Polar interactions drive drug absorption
26 Jun 2012
Being able to predict the absorption of drugs is highly relevant to drug discovery and drug development. In this respect, the concept of the polar surface area (PSA) has been successful. The PSA is defined as the combined surface area of oxygen and nitrogen atoms and the hydrogen atoms bound to these. To contribute to improving the correlation between PSA and absorbed drug fraction, Gijs Schaftenaar and Jacob de Vlieg (CMBI, Nijmegen) approached the problem from a quantum mechanical perspective. They focused on the role of the quantum mechanical electrostatic potential in drug absorption and were able to establish a correlation between the absorbed fraction and the so-called Quantum Mechanical Polar Surface Area (QMPSA) for structures where the carboxyl groups are deprotonated. Calculations on neutral gas phase optimized structures resulted in a much weaker correlation. According to the authors, this suggests that the polar interactions of the drug molecules in solution strongly determine the absorption process.
Schaftenaar G and de Vlieg J
Quantum Mechanical Polar Surface Area
J. Comput. Aided Mol. Des. 2012, 26(3):311-318, doi:10.1007/s10822-012-9557-y