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Molecular dynamics study of uncharged bupivacaine enantiomers in phospholipid bilayers
Author(s) -
Martini M. Florencia,
Pickholz Mónica
Publication year - 2012
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.24208
Subject(s) - popc , chemistry , enantiomer , lipid bilayer , molecular dynamics , bilayer , phospholipid , phosphatidylcholine , membrane , stereochemistry , computational chemistry , biochemistry
To investigate the effects of the uncharged bupivacaine (BVC) on the properties of model membranes of 1‐palmitoyl‐2‐oleoyl‐ sn ‐glycero‐3‐phosphatidylcholine (POPC), we have performed a series of molecular dynamics simulations. A very particular characteristic of the local anesthetic BVC, that is being discuss in the recent literature, is that their enantiomers R‐(+) (R‐BVC) and S‐(−) (S‐BVC) present different activities. In this way, we have studied both enantiomers in a POPC phospholipids bilayers at a high molar ratios [local anesthetic (LA):lipid of 1:3]. The simulations were able to capture important features of the BVC–phospholipid bilayer interactions: BVC molecules are found in the interior of the bilayer. The R‐BVC enantiomer follows a bimodal distribution with access to the water–lipid interface; while the S‐BVC is found, in more uniform distribution, at the hydrophobic region. A decrease in the acyl chain segment order parameters, S CD , compared to neat bilayers, is found. Furthermore, this behavior is more noticeable for the R‐BVC form. The found decrease in S CD is attributed to a larger accessible volume per lipid in the tail region. Our results could help to understand the higher toxicity of this enantiomer. © 2012 Wiley Periodicals, Inc.