Novel Approaches to Modifications of Nucleosides and Related Heterocycles

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With this award, the Chemical Synthesis Program of the NSF Division of Chemistry is supporting the research of Professor Mahesh K. Lakshman in the Department of Chemistry & Biochemistry at The City College of New York. Professor Lakshman is working with graduate and undergraduate students to develop ways to modify nucleosides, which are molecules that are the building blocks of DNA and RNA. Modified nucleosides are important because they are used in medicinal applications, as plant cell growth stimulants, and as probes for understanding biological processes. Nucleosides consist of two linked parts: a sugar and a base pair. This program is focused on determining how to use a mild oxidant to change the structure of the base pair and to attach the base pair to the sugar portion of the nucleoside. Since nucleosides have many reactive parts, these studies are determining how to control the modification procedures to give a single product. This work is also establishing a fundamental understanding of the reactivity of mild oxidants with nucleosides. Professor Lakshman’s research group is ethnically and gender diverse, contributing to the diversity of the future workforce. These students obtain professional hands on experience in planning, developing, and performing chemical reactions, as well as soft skills such as teamwork, oral and written dissemination of scientific information, and communication abilities. Professor Lakshman has been associated with significant research infrastructure development and outreach activities, where the latter has providedyoung students with hands-on experience in science. It also allows for parents to interact with faculty and to understand the role of science, which serves to better a general understanding and perception of science, education, and research, and their impact on society.Nucleosides are an important class of biomolecule due to their presence in all living systems. Modified nucleosides have been developed for medicinal purposes in the control of cancer and viral diseases, as detection tools, and as probes of biochemical and biological processes. The development of new ways to synthesize unknown nucleoside structures will provide access to new applications. Professor Lakshman is developing oxidative coupling processes to modify purine and pyrimidine nucleosides and to connect base pairs to sugars. This project is using iodonium reagents to achieve these transformations and is applying fundamental reactivity studies to determine trends that will facilitate the prediction of selectivity. These studies are overcoming challenges with nucleoside modification due to the inherent reactivity of these compounds. Professor Lakshman’s diverse research group includes students at all educational levels (Ph.D., MS, 5-year BS-MS, and BS).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.