Abstract：
The quercetin dioxygenases (QDOs) are unusual metalloenzymes in that they display ring-opening dioxygenase activity with several different first-row transition metal ions which do not undergo redox changes during turnover. The QDOs are also unique in that the substrate binds as an η1-flavonolate rather than the η2 -bidentate mode seen in all reported model complexes. The flavonol substrates were early examples of excited state intramolecular proton transfer (ESIPT) phenomena, in which photoexcitation causes an H-atom exchange between the adjacent hydroxyl and ketone, generating an oxidopyrylium emissive state. These oxidopyryliums undergo ring-opening dioxygenations analogous to the enzymatic reactions. Our hypothesis is that lability of the divalent metal ion may allow access to a reactive oxidopyrylium intermediate via coordination switching from the oxy to ketone position, which allows reaction with O2. In this report, we use a straight-forward methylation strategy to generate a panel of flavonol and thioflavonol derivatives modeling several η1- and η2-coordination modes. Methylation of 3-hydroxythioflavone generates an air stable η1 hydroxopyrylium salt, which undergoes rapid ring-opening dioxygenation by deprotonation or photoexcitation. By comparison, the η1-methoxyflavonol does not react with O2 under any condition. We find that any of the studied flavonol derivatives, η1 or η2, which demonstrates ESIPT-like oxidopyrylium emissions undergo QDO-like ring-opening reactions with dioxygen. The implications of these results concerning the mechanism of QDOs and related dioxygenases is discussed.
摘要：
槲皮素双加氧酶（QDOs）是不寻常的金属酶，因为它们显示开环双加氧酶活性，具有几种不同的第一行过渡金属离子，在周转过程中不会发生氧化还原变化。QDO也是独特的，因为底物以η1-黄酮醇盐的形式结合，而不是在所有报道的模型复合物中看到的η2-双齿模式。黄酮醇底物是激发态分子内质子转移（ESIPT）现象的早期例子，其中光激发导致相邻羟基和酮之间的H原子交换，产生氧化吡喃释放态。这些氧化吡喃进行类似于酶促反应的开环双氧化。我们的假设是，二价金属离子的不稳定性可以通过从氧位置到酮位置的配位转换来获得反应性氧吡喃基中间体，允许与O2反应。在这份报告中,我们使用直接的甲基化策略来生成一组黄酮醇和硫代黄酮醇衍生物，模拟几种η1-和η2-配位模式。3-羟基硫代黄酮的甲基化产生空气稳定的η1羟基吡喃铵盐，通过去质子化或光激发进行快速开环双氧化。相比之下,η1-甲氧基黄酮醇在任何条件下都不与O2反应。我们发现任何研究过的黄酮醇衍生物，η1或η2，表明ESIPT样的氧化吡喃鎓发射与双氧发生QDO样的开环反应。讨论了这些结果对QDOs和相关双加氧酶机制的影响。
