Unusual η2‐Allene Osmacycle with Apoptotic Properties |
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| Authors: | Xumin He Prof. Dr. Lei Gong Dr. Katja Kräling Katharina Gründler Corazon Frias Richard D. Webster Prof. Dr. Eric Meggers Prof. Dr. Aram Prokop Dr. Haiping Xia Prof. Dr. |
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| Affiliation: | 1. State Key Laboratory of Physical Chemistry of Solid Surfaces, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005 (China), Fax: (+86)?592‐218‐6628;2. Fachbereich Chemie, Philipps‐Universit?t Marburg, Hans‐Meerwein‐Strasse, 35032 Marburg (Germany), Fax(+49)?6421‐2821535;3. Kliniken der Stadt K?ln gGmbH, Neufelder Strasse 34, 51067 K?ln (Germany), Fax: (+49)?221‐89075395;4. Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, SPMS‐CBC‐04‐06, 21 Nanyang Link, Singapore 637371 (Singapore) |
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| Abstract: | Screening of a library of structurally unusual osmacyclic complexes for their antiproliferate properties in HeLa cells led to the discovery of a highly cytotoxic η2‐allene osmacycle. In this remarkably stable complex, osmium constitutes part of a metallacycle through the formation of a σ‐bond to a carbon in combination with coordination to an allene moiety. The osmacycle strongly induces apoptosis in Burkitt‐like lymphoma cells at submicromolar concentrations. The reduction of the mitochondrial membrane potential, the induction of DNA fragmentation, and the activation of caspases‐9 and ‐3 reveal that programmed cell death occurs through the intrinsic mitochondrial pathway. From the lipophilic and cationic nature of the osmacycle, in addition to a low oxidation potential (E1/2=+0.27 V vs. Fc/Fc+, Fc=ferrocene) it is proposed that mitochondria are the cellular target where oxidative decomposition initiates apoptosis. |
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| Keywords: | antitumor agents apoptosis cytotoxicity metallacycles osmium |
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