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，有助于血压调节，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效应归因于一氧化氮的分子衍生物，其自然存在于血液和细胞中。 这项研究旨在了解这些物种形成和相互转化的离散分子途径，以更深入地了解一氧化氮作为信息分子的作用。 参与该项目的研究生，本科生和高中生将获得广泛的科学经验，因为他们使用专门设计的化学模型来探测这些反应，这些化学模型模拟了与一氧化氮相互作用的许多类蛋白质的关键特征。 对年轻学生（5 - 8年级）的宣传将以有趣和引人入胜的方式展示大自然如何使用分子进行生物通讯。 有了这个奖项，化学系的生命过程计划的化学是资助教授蒂莫西H。Warren博士的研究课题是通过采用专门设计的合成模型，研究NO、S-亚硝基硫醇（RSNOs）和亚硝酸盐（NO2-）在相关铜和锌生物位点的相互转化，来研究一氧化氮（NO）信号传导的分子机制。 将检查NO在模拟1型铜位点的铜-硫醇盐处的结合以及RSNO与锌-硫醇盐的相互作用，以观察可逆的S-NO键形成和裂解。 特别是在锌体系中，这些研究将为建立气体传递体H_2S与NO和NO_2 ~-的金属中心反应性的联系奠定基础。 此外，将检查NO在无硫醇铜（I）和铜（II）络合物的结合，以了解控制铜结合NO的反应性的因素，包括与N2 O形成相关的不寻常的厌氧氧化行为。通过与国内和国际合作伙伴的光谱和计算合作，将进一步加强对NO及其氧化还原同系物在铜和锌位点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.