Study of the benzocaine transfer from aqueous solution to the interior of a biological membrane.
The precise molecular mechanism of general anesthetics remains unknown. It is therefore important to understand where molecules with anesthetic properties localize within biological membranes. We have determined the free energy profile of a benzocaine molecule (BZC) across a biological membrane using molecular dynamics simulation. We use an asymmetric phospholipid bilayer with DPPS in one leaflet of a DPPC bilayer (Lopez Cascales et al. J. Phys. Chem. B 2006, 110, 2358-2363) to model a biological bilayer. From the free energy profile, we predict the zone of actuation of a benzocaine is located in the hydrocarbon region or at the end of the lipid head, depending of the presence of charged lipids (DPPS) in the leaflet. We observe a moderate increase in the disorder of the membrane and in particular an increase in the disorder of DPPS. Static and dynamic physicochemical properties of the benzocaine, such as its dipole orientation, translational diffusion coefficient, and rotational relaxation time were measured.
Porasso
Rodolfo D
RD
Instituto de Matemática Aplicada San Luis (IMASL)-Departamento de Física, Universidad Nacional de San Luis/CONICET, D5700HHW, San Luis, Argentina.
Bennett
W F Drew
WF
Oliveira-Costa
S D
SD
López Cascales
J J
JJ
D001566:Benzocaine / Q000737:chemistry*; D003198:Computer Simulation; D008051:Lipid Bilayers / Q000737:chemistry*; D008567:Membranes, Artificial; D008956:Models, Chemical; D010718:Phosphatidylserines / Q000737:chemistry*; D010743:Phospholipids / Q000737:chemistry*; D012996:Solutions; D013816:Thermodynamics; D013997:Time Factors; D014867:Water / Q000737:chemistry
D008051:Lipid Bilayers; D008567:Membranes, Artificial; D010718:Phosphatidylserines; D010743:Phospholipids; D012996:Solutions; D014867:Water; C038694:dipalmitoylphosphatidylserine; D001566:Benzocaine