Metastable photoacids (mPAH), such as protonated merocyanine, are organic molecules that release protons under illumination, providing spatiotemporal control of pH. While merocyanine-type photoacids enable fully reversible pH cycling in water, their solubility is limited and chemical stability <24 hours. In recent studies, structure modifications have been the main direction in improving photoacid properties. In this work we introduce a new pathway to increase stability and solubility of photoacids by tuning their solvation in binary solvent mixtures. We show that a modified solvation environment supports highly reversible, large and stable pH modulation. We demonstrate >350 hours of light-induced pH cycling with 10 times more protons released per cycle in water-DMSO mixtures compared to pure water. This solva-tion engineering approach can be applied to other metastable photoacids, serving as a steppingstone towards practical use in applications where long-term stability is critical.

Metastable photoacids (mPAH), such as protonated merocyanine, are a unique class of organic molecules that offer spatiotemporal control of pH by reversibly releasing protons under UV-visible light. While merocyanine-type photoacids enable fully reversible pH cycling in water, their solubility and chemical stability are both limited to the range of sub-mM and less than 24 hours, respectively. In recent studies, structure modifications have been the key direction in improving photoacid properties. This work introduces a pathway to improve stability and solubility of photoacids using water-DMSO mixtures. DMSO was selected as co-solvent because, although the pH-switch in DMSO is irreversible, merocyanine is 100 times more soluble and chemically stable. We show that in water-DMSO solvent mixtures, a complete reversibility of pH-jumps can be achieved with at least tenfold increase in chemical stability and solubility. Molecular dynamics simulations with polarizable force fields revealed the crucial role of the photoacid solvation environment in the observed enhancements. This solvation engineering approach to improving solubility and long-term stability of photoacids in water-DMSO mixtures, can be applied to other metastable photoacids.