Hydrogen-Bond Donor-Acceptor Asymmetries in Drug Design (Exscientia 24-Oct-2024)

The presentation discusses how polarity values derived from alkane/water logP measurements enable HBDs to be compared with HBAs in the context of aqueous solvation. In molecular structures of interest to drug designers HBAs are typically more polar and more numerous than HBDs and these HBD-HBA ‘asymmetries’ are relevant when optimizing aqueous solubility and membrane permeability. The presence of an HBD in a molecular structure generally implies that an HBA is also present (but not vice versa) and this HBD-HBA asymmetry is relevant when optimizing binding affinity for targets.