title: Hydrogen Bond Basicity Prediction for Medicinal Chemistry Design.
abstract: Hydrogen bonding is discussed in the context of medicinal chemistry design. Minimized molecular electrostatic potential (Vmin) is shown to be an effective predictor of hydrogen bond basicity (pKBHX), and predictive models are presented for a number of hydrogen bond acceptor types relevant to medicinal chemistry. The problems posed by the presence of nonequivalent hydrogen bond acceptor sites in molecular structures are addressed by using nonlinear regression to fit measured pKBHX to calculated Vmin. Predictions are made for hydrogen bond basicity of fluorine in situations where relevant experimental measurements are not available. It is shown how predicted pKBHX can be used to provide insight into the nature of bioisosterism and to profile heterocycles. Examples of pKBHX prediction for molecular structures with multiple, nonequivalent hydrogen bond acceptors are presented.
authors.affiliation: Grupo de Estudos em Química Medicinal-NEQUIMED, Instituto de Química de São Carlos, Universidade de São Paulo , Av. Trabalhador Sancarlense, 400, 13560-590 São Carlos, São Paulo, Brazil.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Kenny
authors.affiliation: Grupo de Estudos em Química Medicinal-NEQUIMED, Instituto de Química de São Carlos, Universidade de São Paulo , Av. Trabalhador Sancarlense, 400, 13560-590 São Carlos, São Paulo, Brazil.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Montanari
authors.affiliation: Grupo de Estudos em Química Medicinal-NEQUIMED, Instituto de Química de São Carlos, Universidade de São Paulo , Av. Trabalhador Sancarlense, 400, 13560-590 São Carlos, São Paulo, Brazil.
authors.forename: Igor M
authors.initials: IM
authors.lastname: Prokopczyk
authors.affiliation: Grupo de Estudos em Química Medicinal-NEQUIMED, Instituto de Química de São Carlos, Universidade de São Paulo , Av. Trabalhador Sancarlense, 400, 13560-590 São Carlos, São Paulo, Brazil.
authors.forename: Jean F R
authors.initials: JF
authors.lastname: Ribeiro
authors.affiliation: Grupo de Estudos em Química Medicinal-NEQUIMED, Instituto de Química de São Carlos, Universidade de São Paulo , Av. Trabalhador Sancarlense, 400, 13560-590 São Carlos, São Paulo, Brazil.
authors.forename: Geraldo Rodrigues
authors.initials: GR
authors.lastname: Sartori
mesh_terms: D002626:Chemistry, Pharmaceutical; D015195:Drug Design; D005461:Fluorine / Q000737:chemistry; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration
chemical_list: D005461:Fluorine