Many chemical methods have been developed to favor a particular product in transformations of compounds that have two or more reactive sites. We explored a different approach to site selectivity using vibrational strong coupling (VSC) between a reactant and the vacuum field of a microfluidic optical cavity. Specifically, we studied the reactivity of a compound bearing two possible silyl bond cleavage sites—Si–C and Si–O, respectively—as a function of VSC of three distinct vibrational modes in the dark. The results show that VSC can indeed tilt the reactivity landscape to favor one product over the other. Thermodynamic parameters reveal the presence of a large activation barrier and substantial changes to the activation entropy, confirming the modified chemical landscape under strong coupling.

Vibrational strong coupling (VSC) has recently emerged as ac ompletely new tool for influencing chemical reactivity.I th arnesses electromagnetic vacuum fluctuations through the creation of hybrid states of light and matter,called polaritonic states,i na no ptical cavity resonant to am olecular absorption band. Here,weinvestigate the effect of vibrational strong coupling of water on the enzymatic activity of pepsin, where aw ater molecule is directly involved in the enzymes chemical mechanism. We observe an approximately 4.5-fold decrease of the apparent second-order rate constant k cat /K m when coupling the water stretching vibration, whereas no effect was detected for the strong coupling of the bending vibration. The possibility of modifying enzymatic activity by coupling water demonstrates the potential of VSC as anew tool to study biochemical reactivity.Vibrational strong coupling entails the formation of hybrid light-matter states,o rp olaritonic states,b yp lacing am olecular species in ap hotonic cavity resonant to one of its vibrational absorption bands under the right conditions ( Figure 1A). [1][2][3][4][5] Ar esonant cavity is as tructure which confines light spatially at well-defined frequencies,f or example,t wo parallel mirrors facing each other form aFabry-Perot cavity (Figure 1Band Supporting Information, Figure 1. Vibration strong coupling and pepsin. A) Schematic outline of strong light-matter interaction with molecular vibrations.I nanon resonancec avity where " hw vibr = " hw cavity ,the ground and first excited state of avibration will combine with the photon numbers tate of the photonic cavity to produce two new polaritons tates, P + and PÀ, separated by the vacuum Rabi splitting " hW R .B )Schematic drawing of the microfluidic cavities used here for studying pepsin-mediated peptide hydrolysis under VSC of the water mid-infrared bands. C) Mechanistic model of peptide bond cleavage in the active site of pepsin based on ref. [8].

Vibrational strong coupling (VSC) is currently emerging as a tool to control chemical dynamics. Here we study the impact of strong coupling strength, given by the Rabi splitting energy (ħΩR), on the thermodynamic parameters associated with the transition state of the desilylation reaction of the model molecule 1-phenyl-2-trimethylsilylacetylene. Under VSC, the enthalpy and entropy of activation determined from the temperature-dependent kinetic studies varied nonlinearly with the coupling strength. The thermodynamic parameters of the noncavity reaction did not show noticeable variation, ruling out concentration effects other than the enhanced ħΩR for the changes observed under VSC. The difference between the total free energy change under VSC and in noncavity was relatively smaller possibly because the enthalpy and entropy of activation compensate each other. This thermodynamic study gives more insight into the role of collective strong coupling on the transition state that leads to modified dynamics and branching ratios.