Metal Ions-Induced Unusual Stability of the Metastable Vesicle-like Intermediates Evolving in the Self-Assembly Process of Phenylalanine: The Role of Hydrophobic Interaction, Metal-Coordination, and Surface Charge Inversion

The underlying mechanism and the intermediates formation in the self-assembly of aromatic amino acids, peptides and proteins remain elusive despite numerous reports. We, for the first time, report that one can modulate the stability of the intermediates by tuning the metal ions-amino acid interaction of carboxybenzyl (Z)-protected phenylalanine (ZF). The microscopic and spectroscopic investigations reveal that the bivalent metal ions lead to the formation of fibrillar networks after a certain interval similar to blank ZF, whereas the trivalent ions develop vesicle-like intermediates which do not undergo fibrillation for a prolonged time. The time-lapse measurement of surface charge reveals that the surface charge of blank ZF and in the presence of bivalent metal ions alters from negative value to zero implying unstable intermediates leading to the fibril network. Strikingly, a prominent charge inversion from an initial negative to a positive value in the presence of trivalent metal ions imparts unusual stability to the metastable intermediates.