Good vibrations: small molecule Raman Optical Probes to Image metabolism in tissue microenvironments Ailsa Geddis 1,2 Fabio De Moliner 1 , Colin Campbell 2 and Marc Vendrell 1
1 Centre for Inflammation Research, University of Edinburgh, UK 2 EaStCHEM School of Chemistry, University of Edinburgh, UK
Imaging of small molecules in biological systems is complex. Fluorescence imaging of biomacromolecules is common; however the size of fluorescent tags and other available imaging tools is often too large to retain the biophysical properties of the native substrates. Small vibrational tags have been developed to image small molecules, such as metabolites, significantly improving the biorthogonality of the probes. These tags can consist of a non-common bond or an isotope that resonates within the biologically silent window of the Raman spectrum (1800-2800 cm -1 ). Previous research within our group focussed on the design of optical Raman analogues of sucrose, the most abundant nutrient in plants, and we demonstrated its application for imaging of metabolism in live plant cells using Stimulated Raman Scattering (SRS) spectroscopy. [1] SRS irradiates a specific wavelength improving spatiotemporal resolution and Raman intensities. [2] This approach has vast potential for biorthogonal real-time in vivo imaging and can be, in principle, extended to many other metabolites and small molecules. Current research is focused on the development and synthesis of a vibrationally active citric acid Raman probe for Raman imaging. These probes are highly versatile and have applications in many areas of research – in metabolomics, for acting as biomarkers in oncology and for determination of citrate transport mechanisms in osteology; this will be demonstrated in a zebrafish embryo model.
Figure 1: Raman active citric acid could be used to demonstrate osteoblast role in high bone citrate concentration. Further research is focusing on synthesis of a Raman active Estrogen probe to determine abnormalities in Estrogen receptors for development of an endometriosis sensor with other potential applications in breast cancer research. Preliminary studies show strong Raman activity of estrone backbone with various vibrational tags attached, with current research into attaching tags to other more biomimetically appropriate regions of the structure.
Figure 2: Estrogen analogue, Ethinylestradiol, has a strong alkyne signal in the “cell-silent” window of a Raman spectrum. References 1. F. De Moliner, K. Knox, D. Gordon, M. Lee, W. J. Tipping, A. Geddis, A. Reinders, J. M. Ward, K. Oparka, M. Vendrell, Angew. Chem. Int Ed. 2021 , 60, 7637-7642. 2. W. J. Tipping, M. Lee, A. Serrels, V. G. Brunton and A. N. Hulme, Chem. Soc. Rev. , 2016 , 45, 2075–208
P12
© The Author(s), 2023
Made with FlippingBook Learn more on our blog