Molecular Dynamics Study of Uncharged Bupivacaine Enantiomers in Phospholipid Bilayers

M.F. MARTINI; M. PICKHOLZ

INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY

JOHN WILEY & SONS INC

Lugar: New York; Año: 2012 vol. 112 p. 2241 - 2246

0020-7608

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-(þ) (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, SCD, compared to neat bilayers, is found. Furthermore, this behavior is more noticeable for the R-BVC form. The found decrease in SCD 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.