Vibrational tags in infrared (IR)-based micro-spectroscopy constitute powerful tools for studies on cellular metabolism. Whereas Raman tags have seen substantial developments, IR tags have not similarly benefitted from systematic design optimization. To improve the utility of IR-based vibrational tags, we modified a series of alkyne-based probes for use in the cell silent region of the IR spectrum. Using density functional theory (DFT) simulations for initial design motifs, the tags were analyzed using linear spectroscopy, and subsequently screened for their utility in cell and tissue imaging. The resulting chemical motifs form a palette of strong vibrational tags for IR-based biological imaging.
Recent developments have shown the utility of vibrational tags in both Raman-based microscopy and infrared-based microspectroscopy. In this context, the availability of probes that feature a strong response is highly desirable. Here we develop vibrational tags that have strong and narrow vibrational lines in the cell silent region of the spectrum. We screened numerous chemical motifs with density functional theory (DFT). Design criteria included a distinct resonance frequency, a long vibrational lifetime, and overall strength of the vibrational response. We discuss the utility of these optimized probes for cellular imaging studies with stimulated Raman scattering and Fourier transform infrared microspectroscopy.
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