This seminar will discuss recent advances in development of the tetrazine ligation– the fastest known bioorthogonal reaction. Tetrazine ligation has been used broadly by the scientific community, and finds application across chemical biology, medicine, nuclear medicine, and material science. The talk will describe advances in photochemistry, flow chemistry, and cross-coupling chemistry that have enabled access to improved trans-cyclooctene and tetrazine reagents with improved properties.  The talk will also discuss the develop efficient catalytic methods for ‘turning on’ rapid bioorthogonal chemistry in cellular context. Discussed will be new tool molecules with high stability in the cellular environment in their ‘off’ state, and the fastest bioorthogonal reactions to date in their ‘on’ state.  Applications to in vivo chemistry in live animals and sub-cellular photochemistry in living cells will be discussed, as will the application of the catalytically inducible tetrazine ligation to drive proximity-directed drug release.

Joseph M. Fox is Professor of Chemistry in the Department of Chemistry and Biochemistry, where he also is the Director of a NIH-funded Center of Biomedical Research Excellence on the Discovery of Chemical Probes and Therapeutic Leads. A native of Philadelphia, Pennsylvania, Fox received his bachelor’s degree from Princeton University, where he conducted undergraduate research as a Pfizer fellow with Maitland Jones Jr. He completed graduate studies under Thomas Katz at Columbia University.  He studied organometallic chemistry with Stephen Buchwald at MIT as an NIH postdoctoral fellow. In 2001, Fox joined the faculty at UD.  Research in the Fox group centers on the development of new types of chemical reactions, the application of these new reactions to the synthesis of natural occurring and designed molecules with biological function, and in the use of design concepts in organic synthesis for applications in materials science. The nature of the research program is highly multidisciplinary, and involves active collaborations with groups in peptide chemistry, bioorganic chemistry, surface science, computational chemistry, materials science, and radioimaging.