The Excited State Behavior of Ru(II) Photodrugs

Ru(II)光药物的激发态行为

• 批准号: 2102459
• 负责人: Sherri McFarland
• 金额: $ 44万
• 依托单位: University of Texas at Arlington
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2102459&HistoricalAwards=false
• 关键词: Excited; State; Behavior; Ru; II

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.

通过这一奖项，化学结构、动力学和机理b项目正在支持德克萨斯大学阿灵顿分校的Sherri McFarland教授的研究，以研究ru基光敏剂的激发态光物理学和氧化还原特性。光敏剂是一种化合物，它可以捕获光能，并利用它来产生有用的化学反应。这方面的例子包括太阳能转换、催化和光药物。这个项目的重点是一类特殊的光敏剂，它们在癌症治疗中显示出希望，但它们的作用方式有许多未解之谜。本研究将研究含低硫噻吩钌化合物的基本光物理和电化学性质，并揭示其参与光催化机制的细节。它还将探讨这些光敏剂的行为如何随着环境的变化而变化，例如，团聚效应和模拟生物结构的影响。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电医学到太阳能转换和化学生物学等前沿多学科领域取得成功的研究科学家所必需的工具。更广泛的影响目标将同时使未来的领导者具备科学传播技能，并使他们接触创业和商业化，因为这与将科学发现从实验室带到社会有关。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现实世界的实验室环境中体验科学研究，从而扩大我们下一代新兴科学家的多样性。该项目将研究含有寡硫吩的Ru（II）配合物的激发态光物理和氧化还原特性，这些化合物作为光敏剂在从太阳能转换到光药物等领域具有重要的应用。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。我们将合成并表征含有寡硫噻吩的Ru（II）光敏剂[Ru(LL)2(IP-nT)]2+，这些光敏剂在噻吩环的数目（nT）、噻吩环上取代基的类型和共配体（LL）上不同。这些修饰被设计成系统地改变氧化还原电位和三重态特征，并改变典型的低硫噻吩的共价和非共价结合。电化学和光物理技术将用于测试复杂底物中假设的光氧化还原催化机制，其中合成和细胞衍生的囊泡将用于模拟光敏剂反应如何在受限基质中调节，例如脂质双分子层。研究结果将进一步推动Ru(II)-寡硫噻吩光敏化研究的发展。随着对含有寡硫吩的Ru（II）光敏剂的机理的了解，有机会为光催化应用创造更好的下一代光敏剂。更广泛的影响活动同样侧重于让STEM科学家接触到基于过去与光分子相互作用相关的转化研究和商业化努力的科学传播和创业精神。该培训项目将涵盖推广、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传播技能的机会。将为本科STEM学生设计和提供基于课程的研究机会，以确保这些学生在学位课程中获得更多的实践研究经验。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。

项目成果

String-Attached Oligothiophene Substituents Determine the Fate of Excited States in Ruthenium Complexes for Photodynamic Therapy.

• DOI: 10.1021/acs.jpca.1c04900
• 发表时间: 2021-08-19
• 期刊: The journal of physical chemistry. A
• 作者: Chettri A;Schneider KRA;Cole HD;Roque JA 3rd;Cameron CG;McFarland SA;Dietzek B
• 通讯作者: Dietzek B

Ru(II) Phenanthroline-Based Oligothienyl Complexes as Phototherapy Agents.

• DOI: 10.1021/acs.inorgchem.3c03216
• 发表时间: 2023-12
• 期刊: Inorganic chemistry
• 影响因子: 4.6
• 作者: H. Cole;Abbas Vali;John A. Roque;Ge Shi;Gurleen Kaur;Rachel O Hodges;A. Francés‐Monerris;M. E. Alberto;Colin G Cameron;S. McFarland

Interaction with a Biomolecule Facilitates the Formation of the Function-Determining Long-Lived Triplet State in a Ruthenium Complex for Photodynamic Therapy.

• DOI: 10.1021/acs.jpca.1c09968
• 发表时间: 2022-03-03
• 期刊: The journal of physical chemistry. A
• 作者: Chettri A;Cole HD;Roque Iii JA;Schneider KRA;Yang T;Cameron CG;McFarland SA;Dietzek-Ivanšić B
• 通讯作者: Dietzek-Ivanšić B

Using Biological Photophysics to Map the Excited-State Topology of Molecular Photosensitizers for Photodynamic Therapy.

利用生物光物理学绘制光动力疗法分子光敏剂的激发态拓扑。

• DOI: 10.1002/anie.202301452
• 发表时间: 2023
• 期刊: Angewandte Chemie (International ed. in English)
• 作者: Chettri,Avinash;Yang,Tingxiang;Cole,HoustonD;Shi,Ge;Cameron,ColinG;McFarland,SherriA;Dietzek-Ivanšić,Benjamin
• 通讯作者: Dietzek-Ivanšić,Benjamin

Intraligand Excited States Turn a Ruthenium Oligothiophene Complex into a Light-Triggered Ubertoxin with Anticancer Effects in Extreme Hypoxia.

• DOI: 10.1021/jacs.2c02475
• 发表时间: 2022-05-11
• 期刊: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
• 影响因子: 15
• 作者: Roque, John A., III;Cole, Houston D.;Barrett, Patrick C.;Lifshits, Liubov M.;Hodges, Rachel O.;Kim, Susy;Deep, Gagan;Frances-Monerris, Antonio;Alberto, Marta E.;Cameron, Colin G.;McFarland, Sherri A.
• 通讯作者: McFarland, Sherri A.