Redox and Excited State Properties of Oligothiophene-Bearing Ru(II) Photodrugs

在化学结构、动力学和机理B(CSDM-B)项目的支持下，阿灵顿得克萨斯大学的Sherri McFarland教授将询问分子构象、电离性和分子间相互作用如何影响光敏剂的行为，特别是含低聚硫酚的Ru化合物。光敏剂是一种利用光能促进理想的物理过程或化学转化的化合物。这种分子在从太阳能转换到化学催化以及光医学等领域都有用处。这个项目专注于一类光敏剂，它展示了癌症治疗的希望，并可能遵循一种独特的多模式作用，将光催化和分子间光化学反应与单线态氧敏化结合在一起。该项目将使用配位化学以及光物理和电化学技术来探索异构化、聚集和限制以及环境在这些途径上的作用。拟议的工作将在化学、生物、物理和工程的结合部培养研究生和本科生进行高度多学科的研究。这种在合成、无机光物理和光谱学以及电化学方面的多方面培训将有助于为未来的科学和技术劳动力做准备。更广泛的影响目标旨在提高科学素养和解决研究中的教育公平问题。麦克法兰团队特别专注于解决本科研究中的教育公平问题，并通过为本科STEM学生提供基于课程的研究经验(CURE)，利用具有社会影响的板凳到床边项目来提高科学素养。该项目旨在让未来的领导者掌握科学交流的技能，并让他们接触到与将实验室的科学发现带给社会相关的企业家精神。在这个奖项下，Sherri McFarland教授和她的团队将研究含低聚硫吩类的Ru(II)配合物的氧化还原和激发态性质，这些化合物在从太阳能转换到光医学等领域具有重要的光敏剂应用。咪唑并[4，5-f][1，10]邻菲咯啉(IP)配体连接在具有足够链长的低聚硫酚(NT)上，具有平面化的最低能量三重态，具有显著的内对齐和电荷转移(ILCT)特征。低聚硫吩类化合物具有氧化还原活性，邻近的IP基团可能通过质子耦合电子转移(PCET)促进3ILCT态的光催化氧化还原反应。这些电荷分离的激发态也可能发生化学二聚反应，生成单线态氧。该项目旨在为这些系统在简单的溶剂和复杂的生物环境中开发一个光物理模型。每个系统都将从分子结构、氧化还原化学和光物理的角度进行研究，并对光疗机制产生更长期的影响。UTA团队将合成并表征低聚硫吩类Ru(II)配合物[Ru(Ll)2(IP-NT)]2，以探索各种因素对所提出的PCET促进的途径的影响：电离态、激发态构象、三重态能量和特征以及双分子过程。合成、光谱和电化学技术将被用来测试具有CT特征的NT基三联体和可电离基团对多峰作用的重要性，并探索基于电离、构象和异构性等因素如何影响生物界面上的激发态动力学。该项目旨在长期推动配位化学、光化学和光物理领域的发展，并最终推动光医学领域的发展。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 support from the Chemical Structure, Dynamics, and Mechanism-B (CSDM-B) program, Professor Sherri McFarland at the University of Texas, Arlington will interrogate how molecular conformation, ionizability, and intermolecular interactions influence the behavior of photosensitizers, particularly oligothiophene-containing ruthenium compounds. Photosensitizers are compounds that harness the light energy to facilitate a desirable physical process or chemical transformation. Such molecules have utility in fields spanning solar energy conversion to chemical catalysis, and also photomedicine. This project focuses on a photosensitizer class that shows promise for cancer therapy and may follow a unique type of multimodal action that combines photocatalysis and intermolecular photochemical reactions with singlet oxygen sensitization. The project will use the tools of coordination chemistry plus photophysical and electrochemical techniques to explore the roles of isomerism, agglomeration and confinement, and environment on these pathways. The proposed work will train graduate students and undergraduates in highly multidisciplinary research at the nexus of chemistry, biology, physics, and engineering. This multifaceted training in synthesis, inorganic photophysics and spectroscopy, and electrochemistry will help to prepare the future workforce in science and technology. The broader impact objectives are aimed at improving scientific literacy and addressing educational equity in research. The McFarland team is particularly focused on addressing educational equity issues in undergraduate research and improving scientific literacy using bench-to-bedside projects with societal impact through curriculum-based research experiences (CUREs) for undergraduate STEM students. The project aims to equip tomorrow’s leaders with skills in science communication and expose them to entrepreneurship as it relates to bringing scientific discoveries from the laboratory to society.Under this award, Professor Sherri McFarland and her team will examine the redox and excited state properties of oligothiophene-containing Ru(II) complexes, compounds that have important applications as photosensitizers in fields ranging from solar energy conversion to photomedicine. Imidazo[4,5-f][1,10]phenanthroline (IP) ligands appended to oligothiophenes (nT) of sufficient chain length n adopt planarized lowest-energy triplet states that are of significant intraligand charge transfer (ILCT) character. Oligothiophenes are redox active, and the neighboring IP group may enable proton coupled electron transfer (PCET) to facilitate catalytic photoredox reactions from the 3ILCT states. These charge-separated excited states may also undergo chemical dimerization and generate singlet oxygen. The project aims to develop a photophysical model for these systems in simple solvents and in complex biological environments. Each system will be studied from the point of view of molecular structure, redox chemistry and photophysics, with longer term implications for phototherapy mechanisms. The UTA team will synthesize and characterize oligothiophene-appended Ru(II) complexes, [Ru(LL)2(IP-nT)]2+, to probe the effects of various factors on the proposed PCET-facilitated pathways: ionization state, excited state conformation, triplet energy and character, and bimolecular processes. Synthetic, spectroscopic, and electrochemical techniques will be used to test the importance of nT-based triplets with CT character and ionizable groups for multimodal action and probe how the excited state dynamics are influenced at biological interfaces based on factors such as ionization, conformation, and isomerism. This project aims to advance the fields of coordination chemistry, photochemistry and photophysics, and ultimately photomedicine, in the longer term.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.