Cyclic Alternating Ring-Opening Metathesis Polymerization (CAROMP). Rapid Access to Functionalized Cyclic Polymers

Abstract

Catalysis of alternating ROMP with (H 2 IMes)Cl 2 Ru=CHPh(OiPr), the second generation Hoveyda-Grubbs catalyst, provided an entirely cyclic alternating polymer. Conditions for the cyclic AROMP were used to prepare a polymer in which one of the repeat units bore a primary alkyl chloride that was used for further elaboration.Cyclic polymers1 exhibit thermodynamic,1b optical,2 and biophysical3 properties different from those of their linear counterparts. However, the potential applications of cyclic polymers that result from these altered properties have yet to be developed. Particularly intriguing are applications in drug delivery.4The pharmacokinetics of cyclic polymers favor their use as vehicles for carrying drugs to solid tumors. Presumably because the minimum cross section of a cyclic polymer is larger than that of the corresponding linear polymer, cyclic polymers are filtered more slowly through the pores of the kidney. Relative to similar linear polymers of comparable molecular weights, they have reduced rates of clearance and extended plasma circulation times.5 In addition, and again as a consequence of topology, cyclic polymers exhibit greater tumor accumulations than the related linear polymers; this difference has been attributed to the enhanced permeation and retention (EPR) effect. 6Cyclic polymers are formed as by-products during the preparation of high molecular weight polymers by intramolecular reactions termed back-biting. In principle, the formation of kathlyn.parker@stonybrook.edu; nicole.sampson@stonybrook.edu. Supporting Information Available. Detailed descriptions of the experimental procedures and spectra. This material is free of charge via the Internet at http://pubs.acs.org. It is likely that there is much to be learned about the synthesis of cyclic polymers.7 , 1b Notable recent contributions include strategies based on ring expansions and on "click chemistry.8 The production of cyclic polymers in ROMP experiments has been optimized by the use of custom-synthesized catalysts.9 NIH Public AccessIn 2009, we reported the preparation of copolymers of cyclobutene-1-carboxylic acid esters (1, monomer A) and cyclohexenes (2, Z = H or D, monomer B) by alternating ring opening metathesis polymerization (AROMP)10 with the 3 rd generation Grubbs catalyst (3) ( Figure 1 and Scheme 1).11Analysis of the 1 H NMR spectrum of the product mixture derived from cyclobutenecarboxylic acid methyl ester (monomer 1a) and cyclohexene D 10 (2-D 10 ) led us to conclude that the anticipated alternating linear polymer PhCH=(AB) n =CH 2 , (1a-2-D 10 ) n was formed, but that it was contaminated with cyclic polymer cyclic (1a-2-D 10 ) n 1a in which there was a single AA repeat and cyclic (1a-2-D 10 ) n .Although we were able to isolate the cyclic AROMP polymers from their linear co-products, this method of preparation was clearly not ideal. Because we recognized the advantages of cyclic polymers for certain applications, we considered modifying the conditions of the AROMP reaction to maximize the back-biting r...

Antibacterial Studies of Cationic Polymers with Alternating, Random, and Uniform Backbones

“…The cyclic Acopolymer-5 was obtained from the corresponding cyclic chloro-substituted polymer that was prepared with catalyst 16 as described in the literature (25). …”

“…Acopolymer-5 exhibited much lower antibacterial activities than Acopolymer-1 . The cyclic polymers formed by our method are estimated to be small, i.e., n = 3–4, on the basis of mass spectra and gel permeation chromatography measurements (25). Therefore, the curvature in this polymer is quite high, and the conformational flexibility is low.…”

Degradable precision polynorbornenes via ring‐opening metathesis polymerization

“…Kinetic control of the monomer sequence has also been shown in anionic polymerization, and ring‐opening metathesis polymerization (ROMP). A few examples in the literature involve the synthesis of alternating copolymers using ROMP, as a result of the catalyst‐monomers pairing, such as in the case of dienes and diacrylates . We previously studied the use of exo norbornenes as functional monomers that when added to the ROMP of the slower endo norbornenes, were rapidly incorporated in the growing polymer chain, thus resulting in copolymers with some control over the monomer sequence .…”

“…A few examples in the literature involve the synthesis of alternating copolymers using ROMP, as a result of the catalyst-monomers pairing, such as in the case of dienes and diacrylates. [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] We previously studied the use of exo norbornenes as functional monomers that when added to the ROMP of the slower endo norbornenes, were rapidly incorporated in the growing polymer chain, thus resulting in copolymers with some control over the monomer sequence. 31 Nevertheless, when attempting the introduction of a single exo norbornene moiety, the precision was limited.…”

A Bicyclo[4.2.0]octene-Derived Monomer Provides Completely Linear Alternating Copolymers via Alternating Ring-Opening Metathesis Polymerization (AROMP)

“…Indeed, we discovered that the use of the Hoveyda–Grubbs II catalysts, which favor cyclizations, resulted in the exclusive formation (within the limits of detection) of cyclic alternating copolymers. 30 Recently, we observed complete inhibition of backbiting upon introduction of bulky side chains into the AROMP monomers. However, the increased steric hindrance near the double bond slows the polymerization propagation rate, resulting in shorter polymers and thus limits the utility of this approach.…”