Role of Hydrogen Bonding in QSAR
Hugo Kubinyi asks: “Last mystery in drug design?”
Log P(oct) has been seen ‘deficient’ since it is not affected by solute H-donor strength
Teague & Davis1 suggest H-bonding much less important in drug-receptor interactions than in the DNA duplex, for example
Abraham & Mitchell2 see solute H-donor important in membrane transport, especially BBB.
H-donor strength measureable by:Log P(O/Chl) = - 1.0 V + 3.2 ?? -0.03where ?? is ‘effective sum of’ H-donor strength3
Presently it appears that not enough dependable Log P(Chl) values available, but approach still promising.
1) Angew. Chem. Int. Ed., 1999, 38 736-749.2) J. Pharm. Sci., 1997, 86, 310-314.3) CHEMTECH, July 1996, 20-29