The ω, phi, and ψ Space of N-Hydroxy-N-methylacetamide and N-Acetyl-N ‘-hydroxy-N ‘-methylamide of Alanine and Their Boron Isosteres

Malde, Alpeshkumar K., Khedkar, Santosh A. and Coutinho, Evans C. (2006) The ω, phi, and ψ Space of N-Hydroxy-N-methylacetamide and N-Acetyl-N ‘-hydroxy-N ‘-methylamide of Alanine and Their Boron Isosteres. Journal of Chemical Theory and Computation, 2 2: 312-321. doi:10.1021/ct050242v

Author Malde, Alpeshkumar K.
Khedkar, Santosh A.
Coutinho, Evans C.
Title The ω, phi, and ψ Space of N-Hydroxy-N-methylacetamide and N-Acetyl-N ‘-hydroxy-N ‘-methylamide of Alanine and Their Boron Isosteres
Journal name Journal of Chemical Theory and Computation   Check publisher's open access policy
ISSN 1549-9618
Publication date 2006-01
Sub-type Article (original research)
DOI 10.1021/ct050242v
Volume 2
Issue 2
Start page 312
End page 321
Total pages 10
Place of publication Washington, D.C.
Publisher American Chemical Society
Language eng
Subject 030701 Quantum Chemistry
Abstract The conformational space of N-hydroxy-N-methylacetamide [CH3−CO−N(OH)CH3, NMAOH] and its boron isostere [CH3−CO−B(OH)CH3, BMAOH] has been studied by quantum chemical methods. The potential energy surface of NMAOH and BMAOH has been built at the HF, B3LYP, and MP2 levels of theory with the 6-31+G* basis set. The minima and transition states for rotations about various torsional angles have been located, and the energy barriers have been estimated. The global minimum energy structure of both peptides exhibits an intramolecular hydrogen bond between the carbonyl oxygen and the hydroxyl group, imparting a conformational rigidity to the peptides. The omega rotation barrier is lower in the boron isostere than in NMAOH. The difference in the rotation barrier has been attributed to second-order orbital interactions, like negative hyperconjugation, as revealed by NBO calculations. In contrast, the rotation barrier around the torsion angle tau (torsion governing rotation about the N−O and B−O bonds) is relatively higher in the boron analogue. This difference is due to the double bond character in the B−O bond as opposed to the N−O bond which has the character of a single bond. As an extension, N-acetyl-N‘-hydroxy-N‘-methylamide of alanine (Ala-NOH) and its boron isostere (Ala-BOH) have been adopted as model peptides to study the conformational preferences about the phi and ψ torsion angles. The study reveals a strong preference for a Type I beta turn as well as inclinations for a left-handed alpha helix, for positive phi torsions, and for extended psi conformations for Ala-NOH; Ala-BOH, on the other hand, shows a leaning toward positive phi and extended psi, with no preference for any regular secondary structure motifs. The replacement of nitrogen by boron changes the electronic and conformational properties of the peptide, extending greater flexibility around the omega angle, a strong preference for positive phi values, and a shift in the site of nucleophilic attack from the carbonyl group to boron.
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Chemistry and Molecular Biosciences
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