Hybrid Chain-Growth/Step-Growth Mechanism Observed in Heterofunctional Thiol-Ene Polymerizations

Traditional methods for polymer synthesis usually afford minimal control over the primary sequence and solid-phase synthesis of sequence-controlled, biomimetic polymers is limited by scalability. Utilizing thiol-X chemistries, first generating sequence-controlled oligomers with the thiolate anion mediated thiol-Michael reaction and then polymerizing with the orthogonal thiyl radical mediated thiol-ene reaction, we have developed a method for producing sequence-ordered periodic copolymers that are capable of diverse side-group customization, with our primary focus being on attaching nucleobases and creating DNA-mimics. In this talk, I will focus on the characteristics of heterofunctional thiol-ene polymerizations in the context of synthesizing sequence-ordered polymers, particularly, the effects of functional group chemistries on the reaction kinetics and the monomer structure on molecular weight (MW) evolution.

            Despite the popularity of thiol-ene coupling (TEC) chemistry in organic synthesis, in general, and polymer chemistry, particularly, heterofunctional thiol-ene monomers (i.e. low MW monomers containing both a thiol and an alkene functional group) have been relatively unexplored, likely due to the inherent instability of thiol and ene functional group chemistries when present in the same formulation. Initially, we investigated the polymerizability and MW evolution of heterofunctional monomers containing various side-group functionalities (e.g. alkyl chains, phenyl groups, nucleobases) and the effect of varying the number of atoms separating the thiol and ene functional groups. Surprisingly, while monitoring MW vs conversion, we observed that high MW species emerged at low conversions (< 20%) when the alkene and thiol are separated by 5 to 7 atoms, which is characteristic of a chain-growth mechanism rather than the expected step-growth mechanism associated with TEC reactions. Utilizing kinetics and MW profiles obtained by real-time Fourier transform (rt-FTIR) spectroscopy and gel permeation chromatography (GPC), respectively, it was determined that, due to the close proximity of the two functional groups, upon generation of the 2° C-radical by thiyl radical propagation into the alkene group, intramolecular chain-transfer to the thiol dominates over intermolecular chain-transfer resulting in the radical remaining on the same polymer chain and an apparent chain-growth/step-growth hybrid mechanism. Although, the potential for high MW polymers in comparison to the MWs achievable by traditional step-growth is desirable, the ease by which these monomers cyclize results in significant reductions in polymer yield (up to 50% monomer cyclization) leading us to develop strategies to eliminate cyclization while maintaining the chain-growth evolution. Incorporation of the monofunctional thiol, thiophenol, into the reaction mixture at an equivalency as low as 1%, facilitates this goal as the low bond dissociation energy of thiophenol’s S—H bond, compared to the monomer contained thiol, ensures that, upon initiation, the radical population is partitioned exclusively into the monofunctional thiol additive, thus preventing cyclization. Further, thiol-ene reactions may be initiated without initiator by the direct photocleavage of the S—H bond with ~254 nm light, but due to the extension of the thiophenol UV absorption spectrum up to 330 nm, the thiophenol S—H bond may be selectively cleaved in the presence of alkyl thiols so that thiophenol can be reacted exclusively in the presence of alkyl thiols, which greatly increases the ability to incorporate thiol-ene chemistries for performing one-pot, sequential reactions.