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Binding energies of five molecular pincers calculated by explicit and implicit solvent models
Author(s) -
Kessler Jiří,
Jakubek Milan,
Dolenský Bohumil,
Bouř Petr
Publication year - 2012
Publication title -
journal of computational chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.907
H-Index - 188
eISSN - 1096-987X
pISSN - 0192-8651
DOI - 10.1002/jcc.23063
Subject(s) - van der waals force , density functional theory , molecular dynamics , chemistry , computational chemistry , computation , binding energy , basis set , molecule , statistical physics , physics , computer science , atomic physics , algorithm , organic chemistry
Molecular pincers or tweezers are designed to hold and release the target molecule. Potential applications involve drug distribution in medicine, environment technologies, or microindustrial techniques. Typically, the binding is dominated by van der Waals forces. Modeling of such complexes can significantly enhance their design; yet obtaining accurate complexation energies by theory is difficult. In this study, density functional theory (DFT) computations combined with dielectric continuum solvent model are compared with the potential of mean force approach using umbrella sampling and the weighted histogram analysis method (WHAM) with molecular dynamics (MD) simulations. For DFT, functional and basis set effects are discussed. The computed results are compared to experimental data based on NMR spectroscopic measurements of five synthesized tweezers based on the Tröger's basis. Whereas the DFT computations correctly provided the observed trends in complex stability, they failed to produce realistic magnitudes of complexation energies. Typically, the binding was overestimated by DFT if compared to experiment. The simpler semiempirical PM6‐DH2X scheme proposed lately yielded better magnitudes of the binding energies than DFT but not the right order. The MD‐WHAM simulations provided the most realistic Gibbs binding energies, although the approximate MD force fields were not able to reproduce completely the ordering of relative stabilities of model complexes found by NMR. Yet the modeling provides interesting insight into the complex geometry and flexibility and appears as a useful tool in the tweezers' design. © 2012 Wiley Periodicals, Inc.