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Preferential mode of cyclization of tetrahydrofuran amino acids containing peptides: some theoretical insights
Author(s) -
Kumar N. V. Suresh,
Sharma Purshotam,
Singh Harjinder,
Koley Dipankar,
Roy Saumya,
Chakraborty Tushar Kanti
Publication year - 2010
Publication title -
journal of physical organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.325
H-Index - 66
eISSN - 1099-1395
pISSN - 0894-3230
DOI - 10.1002/poc.1609
Subject(s) - chemistry , intramolecular force , tetrahydrofuran , tripeptide , natural bond orbital , intermolecular force , molecule , hydrogen bond , computational chemistry , density functional theory , solvent , stereochemistry , amino acid , organic chemistry , biochemistry
Theoretical insights have been provided for the observed preference of cyclodimerization over intramolecular cyclization reactions in linear tripeptides containing “2,5‐ cis ” (2S,5R)‐tetrahydrofuran amino acid as well as in those containing “2,5‐ trans ” (2S,5S)‐tetrahydrofuran amino acid, using quantum chemical methods. The geometries of species involved as well as the feasibility of cyclization reactions are studied at the B3LYP/6‐31G(d,p) level of theory in gas phase as well as in solvent phase. Thermodynamic data from Hessian calculations favor the intermolecular cyclization. Analysis of optimized geometries reveals the existence of additional stabilizing hydrogen bonding interactions in intermolecularly cyclized products. The existence of these second‐order interactions is substantiated by topological (atoms in molecules (AIM)) and natural bond orbital (NBO) analyses. Such interactions are absent in the intramolecular cyclization products. Further justification for the presence of stabilizing interactions in intermolecularly cyclized products comes from the molecular electrostatic potentials and electron density surfaces. Kinetic control favoring the intermolecularly cyclized products due to additional entropy of activation in the intramolecular case is surmised. Copyright © 2009 John Wiley & Sons, Ltd.