Interaction of aluminum species with deoxyribonucleic acid

Abstract

Interactions of aluminum with deoxyribonucleic acid (DNA) have been studied by thermal denaturation, circular dichroism, and fluorescent dye binding; a pH- and concentration-dependent alteration in the interaction of aluminum with DNA was observed. Three distinguishable complexes are produced when DNA is denaturated at pH 5.0-7.5 and in aluminum to DNA mole ratios of 0-0.7. Complex I appears at neutral pH and stabilizes a portion of DNA. Complex II is observed at acidic pH, destabilizes a fraction of the DNA double-helical molecule, and produces intrastrand cross-links. Complex III occurs at all pHs, is maximal at intermediate pH values, and is characterized by a noncooperative melting profile and cross-linking at low pH (less than 6.0). The DNA in complexes II and III can be renatured by treatment with either ethylenediaminetetraacetic acid (EDTA) or a high concentration of sodium chloride. The properties of complexes I and II are consistent with what could be expected for DNA complexes of Al(OH)2+ and Al3+, respectively. Complex III has intermediate properties that are consistent with a structure in which both ions bind the DNA simultaneously. The characteristics of complex III depend on the ratio of Al3+/Al(OH)2+ in solution. Aluminum-DNA complexes differ from other metal-DNA complexes in that melting profiles under many conditions are biphasic. Apparently more than one form of DNA can exist at any time in the presence of aluminum. The different DNA-aluminum complexes, which arise from the multiple species of aluminum in aqueous solution, lead to a variety of reactions with DNA.