Hidden Dynamics of Noble-metal-bound Thiol Monolayers Revealed by SERS-monitored Entropy-driven Exchange of Cysteine Isotopologues

Vibrational spectroscopy coupled with isotopic labeling provides insight into the dynamics of various molecular processes. Here, a newfound approach in surface-enhanced Raman scattering (SERS) spectroscopy to study noble metal-anchored thiol monolayers is demonstrated for a pair of L-cysteine isotopologues competing for binding to silver nanoparticles (AgNPs): Cys-cabn (all 12C/14N) and Cys-CABN (all 13C/15N). As predicted by our DFT calculations, a distinct difference in the Raman shift value (>50 cm−1) of the ν(C = O) band was observed for these two AgNP-anchored isotopologues. SERS intensity ratio of these two peaks allowed for quantitative monitoring of an exclusively entropy-driven exchange of Cys molecules between the surface and the solution, revealing a reversible and rapid activation after a mild temperature increase (50 °C). This behavior is attributed to the collective phase transition within the monolayer. This work highlights unexplored potential of SERS spectroscopy coupled with isotopic exchange to study dynamic phenomena within a metal-anchored layer.