Unusual η²‐Allene Osmacycle with Apoptotic Properties

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 eta2-allene osmacycle. In this remarkably stable complex, osmium constitutes part of a metallacycle through the formation of a sigma-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.

Recent Advances in Metallaaromatic Chemistry

“…[90,92] In addition, metallabenzenes have been reported to have promising electrochemical, [51,56,90] optical [93,115] and cytotoxic properties. [47,51,116] It can be expected that further unusual applications for these intriguing compounds will emerge as studies in this area continue to expand.…”

Development of anticancer agents: wizardry with osmium

“…The outstanding stability of this complex was associated with the formation of a metallacycle, in which osmium is -coordinated to an allene moiety and simultaneously σ-linked to a carbon atom of a terminal double bond. The mode of action of 11 was related to the induction of apoptosis through the intrinsic mitochondrial pathway, as evident by the reduction of the mitochondrial membrane potential, and the activation of caspases-9 and -3 in Burkitt-like lymphoma cells [31].…”

Bucket Effect to Improve Third‐Order Nonlinear Optical Response on Metal‐Heteroaromatic Compounds

“…[ 13 ] Metal‐heteroaromatics compounds have flourished in recent decades since they were proposed by Hoffmann in 1979. [ 14 ] Representatively, carbolong, a class of metal‐heteroaromatic compounds, has been widely used in various application fields, [ 15‐16 ] including organic catalysis, [ 17‐19 ] photoluminescence, [ 20‐21 ] biomedicine, [ 22 ] and solar cells. [ 23 ] However, the unique π‐conjugated systems of carbolong provide the possibility for third‐order NLO, which remains to be explored.…”