An important goal of organic chemistry has centered on the development of methods to assemble and disassemble molecular modules.  The wide scope of easily reversible reactions opens a door to this manipulation of modules.  The focus of this work is the development of a simple molecular tether to reversibly bind amines and thiols in aqueous conditions at neutral pH. Described herein are the details of reactions using a Meldrum’s acid-derived conjugate acceptor and its utility in various areas of chemistry.  Initially, a screening of different homobifunctional crosslinkers for thiols and amines was undertaken, pointing to the Meldrum’s acid derivative as the fastest and most efficient.  Then, the addition (“clicking”) of  amines and thiols, and the chemically triggered “declicking” back to these unaltered units was explored.  An extensive study determined whether the amine and thiol should be added simultaneously or if they reacted better sequentially.  Finally, this conjugate acceptor was introduced to applications in biochemistry, supramolecular assemblies, and polymer chemistry.  In all cases the assembly quickly and quantitatively disassembled to the amine and thiol starting materials. Of particular emphasis is the advance of novel degradable oligomers and polymers for applications ranging from biotechnology to nanoscale etching of thin films for the improvement of microchips.  Other current efforts aim to synthesize a more water-soluble version of the conjugate acceptor in order to expand its utility and separately improve the rate and efficiency of the thiol scrambling reaction.  Because of the simplicity and versatility of the reaction sequences described herein, we anticipate that many more applications throughout different areas of chemistry will be discovered for this conjugate acceptor.

Thio-amine click and declick reactions

253rd National Meeting (2017)

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