Gas Phase Formation of a 310-Helix in a Three-Residue Peptide Chain: Role of Side Chain-Backbone Interactions as Evidenced by IR−UV Double Resonance Experiments

Abstract: The first spectroscopic evidence for the gas-phase formation of helical structures in short peptide chains is reported, using the IR−UV double resonance technique and DFT quantum chemistry calculations. The study involves three chemically protected peptides, all based on the same Ac-(Ala)3-NH2, (Ac = acetyl, Ala = alanine) tripeptide, in which one of the Ala residues is substituted by the aromatic phenylalanine residue. For the three molecules, only one main conformer is observed in the supersonic expansion. IR analysis shows that the structure of this conformer is strongly dependent upon the substitution site: the helical 310-type structure is observed only when Phe occupies the central residue of the chain. The present work also emphasizes that the 310-helix formation does compete with other archetypal H-bonding patterns, such as 27-ribbon or mixed structures, whose relative energetics can be greatly influenced by a modest NH-aromatic interaction.

High pressure NMR reveals active-site hinge motion of folate-bound Escherichia coli dihydrofolate reductase.

Abstract: A high-pressure (15)N/(1)H two-dimensional NMR study has been carried out on folate-bound dihydrofolate reductase (DHFR) from Escherichia coli in the pressure range between 30 and 2000 bar. Several cross-peaks in the (15)N/(1)H HSQC spectrum are split into two with increasing pressure, showing the presence of a second conformer in equilibrium with the first. Thermodynamic analysis of the pressure and temperature dependencies indicates that the second conformer is characterized by a smaller partial molar volume (DeltaV = -25 mL/mol at 15 degrees C) and smaller enthalpy and entropy values, suggesting that the second conformer is more open and hydrated than the first. The splittings of the cross-peaks (by approximately 1 ppm on (15)N axis at 2000 bar) arise from the hinges of the M20 loop, the C-helix, and the F-helix, all of which constitute the major binding site for the cofactor NADPH, suggesting that major differences in conformation occur in the orientations of the NADPH binding units. The Gibbs free energy of the second, open conformer is 5.2 kJ/mol above that of the first at 1 bar, giving an equilibrium population of about 10%. The second, open conformer is considered to be crucial for NADPH binding, and the NMR line width indicates that the upper limit for the rate of opening is 20 s(-)(1) at 2000 bar. These experiments show that high pressure NMR is a generally useful tool for detecting and analyzing "open" structures of a protein that may be directly involved in function.

A DFT-based theoretical study on the photophysics of 4-hydroxyacridine: single-water-mediated excited state proton transfer.

Abstract: Study of intra- and intermolecular hydrogen-bonding interaction and excited state proton transfer reaction has been carried out in 4-hydroxyacridine (4-HA) and its hydrated clusters theoretically. Density functional theory [B3LYP/6-311++G(d,p)] has been exploited to calculate structural parameters and relative energies of different conformers of 4-HA and its hydrates. The substantial impact of solvent reaction field on hydrogen-bond energies, conformational equilibrium, and tautomerization reaction in aqueous medium have been realized by employing Onsager and PCM reaction field methods, and the stability of the conformers of 4-HA is found to be profusely modulated by the electrostatic influence of the solvent. A deeper insight into the nature of H-bonding in 4-HA and its hydrated clusters has been achieved under the provision of natural bond orbital and atoms in molecule analysis. Elucidation of potential energy curves for proton transfer reaction reveals that an intrinsic and two-water-molecule-assisted ...

The Role of Arene–Arene Interactions in the Folding of ortho-Phenylenes

Abstract: The ortho-phenylenes are a simple class of helical oligomers and representative of the broader class of sterically congested polyphenylenes. Recent work has shown that o-phenylenes fold into well-defined helical conformations (in solution and, typically, in the solid state); however, the specific causes of this folding behavior have not been determined. Here, we report the effect of substituents on the conformational distributions of a series of o-phenylene hexamers. These experiments are complemented by dispersion-corrected DFT calculations on model oligomers (B97-D/TZV(2d,2p)). The results are consistent with a deterministic role for offset arene–arene stacking interactions on the folding behavior. On the basis of the experimental and computational results, we propose a model for o-phenylene folding with two simple rules. (1) Conformers are forbidden if they include a particular sequence of biaryl torsional states that causes excessive steric strain. These “ABA” states correspond to consecutive dihedral...