Dr. Ruggles received his B.S. in Chemistry from Ithaca College under Heinz Koch where he synthesized highly halogenated styrene analogs.  He subsequently got his M.S. in Chemistry from Bucknell University under Thomas T. Shawe where he used a tandem ozonolysis reductive amination approach for the construction of novel quinocarcin analogues.  Dr. Ruggles then received his Ph.D. in Organic Chemistry in 2003 from Michigan State University in the lab of Robert E. Maleczka Jr. where he elucidated chlorinative carbocation rearrangements of vinylic carbinols.  His postdoctoral training began in the lab of Gregory K. Friestad in the Chemistry Department at the University of Vermont where he studied enantioselective radical additions to N-acylhydrazones mediated by chiral Lewis acids.  He then continued his postdoctoral training at UVM in the Biochemistry Department under Robert J. Hondal as a NIH University Postdoctoral Fellow where he investigated the synthesis, conformations, and redox properties of disulfide containing eight-membered rings with application to thioredoxin reductases.

Research Interests:

Synthetic Organic Chemistry
Physical Organic Chemistry
Enzymology

Project Description:

The areas of research listed below are synthetic organic and physical organic subsets to the impressive projects found within Dr. Hondal’s group here at the University of Vermont.  My research in synthetic organic chemistry involves the elucidation of new methodologies for the construction of amino acid isosteres with particular emphasis on oxidized vicinal cysteinyl cysteine dyads.  These oxidized vicinal cysteinyl cysteine dyads form an eight-membered disulfide ring with multiple conformations and are rare substructural element in proteins.  They are often found in specific ?-turn types and this unit is of functional importance to those few that possess its structure such as with the thioredoxin reductases (TRs).  During construction of these dyads elements of flexibility and rigidity are installed so that we can come to an understanding of how substitution affects conformation of the vicinal disulfide ring and how it affects activity within TRs.  Unrelated to TR, this research has elucidated a number of possible ?-turn mimics that have been hitherto unknown.  My research in physical organic chemistry deals with determining how conformation of the vicinal disulfide ring affects the redox potential of the disulfide.  Thiol-disulfide exchange reactions monitored via HPLC or NMR allow these potentials to be determined.  The ability to relate conformation of the ring to redox potential provides a guide as to what types of ring structure prefer to be in the reduced (dithiol) or oxidized (disulfide) state.  This can then provide insight as to what type of conformations are needed for redox cycling to occur in the TRs.