Deliberate Design and Synthesis of Thionated Organic Photosensitizers Activated by One- and Two-Photon Absorption in the Near-Infrared

在化学系化学结构、动力学机制-B（CSDM-B）项目的支持下，卡洛斯E.凯斯西储大学化学系的Crespo-Hernández正在开发新的有机化合物类别，这些化合物在近红外（NIR）中吸收一个或两个光子。本研究的目的是设计和合成生物相容的有机化合物吸收在近红外光动力学治疗和其他光诱导的应用。该项目包括有机，物理，计算和材料化学的元素，因此非常适合早期职业科学家的教育和培训。计划将涉及经济上处于不利地位和代表性不足的高中学生的外联和以研究为重点的活动作为资助项目的一个组成部分。通过教授卡洛斯E. Crespo-Hernández的持续合作，学生获得独特的跨学科和多文化的培训研究经验，具有美国化学学生和国外学生之间的国际交流和参与的潜力，与科学和技术的全球化相称。开发新的有机化合物并控制其发射和系统间交叉特性是许多对社会有重要意义的现象的主要优先事项。这项研究可能是开发用于治疗癌症的新型光药物，成像引导癌症光疗，微生物的光动力灭活以及荧光生物标志物的开发的关键，这将促进其在生物技术和生物医学应用中的应用。例如，光动力疗法（PDT）是临床上批准的治疗程序，其正迅速进入癌症治疗的主流。PDT的研究主要集中在开发掺入重过渡金属以增加其三重态产率的光敏剂（PS）上。除了对靶组织的选择性差之外，这种金属络合物经常遭受高暗细胞毒性，并且通常昂贵且难以合成。卡洛斯E. Crespo-Hernández的小组率先开发了基于核酸衍生物的硫代化的PS。基于这一发现，本研究的重点是羰基和硫代羰基含生色团的合成和它们的单光子和双光子吸收特性的研究后，近红外激光激发。它们的电子物理性质，包括单重态-三重态自旋轨道耦合常数，三重态衰变寿命和单重态氧产生的量子产率，将被测量。拟议的化学物质预计将产生新的有机PS能够吸收一个或两个光子在近红外治疗窗口，一个必要的先决条件，为开发一个有效的PDT agent.This奖项反映了NSF的法定使命，并已被认为是值得通过评估使用基金会的智力价值和更广泛的影响审查标准的支持。

With support from the Chemical Structure, Dynamics & Mechanisms-B (CSDM-B) Program of the Chemistry Division, Professor Carlos E. Crespo-Hernández of the Department of Chemistry at Case Western Reserve University is developing new classes of organic compounds absorbing one or two photons in the near-infrared (NIR). The goal of this research is to design and synthesize biocompatible organic compounds absorbing in the NIR for photodynamic therapy and other light-induced applications. The project includes elements of organic, physical, computational, and materials chemistry, and is therefore well suited to the education and training of early career scientists. Outreach and research-focused activities involving economically disadvantaged and underrepresented high school students are planned as an integral part of the funded project. Through Professor Carlos E. Crespo-Hernández's ongoing collaborations, students receive a unique cross-disciplinary and multi-cultural training research experience, with the potential for international exchange and engagement between US chemistry students and those abroad, commensurate with the globalization of science and technology. Developing new organic compounds and controlling their emissive and intersystem crossing properties represent a major priority for many phenomena of significance to society. This research may hold the key to the development of new photo-drugs for the treatment of cancer, imaging-guided cancer phototherapy, photodynamic inactivation of microorganisms, and the development of fluorescent biomarkers, which will facilitate their use in biotechnical and biomedical applications. For example, photodynamic therapy (PDT) is a clinically approved therapeutic procedure that is rapidly entering the mainstream of cancer treatments. Research in PDT has concentrated primarily on the development of photosensitizers (PSs) that incorporate heavy transition metals to increase their triplet yields. Besides poor selectivity for the target tissue, such metal complexes frequently suffer from high dark cytotoxicity and are often costly and difficult to synthesize. Professor Carlos E. Crespo-Hernández's group has spearheaded the development of PSs based on the thionation of nucleic acid derivatives. Building on this discovery, this research focuses on the synthesis of carbonyl- and thiocarbonyl-containing chromophores and the study of their one- and two-photon absorption properties upon NIR laser excitation. Their photophysical properties, including singlet-triplet spin-orbit coupling constants, triplet decay lifetimes, and quantum yields of singlet oxygen generation, will be measured. The proposed chemistry is expected to yield new organic PSs capable of absorbing one or two photons in the NIR therapeutic window, a necessary pre-condition for developing an effective PDT agent.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.