Organic Nucleation: Water Rearrangement Reveals the Pathway of Ibuprofen.

The organic nucleation of the pharmaceutical ibuprofen is investigated, as triggered by the protonation of ibuprofen sodium salt at elevated pH. The growth and aggregation of nanoscale solution species by Analytical Ultracentrifugation and Molecular Dynamics (MD) simulations is tracked. Both approaches reveal solvated molecules, oligomers, and prenucleation clusters, their size as well as their hydration at different reaction stages. By combining surface-specific vibrational spectroscopy and MD simulations, water interacting with ibuprofen at the air-water interface during nucleation is probed. The results show the structure of water changes upon ibuprofen protonation in response to the charge neutralization. Remarkably, the water structure continues to evolve despite the saturation of protonated ibuprofen at the hydrophobic interface. This further water rearrangement is associated with the formation of larger aggregates of ibuprofen molecules at a late prenucleation stage. The nucleation of ibuprofen involves ibuprofen protonation and their hydrophobic assembly. The results highlight that these processes are accompanied by substantial water reorganization. The critical role of water is possibly relevant for organic nucleation in aqueous environments in general.

Role of Water during the Early Stages of Iron Oxyhydroxide Formation by a Bacterial Iron Nucleator.

Understanding the nucleation of iron oxides and the underlying hydrolysis of aqueous iron species is still challenging, and molecular-level insights into the orchestrated response of water, especially at the hydrolysis interface, are lacking. We follow iron(III) hydrolysis in the presence of a synthetic bacterial iron nucleator, which is a magnetosome membrane specific peptide, by using a constant pH titration technique. Three distinct hydrolysis regimes were identified. Interface-selective sum frequency generation (SFG) spectroscopy was used to probe the interfacial reaction and water in direct contact with the peptide. SFG data reveal that iron(III) species react quickly with interfacial peptides while continuously enhancing water alignment into the later stages of hydrolysis. The gradually aligning water molecules are associated with initially promoted (regimes I and II) and later suppressed (regime III) hydrolysis after the saturation of water alignment has occurred until regime II. These interfacial insights are crucial for understanding the early stage of iron oxide biomineralization.