Environmentally-relevant concentrations of Al(III) and Fe(III) cations induce aggregation of free DNA by complexation with phosphate group.

Environmental persistence of free DNA is influenced by its complexation with other chemical species and its aggregation mechanisms. However, it is not well-known how naturally-abundant metal ions, e.g., Al(III) and Fe(III), influence DNA aggregation. This study investigated aggregation behaviors of model DNA from salmon testes as influenced by metal cations, and elucidated the predominant mechanism responsible for DNA aggregation. Compared to monovalent (K+ and Na+ ) and divalent (Ca2+ and Mg2+ ) cations, Al(III) and Fe(III) species in aqueous solution caused rapid DNA aggregations. The maximal DNA aggregation occurred at 0.05 mmol/L Al(III) or 0.075 mmol/L Fe(III), respectively. A combination of atomic force microscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy revealed that Al(III) and Fe(III) complexed with negatively charged phosphate groups to neutralize DNA charges, resulting in decreased electrostatic repulsion and subsequent DNA aggregation. Zeta potential measurements and molecular computation further support this mechanism. Furthermore, DNA aggregation was enhanced at higher temperature and near neutral pH. Therefore, DNA aggregation is collectively determined by many environmental factors such as ion species, temperature, and solution pH.