title: Ring Structure and Aromatic Substituent Effects on the pK a of the Benzoxaborole Pharmacophore.
abstract: In this work, we present an investigation into the physical properties of a unique class of aromatic boronic acids, the benzoxaboroles. Using spectrophotometric methods, the ionization constants of a family of substituted benzoxaboroles are determined. Heterocyclic ring modifications are examined to determine their effects on the ionization of the boronic acid moiety. It is also shown that the substituent effects about the aromatic ring follow a Hammett relationship with the compounds' measured pK a values. Finally, these substituent effects are also shown to extend to the sugar binding properties of these compounds under physiologically relevant conditions. Combined, these data will inform medicinal chemists wishing to tailor the ionization and/or ability of this class of compound to bind diol-containing biomolecules.
authors.affiliation: Chemistry Department, The Pennsylvania State University , 104 Chemistry Building, University Park, Pennsylvania 16802, United States.
authors.forename: John W
authors.initials: JW
authors.lastname: Tomsho
authors.affiliation: Department of Chemistry, University of Alberta , Edmonton, Alberta T6G 2G2 Canada.
authors.forename: Arnab
authors.initials: A
authors.lastname: Pal
authors.affiliation: Department of Chemistry, University of Alberta , Edmonton, Alberta T6G 2G2 Canada.
authors.forename: Dennis G
authors.initials: DG
authors.lastname: Hall
authors.affiliation: Chemistry Department, The Pennsylvania State University , 414 Wartik Building, University Park, Pennsylvania 16802, United States.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Benkovic
keywords: Benzoxaborole; Hammett relationship; benzoboroxole; benzoxaborin; boronic acid; diol binding; oxaborole; pKa prediction