title: Characterization of the aqueous iron(III) chelation chemistry of a potential Trojan Horse antimicrobial agent: chelate structure, stability and pH dependent speciation.
abstract: The aqueous solution equilibria of a β-lactam antimicrobial agent containing a 3-hydroxy, 4-pyridinone group (L                         (PF)) binding to Fe(III) in aqueous solution has been characterized through spectrophotometric and potentiometric titrations. The metal-free ligand has four observable protonation constants, pK(a1) = 2.6, pK(a2) = 3.43, pK(a3) = 6.43, and pK(a4) = 9.62. L                         (PF) forms a 3:1 ligand:Fe(III) complex in aqueous solution through coordinate-covalent bond formation exclusively involving the bidentate hydroxypyridinone moiety. This 3:1 L                         (PF):Fe complex was found to have a stability constant of log β(130) = 33.46. A speciation diagram for the L                         (PF) system demonstrates that in the region of physiological pH the tris-(L                         (PF))Fe(III) complex, Fe(L(PF))                            (3)                                      (6-)                         , predominates. This complex exhibits two irreversible reduction waves in solution at -30 mV versus NHE, corresponding to a ligand-based reduction, and at -385 mV versus NHE, corresponding to an irreversible Fe(3+)/Fe(2+) reduction of the Fe(L(PF))                            (3)                                      (6-)                          complex.
authors.affiliation: Department of Chemistry, Duke University, Durham, NC 27708-0346, USA.
authors.forename: James M
authors.initials: JM
authors.lastname: Harrington
authors.forename: Tom
authors.initials: T
authors.lastname: Gootz
authors.forename: Mark
authors.initials: M
authors.lastname: Flanagan
authors.forename: Majinder
authors.initials: M
authors.lastname: Lall
authors.forename: John
authors.initials: J
authors.lastname: O'Donnell
authors.forename: Jennifer
authors.initials: J
authors.lastname: Winton
authors.forename: John
authors.initials: J
authors.lastname: Mueller
authors.forename: Alvin L
authors.initials: AL
authors.lastname: Crumbliss
mesh_terms: D000890:Anti-Infective Agents / Q000737:chemistry*; D004355:Drug Stability; D055664:Electrochemical Techniques; D005290:Ferric Compounds / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007502:Iron Chelating Agents / Q000737:chemistry*; D008024:Ligands; D015394:Molecular Structure; D010084:Oxidation-Reduction; D011199:Potentiometry; D012996:Solutions; D013053:Spectrophotometry; D014867:Water; D047090:beta-Lactams / Q000737:chemistry*
chemical_list: D000890:Anti-Infective Agents; D005290:Ferric Compounds; D007502:Iron Chelating Agents; D008024:Ligands; D012996:Solutions; D047090:beta-Lactams; D014867:Water