Mechanisms of Radical-Initiated Alkylation of Alkenes, Peptides and Proteins - A Green Chemistry Route

在这项由化学系化学结构、动态和机制B计划资助的项目中，巴尔的摩县马里兰大学(UMBC)化学系的Lisa Kelly教授正在使用长波吸收光的新前体来研究活性自由基的光诱导产生和去向。自由基是一类用途广泛的活性化学物种，在不需要有毒试剂或苛刻反应条件的情况下，有助于实现碳-碳键的形成。在聚合物化学中，自由基引发聚合物的形成。在生物化学中，自由基可以用来标记蛋白质，以确定分子间弱相互作用的位置。材料科学利用自由基将特定的分子附着在表面上。这项研究使用了一类被称为萘二亚胺的化合物，它们在光诱导下释放二氧化碳(CO2)来产生活性自由基。该化学是在水溶液中用光进行的，不需要其他有害的添加剂。因为这种化学只产生二氧化碳作为副产品，所以它代表了一条进行原本困难的化学转化的绿色路线。结合她的研究活动，Kelly教授开发了课程创新，向企业家化学家和化学工程师传授如何制作现场便携式计算机化传感器平台，以监控环境中的光化学反应。通过这些高级实验室项目，化学专业的学生可以建造电子电路，并发展基本的计算机编程技能，这些技能可能会成为未来创业的技术基础。凯利教授是密歇根大学促进多样性倡议的积极参与者。这些活动包括通过分享她的经验和促进与政府、工业和学术界的研究生校友建立联系的机会，为属于代表性不足的少数族裔的化学和生物化学学生提供指导。光化学转化很有吸引力，因为它们不需要热量，而且可以根据需要在特定位置启动。利用脉冲激光光谱学，本研究确定并绘制了光致电子转移(PET)诱导的脱羧基的机理。生色团--萘二亚胺在光谱的长波紫外区有很强的吸收，与其他产生自由基的化合物相比，需要的浓度要低得多。合成了一系列新型的萘二酰亚胺化合物，并测定了它们的自由基产生和衰变的速率常数。这项工作的具体目的是首先了解自由基产生的动力学和量子效率，然后研究与蛋白质标记和聚合物形成相关的可行的反应性目标。在光亲和标记和特定酶的失活方面的应用也在测试中。虽然光脱羧基的产物已经在一些多肽和烷基羧酸盐中得到了表征，但几乎没有直接证据表明碳中心自由基参与了这一过程。该奖项反映了NSF的法定使命，通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为是值得支持的。

In this project, funded by the Chemical Structure, Dynamic & Mechanism B Program of the Chemistry Division, Professor Lisa Kelly of the Department of Chemistry at the University of Maryland, Baltimore County (UMBC) is investigating the light-induced production and fate of reactive free radicals using new precursors which absorb light at long wavelength. Radicals are a versatile class of reactive chemical species that are useful to carry out carbon-carbon bond formation without the requirement of toxic reagents or harsh reaction conditions. In polymer chemistry, radicals initiate formation of the polymer. In biochemistry, radicals can be used to label proteins in order to identify the sites of weak intermolecular interactions. Materials science makes use of radicals to attach specific molecules onto surfaces. This research uses a class of compounds called naphthalene diimides that undergo the light-induced release of carbon dioxide (CO2) to produce reactive radicals. The chemistry is carried out with light in aqueous solution and does not require other harmful additives. Because this chemistry produces only CO2 as a byproduct, it represents a green route to carry out otherwise difficult chemical transformations. Integrated with her research activities, Professor Kelly develops curriculum innovations to teach entrepreneurial chemists and chemical engineers how to make field-portable computerized sensor platforms that monitor photochemical reactions in the environment. Through these advanced laboratory projects, chemistry students build electronic circuits and develop basic computer programming skills that might serve as a technology basis for future start-up ventures. Professor Kelly is an active participant in UMBC's diversity-advancement initiatives. These activities include mentorship for chemistry and biochemistry students who are members of underrepresented minorities by sharing her experiences and facilitating networking opportunities with graduate alumni in government, industry and academia. Photochemical transformations are attractive because they do not require heat and can be initiated in specific locations "on demand." Using pulsed laser spectroscopies, this research identifies and maps the mechanism of photoinduced electron transfer (PET)-induced decarboxylation. The chromophores, naphthalene diimides, absorb very strongly in the long-wavelength UV region of the spectrum, requiring significantly lower concentrations than other radical-producing compounds. A novel set of the naphthalene diimides are synthesized and the rate constants for radical production and decay are measured. Specific aims of this work are to first understand the kinetics and quantum efficiency of radical production, then investigate viable reactivity targets that are relevant to protein labeling and polymer formation. Applications in photoaffinity labeling and deactivation of specific enzymes are also being tested. While the products from photodecarboxylation have been characterized in a number of peptide and alkyl carboxylates, there has been little direct evidence for the involvement of carbon-centered radicals. Photoinduced decarboxylation of naphthalene diimides is expected to have broad utility in environmentally friendly synthetic organic chemistry.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.