Thioester exchange is one of the most explored transformations in the literature particularly employed with biomolecules in aqueous solutions. Particularly for peptide synthesis, thioesters are the key factor of the reaction regioselectivity in native chemical ligation because of the freely reversible thiol-thioester exchange steps and exceptionally fast reaction kinetics. However, few investigations have been reported utilizing thioesters in non-aqueous systems. Recently, we demonstrated the exceptionally low activation energies for thiol-thioester exchange reactions in various organic systems.<br/>Here we present the straightforward, scalable synthesis of thiolactone appended thymidine and deoxycytidine monomers derived from their natural counterparts and their polymerization to form responsive DNA-like polythioesters in high conversions, good yields of the polymer with low polydispersities. The thiol-end group was found to be quantitatively functionalized via the thiol-Michael reaction to add water solubilizing groups or fluorescent tags.<br/>Finally, as each repeat unit is separated by a thioester functional group, dynamic behavior of the polymer is feasible via the thiol/thioester exchange, which is demonstrated here two-fold by the blending of two polymers of different chemical composition (those derived from thymidine and cytidine) and the complete depolymerization of the polymers under extremely mild conditions. As our polymeric material shares many structural, spatial, and stereochemical similarities with DNA we anticipate strong binding to native strands of DNA. This work constitutes the first step towards a platform which we hope will culminate in the routine synthesis of functional sequence controlled polymers via dynamic template directed synthesis. Synthesis, polymerizations and the dynamic behavior of the resulting polymers will be presented.

Responsive DNA-like polymers via the ring opening polymerization of nucleobase appended thiolactones

255th National Meeting (2018)

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