Department of Chemistry and RECETOX, Faculty of Science, Masaryk University, Kamenice 5, 62500, Brno, Czech Republic.
Institute of Medical Biochemistry and Laboratory Diagnostics, General Faculty Hospital and 1st Faculty of Medicine, Charles University, Na Bojišti 3, 12108, Praha 2, Czech Republic.
Chemistry. 2020 Oct 15;26(58):13184-13190. doi: 10.1002/chem.202003272. Epub 2020 Sep 4.
Carbon monoxide (CO) is an endogenous signaling molecule that controls a number of physiological processes. To circumvent the inherent toxicity of CO, light-activated CO-releasing molecules (photoCORMs) have emerged as an alternative for its administration. However, their wider application requires photoactivation using biologically benign visible and near-infrared (NIR) light. In this work, a strategy to access such photoCORMs by fusing two CO-releasing flavonol moieties with a NIR-absorbing cyanine dye is presented. These hybrids liberate two molecules of CO in high chemical yields upon activation with NIR light up to 820 nm and exhibit excellent uncaging cross-sections, which surpass the state-of-the-art by two orders of magnitude. Furthermore, the biocompatibility and applicability of the system in vitro and in vivo are demonstrated, and a mechanism of CO release is proposed. It is hoped that this strategy will stimulate the discovery of new classes of photoCORMs and accelerate the translation of CO-based phototherapy into practice.
一氧化碳（CO）是一种内源性信号分子，能够控制许多生理过程。为了规避 CO 的固有毒性，用光激活的 CO 释放分子（photoCORMs）已经作为其给药的替代方法出现。然而，它们的更广泛应用需要使用生物相容性良好的可见光和近红外（NIR）光进行光激活。在这项工作中，提出了一种通过将两个 CO 释放黄酮醇部分与近红外吸收的菁染料融合来获得这种 photoCORMs 的策略。这些杂化分子在近红外光（高达 820nm）的激活下以高化学产率释放出两个 CO 分子，并表现出优异的光解交叉截面，超过了现有技术两个数量级。此外，还证明了该系统在体外和体内的生物相容性和适用性，并提出了 CO 释放的机制。希望这一策略能够激发新型 photoCORMs 的发现，并加速基于 CO 的光疗向实际应用的转化。
