Conformational isomerism

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

Theoretical study of the relative stability of rotational conformers of α and β-D-glucopyranose in gas phase and aqueous solution

Abstract: The α−β anomer energy difference and the stability of 10 rotamers of counterclockwise d-glucopyranose were studied in vacuo and in aqueous solution at the B3LYP/6-31+G(d,p) level. To obtain the solute charge distribution and the solvent structure around it, we used the averaged solvent electrostatic potential from molecular dynamics method, ASEP/MD, which alternates molecular dynamics and quantum mechanics calculations in an iterative procedure. The main characteristics of the anomeric equilibrium, both in vacuo and in solution, are well reproduced. The relative stability of the different anomers is related to the availability of the free pairs of electrons in the anomeric oxygen to interact with the water molecules. The influence of solvation in the conformer equilibrium is also analyzed.

Conformational analysis of synthetic heparin-like oligosaccharides containing α-L-idopyranosyluronic acid†

Abstract: High-field NMR spectroscopy of synthetic heparin-like di- and trisaccharides has afforded a complete set of inter-proton-coupling data on α-L-idopyranosyluronic acid, which have been used for conformational analysis. These data lead to the conclusion that α-L-iduronic acid may display considerable conformational freedom including 1C4, 4C1 and 2S0 (e.g. compound 1) conformers. The 2-O-sulphate substituent at iduronic acid tends to stabilize the 1C4 conformation (e.g. compounds 2 and 4). In addition carbohydrate substituents at position 4 hinder the 4C1 conformation (e.g. compound 3a,b versus 1). Furthermore, the conformation of α-L-idopyranosyluronic acid 2-sulphate is affected seriously by the substituent at position 2 of the non-reducing glucosamine residue. Thus the presence of an ammonium group (i.e. compound 7) leads to unexpected deformation of the 1C4 form of iduronic acid, whereas a sulphamino substituent at this position (e.g. compound 5a,b) brings about the 2S0 skew boat conformation. The iduronic acid moiety of a trisaccharide (compound 6), which represents a part of the anti-thrombin III-binding site of heparin, shows conformational preference for the 2S0 form in aqueous solution under low ionic conditions. However, increasing the ionic strength (e.g. 3 M NaCl) causes the conformational equilibrium to incline towards the 1C4 chair conformer. This feature may be indicative for the mechanism of conformational control as exerted by the AT-III protein upon heparin binding. Several molecular models of preferred conformers have been constructed; Nuclear Overhauser Enhancement data, exo-anomeric effect and Van der Waals interactions have been taken into account.

Design, synthesis, and conformational analysis of a novel spiro-bicyclic system as a type II β-turn peptidomimetic

Abstract: A novel highly constrained spiro-bicyclic system (5) has been developed to mimic the type II β-turn, a secondary structural feature found in many bioactive peptides. This system simultaneously restricts three (Φ 2 , Ψ 2 , and Φ 3 ) of the four torsion angles that characterize the type II β-turn. As a test of the design, the asymmetric synthesis and conformational analysis of derivative 6 starting from (R)-2-allylproline is reported. Temperature dependent NMR chemical shift studies in CDCl 3 suggest that the amide proton of 6 is involved in an intramolecular hydrogen bond.Aso,NOE measurements place this hydrogen under the plane of the bicyclic ring system in proper proximity for this hydrogen bond to form with the acetyl carbonyl oxygen.Modeling studies of 6 produced eight minimum-energy conformations with torsion angles close to those of the classical type II β-turn.A comparison of the minimum-energy conformer of this molecule with the classical type II β-turn gave an RMS fit=0.161 A °