New trends in the chemistry of iron(III) citrate complexes: correlations between X-ray structures and solution species probed by electrospray mass spectrometry and kinetics of iron uptake from citrate by iron chelators.

Despite the crucial role of "iron(III) citrate systems" in the iron metabolism of living organisms (bacteria as well as plants or mammals), the coordination chemistry of ferric citrate remains poorly defined. Variations in the experimental conditions used for the preparation of so-called ferric citrates (iron salt, Fe:cit molar ratio, base, pH, temperature, solvent) lead to several different species, which are in equilibrium in solution. To date, six different anionic complexes have been structurally characterized in the solid state, by ourselves or others. In the work described herein, we have established the experimental conditions leading to each of them. Five were obtained from aqueous solution. With the exception of a nonanuclear species (of which fragments have been detected), all were identified in aqueous solution on the basis of electrospray ionization mass spectrometry. In addition, the spectra revealed a new trinuclear species, which could not be crystallized. Kinetic studies of iron uptake from citrate species by iron chelators confirmed the results indicated by the ESI-MS studies. These studies also allowed the relative molar fraction of mononuclear versus polynuclear complexes to be determined, which depends on the Fe:cit molar ratio.

[1]  Paul Cooper,et al.  Synthesis and structure of a new aluminium citrate trimer from aqueous solution at very low pH , 2003 .

[2]  W. Yue,et al.  Structural evidence for iron-free citrate and ferric citrate binding to the TonB-dependent outer membrane transporter FecA. , 2003, Journal of molecular biology.

[3]  Zhepeng Wang,et al.  Competition between transferrin and the serum ligands citrate and phosphate for the binding of aluminum. , 2003, Inorganic chemistry.

[4]  A. Salifoglou,et al.  Correlations of synthetic, spectroscopic, structural, and speciation studies in the biologically relevant cobalt(II)-citrate system: the tale of the first aqueous dinuclear cobalt(II)-citrate complex. , 2003, Inorganic chemistry.

[5]  I. Bányai,et al.  1H- and 13C-NMR as tools to study aluminium coordination chemistry-aqueous al(III)-citrate complexes , 2002 .

[6]  I. Bányai,et al.  Slow dynamics of aluminium-citrate complexes studied by 1H- and 13C-NMR spectroscopy , 2002 .

[7]  Andrew D. Ferguson,et al.  Structural Basis of Gating by the Outer Membrane Transporter FecA , 2002, Science.

[8]  A. Salifoglou,et al.  Synthesis, pH-dependent structural characterization, and solution behavior of aqueous aluminum and gallium citrate complexes. , 2001, Inorganic chemistry.

[9]  P. O’Brien,et al.  Solid and Solution State NMR Spectra and the Structure of the Gallium Citrate Complex (NH4)3[Ga(C6H5O7)2]·4H2O , 2001 .

[10]  A. Salifoglou,et al.  Manganese citrate chemistry: syntheses, spectroscopic studies, and structural characterizations of novel mononuclear, water-soluble manganese citrate complexes. , 2000, Inorganic Chemistry.

[11]  I. Gautier-Luneau,et al.  Iron and citric acid: A fuzzy chemistry of ubiquitous biological relevance , 2000, Biometals.

[12]  K. Herlihy,et al.  Kinetics of Iron(III) Chelation from Polynuclear Oxo-Hydroxy Aggregates by Hydroxamic Acids: Understanding Ferritin Iron(III) Sequestration , 1999 .

[13]  F. Thomas,et al.  Thermodynamic and kinetic studies of the sulfonated derivative of the iron chelator TRENCAM, an analog of enterobactin , 1999 .

[14]  A. Salifoglou,et al.  Synthesis, Structural Characterization, and Solution Behavior of the First Mononuclear, Aqueous Aluminum Citrate Complex , 1999 .

[15]  A. Salifoglou,et al.  Synthesis, Spectroscopic and Structural Characterization of the First Mononuclear, Water Soluble Iron−Citrate Complex, (NH4)5Fe(C6H4O7)2·2H2O , 1998 .

[16]  S. Lippard,et al.  A Novel Nonairon(III) Citrate Complex: A “Ferric Triple-Decker” , 1998 .

[17]  P. O’Brien,et al.  The X-ray Single Crystal Structure of a Gallium Citrate Complex (NH4)3[Ga(C6H5O7)2]·4H2O , 1997 .

[18]  H. Boukhalfa,et al.  O-TRENSOX, a New Tripodal Iron Chelator Based on 8-Hydroxyquinoline Subunits: Thermodynamic and Kinetic Studies , 1997 .

[19]  Michael R. Wasielewski,et al.  Design and synthesis of metal ion-recognition-induced conjugated polymers: An approach to metal ion sensory materials , 1997 .

[20]  H. Boukhalfa,et al.  O-TRENSOX: A Promising Water-Soluble Iron Chelator (Both FeIII and FeII) Potentially Suitable for Plant Nutrition and Iron Chelation Therapy , 1995 .

[21]  V. Braun,et al.  Signal transfer through three compartments: transcription initiation of the Escherichia coli ferric citrate transport system from the cell surface. , 1995, The EMBO journal.

[22]  S. Lippard,et al.  Syntheses, Structures, and Magnetic Properties of Two Dinuclear Iron(III) Citrate Complexes , 1994 .

[23]  B. Faller,et al.  Kinetics and Mechanism of Iron(III) Removal from Citrate by Desferrioxamine B and 3-Hydroxy-1,2-Dimethyl-4-Pyridone , 1994 .

[24]  P. Gurian,et al.  Aluminum citrate: isolation and structural characterization of a stable trinuclear complex , 1990 .

[25]  P. Sadler,et al.  Non-transferrin-bound iron in plasma or serum from patients with idiopathic hemochromatosis. Characterization by high performance liquid chromatography and nuclear magnetic resonance spectroscopy. , 1989, The Journal of biological chemistry.

[26]  Martin Rb.  Citrate binding of Al3+ and Fe3+. , 1986 .

[27]  J. Glusker.  Citrate conformation and chelation: enzymic implications , 1980 .

[28]  E. Rachmilewitz,et al.  Non‐Specific Serum Iron in Thalassaemia: an Abnormal Serum Iron Fraction of Potential Toxicity , 1978, British journal of haematology.

[29]  S. W. Layten,et al.  Structural studies of transition metal complex of triionized and tetraionized citrate. Models for the coordination of the citrate ion to transition metal ions in solution and at the active site of aconitase. , 1977, Journal of the American Chemical Society.

[30]  T. Spiro,et al.  Hydrolytic polymerization of ferric citrate. II. Influence of excess citrate , 1967 .

[31]  L. O. Tiffin.  Iron Translocation II. Citrate/Iron Ratios in Plant Stem Exudates. , 1966, Plant physiology.

[32]  F. Palilla,et al.  Determination of Iron by Ultraviolet Spectrophotometry , 1956 .

[33]  I. Gautier-Luneau,et al.  Synthesis, structure and magnetic properties of a novel octairon(III) citrate complex , 2001 .

[34]  A. Salifoglou,et al.  Synthesis, spectroscopic, and structural characterization of the first aqueous cobalt(II)-citrate complex: toward a potentially bioavailable form of cobalt in biologically relevant fluids , 2000, JBIC Journal of Biological Inorganic Chemistry.

[35]  K. Seifert,et al.  Effect of nicotianamine on iron uptake and citrate accumulation in two genotypes of tomato, Lycopersicon esculentum Mill.* , 1991 .