Photoinduced\nElectron-Transfer-Mediated Differential\nRecognition of Proteins on Plasmonic Surfaces

Photoinduced\nenhanced Raman spectroscopy (PIERS) has emerged as\nan efficient technique for enhancing the vibrational modes of analyte\nmolecules adsorbed on a plasmonic nanoparticle-semiconductor hybrid\nmaterial through chemical enhancement governed by electron transfer\nfrom the semiconductor to the plasmonic nanoparticles under an additional\nultraviolet (UV) preirradiation step. The increase in chemical enhancement\nis imperative in analyzing and detecting pharmaceutically important\nmoieties, such as amino acids and proteins, with a low Raman scattering\ncross section, even in complex biological environments. Herein, we\ndemonstrate that UV preirradiation induced the creation of additional\noxygen vacancies by introducing a low concentration (≈1%) of\nNi as a dopant in the 2D platelike morphology of the BiOCl semiconductor;\ni.e., defect states in the semiconductor can induce charge transfer\nfrom the semiconductor to the plasmonic nanoparticles. This phenomenon\nfacilitates electron transfer to the adsorbed analyte on the plasmonic\nsurface. Additionally, we have shown the usefulness of this method\nin protein immobilization on the substrate surface, followed by the\nidentification of a specific protein in the mixture of proteins. Proteins\ncontaining cysteine residues capture these electrons to form a surface-bound\nthiol group via a transient disulfide electron adduct radical. This\nallows differential binding of the protein molecules to the semiconductor\nplasmonic hybrid depending on the concentration of surface cysteine\nresidues in proteins. Through PIERS and principal component analysis,\nwe demonstrate the possibility of probing and distinguishing biomolecules\nbased on their surface composition and secondary structure components\neven in their mixtures, thus paving the way for efficient analysis\nof complex biological systems.