EXPERIMENTAL AND THEORETICAL-ANALYSIS OF AL3+ COMPLEXATION WITH ADP AND ATP

Al3+ ion is known to interact significantly with a number of biochemic al systems, and has been linked to a number of human diseases. Owing t o the affinity elf Al3+ for phosphate oxygens, much recent interest ha s focused on complexes that Al3+ can form with nucleoside di-and tri-p hosphates. ATP, for exam major intracellular chelator of Al3+ While po tentiometric titrations have provided a wealth of information on the n ature of various nucleoside phosphate-Al3+ species which can exist in solution under a given set of conditions, this approach alone cannot d istinguish between all possible complexes that may exist, especially w here dimers or high multimeric forms are present. In this paper, 500 M Hz H-1 NMR data collected on samples that vary in the nature of the nu cleoside phosphate (i.e., either ADP or ATP), the concentration of nuc leoside phosphate from 0.5 to 10 mM), the pH from 5.0 to 7.0), and the ratio of total Al3+ to total nucleoside phosphate (from 0.455 to 1.0) were simultaneously analyzed by a nonlinear least squares procedure, providing evidence for several Al3+-nucleoside phosphate complexes alo ng with the associated formation constants (all fits being characteriz ed by apparent a values < 0.05 in mole fraction units). in neutral sol utions the main species present with equal amounts of Al3+ and nucleot ide are HOM2L2 and ML, while with excess ligand ML, complexes predomin ate. Bases in the ML, complexes are about 87% stacked. (C) 1997 Elsevi er Science lnc.