RESUMEN
The selective interaction of cytochrome c (Cyt c) with cardiolipin (CL) is involved in mitochondrial membrane permeabilization, an essential step for the release of apoptosis activators. The structural basis and modulatory mechanism are, however, poorly understood. Here, we report that Cyt c can induce CL peroxidation independent of reactive oxygen species, which is controlled by its redox states. The structural basis of the Cyt c-CL binding was unveiled by comprehensive spectroscopic investigation and mass spectrometry. The Cyt c-induced permeabilization and its effect on membrane collapse, pore formation, and budding are observed by confocal microscopy. Moreover, cytochrome c oxidase dysfunction is found to be associated with the initiation of Cyt c redox-controlled membrane permeabilization. These results verify the significance of a redox-dependent modulation mechanism at the early stage of apoptosis, which can be exploited for the design of cytochrome c oxidase-targeted apoptotic inducers in cancer therapy.
Asunto(s)
Citocromos c , Espectrometría Raman , Citocromos c/química , Citocromos c/metabolismo , Citocromos c/farmacología , Complejo IV de Transporte de Electrones/metabolismo , Oxidación-Reducción , Cardiolipinas/química , Cardiolipinas/metabolismo , Cardiolipinas/farmacología , Membranas Mitocondriales/metabolismo , ApoptosisRESUMEN
A novel electron-transporting unit, imidazo [1,2-b]pyridazine (IP), was first reported for developing host materials. The IP moiety possesses excellent electron-transporting ability and great thermal stability. Using carbazole as p-type units and IP as n-type units, several bipolar host materials, namely, IP6Cz, IP68Cz, IP36Cz, and IP368Cz, were developed through altering the substitution site of the IP core. Among these four materials, 6-site-substituted IP6Cz and 6,8-site-substituted IP68Cz exhibit the best electroluminescence (EL) performance. IP6Cz- and IP68Cz-based red phosphorescent organic light-emitting diodes using Ir(pq)2acac as the emitter exhibit extremely high EL efficiency with the maximum external quantum efficiency (ηext,max) of 26.9 and 25.2% and an insignificant efficiency roll-off. Moreover, IP6Cz- and IP68Cz-based deep-red devices doped by Ir(piq)2acac also show satisfactory EL performance with a ηext,max of 20.5 and 19.9%, respectively. The influence of different substitution sites of the IP core on the photophysical and electrochemical properties was systematically investigated. This study demonstrates that IP could be a first-rate electron-transporting unit for bipolar materials for red-emitting devices.