Stability constants of phosphonic acid derivatives with aluminum

Aluminum is the most abundant metal ion in the earth's crust and the third-most abundant element after oxygen and silicon. Because of the effects of acid rain and the use of acidifying fertilizers, the concentration of the free Al3+ has increased in the soil, in lakes and in rivers. Therefore, aluminum has become more accessible to living organisms. Health problems associated with aluminum toxicity have been reported among patients with chronic renal failure. The aluminum ion may also be involved in the progression of Alzheimer's disease. The only aluminum-sequestering drug currently in use is desferrioxamine, which is orally ineffective. There is a clear need for an orally effective aluminum chelator.;In this work, potentiometric titration, multinuclear NMR, ultraviolet absorption spectroscopy (UV) and infrared spectroscopy (IR) were used to evaluate the chelation of aluminum by a series of phosphonic acids. The phosphonate ligands also contained other functional groups. Some of these ligands were commercially available, while others were synthesized.;The ligands included in this study are aminomethylphosphonic acid (AMPA), aminoethylphosphononic acid (AEPA), phosphonoacetic acid (PAA), phosphonoformic acid (PFA), methylenediphosphonic acid (MDP), hydroxybenzylaminomethylphosphonic acid (HBAMPA), hydroxybenzylalanine (HBA) and pyridoxalaminomethylphosphonic acid (PYAMPA). Strong complexation was observed with the tridentate ligand PYAMPA, which coordinates through phosphonate, amine, and phenolate donor groups. However, the weak binding of the amine groups to Al3+ weakened the complexation of several of the ligands studied. Strong complexation was also observed for PAA.;We also measured a new, internally consistent set of stability constants for the Al3+-citrate system to modify the speciation models of the low molecular weight aluminum pool in serum. In this new set of binding constants, the trinuclear 33-4 complex was the dominant species and no 11-2 complex formed under the potentiometric conditions.