Carbon monoxide (CO) is a gaseous signaling molecule produced in humans via the breakdown of heme in an O₂-dependent reaction catalyzed by heme oxygenase enzymes. A long-lived species relative to other signaling molecules (e.g., NO, H₂S), CO exerts its physiological effects via binding to low-valent transition metal centers in proteins and enzymes. Studies involving the administration of low doses of CO have shown its potential as a therapeutic agent to produce vasodilation, anti-inflammatory, antiapoptotic, and anticancer effects. In pursuit of developing tools to define better the role and therapeutic potential of CO, carbon monoxide releasing molecules (CORMs) were developed. To date, the vast majority of reported CORMs have been metal carbonyl complexes, with the most well-known being Ru₂Cl₄(CO)₆ (CORM-2), Ru(CO)₃Cl(glycinate) (CORM-3), and Mn(CO)₄(S₂CNMe(CH₂CO₂H)) (CORM-401). These complexes have been used to probe the effects of CO in hundreds of cell- and animal-based experiments. However, through recent investigations, it has become evident that these reagents exhibit complicated reactivity in biological environments. The interpretation of the effects produced by some of these complexes is obscured by protein binding, such that their formulation is not clear, and by CO leakage and potential redox activity. An additional weakness with regard to CORM-2 and CORM-3 is that these compounds cannot be tracked via fluorescence. Therefore, it is unclear where or when CO release occurs, which confounds the interpretation of experiments using these molecules. To address these weaknesses, our research team has pioneered the development of metal-free CORMs based on structurally tunable extended flavonol or quinolone scaffolds. In addition to being highly controlled, with CO release only occurring upon triggering with visible light (photoCORMs), these CO donors are trackable via fluorescence prior to CO release in cellular environments and can be targeted to specific cellular locations.

中文翻译：

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可触发、可追踪和可靶向的一氧化碳释放分子的开发。

一氧化碳 (CO) 是一种气体信号分子，通过血红素在血红素加氧酶催化的 O ₂依赖性反应中分解血红素产生。相对于其他信号分子（例如，NO、H ₂S)，CO 通过与蛋白质和酶中的低价过渡金属中心结合来发挥其生理作用。涉及低剂量 CO 给药的研究表明，它具有作为治疗剂产生血管舒张、抗炎、抗细胞凋亡和抗癌作用的潜力。为了寻求开发工具以更好地定义 CO 的作用和治疗潜力，开发了一氧化碳释放分子 (CORM)。迄今为止，绝大多数报道的 CORM 都是金属羰基配合物，最著名的是 Ru ₂ Cl ₄ (CO) ₆ (CORM-2)、Ru(CO) ₃ Cl(甘氨酸盐) (CORM-3) , 和 Mn(CO) ₄ (S ₂ CNMe(CH ₂ CO ₂H)) (CORM-401)。这些复合物已被用于在数百个基于细胞和动物的实验中探测 CO 的影响。然而，通过最近的研究，很明显这些试剂在生物环境中表现出复杂的反应性。其中一些复合物产生的效应的解释被蛋白质结合所掩盖，因此它们的配方不清楚，以及 CO 泄漏和潜在的氧化还原活性。CORM-2 和 CORM-3 的另一个弱点是这些化合物无法通过荧光进行追踪。因此，不清楚在何处或何时发生 CO 释放，这混淆了对使用这些分子的实验的解释。为了解决这些弱点，我们的研究团队率先开发了基于结构可调的扩展黄酮醇或喹诺酮支架的无金属 CORM。除了受到高度控制之外，CO 释放仅在可见光 (photoCORM) 触发时发生，这些 CO 供体可以在细胞环境中 CO 释放之前通过荧光进行追踪，并且可以靶向特定的细胞位置。