Emeritus (Swiss Federal Institute of Technology), Schwändibergstrasse 25, CH-8784 Braunwald, Switzerland.
Biotronik AG, Ackerstrasse 6, CH-8180 Bülach, Switzerland.
Chem Res Toxicol. 2020 Jul 20;33(7):1516-1527. doi: 10.1021/acs.chemrestox.9b00309. Epub 2020 May 20.
In biology, the reaction of ONOO with CO is the main sink for ONOO. This reaction yields CO, NO, NO, and CO. There is a long-standing debate with respect to the yield of the radicals relative to ONOO. The reaction of ONOO with CO results at first in ONOOCO. According to one hypothesis, ONOOCO is extremely short-lived and devolves into a solvent cage that contains CO and NO. Of these solvent cages, approximately two/thirds result in NO and CO, and approximately one/third release CO and NO that oxidize the substrate. According to our hypothesis, ONOOCO is formed much faster, is relatively long-lived, and may also be an oxidant; the limited yield is the result of ONOOCO being scavenged by a second CO under conditions of a high CO concentration. We disagree with the first hypothesis for three reasons: First, it is based on an estimated for the reaction of ONOO with CO to form ONOOCO of ∼1 M, while experiments yield a value of 4.5 × 10 M. Second, we argue that the solvent cage as proposed is physically not realistic. Given the less than diffusion-controlled rate constant of CO with NO, all radicals would escape from the solvent cage. Third, the reported ∼33% radical is not supported by an experiment where mass balance was established. We propose here a hybrid mechanism. After formation of ONOOCO, it undergoes homolysis to yield CO with NO, or, depending on [CO], it is scavenged by a second CO; CO oxidizes ONOO, if present. These reactions allow us to successfully simulate the reaction of ONOO with CO over a wide range of ONOO/CO ratios. At lower ratios, fewer radicals are formed, while at higher ratios, radical yields between 30% and 40% are predicted. The differences in radical yields reported may thus be traced to the experimental ONOO/CO ratios. Given a physiological [CO] of 1.3 mM, the yield of CO and NO is 19%, and lower if ONOOCO has a significant reactivity of its own.
在生物学中，ONOO 与 CO 的反应是 ONOO 的主要消耗途径。该反应生成 CO、NO、NO 和 CO。关于相对 ONOO 的自由基产率，一直存在争议。ONOO 与 CO 的反应最初生成 ONOOCO。根据一种假设，ONOOCO 极不稳定，会分解成包含 CO 和 NO 的溶剂笼。在这些溶剂笼中，约有三分之二生成 NO 和 CO，约有三分之一释放 CO 和 NO，从而氧化底物。根据我们的假设，ONOOCO 的形成速度更快，相对寿命更长，也可能是一种氧化剂；有限的产率是由于在高 CO 浓度条件下，第二个 CO 消耗了 ONOOCO。我们不同意第一个假设，原因有三：首先，它基于对 ONOO 与 CO 反应形成 ONOOCO 的估计反应速率常数∼1 M，而实验得到的数值为 4.5×10 M。其次，我们认为所提出的溶剂笼在物理上是不现实的。考虑到 CO 与 NO 的反应速率常数小于扩散控制，所有自由基都会从溶剂笼中逸出。第三，实验中没有支持报告的约 33%自由基的实验结果。在这里，我们提出一种混合机制。形成 ONOOCO 后，它会发生均裂，生成 CO 和 NO，或者，根据[CO]的浓度，它会被第二个 CO 消耗；如果存在 ONOO，则 CO 会氧化 ONOO。这些反应使我们能够成功地模拟 ONOO 与 CO 在广泛的 ONOO/CO 比范围内的反应。在较低的比值下，形成的自由基较少，而在较高的比值下，预测自由基产率在 30%到 40%之间。因此，报告的自由基产率差异可能归因于实验中的 ONOO/CO 比值。在生理[CO]为 1.3 mM 的情况下，CO 和 NO 的产率为 19%，如果 ONOOCO 本身具有显著的反应活性，则产率会更低。
