Demonstrating accuracy of the proposed protocol for structure elucidation of cyclodextrin inclusion complexes by validation using DFT studies

摘要

Escalating interests in computational chemistry call for the modeling procedures that provide higher degree of accuracy and reliability. In the present work, atom accurate structures of the inclusion complexes formed between gamma-cyclodextrin (gamma-CD) and cetirizine (CIT) have been determined by a combination of experimental and computational methods i.e. MD simulations and quantitative ROESY analysis, as developed by us previously. Density functional theory (DFT) is a quantum mechanical approach and an already established method. We therefore performed DFT studies to ascertain the accuracy of the structures generated through our method in terms of atomic coordinates. DFT studies for the complexes formed by the phenyl and chlorophenyl rings of CIT with gamma-CD were carried out using the hybrid functional-B3LYP followed by quantitative ROESY analysis. Comparison of calculated ROESY peak intensities of the structures obtained from our method and from DFT studies with the experimental intensities showed parallel results. This validates the atom accuracy of the structures obtained by our strategy. Moreover, an advantage of the procedure developed by us over DFT studies is that it is less time consuming and can be performed at lower computational cost. (C) 2020 Elsevier B.V. All rights reserved.