Tracking Reactions of Asymmetric Organo‐Osmium Transfer Hydrogenation Catalysts in Cancer Cells
| Autor: | Elizabeth M. Bolitho, James P. C. Coverdale, Hannah E. Bridgewater, Guy J. Clarkson, Paul D. Quinn, Carlos Sanchez‐Cano, Peter J. Sadler |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
RM
Cell Survival Anticancer Complexes | Hot Paper X-ray fluorescence Molecular Conformation chemistry.chemical_element Antineoplastic Agents 010402 general chemistry Transfer hydrogenation 01 natural sciences Redox Catalysis RS chemistry.chemical_compound Bromide Cell Line Tumor Humans Osmium organo-osmium complexes Research Articles Metal-Organic Frameworks Cell Proliferation 010405 organic chemistry Ligand bioorganometallic chemistry Bioorganometallic chemistry Enantioselective synthesis General Medicine General Chemistry Combinatorial chemistry 0104 chemical sciences anticancer catalysts chemistry transfer hydrogenation Hydrogenation Research Article |
| Zdroj: | Angewandte Chemie (International Ed. in English) |
| ISSN: | 1521-3773 1433-7851 |
| Popis: | Most metallodrugs are prodrugs that can undergo ligand exchange and redox reactions in biological media. Here we have investigated the cellular stability of the anticancer complex [OsII[(η6‐p‐cymene)(RR/SS‐MePh‐DPEN)] [1] (MePh‐DPEN=tosyl‐diphenylethylenediamine) which catalyses the enantioselective reduction of pyruvate to lactate in cells. The introduction of a bromide tag at an unreactive site on a phenyl substituent of Ph‐DPEN allowed us to probe the fate of this ligand and Os in human cancer cells by a combination of X‐ray fluorescence (XRF) elemental mapping and inductively coupled plasma‐mass spectrometry (ICP‐MS). The BrPh‐DPEN ligand is readily displaced by reaction with endogenous thiols and translocated to the nucleus, whereas the Os fragment is exported from the cells. These data explain why the efficiency of catalysis is low, and suggests that it could be optimised by developing thiol resistant analogues. Moreover, this work also provides a new way for the delivery of ligands which are inactive when administered on their own. This chiral organo‐osmium complex catalyses enantioselective reduction of pyruvate to lactate in cancer cells. The bromine tag on the chelated ligand and osmium have been jointly mapped in cells by X‐ray fluorescence and inductively coupled plasma‐mass spectrometry, revealing facile displacement of the ligand and its translocation to the nucleus. |
| Databáze: | OpenAIRE |
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