Abstract:

Singlet oxygen is known to be involved in a large number of biological processes, both in healthy and diseased states of organisms. Its photosensitized generation is at the core of “photodynamic” action, commonly presented as photodynamic therapy (PDT). Since light in the visible to near-IR region is severly absorbed, scattered or reflected in mammalian tissues, photo-initated processes have very limited therapeutic applications. With this understanding, in our group we are interested in controlling the chemical generation of singlet oxygen for potential biological and therapeutic relevance. As the chemical source for singlet oxygen, we work with endoperoxides of naphthalene or 2-pyridone derivatives. These endoperoxides can be designed to have very different reaction rates in producing singlet oxygen.

However, to be able to switch the reaction rates on demand would be even more valuable. To that end, we synthesized stable endoperoxides which can be transformed chemically or enzymatically into more labile forms. Considering the ctotoxic nature of singlet oxygen, these can be considered as the first steps towards an endoperoxide-based prodrug design. Also, another approach we are undertaking is to target endoperoxides by attaching ligands which could selectively interact with cancer related receptors such as PSMA. The results confirm that selective targeting can yield differentiation of cancerous prostate cells from normal prostate cells. In a more recent work, we demonstrated that the prodrug approach can be extended to a TMS-derivative of naphthalene endoperoxide by establishing a biorthogonal metabolic shunt. We will discuss our work towards smart and selective therapeutic agents, with precise spatio-temporal targeting of singlet oxygen. Our most recent work in transforming endoperoxides into oxygen (ground state) carrier shecIes wIl also be presented.

Short Biography of the Speaker:

Prof. Dr. Engin Umut Akkaya received his PhD in 1989 from the Ohio State University, Columbus, Ohio, USA. After a few years of postdoctoral studies at the Ohio State and Maryland Universities, he accepted a faculty position at the Middle East Technical University, Department of Chemistry, and worked there between the years 1995-2007. In 2007, he moved to Bilkent University, Chemistry Department, with a joint affiliation in UNAM. In 2018, Prof. Akkaya accepted a faculty position in Dalian University of Technology (DLUT) in Dalian, Liaoning, China. Since 2020, he is a XingHai scholar of the DLUT. Prof. Akkaya is the recipient of international “TWAS”, “Czarnik” and “COMSTECH” awards, He was also awarded the highest national accolades of TÜBiTAK and TÜSEB, and also those of Mustafa Parlar and Elginkan Foundations, among others. He is a member of the Science Academy (Bilim Akademisi) of Turkey, and a Fellow of the Royal Society of Chemistry, U.K. (FRSC). His current research interests are exploration of singlet oxygen as a therapeutic tool, programmable nanostructures and molecular automata.