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. 

Work from my group has led to the 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.  Our group has also developed the only general method for the synthesis of trans-cyclooctenes, molecules of high importance to the field of bioorthogonal chemistry. Using this method as a key step, we have synthesized new trans-cyclooctene analogs with exceptionally fast kinetics.  More recently, our group has collaboratively developed a method for ‘turning-on’ rapid bioorthogonal chemistry through enzymatic or long wavelength photocatalytic activation of the tetrazine ligation. This new reaction is being used as the basis of a new, catalytic approach to in vivo prodrug activation.  Collaboratively, our group has used the interfacial nature of tetrazine ligation as a new way to create and pattern biomaterials. Through interfacial polymerization, we create biomimetic fibers that can be functionalized by proteins or peptides, and subsequently be used as materials capable of mediating contact guidance of cells.

In other projects, our group has developed catalysts and the first general conditions for Rh-catalyzed reactions of alkyldiazo esters with preference over ß-hydride elimination.  The reactions have led to the development of efficient and stereoselective methods that lead to cyclopropane, cyclopropene, bicyclobutane, insertion products and carbonyl-ylide derived cycloadducts.  We have also developed new syntheses and reactions of cyclopropenes, methylenecyclopropanes, bicyclobutanes and trans-cycloalkenes. These molecules and their transformations have been utilized for applications in synthetic methodology, total synthesis and biology. 

The Fox Group             Designing New Reactions for Chemical Biology

New Reactions for Biology


Synthetic Methods