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、动力学和机理B(CSDM-B)计划的支持下，凯斯西储大学化学系的Carlos E.Creso-Hernández教授正在开发在近红外(NIR)中吸收一到两个光子的新型有机化合物。这项研究的目标是设计和合成吸收近红外的生物相容有机化合物，用于光动力疗法和其他光诱导应用。该项目包括有机、物理、计算和材料化学的元素，因此非常适合于早期职业科学家的教育和培训。计划将涉及经济困难和任职人数不足的高中生的外联和注重研究的活动作为资助项目的一个组成部分。通过卡洛斯·E·克雷斯波-埃尔南德斯教授的持续合作，学生们获得了独特的跨学科和多文化培训研究体验，并有可能在美国化学学生和海外学生之间进行国际交流和参与，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跨系统的性能是许多具有社会意义的现象的主要优先事项。这项研究可能是开发治疗癌症的新的光药物、影像引导的癌症光疗法、光动力学灭活微生物以及开发荧光生物标记物的关键，这将促进它们在生物技术和生物医学应用中的应用。例如，光动力疗法(PDT)是一种临床批准的治疗方法，正在迅速进入癌症治疗的主流。PDT的研究主要集中在光敏剂(PSS)的开发上，这种光敏剂可以加入重金属过渡金属来增加它们的三重态产量。除了对靶组织的选择性较差外，这类金属络合物还经常遭受高度的暗细胞毒性，而且往往昂贵且难以合成。卡洛斯·E·克雷斯波-埃尔南德斯教授的团队带头开发了基于核酸衍生物硫化的PSS。在这一发现的基础上，本研究重点研究了含有羰基和硫代羰基的发色团的合成及其在近红外激光激发下的单光子和双光子吸收特性。将测量它们的光物理性质，包括单态-三态自旋-轨道耦合常数、三态寿命和单态氧产生的量子产额。拟议的化学预计将产生新的有机PS，能够在近红外治疗窗口中吸收一到两个光子，这是开发有效的PDT试剂的必要前提条件。这一奖项反映了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 & 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.