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Efforts to delineate the interactions of neurotoxic Al(III) with low molecular mass substrates relevant to neurodegenerative processes, led to the investigation of the pH-specific synthetic chemistry of the binary Al(III)-[N-(phosphonomethyl) iminodiacetic acid] (Al-NTAP), Al(III)-[nitrilo-tris(methylene-phosphonic acid)] (Al-NTA3P), and Al(III)-[1-hydroxy ethylidene-1,1-diphosphonic acid] (Al-HEDP) systems, in correlation with solution speciation studies. Reaction of Al(NO(3))(3).9H(2)O with NTAP at pH 7.0 and 4.0 afforded the new species (CH(6)N(3))(4)[Al(2)(C(5)H(6)NPO(7))(2)(OH)(2)].8H(2)O (1) and (NH(4))(2)[Al(2)(C(5)H(6)NPO(7))(2)(H(2)O)(2)].4H(2)O (2), while reaction of Al(NO(3))(3).9H(2)O with NTA3P led to K(8)[Al(2)(C(3)H(6)NP(3)O(9))(2)(OH)(2)].20H(2)O (3). Complexes 1-3 were characterized by elemental analysis, FT-IR, (13)C, (31)P, (1)H NMR (for 1-2 solid state and solution NMR where feasible), and X-ray crystallography. The structures of 1-3 reveal the presence of uniquely defined dinuclear complexes of octahedral Al(III) bound to fully deprotonated phosphonate ligands, water and hydroxo moieties. The aqueous solution speciation studies on the aforementioned binary systems project a clear picture of the binary Al(III)-(carboxy)phosphonate interactions and species under variable pH-conditions and specific Al(III):ligand stoichiometry. The concurrent solid state and solution work (a) exemplifies essential structural and chemical attributes of soluble aqueous species, reflecting well-defined interactions of Al(III) with phosphosubstrates and (b) strengthens the potential linkage of neurotoxic Al(III) chemical reactivity toward O,N-containing (carboxy)phosphate-rich cellular targets.

The interactions of Al(III) with the dipeptide AspAsp and the tripeptide AspAspAsp in aqueous solutions were studied by pH-potentiometry and multinuclear 1H- and 13C- nuclear magnetic resonance (NMR) spectroscopy. Their numerous negatively charged COO(-) functions allow these ligands to bind Al(III) even in weakly acidic solutions. Various mononuclear 1:1 complexes are formed in different protonation states. 13C-NMR spectroscopy unambiguously proved participation of the COO(-) functions in a monodentate or chelating mode in Al(III) binding, however, the terminal-NH(2) group seems to be excluded from the coordination. Depending on the metal ion to ligand ratio precipitation occurs at pH approximately 5 to 6. This indicates that the COO(-) groups at the low level of preorganization in such small peptides are not sufficient to keep the Al(III) ion in solution and to prevent the precipitation of Al(OH)(3) at physiological pH. To achieve this, a more specific arrangement of the side-chain donors seems necessary., (Copyright 2003 Elsevier Science Inc.)