Dynamic Combinatorial Chemistry (DCC)
Dynamic Combinatorial Chemistry (DCC) is a powerful method for studying molecular recognition. Dynamic Combinatorial Libraries (DCL) are typically composed of bifunctional monomers that form equilibrating mixtures of cyclic and/or linear oligomers. Templates can disrupt this equilibrium by binding to the best receptor in the mixture, which causes the library to respond by shifting towards it. The best binder is therefore AMPLIFIED relative to the unperturbed DCL. Below a dimer is amplified.
We are currently utilizing DCC to discover enantioselective receptors for chiral bioactive compounds (biomolecules, drugs, etc). Discovering chirally-selective receptors poses a unique challenge since the DCC experiment does not typically report differential binding strengths (needed to differentiate between binding + and – enantiomers of a chiral species). To accomplish this we have developed two methods that utilize racemic libraries to discover enantioselective receptors.
The most common method for identifying which component of a DCL has been amplified is HPLC, and when a polarimeter detector (LP) is also used, then one can simultaneously measure the optical rotation of every peak in the chromatogram. When the library is racemic there is no optical activity in the components, however, if a chiral analyte (the biomolecule) is utilized and one enantiomer of a receptor is amplified (occurs when the receptor is enantioselective) then this optical activity can be detected and measured by the LP detector. Thus a racemic library can furnish an enantioselective receptor. A proof of this principle was recently reported for the enantioselective binding to (–)-adenosine using cyclic dipeptide libraries.
We are currently extending this concept to include transition metals in the DCL with the guiding notion that since metals play important roles in bioinorganic chemistry (both as structural and reactive elements), including them in a DCL will enhance the chances of discovering interesting receptors. In addition to significantly enhancing the diversity of structures that a DCL can access, this also gives us a handle for discovering new catalysts via DCC.
The Gagné group is interested in synthesis, catalysis, and how molecular recognition can be used to find new approaches to solving difficult problems.
Students and postdocs come from a variety of backgrounds but primarily include organic and inorganic coworkers.
Our projects, generally speaking, straddle these areas, though some projects have a strong emphasis on synthesis and/or organometallic chemistry/catalysis.