Strategy for Rapid and High-Purity Monocyclic Polymers by CuAAC “Click” Reactions

Abstract

Cyclization of linear polymers by coupling end-groups together to form monocyclic polymers using the very fast Cu-catalyzed azide/alkyne cycloaddition (CuAAC) “click” reaction has been used for many polymer systems. However, the strategy based on the CuAAC methodology has not been guided by theory and relies on the very slow feed of polymer into a highly dilute reaction mixture of solvent and Cu catalyst. This leads to the production of monocyclic polymer in very low concentrations over long periods of time (>10 h) and at high temperatures (>100 °C). In this work we use the Jacobson−Stockmayer theory to predict the % monocyclic polystyrene (c-PSTY) in a one-pot reaction at 25 °C and find from an empirical relationship based on experimental diffusion-controlled rate coefficients for cyclization and condensation of α,ω-polymer chains that the Jacobson−Stockmayer theory is applicable for the CuAAC reaction. This means the % monocyclic can be predicted from theory and is independent of reaction rate parameters (such as catalytic concentration and temperature) and only dependent on polymer concentration. Given this quantitative knowledge, we investigated the effect of l-PSTY concentration, temperature, feed rate, Cu(I)Br concentration, and linear-PSTY molecular weight to find the optimum conditions for the synthesis of monocyclic polymers. It was found that for feed rates greater than or equal to the reaction rate high % monocyclic polymers could be formed. Our strategy allowed us to produce c-PSTY (with 51 monomer units) with high purity (>95%) at a concentration of 1.85 × 10−3 M in less than 9 min at 25 °C. This is the highest concentration, shortest time, and lowest temperature, to our knowledge, that anyone has used to obtain macrocycles in high purity by the CuAAC methodology. It also allowed us to develop strategies to produce high % monocyclic from parent l-PSTY with higher molecular weights.

Cyclic polymers: Methods and strategies

“…The reason stems for the fact that the faster the reaction the faster the monocyclic will be formed in the reaction mixture, and thus higher feed rates and weight fractions of polymer can be used. 114 Lonsdale et al 12 found that they could significantly increase the weight fraction of starting polymer N 3 -PSTY-B (polystyrene, PSTY) through knowledge of the cyclization kinetics described by the Jacobson-Stockmayer equations above. By choosing the solvent and ligand to obtain a very fast rate of CuAAC, Lonsdale et al 12 could form PSTY cyclic polymer in less than 9 min at 25 C. This data was further conformed by kinetic simulations.…”

“…114 Lonsdale et al 12 found that they could significantly increase the weight fraction of starting polymer N 3 -PSTY-B (polystyrene, PSTY) through knowledge of the cyclization kinetics described by the Jacobson-Stockmayer equations above. By choosing the solvent and ligand to obtain a very fast rate of CuAAC, Lonsdale et al 12 could form PSTY cyclic polymer in less than 9 min at 25 C. This data was further conformed by kinetic simulations. 114 Cyclic building blocks could further be coupled using ''click'' reactions to create a wide range of cyclic topologies, 64,70 and even used to probe the self-assembly properties of cyclic polymers in water.…”

“…The correct solvent and temperature condition must be found for each system, and in some cases baseline resolution of all species is not found. 12 Kinetic simulations provides a non-experimental means of probing the system, but all kinetic rate coefficients and all side reactions should be known. The most used method of analysis is through SEC based on refractive index (RI) detection using a linear PSTY calibration curve.…”

“…11 The more compact nature of cyclic polymers compared to their linear counterparts as also found from the lower hydrodynamic diameter is a characteristic feature usually used to identify the presence of cyclic polymers by size exclusion chromatography (SEC). 12 There has been some debate over the physical properties found experimentally. 13 The main issue stems from the purity of the cyclic polymer synthesized by coupling the chainends of the polymer together.…”

New insights into copper-mediated polymerization and polymer topologies

“…137 It was also reported that certain water soluble ligands can significantly increase reaction rates. 138 However, for biological applications copper use is detrimental due to the 70 (c), 148 (d), 149 (e), 150 (f), 151 (g), 152 (h), 153 (i), 154 (j), 155 (k), 156 (l), 157 (m), 158 (n), 159 (o), 160 (p), 113 (q), 161 (r), 162 (s), 112 (t), 28 (u), 163 (v), 164 (w), 165 (x), 166 (y), 167 (z). 168 Specific properties of the polymer topologies have been employed in a wide range of applications.…”