Current Research Projects

For several years, our research group has been studying the use of organosilicon derivatives as a synthetic pivot in metallocatalyzed cross-coupling reactions. Current associated projects are focused on the coupling of silicon compounds with modern electrophiles, as well as the development of different organosilicon derivatives. The objective of these studies is to allow easy access to interesting coupling products that are difficult to access by conventional methods.

Representative publications:

• K. Indukuri, L. Cornelissen, O. Riant, Synthesis 2016, 48, 4400-4422
• L. Cornelissen, V. Cirriez, S. Vercruysse, O. Riant, Chem. Comm. 2014, 50, 8018-8020
• L. Cornelissen, M. Lefrancq, O. Riant, Org. Lett. 2014, 16, 3024-3027
• L. Cornelissen, S. Vercruysse, A. Sanhadji, O. Riant, Eur. J. Org. Chem. 2014, 2014, 35-38

In the framework of an ARC (Action de Recherche Concertée) involving three professors of the Université Catholique de Louvain (Sophie Demoustier, Sophie Hermans, and Olivier Riant), the CaScadOS project aims to develop nanostructure-supported photocatalysis. Olivier Riant’s team is focused on the synthesis and functionalization of organic or metal-based (with Iridium or Ruthenium centers) photoactive molecules. These molecules are then immobilized on different supports such as silica or alumina, thus giving efficient and recyclable heterogeneous photocatalysts. Various nanostructures are being investigated, starting from simple nanospheres to nanotubes of various dimensions. This project envisions the immobilization of different types of catalysts on nanotubes, namely membranes with interconnected pores (3D structure), to enhance their photocatalytic behavior and permit multi-catalysis.

Representative publications:

• F. Drault, E. Ferain, M.C. Lisboa, S. Hermans, S. Demoustier-Champagne, Nanoscale 2023, 15, 14981-14993
• F. Drault, P. Eloy, S. Demoustier-Champagne, S. Hermans, Catalysis Today 2023, 114472
• N. Body, R. Bevernaegie, C. Lefebvre, I. Jabin, S. Hermans, O. Riant, L. Troian-Gautier; Chem. A Eur. J. 2023, 29, e2023012

Peptide stapling consists in covalently linking two amino acid side chains, in order to restrict the conformational freedom of a peptide. As this can increase the helical propensity of Peptide stapling consists in covalently linking two amino acid side chains to restrict the conformational freedom of a peptide. This macrocyclization approach is frequently carried out to increase the helical propensity of bioactive peptides, and so improve their interaction with a biological target.

In this work, various reported Cys-Cys stapling methods are used to design cyclic peptides targeting the lactate dehydrogenase B (LDHB), which represents a key enzyme in the survival of cancer cells.

Original stapling methodologies are also developed, taking advantage of the difference in nucleophilicity between thiol and amine groups. In this context, transition metal-catalyzed reactions such as A³-coupling and Tsuji-Trost allylation are being investigated. As the incorporation of two contiguous staples (also known as peptide stitching) could be beneficial in terms of resulting helicity, these methods will also be applied to the synthesis of bicyclic peptides.

Representative publications:

• L. Thabault, L. Brisson, C. Brustenga, R. Frédérick et al., J. Med. Chem. 2020, 63, 4628-4643
• H. Jo, N. Meinhardt, Y. Wu, S. Kulkarni, et al., J. Am. Chem. Soc. 2012, 134, 17704-17713
• A. Rojas, C. Zhang, B. Pentelute, S. Buchwald, et al., Chem. Sci. 2017, 8, 4257-4263
• Y. Zhang, Q. Zhang, C. Wong, X. Li, J. Am. Chem. Soc. 2019, 141, 12274-12279
• J. Ceballos, E. Grinhagena, G. Sangouard, C. Heinis, J. Waser, Angew. Chem. Int. Ed. 2021, 60, 9022-9031
• M. Silva, H. Faustino, J. Coelho, P. Gois, et al., Angew. Chem. Int. Ed. 2021, 60, 10850-10857

Our lab is interested in harnessing the inherent redox properties of palladium complexes for advancing cancer treatment, in collaboration with the Intitute of Experimental and clinical research. These complexes exhibit adept catalysis, offering a unique pathway for delivering bioactive molecules within cancer cells. Our focus is on strategically activating PdII precatalysts in tumor microenvironments, enhancing cancer cell selectivity. Through the design of biocompatible organometallic Pd complexes, we selectively activate anticancer prodrugs, showcasing promising candidates. Our in-cellulo assessments demonstrate successful drug activation and significant inhibition of cancer energy metabolism. Additionally, our study highlights a palladium-catalyzed fluorogenic cascade reaction, emphasizing the potential for targeted drug delivery.

Representative publications:

• Y. Tan, M. Lefevre, F. Pierrard, M. Soetens, M. Shoueiry, E. Yildiz, S. Ibanez, K. Ozkan, O. Feron, R. Frédérick, O. Riant, J. Organomet. Chem. 2023, 996, 122743