Fatty Alcohol Membrane Model for Quantifying and Predicting Amphiphilicity

Amphiphilicity is an important property for drug development
and
self-assembly. This paper introduces a general approach based on a
simple fatty alcohol (dodecanol) membrane model that can be used to
quantify the amphiphilicity of small molecules that are in good agreement
with experimental surface tension data. By applying the model to a
systematic series of compounds, it was possible to elucidate the effect
of different motifs on amphiphilicity. The results further indicate
that amphiphilicity correlates strongly with water–octanol
partition coefficients (logP) for the 29 organic
molecules examined in the 0 < logP < 4 range.
Importantly, the simulation of the model membrane is an order of magnitude
faster than a phospholipid membrane (e.g., 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) simulation and offers a simple
atomistic approach for quantifying and predicting amphiphilicity of
small drug-like molecules that could be used in quantitative structure–activity
relationship studies.