Vibrational snapshots of ultrafast C-H bond photoactivation inside a water-soluble nanocage

Triggering C-H bond photoactivation reactions inside enzyme-like nanocavities will enable development of green methods to carry out selective organic transformations in water. Recently it was shown that host-guest charge transfer (CT) interactions inside water-soluble cationic nanocages can be used to drive ultrafast C-H bond photoactivation to catalytically form selective products in water via a sequential proton-coupled electron transfer (PCET) reaction. However, the primary structural events after light absorption that couple the electron and proton transfer steps during the PCET process have remained elusive, thereby limiting the diversity of cage-confined photoredox catalysis in water. Here we employ structure-sensitive femtosecond stimulated Raman spectroscopy to track the PCET driven catalytic photoactivation of the C-H bond in cage-confined 5-(5-methylthiophene-2-yl)-thiophene-carbaldehyde (BTMC), and its subsequent selective oxidation to the corresponding aldehyde at room temperature in water. Resonance-selective Raman snapshots of the photogenerated radical cation reveal the rich vibrational dynamics of the bithiophene rings leading to formation of a neutral radical at the methyl-carbon site while suggesting kinetic heterogeneity of the deprotonation event. In combination with broadband transient absorption and solvent water kinetic isotope effects, we demonstrate a key role of the pre-organized water cluster around the host-guest complex during C-H bond photoactivation. Our work illustrates the significance of controlling guest self-assembly inside the cage to tune the rate of preorganized proton transfer, and therefore opens a temporal framework for developing universal PCET-guided photoredox transformations in water.