Cross-Linked Protein Crystals With an Intense Nonconventional Full-Color Photoluminescence Originating From Through-Space Intermolecular Interaction

The emergence of nonconventional luminescent materials (NLMs) has attracted significant attention due to their sustainable synthesis and tunable optical properties. Yet, establishing a clear structure–emission relationship remains a challenge. In this work, we report a previously unknown class of NLMs: cross-linked protein crystals that exhibit intense photoluminescence (PL) in the visible range (425–680 nm). We systematically investigated seven natural protein crystals (concanavalin, catalase, lysozyme, hemoglobin, α-chymotrypsin, pepsin, and β-lactoglobulin) cross-linked with glutaraldehyde and demonstrated that cross-linking induces broadband emission that is absent in natural crystals. Focusing on polymorphic lysozyme crystals (tetragonal, orthorhombic, and monoclinic), we found excitation-dependent fluorescence with lifetimes in the nanosecond range and quantum yields up to 20% (in the monoclinic phase under 450 nm excitation). Single- and two-photon spectroscopy, as well as pressure- and solvent-modulated PL studies, confirm that the emission is due to intermolecular through-space interactions (TSI) within the crystal lattice. Compression enhances TSI and redshifts the emission, whereas the solvent (DMSO)-induced swelling reduces TSI and causes a blue shift, establishing a direct structure–emission correlation. This work establishes protein crystals as programmable NLMs with tunable emission and provides a mechanistic framework for the design of nonconventional luminogens through protein crystal engineering.