2022/10/25 by Peter W. Kenny · 1 voice · 7 citations
Chemistry · Computer Science · Biochemistry, Genetics and Molecular Biology · #Crystallography and molecular interactions #Computational Drug Discovery Methods #Chemical Synthesis and Analysis
paper · doi:10.1021/acs.jmedchem.2c01147
openalex publication_date 2022/10/25 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/31
Hydrogen-bond donors are seen to cause more problems for drug designers than hydrogen-bond acceptors. Most of the polarity in drug-like compounds comes from hydrogen-bond acceptors since they typically exceed the hydrogen-bond donors in number and are more heavily solvated on an individual basis. The implications of this polarity imbalance for optimization of permeability and aqueous solubility are discussed. A factor that should be considered in optimization of ligand recognition by targets is that the presence of a hydrogen-bond donor generally implies that a hydrogen-bond acceptor is also present (but not vice versa). Frustrated solvation and secondary electrostatic interactions result from aligned hydrogen-bond donors and acceptors, and the design opportunities presented by these phenomena are discussed. Hydrogen-bond donors based on oxygen, nitrogen and carbon are compared as target recognition elements, and halogen- and chalcogen-bond donors are discussed as hydrogen-bond donor equivalents.