Molecular dynamics study of uncharged bupivacaine enantiomers in phospholipid bilayers

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.