SPECIATION OF ALUMINUM IN BIOLOGICAL-SYSTEMS

As a ''hard'' trivalent metal ion, Al3+ binds strongly to oxygen-donor ligands such as citrate and phosphate. The aqueous coordination chemi stry of Al is complicated by the tendency of many Al complexes to hydr olyze and form polynuclear species, many of which are sparingly solubl e. Thus there is considerable variation among the Al stability constan ts reported for several important ligands. The complexity in the aqueo us chemistry of Al has also affected Al toxicity studies, which have o ften utilized poorly characterized Al stock solutions. Serum fractiona tion studies show that most Al is protein bound, primarily to the seru m iron transport protein transferrin. Albumin appears to play little, if any, role in serum transport. There is little agreement as to the s peciation of the remaining low-molecular-mass fraction of serum Al. Th e lability of the Al3+ ion precludes the simple separation and identif ication of individual Al complexes. Computational methods are availabl e for detailed computer calculations of the Al speciation in serum, bu t efforts in this area have been severely hampered by the uncertaintie s regarding the stability constants of the low molecular mass Al compl exes with Citrate, phosphate, and hydroxide. Specific recommendations for further research on Al speciation include: (1) Determine more accu rate Al stability constants with critical low molecular mass ligands s uch as citrate and phosphate; (2) supplement traditional potentiometri c studies on Al complexes with data from other techniques such as Al-2 7-NMR and accelerator mass spectrometry with Al-26; (3) develop new me thods for generating reliable linear free energy relationships for Al complexation; (4) determine equilibrium and rate constants for Al bind ing to transferrin al 37 degrees C; (5) confirm the possible formation of low-molecular-mass Al-protein complexes following desferrioxamine therapy; (6) continue research efforts to incorporate kinetic consider ations into the present equilibrium speciation calculations; (7) impro ve methods for preparing chemically well-defined stock solutions for t oxicological studies; (8) incorporate more detailed speciation data in to studies on Al toxicity and pharmacokinetics; and (9) incorporate mo re detailed speciation data into future epidemiological studies on the relationship between Al toxicity and various water quality parameters .