Characterization of the aqueous iron(III) chelation chemistry of a potential Trojan Horse antimicrobial agent: chelate structure, stability and pH dependent speciation.


Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Harrington, JM; Gootz, T; Flanagan, M; Lall, M; O'Donnell, J; Winton, J; Mueller, J; Crumbliss, AL

Published Date

  • October 2012

Published In

Volume / Issue

  • 25 / 5

Start / End Page

  • 1023 - 1036

PubMed ID

  • 22855208

Pubmed Central ID

  • 22855208

Electronic International Standard Serial Number (EISSN)

  • 1572-8773

International Standard Serial Number (ISSN)

  • 0966-0844

Digital Object Identifier (DOI)

  • 10.1007/s10534-012-9568-0


  • eng