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Drug release by pH‐responsive molecular tweezers: Atomistic details from molecular modeling
Author(s) -
Mohammed Ahmed A. K.,
Burger Steven K.,
Ayers Paul W.
Publication year - 2014
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.23652
Subject(s) - molecular tweezers , molecular dynamics , optical tweezers , chemistry , tweezers , molecule , molecular mechanics , drug delivery , drug , computational chemistry , molecular recognition , nanotechnology , biophysics , chemical physics , supramolecular chemistry , materials science , organic chemistry , physics , quantum mechanics , biology , psychology , psychiatry
pH‐responsive molecular tweezers have been proposed as an approach for targeting drug‐delivery to tumors, which tend to have a lower pH than normal cells. We performed a computational study of a pH‐responsive molecular tweezer using ab initio quantum chemistry in the gas‐phase and molecular dynamics (MD) simulations in solution. The binding free energy in solution was calculated using steered MD. We observe, in atomistic detail, the pH‐induced conformational switch of the tweezer and the resulting release of the drug molecule. Even when the tweezer opens, the drug molecule remains near a hydrophobic arm of the molecular tweezer. Drug release cannot occur, it seems, unless the tweezer is in a hydrophobic environment with low pH. © 2014 Wiley Periodicals, Inc.