hydrogenbondaccepting

Hydrogenbondaccepting refers to the ability of a site within a molecule to accept a hydrogen atom from a hydrogen bond donor. In most contexts, hydrogen bond accepting sites are electronegative atoms bearing lone pairs, such as oxygen, nitrogen, or sulfur. The concept contrasts with hydrogen bond donating, where a hydrogen atom is attached to an electronegative atom and can donate a bond to an acceptor.

Common hydrogen bond acceptors include carbonyl oxygens (as in aldehydes, ketones, and carboxylates), ether and alcohol oxygens, nitrile nitrogens, and imine nitrogens. Sulfur-containing groups such as thioethers and thiols can also act as acceptors, though often more weakly. Aromatic heterocycles like pyridine provide classic HBAs. Amide nitrogens are generally not considered effective acceptors, whereas the amide carbonyl oxygen is a strong HBA. The protonation state of an atom matters: when an potential acceptor is protonated or positively charged, its ability to accept hydrogen bonds is reduced or lost.

In medicinal chemistry and cheminformatics, the hydrogen bond acceptor count is a descriptor used to assess drug-likeness and ADMET properties. It counts heteroatoms with lone pairs capable of accepting a hydrogen bond, typically excluding positively charged or strongly delocalized nitrogens. Lipinski's rule-of-five and related guidelines use HBA as one component to estimate a molecule’s pharmacokinetic behavior.

Limitations include context dependence: geometry, solvent effects, pH, and tautomeric states can alter HBA behavior. Computational estimates of hydrogen bond accepting are approximations that rely on structural and electronic assumptions.