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，阿灵顿德克萨斯大学的Sherri McFarland教授将研究分子构象、电离性和分子间相互作用如何影响光敏剂的行为，特别是含低硫噻吩的钌化合物。光敏剂是利用光能促进理想的物理过程或化学转化的化合物。这些分子在太阳能转化、化学催化以及光医学等领域都有应用。该项目重点研究一类光敏剂，该光敏剂有望用于癌症治疗，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相结合。本项目将利用配位化学、光物理和电化学技术来探索同分异构、团聚和约束以及环境在这些途径中的作用。这项工作将培养研究生和本科生在化学、生物、物理和工程领域进行高度跨学科的研究。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好准备。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。麦克法兰团队特别关注解决本科研究中的教育公平问题，并通过基于课程的研究经验（CUREs）为本科STEM学生提供具有社会影响的从实验到临床的项目，提高科学素养。该项目旨在为未来的领导者提供科学传播技能，并让他们了解创业精神，因为这与将实验室的科学发现带到社会有关。根据该奖项，Sherri McFarland教授和她的团队将研究含有寡硫吩的Ru（II）配合物的氧化还原和激发态性质，这些化合物作为光敏剂在从太阳能转换到光医学等领域具有重要应用。咪唑[4,5-f][1,10]邻菲罗啉（IP）配体附着在足够链长n的寡硫吩（nT）上，采用平面化的最低能三重态，具有显著的配体内电荷转移（ILCT）特征。低硫噻吩具有氧化还原活性，相邻的IP基团可以使质子偶联电子转移（PCET）促进3ILCT态的催化光氧化还原反应。这些电荷分离的激发态也可以发生化学二聚化并产生单线态氧。该项目旨在开发这些系统在简单溶剂和复杂生物环境中的光物理模型。每个系统将从分子结构，氧化还原化学和光物理的角度进行研究，并对光疗机制产生长期影响。UTA团队将合成并表征寡硫吩附加的Ru（II）配合物[Ru(LL)2(IP-nT)]2+，以探索各种因素对pcet促进途径的影响：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、光谱学和电化学技术将用于测试具有CT特征和可电离基团的nt - triplets对多模态作用的重要性，并探索基于电离、构象和异构等因素如何影响生物界面上的激发态动力学。从长远来看，该项目旨在推动配位化学、光化学和光物理领域的发展，并最终推动光医学的发展。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值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.