PHOTOCYLINDER · Photodynamic therapy enabled DNA-fork-binding metallo-cylinders: drugs and release triggers

Photodynamic therapy enabled DNA-fork-binding metallo-cylinders: drugs and release triggers

Final Report Summary- PHOTOCYLINDER (Photodynamic therapy enabled DNA-fork-binding metallo-cylinders: drugs and release triggers) Reporting period: 2019-09-03 to 2021-09-02 PHOTOCYLINDER project was aimed to accomplish two principal objectives: (1) Synthesis of novel Photo cylinders (2) Evaluation of the efficiency of the photo cylinder to bind to DNA 3-way junction and their photodynamic potential in cancer cells. In order to achieve these objectives research project was divided into work packages (details are provided in following sections). The first objective of this research has been successfully achieved. We have synthesized and characterized two new photo cylinders. With the newly designed photo cylinders we have evaluated the ability of the photo cylinders to bind DNA 3-way junctions. We found that these cylinders did not form DNA 3-way Junctions. In order to achieve second objective of the project we established a new collaboration with Prof. Palin at the School of Dentistry, University of Birmingham. We studied the photocytotoxicity and cellular localization and uptake of the cylinders in Sarcoma osteogenic -2 cell lines. Substantial time was lost due to university closure during the COVID crisis. During this period, a research project was developed for SARS- CoV-2 inhibition and the work was performed as soon as lab reopen. The result was published in Angew Chem. Another interesting variation of the PHOTOCYLINDER is the new method for the synthesis of Ru nano cylinder to increase the yield by 5 times with a simpler reaction protocol even without using any chromatographic separation technique. Dissemination of the results: The project fellow collaborated with two of the post-graduate students from the host group and published a paper as a co-author in JACS (J. Am. Chem. Soc., 2020, 142, 20651-20660) and Angew Chem (Angew Chem Int Ed Engl. 2021, 60, 18144-1815.). We expect that at least 1 additional paper will come out in near future. Conclusions: The MC Fellowship has offered the necessary support and funding for the development of photo cylinder chemistry using supramolecular nano cylinder as preliminary construct. The work has generated different photo cylinders and their photo activity has been evaluated in cancer cells. The preparation of the manuscript is underway and soon it will be submitted for publication. Developing newer method for synthesis of nano cylinder was another interesting variation during this project. These interesting synthetic methodologies will help to further explore them as drug candidates and offers several future options for other potential applications.

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