Ab Initio Conformational Study of Two Lewis X Analogues

Abstract

This paper presents the first ab initio conformational study for analogues of a histo-blood group carbohydrate antigen, Le x (Gal--1,4-[Fuc-R-1,3]-GlcNAc). In these analogues, the GlcNAc group of Le x was replaced by a cyclohexanediol or an ethanediol group. The lowest energy conformers of these molecules were first found by the MM2*-SUMM conformational search technique. The molecular geometries and energies of lowest energy rotamers (within a 3 kcal/mol energy window) were further analyzed at the HF/6-31G(d) level of theory. This study provides a detailed description of the hydrogen-bonding properties of the low-energy conformers yielded by the MM2* and ab initio methods. The key torsion angles for Fuc-R-1,3-GlcNAc and Gal--1,4-GlcNAc glycosidic bonds in Le x mostly keep their value in the different environments (solid, liquid, and gas phase). The ab initio torsion angles agree considerably better with the experimental results than the MM2* results. Another essential difference between the MM2* and ab initio results is that the latter provide better differentiation of the rotamers. Complexes with selectins introduced varying levels of distortion of Le x , with the most tightly bound structure being most distorted. Nonstacked rotamers occur only once among the rotamers of 1,2-cyclohexanediol analogue, and that rotamer is not particularly stable (∆E ) 2.3 kcal/ mol). However, such kind of rotamers are more frequent among the rotamers of 1,2-ethanediol analogue. This clearly shows that while the conformational space of 1,2-cyclohexanediol analogue is rather similar to that of Le x , the conformational space of 1,2-ethanediol analogue is considerably less similar.

Quantum Mechanics Studies of the Intrinsic Conformation of Trehalose

“…The remaining four sets were based on searches with MM3 calculations 51 and others using the AMBER* potential energy function in MacroModel. Similar methods to select structures for subsequent QM calculations have been used by McCarren et al, for monosaccharides, and by Csonka and Sosa who did some HF/6-31G* calculations on trisaccharides . However, the use of these techniques at each point on a φ, φ‘ map for a disaccharide is apparently novel.…”

“…Similar methods to select structures for subsequent QM calculations have been used by McCarren et al, for monosaccharides, 52 and by Csonka and Sosa who did some HF/6-31G* calculations on trisaccharides. 53 However, the use of these techniques at each point on a φ, φ′ map for a disaccharide is apparently novel.…”

Comparative performance of MM3(92) and two TINKER™ MM3 versions for the modeling of carbohydrates

“…On the other hand, the application of more rigorous methods were hindered by the rotameric complexity of the exo‐cyclic substituents (the “multiple minimum problem”2, 3), requiring several hundreds or thousands of minimizations for each structure 4. Therefore, although several DFT/ ab initio studies were carried out for monosaccharides,5–14 only a few were made for disaccharides or analogs 15–21. These larger structures were studied mostly by molecular mechanics using different force fields, with MM322, 23 being used for most of the systematic studies given its ability to handle directional hydrogen bonding and its parameterization of anomeric and exo ‐anomeric effects 3.…”

Relaxed energetic maps of κ‐carrabiose: A DFT study

“…Following the recommendations and symbols proposed by the IUPAC,33 we have used in this article (Φ, Ψ) for the disaccharide, (such as Φ = O5′C1′O1′C4 and Ψ = C1′O1′C4C5), the primes (in accordance with previously published works11–35) refer to atoms of the reducing sugar unit (see Fig. 1).…”

“…DFT and, in general, ab initio methods are not so simple to use when dealing with compounds that have a variety of conformers, such as carbohydrates, as, calculation of the conformational space or the energy hypersurface of mono, di, or trisaccharides by such methods requires enormous CPU time 22–25…”