Zwitterionic Polymerization: A Kinetic Strategy for the Controlled Synthesis of Cyclic Polylactide

Abstract

The zwitterionic ring-opening polymerization of lactide initiated by N-heterocyclic carbenes generates cyclic polylactides with well-defined molecular weights between M(n) = 5000 and 30,000 g/mol with narrow polydispersities (M(w)/M(n) < or = 1.31). These zwitterionic polymerizations are extremely rapid (k(p) = 48.7 M(-1) s(-1)), but also exhibit exceptional control of molecular weight and molecular weight distribution. The unusual kinetic features of these zwitterionic polymerizations are illuminated with kinetic and mechanistic investigations, which implicate a mechanism that involves a slow initiation step (second order in [M]), a propagation step (first order in [M]) that is much faster than initiation (k(i) = 0.274 M(-2) s(-1)), cyclization (k(c) = 0.0575 s(-1)), and depropagation (k(d) = 0.208 s(-1)). Numerical and stochastic simulations of the kinetic data provide a kinetic rationale for the evolution of molecular weight with monomer conversion: the molecular weights increase with increasing monomer conversion, exhibit a nonzero intercept near 0% monomer conversion, and are relatively insensitive to the initial monomer-to-initiator ratio. The observed narrow molecular weight distributions are due to a high rate of propagation relative to cyclization and chain transfer. Kinetic simulations define the kinetic criteria under which the active zwitterions remain in solution; these simulations were substantiated by chain-extension experiments, which provide experimental evidence for chain extension of the zwitterions and reinitiation by the N-heterocyclic carbenes liberated upon macrocyclization. The kinetic model rationalizes some of the unique features of zwitterionic ring-opening polymerization and provides a useful mechanistic framework to optimize these polymerizations as a strategy to generate well-defined cyclic polyesters.

Zwitterionic Ring Opening Polymerization with Isothioureas

“…Similar behavior was observed for the zwitterionic ring-opening polymerization of lactones 1,16,20−22 and is attributed to a slow rate of initiation relative to propagation. 20,22 This is also evident in the kinetic behavior, where an induction period is observed followed by a first order disappearance of monomer ( Figures S6 and S7, Supporting Information).The cyclic structure of the PLA generated from isothioureas 1 and 2 was inferred by a combination of 1 H NMR spectroscopy, MALDI-TOF mass spectrometry, and dilute solution viscosity measurements. The 1 H NMR spectra of the PLA shows no observable end groups ( Figure S1).…”

“…1,4,20,21 The ZROP of lactide with N-heterocyclic carbenes is rapid (minutes), but molecular weights >30 kDa are difficult to obtain. 16,22,23 We recently reported that the amidine 1,8-diazabicyclo- [5.4.0]undec-7-ene (DBU) was sufficiently nucleophilic to mediate the ZROP of lactide to generate cyclic polylactides but was accompanied by the cogeneration of linear polylactides. 11 We had proposed that the linear polylactides might arise from competitive deprotonation of the amidininium zwitterion to generate the neutral ketene aminal (KA, Scheme 2).…”

Cyclic polymers: Methods and strategies

“…The authors recently demonstrated 8 the synthesis of high-molecular weight cyclic poly(e-caprolactone) (as high as 114k) with polydispersities in most cases above 1.7. The kinetic data suggest that the carbene initiator was much less reactive for poly(e-caprolactone) than for polylactide, and strongly suggests based on the kinetic mechanism proposed 96 that about 3% of initiator is consumed or bound to the polymer at 50% conversion.…”

“…The kinetic mechanism for this polymerization is given in Scheme 8 based on a kinetic analysis and Monte Carlo simulations. 96 For the low polydispersities found, the initiation rate coefficient, k i , must be relatively high and much greater than ring closure, k c . The simulations SCHEME 4 Various multicyclic-and linear-cyclic copolymer topologies constructed by the ESA-CF process.…”

Experimental and Computational Studies on the Mechanism of Zwitterionic Ring-Opening Polymerization of δ-Valerolactone with N-Heterocyclic Carbenes

“…Kinetic studies of the ZROP of lactide with IMes demonstrated that the formation of the initial zwitterion Z 1 (initiation) was slower than addition of monomer to growing zwitterions Z n . Experimental studies indicated that the rate of polymerization as well as the molecular weights and molecular weight distributions of the resulting cyclic polyesters are a complicated function of the rates of initiation, propagation, and cyclization, 12 but the influence of the nucleophile or electrophile on these relative rates is not yet clear.…”