The Excited State Behavior of Ru(II) Photodrugs

通过这一奖项，化学结构、动力学和机制-B项目支持德克萨斯大学阿灵顿分校的Sherri McFarland教授研究基于Ru的光敏剂的激发态光物理和氧化还原特性。光敏剂是一种化合物，它可以捕获光能，并利用它来实现有用的化学反应。这方面的例子包括太阳能转换、催化和光药。这个项目专注于一类特殊的光敏剂，这些光敏剂在癌症治疗中表现出希望，但关于它们的作用模式有许多悬而未决的问题。这项工作将专门研究含低聚并噻吩Ru化合物的基本光物理和电化学性质，并揭示它们可以参与的光催化机理的细节。它还将探索这些光敏剂的行为如何随着环境的变化而变化，例如，聚集效应和模拟生物结构的影响。拟议的工作将培养研究生和本科生在化学、生物、物理和工程学的界面上进行高度多学科的研究。这些学员将获得的知识和技能将使他们成为未来在从光医学到太阳能转换和化学生物学等尖端多学科领域的研究科学家取得成功所必需的工具。更广泛的影响目标将同时使未来的领导者掌握科学传播方面的技能，并使他们接触到创业和商业化，因为这涉及到将科学发现从实验室带到社会。它还将为本科生提供基于课程的研究机会，否则他们将没有机会在真实世界的实验室环境中体验科学研究，扩大我们的下一代新兴科学家的多样性。这个项目将研究含低聚并噻吩Ru(II)配合物的激发态光物理和氧化还原性质，这些化合物在从太阳能转换到光药等领域具有重要的光敏剂应用。该项目还旨在开发这些光敏剂在复杂生物环境中的光物理模型(S)。我们将合成并表征低聚硫杂环的Ru(II)光敏剂，[Ru(Ll)_2(IP-NT)]~(2+)具有不同的噻吩环数目(NT)、不同的取代基类型和不同的共配体(LL)。这些修饰旨在系统地改变氧化还原电位和三重态特征，并改变低聚硫吩类典型的共价和非共价缔合。电化学和光物理技术将被用来测试复杂基质中假想的光氧化还原催化机理，其中合成的和细胞衍生的小泡将被用来模拟光敏剂响应如何在受限的基质中进行调制，例如，脂质双层。这一结果将促进Ru(II)-低聚硫吩光敏化领域的发展。随着对含低聚硫吩类Ru(II)光敏剂机理的了解，有机会创造出更好的下一代光敏剂用于光催化应用。更广泛的影响活动同样侧重于根据过去与光-分子相互作用有关的转化研究和商业化努力，让STEM科学家接触科学、交流和创业精神。培训计划将涵盖外展、教育和课程，强调从基础发现到社会应用的过程，并为研究人员提供提高科学交流技能的机会。为本科STEM学生提供的基于课程的研究机会将被设计和提供，以确保这些学生中更大比例的学生在学位课程期间获得实践研究经验。该奖项反映了NSF的法定使命，并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，被认为值得支持。

With this award, the Chemical Structure, Dynamics, and Mechanism-B program is supporting the research of Professor Sherri McFarland at the University of Texas, Arlington to examine the excited state photophysics and redox properties of Ru-based photosensitizers. Photosensitizers are compounds that can trap the energy of light and use it to effect a useful chemical reaction. Examples of this include solar energy conversion, catalysis, and photodrugs. This project focuses on a particular class of such photosensitizers that show promise in cancer therapy, but have many unanswered questions about their mode of action. The work will investigate the fundamental photophysical and electrochemical properties of oligothiophene-containing ruthenium compounds specifically, and reveal the details of photocatalytic mechanisms in which they can participate. It will also explore how the behavior of these photosensitizers can change as a function of its environment, e.g., agglomeration effects and the influence of simulated biological structures. The proposed work will train graduate and undergraduate students in highly multidisciplinary research at the interface of chemistry, biology, physics, and engineering. The knowledge and skills these trainees will acquire will give them tools necessary for success as future research scientists in cutting-edge multidisciplinary fields ranging from photomedicine to solar energy conversion and chemical biology. The broader impact objectives will simultaneously equip tomorrow’s leaders with skills in science communication and expose them to entrepreneurship and commercialization as it relates to bringing scientific discoveries from the laboratory to society. It will also provide curriculum-based research opportunities for undergraduate students that would otherwise not have the opportunity to experience scientific research in a real-world laboratory setting, expanding diversity in our next generation of emerging scientists.This project project will examine the excited state photophysics and redox properties of oligothiophene-containing Ru(II) complexes, compounds that have important applications as photosensitizers in fields ranging from solar energy conversion to photodrugs. The project also aims to develop the photophysical model(s) for these photosensitizers in complex biological environments. We will synthesize and characterize oligothiophene-appended Ru(II) photosensitizers, [Ru(LL)2(IP-nT)]2+ that differ in the number of thiophene rings (nT), the types of substituents on the thiophene rings, and the co-ligands (LL). The modifications are designed to systematically vary redox potentials and triplet state characteristics, and to alter the covalent and noncovalent associations typical of oligothiophenes. Electrochemical and photophysical techniques will be used to test hypothetical photoredox catalysis mechanisms in complex substrates, where synthetic and cell-derived vesicles will be used to model how photosensitizer response modulates in confined matrices, e.g., a lipid bilayer. The results will advance the field of Ru(II)-oligothiophene photosensitization. With a mechanistic understanding of oligothiophene-containing Ru(II) photosensitizers, there exists the opportunity to create better next-generation photosensitizers for photocatalytic applications. The broader impact activities are equally focused on exposing STEM scientists to science communication and entrepreneurship based on past translational research and commercialization efforts related to light-molecule interactions. The training program will cover outreach, education, and curriculum, emphasizing the process from fundamental discovery to societal application, and provide opportunities for researchers to improve their science communication skills. Curriculum-based research opportunities for undergraduate STEM students will be designed and delivered to ensure that a larger percentage of these students receive hands-on research experience during their degree programs.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.