Design, Synthesis, and Analytical Evaluation of Fsp3‐Inspired Raman Probes for Cellular Imaging

Craig F. Steven, Martin Lee, Gary S. Nichol, Paul R. J. Davey, Elisabetta Chiarparin, Valerie G. Brunton, Alison Nicola Hulme

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

The fraction of sp 3 -hybdrised carbons (Fsp 3 ) in drug candidates and other biologically relevant compounds has been proposed to be an important physicochemical consideration within medicinal chemistry. Currently available small-molecule probes for Raman imaging are not optimised for biological applications. We sought to improve upon the highly Raman-active, yet rigid, lipophilic, and aggregative, bisarylbutadiyne (BADY) motif by introducing Fsp 3 character. BADY analogues were designed, efficiently synthesised, and analysed by mass spectrometry – revealing a statistical correlation between compound aggregation and cLog P , but no correlation with sp 3 . However, X-ray crystallography demonstrated that the modifications to the BADY structure had a marked effect on crystal packing, suggesting Fsp 3 may still be important in reducing intermolecular stacking, and thus aggregation, of BADY. Cellular imaging by stimulated Raman scattering (SRS) microscopy allowed comparison of the intracellular distribution of the tags, guiding the design of future Raman probes.
Original languageEnglish
JournalEuropean Journal of Organic Chemistry
Early online date17 Jun 2022
Publication statusE-pub ahead of print - 17 Jun 2022


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