Thermodynamic parameters for the association of fluorinated benzenesulfonamides with bovine carbonic anhydrase II

Vijay M. Krishnamurthy, Brooks R. Bohall, Chu Young Kim, Demetri T. Moustakas, David W. Christianson, George M. Whitesides

Research output: Contribution to journalArticlepeer-review

Abstract

This paper describes a calorimetric study of the association of a series of seven fluorinated benzenesulfonamide ligands (C6HnF 5-nSO2NH2) with bovine carbonic anhydrase II (BCA). Quantitative structure-activity relationships between the free energy, enthalpy, and entropy of binding and pKa and log P of the ligands allowed the evaluation of the thermodynamic parameters in terms of the two independent effects of fluorination on the ligand: its electrostatic potential and its hydrophohicity. The parameters were partitioned to the three different structural interactions between the ligand and BCA: the ZnII cofactor-sulfonamide bond (≈ 65% of the free energy of binding), the hydrogen bonds between the ligand and BCA (≈10%), and the contacts between the phenyl ring of the ligand and BCA (≈25%). Calorimetry revealed that all of the ligands studied bind in a 1:1 stoichiometry with BCA; this result was confirmed by 19F NMR spectroscopy and X-ray crystallography (for complexes with human carbonic anhydrase II).

Original languageEnglish (US)
Pages (from-to)94-105
Number of pages12
JournalChemistry - An Asian Journal
Volume2
Issue number1
DOIs
StatePublished - 2007
Externally publishedYes

Keywords

  • Calorimetry
  • Fluorinated ligands
  • Ligand design
  • Rational drug design
  • Structure-activity relationships

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry

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