Investigating the Role of pH and Counterions in the Intrinsic Fluorescence of Solid-State l -Lysine

There is currently a growing interest in understanding the origins of intrinsic fluorescence as a way to design noninvasive probes for biophysical processes. In this regard, understanding how pH influences fluorescence in nonaromatic biomolecular assemblies is key to controlling their optical properties in realistic cellular conditions. Here, we combine experiments and theory to investigate the pH-dependent emission of solid-state l-Lysine (Lys). Lys aggregates prepared at different pH values using HCl and H2SO4 exhibit protonation- and counterion-dependent morphology and fluorescence, as shown by microscopy and steady-state measurements. We find an enhancement in the fluorescence moving from acidic to basic conditions. To uncover the molecular origin of these trends, we performed nonadiabatic molecular dynamics simulations on three Lys crystal models representing distinct protonation states. Our simulations indicate that enhanced protonation under acidic conditions facilitates nonradiative decay via proton transfer, whereas basic conditions favor radiative decay. Our combined experimental–theoretical work highlights pH and counterion identity as key factors tuning fluorescence in Lys assemblies, offering insights for designing pH responsive optical materials based on nonaromatic amino acids.