A new general synthetic approach to sequenced macromolecules was developed and applied to the synthesis of polymers comprising lactic acid (L), glycolic acid (G), and εcaprolactone (C)-derived monomer units. The new method employs entropy-driven ring-opening metathesis polymerization (ED-ROMP) to prepare copolymers with embedded sequences and controlled molecular weights. Cyclic macromonomer precursors were prepared by ring-closing metathesis of ethylene glycol (Eg)-linked sequenced oligomers bearing terminal olefins. ED-ROMP of the resulting macrocycles using Grubbs' second generation catalyst yielded poly(CL-Eg-LC-Oed), poly(CLL-Eg-LLC-Oed), poly(LGL-Eg-LGL-Oed), and poly(LGL-Eg-LGL-Hed) (Oed = octenedioc acid; Hed = hexenedioc acid). Hydrogenation produced the saturated sequenced copolymers. Molecular weight was well-controlled and could be adjusted by varying the monomer-to-catalyst ratio. M n s of 26−60 kDa were obtained (dispersities = 1.1−1.3). The methodology proved general for three different sequences and two olefinic metathesis groups.

The bulk properties of a copolymer are directly affected by monomer sequence, yet efficient, scalable, and controllable syntheses of sequenced copolymers remain a defining challenge in polymer science. We have previously demonstrated, using polymers prepared by a step-growth synthesis, that hydrolytic degradation of poly(lactic-co-glycolic acid)s is dramatically affected by sequence. While much was learned, the step-growth mechanism gave no molecular weight control, unpredictable yields, and meager scalability. Herein, we describe the synthesis of closely-related sequenced polyesters prepared by entropy-driven ring-opening metathesis polymerization (ED-ROMP) of strainless macromonomers with imbedded monomer sequences of lactic, glycolic, 6hydroxy hexanoic, and syringic acids. The incorporation of ethylene glycol and metathesis linkers facilitated synthesis and provided the olefin functionality needed for ED-ROMP. Ring-closing to prepare the cyclic macromonomers was demonstrated using both ring-closing metathesis and macrolactonization reactions. Polymerization produced macromolecules with controlled molecular weights on a multigram scale. To further enhance molecular weight control, the macromonomers were prepared with cis-olefins in the metathesis-active segment. Under these selectivity-enhanced (SEED-ROMP) conditions, first-order kinetics and narrow dispersities were observed and the effect of catalyst initiation rate on the polymerization was investigated. Enhanced living character was further demonstrated through the preparation of block copolymers. Computational analysis suggested that the enhanced polymerization kinetics were due to the cis-macrocyclic olefin being *

Repeating sequence copolymers of poly(lactic‐co‐caprolactic acid) (PLCA), poly(glycolic‐co‐caprolactic acid) (PGCA), and poly(lactic‐co‐glycolic‐co‐caprolactic acid) (PLGCA) have been synthesized by polymerizing segmers with a known sequence in yields of 50–85% with Mns ranging from 18–49 kDa. The copolymers exhibited well‐resolved NMR resonances indicating that the sequence encoded in the segmers used in their preparation is retained and that transesterification is minimal. The exact sequences allowed for unambiguous assignment of the NMR spectra, and these standards were compared with the data previously reported for random copolymers. The glass transition temperatures (Tgs) of the PLCA and PGCA copolymers were found to depend primarily on monomer ratio rather than sequence. Sequence dependent Tgs were, however, noted for the PLGCA polymers with 1:1:1 L:G:C ratios; poly LGC and poly GLC exhibited Tgs that differed by nearly 8 °C. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011

A series of repeating sequence poly(lactic-co-glycolic acid) copolymers (RSC PLGAs) has been prepared with the precise incorporation of a pendant benzyl-ether substituted monomer derived from serine. Copolymers were synthesized from the assembly of sequence-specific, stereopure dimeric, and trimeric segmers of lactic, glycolic, and (S)-3-benzyloxy-2-hydroxypropionic acids with controlled and varied tacticities. Deprotection of the hydroxyl groups was accomplished by catalytic hydrogenolysis to yield highly functionialized, hydrophilic polyesters. The (1)H and (13)C NMR spectra for all of the copolymers were consistent with sequence and stereochemical retention and lacked the signal broadening that is inherent with more random copolymers.

The hydrolytic behavior and physical properties of a polymer are directly related to its constituent monomer sequence, yet the scalable and controllable synthesis of sequenced copolymers remains scarcely realized. To address this need, an enhanced version of entropy-driven ring-opening metathesis polymerization (ED-ROMP) has been developed. An unprecedented level of control is obtained by exploiting the kinetic and thermodynamic differences in the metathesis activity of cis- and trans-olefins embedded in large, unstrained macrocycles. First-order rate kinetics were observed, and polymer molecular weights were found to be proportional to catalyst loading. Computational analysis suggests that incorporation of a cis-olefin into the monomer backbone both introduces a thermodynamic driving force and increases the population of metathesis-active conformers. This approach offers a generally applicable method for enhancing living character in ED-ROMP.