Model-Based Design To Push the Boundaries of Sequence Control

An innovative model-based design strategy to synthesize well-defined sequence-controlled polymers is presented, enabling selection of both the most appropriate mediating agent and reaction conditions. In combination with experimental analysis, advanced kinetic Monte Carlo simulations are conducted, allowing a visualization of the connectivity of all monomer units of ca. 105 individual copolymer chains. The product quality can therefore be uniquely and unambiguously predicted for the first time at the molecular level, explicitly accounting for chain-to-chain deviations. The strategy is illustrated for BlocBuilder MA-initiated nitroxide-mediated polymerization, with styrene and N-benzyl­maleimide as comomomers, and is generally applicable for all reversible deactivation radical polymerization (RDRP) techniques. Further design of the nitroxide-mediating capabilities and the reaction conditions allows the realization of a targeted (multi)­functionalization pattern, including an increase of the contribution of trifunctionalized chains above 75%. The reported results are interpreted in terms of the individual activation–growth–deactivation cycles and provide an unprecedented mechanistic understanding of RDRP in general.