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

Case Western Reserve University, Cleveland OH

Investigators

Abstract

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.