重新评估 CORM-A1：广泛使用的一氧化碳供体的氧化还原化学和异质 CO 释放特性,Chemical Science

当前位置： X-MOL 学术 › Chem. Sci. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

重新评估 CORM-A1：广泛使用的一氧化碳供体的氧化还原化学和异质 CO 释放特性
Chemical Science ( IF 8.4 ) Pub Date : 2023-02-24 , DOI: 10.1039/d3sc00411b
Nicola Bauer ₁ , Xiaoxiao Yang ₁ , Zhengnan Yuan ₁ , Binghe Wang ₁

Affiliation

一氧化碳 (CO) 是一种内源性信号分子，具有调节免疫反应和参与生物钟关键组成部分的能力。此外，CO 已通过药理学验证其在各种病理条件下的动物模型中的治疗益处。对于基于 CO 的疗法的开发，需要新的递送形式来解决使用吸入 CO 进行治疗应用的固有局限性。沿着这条线，已经有金属-和硼烷-羰基络合物被报道为用于各种研究的 CO 释放分子 (CORM)。CORM-A1 是检测 CO 生物学中使用最广泛的四种 CORM 之一。此类研究基于以下假设：CORM-A1 (1) 在常用实验条件下有效且可重复地释放 CO，并且 (2) 没有有意义的 CO 独立活动。在这项研究中，我们展示了 CORM-A1 的重要氧化还原特性，导致 NAD 等生物相关分子的减少⁺和 NADP⁺在接近生理条件下；这种减少相互促进了 CORM-A1 中的 CO 释放。我们进一步证明 CORM-A1 的 CO 释放产量和速率高度依赖于各种因素，例如使用的介质、缓冲液浓度和氧化还原环境；这些因素似乎非常特殊，以至于我们无法找到统一的机械解释。在标准实验条件下，发现 CO 释放产量在最初 15 分钟内很低且变化很大 (0.5–15%)，除非存在某些试剂，例如NAD⁺或高浓度缓冲液。CORM-A1 的显着化学反应性和在接近生理条件下 CO 释放的高度可变性表明需要更多地考虑适当的控制（如果可用），并谨慎使用 CORM-A1 作为生物学研究中的 CO 替代物。

"点击查看英文标题和摘要"

Reassessing CORM-A1: redox chemistry and idiosyncratic CO-releasing characteristics of the widely used carbon monoxide donor

Carbon monoxide (CO) is an endogenous signaling molecule with demonstrated ability to modulate immune responses and to engage key components of the circadian clock. Further, CO has been pharmacologically validated for its therapeutic benefits in animal models of various pathological conditions. For the development of CO-based therapeutics, new delivery forms are needed to address the inherent limitations of using inhaled CO for therapeutic applications. Along this line, there have been metal– and borane–carbonyl complexes reported as CO-release molecules (CORMs) for various studies. CORM-A1 is among the four most widely used CORMs in examining CO biology. Such studies are predicated on the assumptions that CORM-A1 (1) releases CO efficiently and reproducibly under commonly used experimental conditions and (2) does not have meaningful CO-independent activities. In this study, we demonstrate the important redox properties of CORM-A1 leading to the reduction of bio-relevant molecules such as NAD⁺ and NADP⁺ under near-physiological conditions; such reduction reciprocally facilitates CO release from CORM-A1. We further demonstrate that CO-release yield and rate from CORM-A1 are highly dependent on various factors such as the medium used, buffer concentrations, and redox environment; these factors seem to be so idiosyncratic that we were unable to find a uniform mechanistic explanation. Under standard experimental conditions, CO release yields were found to be low and highly variable (0.5–15%) in the initial 15 min unless in the presence of certain reagents, e.g. NAD⁺ or high concentrations of buffer. The significant chemical reactivity of CORM-A1 and the highly variable nature of CO release under near-physiological conditions suggest the need for much more consideration of appropriate controls, if available, and caution in using CORM-A1 as a CO surrogate in biological studies.

更新日期：2023-02-28

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南

全部期刊列表>>