A Novel Dinuclear Species in the Aqueous Distribution of Aluminum in the Presence of Citrate Maria Dakanali, † Catherine P. Raptopoulou, ‡ Aristidis Terzis, ‡ Andrea Lakatos, § Istvan Banyai, | Tamas Kiss, § and Athanasios Salifoglou* ,† Department of Chemistry, UniVersity of Crete, Heraklion 71409, Greece, Institute of Materials, NCSR “Demokritos”, Aghia ParaskeVi 15310, Attiki, Greece, Department of Physical Chemistry, UniVersity of Debrecen, Debrecen, H-6720 Hungary, and Biocoordination Chemistry Research Group of the Hungarian Academy of Sciences, Department of Inorganic and Analytical Chemistry, UniVersity of Szeged, Szeged, H-6720 Hungary Received June 18, 2002 The chemistry of aluminum was explored in the presence of the physiological ligand citric acid and in low-pH aqueous media. As a result, the first dinuclear aluminum-citrate complex (NH 4 ) 4 [Al 2 - (C 6 H 4 O 7 )(C 6 H 5 O 7 ) 2 ]‚4H 2 O was isolated at low pH (∼3.5), and was characterized by FT-IR spectroscopy and X-ray crystallography. The structural analysis reveals the presence of a dinuclear assembly of two aluminum ions octahedrally coordinated to three citrate ligands of differing protonation state. The NMR solution behavior of this complex emphasizes its time-dependent transfor- mation into a number of variable nature species, ultimately leading to the thermodynamically stable trinuclear species. It also establishes the participation of the dinuclear complex as a viable component of the aqueous Al(III)-citrate speciation. The chemical and structural features of this novel low molecular mass species provide considerable insight into citrate’s ability, as a natural ligand, to influence the chemistry of aluminum in a pH-dependent fashion, and potentially affect aluminum’s (bio)distribution, absorption, accumulation, and biotoxicity at sensitive biological sites. Aluminum biotoxicity has been the subject of considerable research in recent years due to the involvement of that element in a number of health-related physiological aberra- tions. 1 Specifically, several diseases have been linked to the toxic influence of aluminum, including numerous dementias, neurodegenerative conditions, like Alzheimer’s disease, encephalopathies, microcytic anemia, and others. 2 The as- sociation of aluminum with the aforementioned clinical conditions has raised questions concerning the processes by which biochemical pathways are influenced by that metal ion. Key to understanding the role of aluminum in such events is the aqueous speciation of that element and the requisite chemistry in biological fluids. Interactions, however, of aluminum at the biological level can occur with both high and low molecular mass biomolecules present in those fluids. Without disregard for the essential contribution of large molecular mass molecules, like transferrin, to the interactive chemistry with aluminum, the corresponding chemistry with low molecular mass molecules is equally important and significant. Prevalent among such molecules is citric acid, which is abundantly present in human plasma (0.1 mM). 3 It is capable of promoting metal-binding chemistry, solubilizing metal ions, like aluminum, and consequently raising their bioavailability and ultimate absorption by various tissues. Therefore, Al(III) speciation in the presence of the low molecular mass ligand citrate emerges as an important feature of that metal ion’s involvement in interactions with biological loci. Unraveling the nature and properties of the various Al- (III) species participating in such pH and concentration dependent distributions may aid in further determining Al- (III) bioavailability and its link to disruption of biochemical processes and/or toxicity. Being aware of these properties, we have investigated the aqueous chemistry of citrate with Al(III) at low pH. Herein, we report on the synthesis and * Author to whom correspondence should be addressed. Tel: +30-281- 0393-652. Fax: +30-281-0393-601. E-mail: salif@chemistry.uoc.gr. † University of Crete. ‡ NCSR “Demokritos”. § University of Szeged. | University of Debrecen. (1) (a) Nayak, P. EnViron. Res. 2002, 89, 101-115 (b) Campbell, A.; Yang, E. Y.; Tsai-Turton, M.; Bondy, S. C. Brain Res. 2002, 933, 60-65. (c) Rondeau, V. ReV. EnViron. 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