Modeling Nitric Oxide Signaling Chemistry at Non-Heme Sites

一氧化氮是生物系统中产生的一种气体，作为分子信使帮助调节血压，增强血液流动，参与心肺健康，并帮助神经沟通。与一氧化氮有关的长期影响被归因于一氧化氮的分子衍生物，一氧化氮自然存在于血液和细胞中。这项研究试图了解这些物种形成和相互转换的离散分子途径，以更深入地了解一氧化氮作为信息分子的作用。从事这一项目的研究生、本科生和高中生将获得广泛的科学经验，因为他们将使用专门设计的化学模型来探索这些反应，这些模型模拟了许多类别与一氧化氮相互作用的蛋白质的共同关键特征。对年轻学生(5-8年级)的接触将以一种有趣和引人入胜的方式展示大自然如何利用分子进行生物交流。获得这一奖项的是普渡大学生命过程化学项目资助的Timothy H.Warren教授，他利用专门设计的合成模型，通过研究NO、S-亚硝硫醇(RSNO)和亚硝酸盐(NO2-)在相关铜和锌生物部位的相互转化，来研究一氧化氮(NO)信号转导的分子机制。我们将考察NO在模拟1型铜位的铜硫酸盐上的结合以及RSNO与硫代锌的相互作用，以观察可逆的S-NO键的形成和断裂。特别是在锌体系中，这些研究将为将气体变送器H_2S的金属中心反应性与NO和NO2-联系起来奠定基础。此外，还将研究NO在无硫酸盐铜(I)和铜(II)络合物上的结合，以了解控制铜结合NO反应活性的因素，包括与N2O形成有关的异常厌氧氧化行为。将通过与国内和国际伙伴的光谱和计算合作，进一步加深对NO及其氧化还原同系物在铜和锌地点的相互转化的详细了解。

Nitric oxide is a gas generated in biological systems that serves as a molecular messenger to assist in blood pressure regulation, enhance blood flow, participate in heart and lung health, and help nerves communicate. Long lasting effects connected to nitric oxide have been attributed to molecular derivatives of nitric oxide, which naturally occur in the blood and cells. This study seeks an understanding of the discrete molecular pathways by which these species form and interconvert to gain a deeper understanding of nitric oxide's role as a messaging molecule. Graduate, undergraduate, and high school students engaged in this project will gain broad scientific experience as they probe these reactions using specially designed chemical models that emulate key features common to many classes of proteins that interact with nitric oxide. Outreach to younger students (5th-8th grade) will show in a fun and engaging way how nature uses molecules for biological communication. With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Professor Timothy H. Warren from Purdue University to examine molecular mechanisms that underlie nitric oxide (NO) signaling by examining the interconversion of NO, S-nitrosothiols (RSNOs) and nitrite (NO2-) at relevant copper and zinc biological sites employing specially designed synthetic models. Binding of NO at copper-thiolates that emulate type 1 copper sites as well as interaction of RSNOs with zinc-thiolates will be examined to observe reversible S-NO bond formation and cleavage. Especially in the zinc system, these studies will form a foundation to connect the metal-centered reactivity of the gasotransmitter H2S with NO and NO2-. Additionally, binding of NO at thiolate-free copper(I) and copper(II) complexes will be examined to understand factors that control the reactivity of copper-bound NO, including unusual anaerobic oxidizing behavior connected with the formation of N2O. Detailed insights obtained for the interconversion of NO and its redox congeners at copper and zinc sites will be further enhanced through spectroscopic and computational collaboration with domestic and international partners.