title: Fe(III) coordination properties of a new saccharide-based exocyclic trihydroxamate analogue of ferrichrome.
abstract: The coordination chemistry of a saccharide-based ferrichrome analogue, 1-O-methyl-2,3,4-tris-O-[4-(N-hydroxy-N-methylcarbamoyl)-n-butyrate]-alpha-d-glucopyranoside (H(3)L), is reported, along with its pK(a) values, Fe(III) and Fe(II) chelation constants, and aqueous-solution speciation as determined by spectrophotometric and potentiometric titration techniques. The use of a saccharide platform to synthesize a hexadentate trihydroxamic acid chelator provides some advantages over other approaches to ferrichrome models, including significant water solubility and hydrogen-bonding capability of the backbone that can potentially provide favorable receptor recognition and biological activity. The pK(a) values for the hydroxamate moieties were found to be similar to those of other trihydroxamates. Proton-dependent Fe(III)-H(3)L and Fe(II)-H(3)L equilibrium constants were determined using a model involving the sequential protonation of the iron(III)- and iron(II)-ligand complexes. These results were used to calculate the formation constants, log beta(110) = 31.86 for Fe(III)L and 12.1 for Fe(II)L(-). The calculated pFe value of 27.1 indicates that H(3)L possesses an Fe(III) affinity comparable to or greater than those of ferrichrome and other ferrichrome analogues and is thermodynamically capable of removing Fe(III) from transferrin. E(1/2) for the Fe(III)L/Fe(II)L(-) couple was determined to be -436 mV from quasi-reversible cyclic voltammograms at pH = 9, and the pH-dependent E(1/2) profile was used to determine the Fe(II)L(-) protonation constants.
authors.affiliation: Department of Chemistry, Duke University, Box 90346 Durham, NC 27708-0346, USA.
authors.forename: Suraj
authors.initials: S
authors.lastname: Dhungana
authors.forename: Susanne
authors.initials: S
authors.lastname: Heggemann
authors.forename: Peter
authors.initials: P
authors.lastname: Gebhardt
authors.forename: Ute
authors.initials: U
authors.lastname: Möllmann
authors.forename: Alvin L
authors.initials: AL
authors.lastname: Crumbliss
mesh_terms: D000465:Algorithms; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D005290:Ferric Compounds / Q000737:chemistry*; D005291:Ferrichrome / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry; D005960:Glucosides / Q000138:chemical synthesis* / Q000737:chemistry; D006877:Hydroxamic Acids / Q000138:chemical synthesis / Q000737:chemistry; D007501:Iron / Q000737:chemistry; D007700:Kinetics; D008024:Ligands; D008956:Models, Chemical; D015394:Molecular Structure; D013816:Thermodynamics
chemical_list: D005290:Ferric Compounds; D005960:Glucosides; D006877:Hydroxamic Acids; D008024:Ligands; D005291:Ferrichrome; D007501:Iron