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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.

SUBMITTER: Tomsho JW

PROVIDER: S-EPMC4025869 | biostudies-other | 2012 Jan

REPOSITORIES: biostudies-other

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Ring Structure and Aromatic Substituent Effects on the pK a of the Benzoxaborole Pharmacophore.

Tomsho John W JW Pal Arnab A Hall Dennis G DG Benkovic Stephen J SJ

ACS medicinal chemistry letters 20111019 1

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 ...[more]

PMID: 24900370

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