Stabilization of Al(iii) solutions by complexation with cacodylic acid: speciation and binding features

Abstract

Aluminium ions are believed to play a role in a number of neurological and skeletal disorders in the human body. The study of the biological processes and molecular mechanisms that underlie these pathological disorders is rendered a difficult task due to the wide variety of complex species that result from the hydrolysis of Al(3+) ions. In addition, this ion displays a pronounced tendency to precipitate as a hydroxide, so certain complexing agents should be envisaged to stabilize Al(III) solutions in near physiological conditions. In this work, we show that the common buffer cacodylic acid (dimethylarsinic acid, HCac) interacts with Al(III) to give stable complexes, even at pH 7. After preliminary analyses of the speciation of the metal ion and also of the ligand, a systematic study of the formation of different Al/Cac complexes at different pH values has been conducted. UV-Vis titrations, mass spectrometry NMR measurements and DTF calculations were performed to enlighten the details of the speciation and stoichiometry of Al/Cac complexes. The results altogether show that Al/Cac dimer complexes prevail, but monomer and trimer forms are also present. Interestingly, it was found that cacodylate promotes the formation of such relatively simple complexes, even under conditions where the polymeric form, Al13O4(OH)24(7+), should predominate. The results obtained can help to shed some light into the reactivity of aluminium ions in biological environments.

Binding of Al(iii) to synthetic RNA and metal-mediated strand aggregation

“…The 27 Al-NMR spectra showed a broad peak around 50ppm for both pH values, advancing a similar structure for the aluminum system (Fig. 4E ESI) and a significant shift of the peak respect to the 27 Al-NMR spectra of Al/Cac (δ=7.5ppm) 29 , thus confirming metal ion binding to the nucleotide. Kinetic experiments, where absorbance changes with time under aluminum excess were measured, showed a hypochromic effect of the adenosine band, agreeing with an interaction of Al/Cac with AMP ( Fig.…”

“…9 On the other hand, M 2 L formation was observed in our previous work. 29 (3) (4) Concerning Al/Cac-poly(rU) at pH=5.0, the reaction orders concur with a model (Equation (5)) where two molecules of cacodylate are released upon interaction of the metal complex with the monomeric unit of RNA (see mechanism in Appendix I, ESI). In Equation 5, k 1 is the forward kinetic constant for the metal-RNA complex formation.…”

“…2A ESI). As the largest peaks in the 1 H-NMR spectra had the same chemical shift as the ones found for the aluminum/cacodylate dimeric forms at pH=5.0, 29 we assumed that the main Aluminum containing species, at pH=7.0 and in the presence of an excess of cacodylate, are dimeric in nature. Therefore, it follows that an excess of cacodylate promotes the disaggregation of the Al 13 oligomer, forming simpler species.…”

“…In a previous study of the Al/Cac system, we found that in 1:1 Al:Cac ratio and at pH=5.0, the Al 2 Cac dimeric form is the major species present in solution, accompanied by minor amounts of the Al 2 Cac 2 dimer, whereas at pH=7.0 formation of remarkable amounts of a Al 13 oligomer is visualized. 29 However, further tests aimed to individuate optimal ligand distribution and concentration for the present study were carried out here. At pH=5.0 no light scattering of aluminum/cacodylate solutions was detected for all the investigated values of the cacodylate concentration, C L ( Fig.…”

“…In the first case, two aquo-ions of M are supposed to interact with the polynucleotide, whereas in the latter case two molecules of M 2 L react with the monomeric RNA units. This could be explained by the fact that at pH=5.0 the cacodylate species is more than 90% protonated (pK A =6.2) 29 and it is a general rule that protonation of the ligand favours its release. To conclude, concerning [poly(rA)] 2 at pH=5.0, the reaction mechanism is given by Equation (9) and the relevant initial rate equation is given by Equation (10) (k 3 / (2K 1 )=(5.0±2.5)x10 -2 s -1 M, Appendix III, ESI).…”