Hydrogen-Bonding Capacity and Brain Penetration

Abstract

Brain penetration has been reported to correlate with Δlog P, defined as log P (octan-1-ol/H₂O) – log P (alkane/H₂O). Another recent development, describing log P as the Sum of a cavity or volume contribution and H-bonding capability, the latter expressed by A_solvent values, prompted us to reinvestigate the properties accounting for brain penetration. It was found that A_alkane and the hydrophilic part of the van der Waals surface both correlate well with brain uptake. These findings offer new opportunities for the design of compounds which either should or should not be active at sites located in the brain.