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The influence of hydrophobic amino acid side groups on the acidity of the aromatic imidazole ring of histidine: A theoretical study
Author(s) -
Najafabadi Reza Izadi,
Housaindokht Mohammad Reza,
Sadeghi Googheri Mohammad Sadegh,
Sargolzaei Mohsen,
Izadyar Mohammad
Publication year - 2011
Publication title -
international journal of quantum chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.484
H-Index - 105
eISSN - 1097-461X
pISSN - 0020-7608
DOI - 10.1002/qua.23270
Subject(s) - solvation , chemistry , imidazole , delocalized electron , implicit solvation , computational chemistry , histidine , ring (chemistry) , gibbs free energy , natural bond orbital , density functional theory , crystallography , stereochemistry , amino acid , organic chemistry , molecule , thermodynamics , biochemistry , physics
In this study we have calculated the acidity constant (p K a) of imidazole ring in Histidine‐Hydrophobic amino acid dipeptides using the quantum chemistry and continuum solvation methods. Density functional theory calculations with the large basis sets are used to determine the Gibbs free energy of deprotonate in the gas and liquid phases. Based on our results Δ G S values are located between −69.38 and −18.82 kcal mol −1 which are related to His + –Gly and His forms, respectively. p K a of the dipeptides in the aqueous phase was obtained from the calculated gas‐phase and solvation free energies through a thermodynamic cycle and the solvation model chemistry of Martin Karplus et al. Solvation effects are treated using a self‐consistent reaction field formalism involving polarized continuum models. According to our calculations p K a values are between 5.50 and 8.19 that are belong to His + –ILe and His + –Ala forms, respectively. Natural bond orbital analysis of dipeptides reveals that the electron delocalization in imidazole ring is the most effective factor in determination of acidity order for these compounds. Structural analysis confirmed that the orientation of carbonyl group with respect to imidazole ring is an effective factor in imidazole ring stability. © 2011 Wiley Periodicals, Inc. Int J Quantum Chem, 2011