Peptide-mediated Al(iii) (oxy)(hydr)oxide formation: the specific stages of phase separation for additive interactions matter

Abstract

We demonstrate how Al(III) interactions with a ‘biomimetic’ model homo-peptide, polyaspartic (pAsp), with a narrow size distribution (around 20 amino acid monomer units), can lead to substantially different outcomes by governing Al(III) hydrolysis/phase separation. The addition of unhydrolysed Al(III) in aqueous peptide solutions results in dominant pAsp20 destabilisation and precipitation from the solution, failing to induce effective Al(III)(oxy)(hydr)oxide formation. Allowing the peptide-free Al(III) system to reach specific hydrolysis/phase separation stages, i.e., just before and slightly after liquid–liquid phase separation, partly dissipating its chemical energy, followed by controlled peptide addition, leads to the formation of respective Al(III)(oxy)(hydr)oxide-peptide hybrids with smaller particles, higher Al(III) content, and well-preserved chemical properties of the peptide. This constitutes a hydrolysis “spin-off” strategy that exploits Al(III)–peptide interactions in distinct hydrolytic precursors, an approach transferable to multiple metals and polymeric systems. The reaction energetics determined by revisited isothermal titration calorimetry assays reflect an Al(III) hydrolysis “footprint” and its role in metal–peptide interactions. These insights are important for various applications of aluminium species, from vaccine adjuvants and related toxicity to enhancements of corrosion resistance.