Alkyne-tagged Raman probes for local environmental sensing by hydrogen-deuterium exchange (Conference Presentation)

Abstract

Alkyne-tagged Raman probes have shown high promise for noninvasive and sensitive visualization of small biomolecules in live cells. Here, we report a general strategy for Raman imaging-based local environment sensing by hydrogen-deuterium exchange (HDX) of terminal alkynes. We first demonstrate, in multiple Raman probes, that deuterations of the alkynyl hydrogens lead to remarkable shifts of alkyne Raman peaks, providing resolvable signals suited for imaging-based analysis with high specificity. Both our analytical derivation and experimental characterizations subsequently establish that HDX kinetics are linearly proportional to both alkyne pKas and environmental pDs. We establish that alkyne-HDX exhibits high sensitivity to various DNA structures and subtle pD variations in live cells. After validating the quantitative nature of this strategy, our work lays the foundation for utilizing alkyne-HDX strategy to quantitatively sense the local chemical and cellular environments.