Research Topic
My research program is dedicated to the development and application of new catalytic methods in the area of organic chemistry in order to facilitate the way organic molecules are made. In addition, we design molecules that exhibit sought-after function in diverse areas such as biology and material science. Thereby, we not only apply rational design, but also develop smart screening strategies and data-driven computational models.
For application in cell membranes, we designed and synthesized imidazolium-based lipid analogs that resemble natural lipids in their amphiphilic structure and therefore many of their biological properties, but can be easily tuned and derivatized for various purposes with regard to the investigation and manipulation of biological membranes. In particular, we designed an imidazolium-based cholesterol analog (CHIM) in which natural cholesterol’s 3-hydroxy group is substituted by a polar, positively charged imidazolium moiety. This design allows for a flexible synthesis and derivatization of this class of analogs, particularly in C2 position of the imidazolium scaffold, while preserving cholesterol’s natural amphiphilic character. Importantly, the directionality of the imidazolium moiety results in the positioning of the C2 modification outside of the membrane and is therefore predicted and has been shown for the CHIM derivatives tested so far to not affect the proper membrane integration of the cholesterol backbone. Thus, the CHIM analog largely exhibits membrane integration as well as metabolic pathway characteristics similar to natural cholesterol. It can easily be modified, e.g. with a clickable linker (CHIM-L), and therefore be used as a versatile tool to probe cholesterol mediated processes and dynamics, for example via fluorescence microscopy. In doing so, we could verify its ability to mimic natural cholesterol, e.g., by preferentially integrating into liquid-ordered phases in biological membranes, by integrating into live cell plasma membranes and, following internalization, by integration into internal compartments such as early and late endosomes, as well as by functionally compensating for the lack of natural cholesterol in living C. elegans.
Selected Publications
- J. Ma, S. Chen, P. Bellotti, R. Guo, F. Schäfer, A. Heusler, X. Zhang, C. Daniliuc, M. K. Brown, K. N. Houk, F. Glorius, Photochemical Intermolecular Dearomative Cycloaddition of Bicyclic Azaarenes with Alkenes, Science 2021, 371, 1338.
- T. O. Paulisch, S. Bornemann, M. Herzog, S. Kudruk, L. Roling, A. L. Linard Matos, H.-J. Galla, V. Gerke, R. Winter, F. Glorius, An Imidazolium‐based Lipid Analogue as Gene Transfer Agent, Chem. Eur. J. 2020, 26, 17176.
- F. Sandfort, F. Strieth-Kalthoff, M. Kühnemund, C. Beecks, F. Glorius, A Structure-Based Platform for Predicting Chemical Reactivity, Chem 2020, 6, 1379.
- S. Singha, E. Serrano, S. Mondal, C. G. Daniliuc, F. Glorius, Diastereodivergent synthesis of enantioenriched α,β-disubstituted-γ-butyrolactones via cooperative N-heterocyclic carbene/Ir catalysis, Nature Catal. 2020, 3, 48.
- Z. Nairoukh, M. Wollenburg, C. Schlepphorst, K. Bergander, F. Glorius, The formation of all-cis-(multi)fluorinated piperidines by a dearomatization–hydrogenation process, Nature Chem. 2019, 11, 264.
- L. Rakers, D. Grill, A. L. L. Matos, S. Wulff, D. Wang, J. Börgel, M. Körsgen, H. F. Arlinghaus, H.-J. Galla, V. Gerke, F. Glorius, Addressable Cholesterol Analogs for Live Imaging of Cellular Membranes, Cell Chem. Biol. 2018, 25, 952-961.e12.
- M. Teders, C. Henkel, L. Anhäuser, F. Strieth-Kalthoff, A. Gómez-Suárez, R. Kleinmans, A. Kahnt, A. Rentmeister, D. Guldi, F. Glorius, The Energy Transfer Enabled Biocompatible Disulfide–Ene Reaction, Nature Chem. 2018, 10, 981.
- P. Drücker, A. Rühling, D. Grill, D. Wang, A. Draeger, V. Gerke, F. Glorius, H.-J. Galla, Imidazolium Salts Mimicking the Structure of Natural Lipids Exploit Remarkable Properties Forming Lamellar Phases and Giant Vesicles, Langmuir 2017, 33, 1333.
- M. P. Wiesenfeldt, Z. Nairoukh, W. Li, F. Glorius, Hydrogenation of Fluoroarenes: Direct access to all-cis-(multi)fluorinated cycloalkanes, Science 2017, 357, 908.
- D. Wang, C. Richter, A. Rühling, P. Drücker, D. Siegmund, N. Metzler-Nolte, F. Glorius, H.-J. Galla, A remarkably simple class of imidazolium-based lipids and their biological properties, Chem. Eur J. 2015, 21, 15123.