לוח שנה משולב

Over years’ transition metal-catalyzed C-H activation has propelled the field of organic synthesis for the construction of structurally complex and diverse molecules in resource-economical fashion. In this context, non-directed C-H activation has gained unprecedented attention for attaining region-specific C-H functionalizations in a step-economic mode. Unlike traditional Fujiwara-Moritani reaction, this approach relies on ligand assistance and thus uses arene as the limiting reagent. However, all existing non-directed C-H functionalizations utilize high thermal energy to induce the functional group which eventually put the regioselectivity at stake. In addition, use of super stoichiometric costly silver salts to regenerate the catalyst produces unwanted metal waste. In aid of developing a more sustainable and environmentally benign approach, we have established a photoredox catalytic system by a merger of palladium/organo-photocatalyst(PC) which forges highly regeiospecific C-H olefination of diverse arenes and heteroarenes. Visible light nullifies the requirement of silver salts and thermal energy in executing “region-resolved” Fujiwara-Moritani reaction.

Dept of Connectomics
Max Planck Institute for Brain Research Frankfurt

Medicine is taking its first steps toward patient-specific cancer care. Nanoparticles have many potential benefits for treating cancer, including the ability to transport complex molecular cargoes, including siRNA and protein, as well as targeting specific cell populations.
The talk will explain the fundamentals of nanotechnology, from ‘barcoded nanoparticles’ that target sites of cancer where they perform a programmed therapeutic task. Specifically, liposomes diagnose the tumor and metastasis for their sensitivity to different medications, providing patient-specific drug activity information that can be used to improve the medication choice.
The talk will also describe how liposomes can be used for degrading the pancreatic stroma to allow subsequent drug penetration into pancreatic adenocarcinoma and how nanoparticle’ biodistribution and anti-cancer efficacy are impacted by the patient’s sex and, more specifically, the menstrual cycle.
The evolution of drug delivery systems into synthetic cells, programmed nanoparticles that have an autonomous capacity to synthesize diagnostic and therapeutic proteins inside the body, and their promise for treating cancer and immunotherapy, will be discussed.


















References:
1) Theranostic barcoded nanoparticles for personalized cancer medicine, Yaari et al. Nature Communications, 2016, 7, 13325
2) Collagenase nanoparticles enhance the penetration of drugs into pancreatic tumors, Zinger et al., ACS Nano, 13 (10), 11008-11021, 2019
3) Targeting neurons in the tumor microenvironment with bupivacaine nanoparticles reduces breast cancer progression and metastases, Science Advances, Kaduri et al., 7 (41), eabj5435, 2021
4) Nanoparticles accumulate in the female reproductive system during ovulation affecting cancer treatment and fertility, Poley et al., ACS nano, 2022

To understand the functional properties of biomolecules, such a small metabolites, protein or nucleic acids, we ought to study them with high resolution in their native context. NMR spectroscopy allows the direct observation of NMR-active nuclei in complex, undefined environments and can thus be employed to investigate isotopically enriched molecules inside live cells. This methodology is known as In-cell NMR and has been used to evaluate the structural properties of proteins, nucleic acids and other biomolecules in physiological environments and to resolve their functional characteristics in a cellular context. These methods have been applied to bacteria, yeasts or cultured mammalian cells. However these cells are clonally grown at high densities in artificial media, lacking the complex tissue context present in higher organisms and its associated biological activities. We funnel our efforts to extend In-cell NMR applications to in vivo conditions using zebrafish embryos and the nematode C. elegans as model organisms. We deliver 15N-isotopically enriched biomolecules, such as small compounds and proteins into fish embryos to delineate their conformational properties and enzymatic conversions. We also enrich live C. elegans with 13C atoms to directly interrogate about their metabolic compositions and enzymatic activities. Combined, these studies provide methodological advancements with regard to high resolution in vivo NMR applications.