REVIEW www.rsc.org/polymers | Polymer ChemistryRecent advances in entropy-driven ring-opening polymerizations

Satu Strandman,a Julien E. Gautrotb and X. X. Zhu*a

Received 1st October 2010, Accepted 4th November 2010

DOI: 10.1039/c0py00328jEntropy-driven ring-opening polymerization (ED-ROP) of unstrained macrocyclic monomers and/or

oligomers employs the ring-chain equilibria between macrocycles and their corresponding polymers

and the associated increase of conformational freedom to achieve high molecular weight materials. The

principles of building macrocyclic compounds, their use in ED-ROP, and the practical considerations

of polymerizations are described, and recent progress in this area is discussed through selected

examples. The various polymerization techniques used for ED-ROP are discussed, including anionic,

radical, coordination/insertion, ring-opening metathesis, and enzymatic polymerization methods.

Emphasis is placed on the potential of ED-ROP in the synthesis of biomaterials and the development of

enzyme-catalyzed green systems.1. Introduction

Ring-opening polymerization (ROP) is a fundamental method of

polymer synthesis and has been employed extensively for small

ring monomers (58 atoms) to produce polymers such as aliphatic

polyesters, polyamides, and polycarbonates, among others.1 The

polymerization of low-molar mass rings is driven by the relief in

ring strain, an enthalpy-driven process. When the ring size is large

enough (usually $14 atoms), changes in enthalpy upon opening

are minimal and polymerization becomes entropy-driven

(ED-ROP) through an increase of conformational freedom.2aDepartement de chimie, University of Montreal, CP 6128 SuccursaleCentre-ville, Montreal, Quebec, H3C 3J7, Canada. E-mail:sstrandman@gmail.com; julian.zhu@umontreal.ca; Fax: +1 514 3405290; Tel: +1 514 340 5172bDepartment of Chemistry, Melville Laboratory for Polymer Synthesis,University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK.E-mail: juliengautrot@yahoo.fr; Fax: +44 1223 334 866; Tel: +44 1223336 401

Satu Strandman

Satu Strandman conducted her

studies at the University of

Helsinki, Finland at the Labo-

ratory of Polymer Chemistry

with Professor H. Tenhu and

received her PhD in 2008 on

amphiphilic star block copoly-

mers. After her PhD, she worked

in the research group of

Professor F. Winnik at the

Universite de Montreal,

Canada, with alkynylpyrenes

and alkynylpyrene-functional-

ized polymers. Recently, she has

joined the research group of

Professor X. X. Zhu. Her

research interests include synthesis and characterization of

complex macromolecular architectures, stimuli-responsive poly-

mers, and biocompatible polymeric systems.

This journal is The Royal Society of Chemistry 2011Although the ED-ROP itself is neither a step-growth nor

a chain-growth process,3 its background lies in the step-growth

polymerizations which produce a fraction of cyclic oligomers

for statistical reasons. The presence of cyclics may significantly

alter the properties of polymeric product if their fraction is

large, i.e., if the synthesis is carried out in high dilution. For

example, cyclic poly(ethylene terephthalate) oligomers can

migrate on the surface of spun fibres and interfere with their

dyeing.2 When the polymerization is carried out neat, the

amount of cyclics can be lower than 2 weight percent of the

product.4 Entropy-driven ROP exploits a ring-chain equilib-

rium between macrocycles and polymer chains, which is

adjustable by altering the concentration of the reaction system.

High dilution favors the monomers or oligomers (macrocycles

of varying size), while high concentration favors the polymeric

product (Fig. 1). The equilibrium nature of entropy-driven

ROP leads to the most probable distribution of molar

masses, Mw/Mn z 2.0.3

Julien E: Gautrot

Julien Gautrot received his PhD

from the University of

Manchester, Department of

Chemistry, in 2004, under the

supervision of Professor P.

Hodge, designing novel bio-

inspired conjugated organic

materials. He then worked as

a postdoctoral researcher with

Professor X. X. Zhu, at the

Universite de Montreal,

Canada, on the synthesis of

novel degradable materials

based on bile acids. In 2007, he

moved back to the UK, where he

currently works with Professor

W. Huck, University of Cambridge, Melville Laboratory, on the

development of novel biofunctional coatings and the study of the

cellmatrix interface.

Polym. Chem., 2011, 2, 791799 | 791

Fig. 1 The ring-chain equilibrium.ED-ROP has been successfully applied to a number of systems

and it can be carried out via several polymerization mechanisms

such as anionic,5,6 insertion/coordination,7 radical,8 enzymatic,9

or ring-opening metathesis polymerization (ROMP).10 ROMP of

small rings by well-defined catalysts exhibits living character

allowing the synthesis of uniform polymers and block copoly-

mers.11 Despite its non-living nature, ED-ROP of large macro-

cycles displays unique advantages. The large number of atoms

constituting the macrocyclic backbone ensures the great diversity

of polymeric structures providing a cornucopia of unexplored

macromolecular systems. The use of macrocycles allows their

functionalization in positions that do not interfere with the ring-

opening activity and hence nearly any chemical moiety can be

inserted in the polymer main chain for optimizing the physical

properties and degradation of materials as well as for introducing

functionalities for molecular recognition, photoluminescence,

supramolecular interactions, and biocompatibility.

Recently, a review has been published on ED-ROP with

a focus on applications of the resulting materials.12 In the current

review article, we wish to emphasize the development of different

polymerization methods and mechanisms of ED-ROP and

discuss recent advances in this field for the design of green

polymerization systems.2. Principles of ED-ROP

2.1. Building macrocycles

The synthesis of macrocyclic compounds has attracted a great

deal of interest due to their importance in organic and naturalX:X: Zhu

X. X. Zhu received his BSc

degree in chemistry from Nan-

kai University in China, and his

PhD degree from McGill

University in Canada. After

postdoctoral work at CNAM,

France and the University of

Toronto, he joined the Chem-

istry Department of Universite

de Montreal in 1992, where he is

now a professor and holds the

Canada Research Chair in

polymeric biomaterials. He and

his group make use of natural

compounds such as bile acids in

the preparation of polymers for

use in biomedical and pharmaceutical applications. He is author of

over 170 research publications and several patents and book

chapters.

792 | Polym. Chem., 2011, 2, 791799compound synthesis as well as in supramolecular and organo-

metallic chemistry. Macrocycles are also common in antitu-

moral, antibiotic, and antifungal compounds.13 More recently,

the potential of macrocyclic compounds in materials synthesis

and engineering has been discovered. In general, cyclic

compounds fall into three categories: (a) strained small rings with

kinetically favored synthesis (n # 7,14 n number of atoms inring); (b) strained medium rings with less kinetically favored

formation (n 813 reported for lactones,14 n 811 forcycloolefins15); and (c) kinetically unfavorable strainless large

rings (n $ 14 reported for lactones,14 n $ 12 for cycloolefins15).

The competition between the intramolecular reaction (cycliza-

tion) and intermolecular reaction (polymerization) brings addi-

tional challenge to the synthesis of macrocycles.

The macrocyclization is highly dependent on the flexibility of

starting compounds.16 An example of this can be taken from the

synthesis of bile acid-based cyclic monomers. Bile acids are

a class of steroids with a rigid bent shape of the steroidal back-

bone (Scheme 1). The rigidity of backbone predisposes the

molecules to form large oligomeric macrocycles in three major

distributions. If spacers between the steroid ring and the reactive

site are sufficiently long and flexible, cyclic monomers prevail.

When slightly smaller and/or more rigid spacers are incorpo-

rated, cyclic dimers are the main product. When the linkers are

absent or too rigid, trimers and tetramers are the main cyclic

oligomers.16

So far, the majority of large-ring macrocycles used in ED-ROP

has been carboxylic acid esters,10,17 carbonates,17 amides,18

alkenes,19 aromatic ether ketones,6b or sulfones.20 A classical

strategy for building macrocycles involves a reaction of a,u-

difunctional compound(s) under high dilution to favor cycliza-

tion over polymerization. If macrocycles are not under dynamic

equilibrium with their oligomers and polymers in the reaction

conditions, the so-called pseudo-high dilution techniques can be

applied.21 In a small-scale synthesis of cyclic oligo-depsipeptides

or oligoesters, oligomers can be built on a polymer support, and

upon cyclization by di-n-butyltin oxide only cyclic species are

released in solution in moderate to good yields.22,23

Ring-closing metathesis (RCM) has gained popularity in

building cyclic alkene derivatives owing to its moderate tolerance

to functional groups24 which facilitates inserting complex moie-

ties such as bile acids,25,26 calix[4]arenes,27 or 1,10-phenanthro-

lines28 in the macrocycle. This method provides cyclization of

bisalkenes by ruthenium-based catalysts in nonpolar solvents

such as toluene or dichloromethane, which favors the initiation

of metathesis reaction.29 Recently, a thorough review has been

published on the equilibrium nature of ring-closing metathesis

reactions.15Scheme 1 General structure of bile acids. The common linker-bearing

groups are circled.

This journal is The Royal Society of Chemistry 2011

A different approach on the preparation of macrocycles

employs ring-chain equilibrium in a reverse way: cyclic species

are formed by depolymerizing macromolecules under high dilu-

tion in the presence of appropriate catalyst or enzyme. The

process is called cyclodepolymerization (CDP) or ring-closing

depolymerization (RC-DP). The first examples of CDP date back

to 1930s on aliphatic polyesters30 and polycarbonates,31 after

which the scope of polymers has been expanded to polyamides,32

polyurethanes,33 high-performance polyethersulfones,34,35 and

polyetherketones.36 In some of these examples cyclics can be

removed by distillation, which makes high dilution unnecessary.

More recent strategies for CDPs have exploited ring-closing

metathesis on alkene-containing aliphatics, polyesters and

polyamides,10,17,18,37 or enzymatic degradation of polyesters.9b,382.2. Theory behind ED-ROP

The theoretical background of ED-ROP lies in the pioneering

work of Jakobson and Stockmeyer39 on intramolecular reaction

in polycondensations. This theory describes the distribution of

cyclic and linear polymers at equilibrium in concentrated solu-

tions and predicts a critical monomer concentration [M]c, below

which the condensing system can be converted entirely into rings.

Since enthalpic effects are neglected and the rings are assumed to

be strainless, the theory overestimates the equilibrium constant

for cyclization and hence the critical monomer concentration for

smaller cyclics.

Later, Kornfield and co-workers40 improved the prediction of

these factors by introducing an enthalpy change due to ring

strain energy and proposing a revised critical monomer

concentration [M]c,N, which can be used for predicting the pol-

ymerizability of cyclic monomers at a given temperature. If the

initial monomer concentration exceeds this critical concentra-

tion, most of the additional monomers contribute to polymeri-

zation.

When enthalpy change is not the driving factor of polymeri-

zation, polymerization conditions need to be such that entropic

changes become significant. The negative and concentration-

dependent translational entropy is high for small rings and

becomes smaller upon increasing ring size. The positive rota-

tional and torsional entropies decrease much less upon increasing

the ring size and can become dominant over the translational

entropy in large rings.41 Ultimately, the positive entropic

contribution upon conformational flexibility of the polymer

chain can become prevalent, thus driving the polymerization of

large macrocycles.15 In a dilute system, the translational entropy

of the monomeric unit is higher and the equilibrium is shifted

towards the cyclics.2.3. Practical considerations

As already emphasized, concentration is a crucial factor for ring-

opening polymerizations. While macrocyclizations and cyclo-

depolymerizations are carried out in a millimolar (mM) range of

concentrations,13,42 ED-ROP is typically carried out in 0.15.0 M

solutions or even in the neat.10 If solvent-free conditions are

employed, the polymerization should be conducted above the

glass transition temperature (Tg) or melting temperature (Tm) of

the polymer and monomer.3 In general, temperatures forThis journal is The Royal Society of Chemistry 2011conducting ED-ROP in solution are low (typically #50 C,

depending on the solvent). No excess heat or volatiles are

released during the entropy-driven polymerization as the large

macrocycles are strainless and the ring-opening involves only

shuffling of linkages between the repeating units.

The effect of solvent, however, goes beyond the concentration

as the solvent quality is expected to influence the extent of

backbiting (cyclization) reactions. A higher value of critical

monomer concentration [M]c is predicted for a thermodynami-

cally good solvent.43 The solvent has also been reported to affect

the equilibrium E/Z ratios of metathesis reactions,37 but other

factors such as the type of catalyst and reaction time have also

been studied.12,44 Finally, the solvent influences the activity of

a metathesis catalyst: the initiation rates of Grubbs 1st genera-

tion catalyst have been reported to be proportional to the

dielectric constant of nonpolar solvents.29

The choice of catalyst is important in ring-opening metathesis

polymerization (ROMP) and ED-ROMP reactions, where high

activity and solubility need to be combined with functional group

tolerance. Since their discovery in the late 1990s, Grubbs Ru-

based catalysts, particularly the 2nd generation catalyst,45 have

become highly popular owing to their robustness and commer-

cial availability.11,44 Despite being less sensitive to oxygen or

water, the susceptibility of the catalyst to coordinating agents

remains a problem.13,15 Also the removal of metals from final

product is challenging, putting pressure towards developing

polymer or inorganic-support immobilized and recyclable cata-

lysts. For this purpose, a variety of polymers have been investi-

gated and summarized in more detail in recent reviews.4648 As an

example, an amphiphilic block copolymer has been synthesized

by Bergbreiter and co-workers by ROMP using polyisobutylene

(PIB) bound ruthenium-based metathesis catalyst. The ligands

PIB chain provided the end group of product polymer chain,

resulting in block copolymerization.49

Another strategy for reducing the amounts of trace metals is

using enzymatic polymerization. Enzymatic ring-opening poly-

merization has been utilized in the synthesis of polyesters,

polycarbonates, polyphosphates, polythioesters, and poly(ester-

amides).5052 This method is particularly suitable for ED-ROPs

as the polymerization can be conducted in bulk, reaction

conditions are mild, and high molar masses are obtained from

the polymerization of macrolides (large ring lactones) with

relative ease.50 Higher rates of lipase-catalyzed polymerization of

macrolides have been reported in comparison to low-molar mass

lactones, which has been assigned to the higher hydrophobicity

of macrolides promoting lactonelipase complex formation53 or

to the conformation-based accessibility of ester group in the

enzymes active site.54 However, comparison of kinetic parame-

ters of polymerization of macrolides of various sizes catalyzed by

Pseudomonas fluorescens lipase suggested that the increased

polymerizability of macrolides would stem rather from the large

ring size than better binding ability.55 More detailed discussion

on the mechanism and kinetics of lipase-catalyzed ROP can be

found elsewhere.52

Finally, supramolecular chemistry has brought an intriguing

contribution on ED-ROP by building noncovalent polymers

through hydrogen bonding. Depending on concentration,

ureidopyrimidinone derivatives formed cyclic dimers or linear

polymers with very high degree of polymerization (DP 3200).56Polym. Chem., 2011, 2, 791799 | 793

Scheme 3 Synthesis of poly(ether ketones and sulfones) via anionic ED-

ROP, K(OPhPhO)K potassium 4,40-biphenoxide.59The ring-chain equilibrium shifted toward linear chains at higher

temperatures. This represents a special case of ED-ROP, because

no catalyst or initiator is needed and no covalent bonds are

formed.

3. Polymerization techniques compatible withED-ROP

3.1. Anionic polymerization

Anionic ring-opening polymerization is commonly used in

synthesizing polyesters from lactones. The polymerization of

large lactone rings occurs by the attack of an anion on carbonyl

carbon atom leading to acyl-oxygen scission and formation of an

alkoxide growing species (Scheme 2).57 ED-ROP of 12- and 13-

membered lactones was carried out by Endo and co-workers5

either in bulk or in THF using sodium, lithium or potassium

methoxides as initiators at various temperatures (0120 C),

resulting in polyesters with good yields. Number-average molar

masses (Mn) of the polyesters were 340013 700 g mol1. The

ring-strain energy was equal for 12- and 13-membered rings, but

the rate of propagation was higher for the larger ring, which the

authors assigned to the difference in s-character of carbon atomic

orbitals on the basis of NMR coupling constants.5

Other groups of macrocycles polymerizable via anionic

mechanism include ether ketones,58,59 ether sulfones20 and

aromatic thioethers,60 although the latter ones undergo also

thermally initiated free radical polymerization.8a,c,61 The anionic

polymerization of cyclic ethers and their derivatives is initiated

by CsF or alkali phenoxides. The phenoxides are considered

more efficient than fluorides, and the efficiency order of the

counterions is Cs > K > Na.20 Highly active catalysts often give

polymers with very high molar masses and/or some branching,

and thus with limited solubility.6b,20,36 In a recent example of the

anionic method by Chen and co-workers,59 macrocyclic aryl

ketone oligomers were synthesized via modified Friedel-Crafts

acylation, and polymerized by anionic ED-ROP catalyzed with

potassium 4,40-biphenoxide in melt, yielding thermostable poly-

(ether ketones and sulfones) (Scheme 3) with poor solubility in

common organic solvents, an indication of high molar masses.

The melt viscosities at the initial stage of polymerization were

low and increased slowly as the cyclic oligomers acted as

a lubricant between the polymer chains.59

3.2. Radical polymerization

The advantages of thermally initiated entropy-driven free radical

ring-opening polymerization lay in the absence of added catalyst,

and in the possibility for reactive molding while avoiding the

problems in processing high melt viscosity polymers. For

instance, nonisothermal heating of low-viscosity macrocyclic

arylene thioether ketones with porous alumina membranesScheme 2 Initiation of anionic polymerization of large-ring lactones.57

794 | Polym. Chem., 2011, 2, 791799produced flexible polymeric microfibrils and microtubules of

200400 nm in diameter (Fig. 2), and free-standing structures

were obtained after removal of the membrane in alkaline con-

ditions.8b Similarly, adhesive polydisulfide films were prepared

from cocyclic arylene disulfide oligomers over thin aluminium

plates.62 In catalytic reactive molding, initiator and monomer are

mixed prior to polymerization, or the membrane can be

impregnated with the initiator such as CsF for anionic poly-

merization, thus confining the polymerization within the pores.633.3. Coordination/insertion polymerization

In addition to anionic polymerization, polyesters are often

synthesized via so-called pseudoanionic or coordination/inser-

tion ring-opening polymerization. In this method, the propaga-

tion proceeds by coordination of the monomer to active species,

followed by insertion of the monomer into metaloxygen bond.

The growing chain remains attached to the metal during the

propagation.64 The most widely used initiators are aluminium

and tin alkoxides and carboxylates, and among them the mostFig. 2 Poly(arylene thioether ketone) microfibrils synthesized within

a porous alumina membrane8b (reprinted with permission from ref. 8b,

Copyright 2010 American Chemical Society).

This journal is The Royal Society of Chemistry 2011

Scheme 5 Synthesis of stereoregular poly(3-methyl-1,4-dioxane-2-one)

by coordination/insertion ED-ROP.7cpopular ones are tin(II) ethylhexanoate also known as stannous

octoate, Sn(Oct)2, and di-n-butyltin oxide, SnO(Bu)2.57

A recent high-throughput application of ED-ROP by Hodge

and co-workers65 with coordination/insertion mechanism has

utilized macrocyclic oligoesters (Scheme 4) for producing

a library of polyesters and copolyesters with variable monomer

ratios and molar masses up to 28 300 g mol1 (Mw). The

syntheses were catalyzed by di-n-butyltin oxide in bulk at small

scale (90 mg of monomers). The method worked well for all the

other esters but phenolic ones, which was thought to be a result

of the nature of the catalyst or unsuitable reaction conditions.

The initial products were nonrandom copolymers as verified by13C NMR spectroscopy, but longer reaction times resulted in

random copolymers.65

While ED-ROP allows introducing main-chain functionalities,

it may also provide control over the sequence of repeating units

when they are included in the same macrocycle. An example of

such control using coordination/insertion mechanism is the work

by Tolman and co-workers,7c who prepared an isomerically pure

14-membered cyclic diester to synthesize isotactic polymers with

perfectly alternating lactic acid and alkylene oxide subunits

(Scheme 5) upon ED-ROP by zinc alkoxide in toluene at room

temperature. The monomer/catalyst ratio controlled linearly the

molar masses at the range of 490072 000 g mol1 (Mn), but some

backbiting reactions were observed at high conversions. The

alternating polymers were completely miscible with atactic poly-

lactide, which allowed tuning of the glass transition temperature

of the blends.7c3.4. Ring-opening metathesis polymerization

Advances in catalyst development have made ring-opening

metathesis polymerization (ROMP) an important class of ROP

reactions. As ring-closing metathesis is convenient for building

macrocyclic compounds with various functional components,

their polymerization via ED-ROMP has become a promising

method for building novel advanced materials. Recently,

a detailed review has highlighted the scope of side chain func-

tionalized materials that are synthesized mainly by enthalpy-

driven ROMP of norbornene derivatives.66

In ROMP, a transition metal (typically Ru or Mo) complex

coordinates to a cyclic olefin double bond and subsequent [2 + 2]-Scheme 4 Macrocyclic oligomers for copolymerization by coordination/

insertion mechanism.65

This journal is The Royal Society of Chemistry 2011cycloaddition gives a four-membered metalla-cyclobutane

intermediate which will further undergo a cycloreversion to

afford a new metal alkylidene, now larger in size. In the propa-

gation stage, analogous steps are repeated until termination

occurs. The propagating centers of the polymer may exist either

in metallacyclobutane or metal alkylidene forms and the poly-

merization is reversible, i.e. ring-chain equilibrium prevails.11

The first studies of modern ED-ROMPs with Ru-based cata-

lysts were conducted by Grubbs and co-workers67 with cyclic

ethers. In comparison to acyclic diene metathesis polymerization

of a,u-dienes (ADMET), ED-ROMP proved to be more efficient

for the formation of high-molar mass products. The highest

molar mass obtained by Grubbs and Maynard through ED-

ROMP was 206 000 g mol1 (Mn).67b Hodge and Kamau10

expanded the ring sizes of macrocyclic olefinic esters to 2184-

membered rings, which polymerized fast upon the evaporation of

solvent: molar masses up to 94 000 g mol1 (Mn) were obtained in

10 minutes. Using olefin-containing cyclic oligoamides was more

problematic due to the poor solubility of amides and their

polymers.18 In addition, macrocyclization of amides by ring-

closing metathesis (RCM) resulted in the deactivation of the

catalyst when an amide group was in close proximity to the

reactive double bond. Nevertheless, ED-ROMP of cyclic oli-

goamides was conducted successfully in solution (THF at 56 C)

and the solubility was improved by copolymerization with cyclic

oligoesters.18

Some incidental observations of the RCM syntheses,68,69 as

well as more detailed knowledge of factors influencing the ring-

chain equilibria15 have inspired researchers to incorporate more

complex functional moieties in cyclic compounds to yield main

chain functionalized polymers. Yang and Swager27 synthesized

main-chain calix[4]arene elastomers by copolymerizing calixar-

ene-derived olefinic macrocycles with cyclooctene and norbor-

nene (Scheme 6). The highest molar mass of a copolymer was

209 000 g mol1 (Mn) with a monomer ratio 1 : 5 : 2, for the

respective monomers. The conformation of calixarenes influ-

enced directly the mechanical properties of corresponding poly-

mers. The more flexible calixarene building blocks provided

higher mechanical strength and toughness by facilitating greater

polymerpolymer interactions.27 An interesting example of ED-

ROMP from Mayer and co-workers involves the polymerization

of olefinic [2]catenanes to yield polypseudorotaxanes with phe-

nanthroline ligands (Scheme 7).28 Threaded macrocycles were

held in the backbone through copperbis-phenanthroline

complexes and released upon a demetallation treatment of poly-

pseudorotaxane with KCN. The bare backbone had a molarPolym. Chem., 2011, 2, 791799 | 795

Scheme 6 Calix[4]arene-based macrocycles and their copolymeriza-

tion.27

Scheme 7 ED-ROMP of [2]catenane for polypseudorotaxanes; n 4.28

Scheme 9 Chemical structures of selected bile acid-based polyesters

synthesized by ED-ROMP.74mass of 93 000 g mol1 (Mw) corresponding to a degree of

polymerization of 63.28

Gross and co-workers polymerized double bond-bearing

natural lactonic sophorolipids by three different Ru catalysts,

which gave polymers with Mn $ 42 200 g mol1 in good yields

($67%) in 5 min at 25 C.70 Sophorolipids are microbial glyco-

lipid biosurfactants with a wide range of potential therapeutic

applications.71 The lactonic sophorolipids with cis double bond

were separated from a mixture of linear and lactonic forms

produced by yeast Candida bombicola.72 The obtained poly-

(sophorolipids) (Scheme 8) comprised of a mixture of cis and

trans isomers.70 The semicrystalline polysophorolipids are

expected to find their applications as bioresorbable materials.73

Another group of natural compound-based main-chain func-

tionalized polymers was introduced by Gautrot, Zhu and co-

workers, who have prepared macrocyclic bile acid-based olefinic

esters and amides (Scheme 9) yielding amorphous thermoplastics

with outstanding thermally activated shape memory properties

(demonstrated in Fig. 3) and tunable mechanicalScheme 8 Chemical structure of a poly(sophorolipid).73

796 | Polym. Chem., 2011, 2, 791799behavior.25,26,74,75 While ADMET of a diene precursor of cyclic

bile acid ester afforded polymers with a typical molar mass value

of 22 300 g mol1 (Mn),26 ED-ROMP of the corresponding cyclic

monomer yielded molar masses up to 152 000 g mol1 (Mn).26 All

polymers were amorphous, as indicated by the transparency of

solvent-casted films and verified by X-ray scattering experi-

ments.75 The shape memory properties, i.e. strain fixity and strain

recovery, which describe the ability of chain segments to fix the

mechanical deformation and the ability of the material to

memorize its permanent shape,76 were among the best reported

for uncrosslinked amorphous polymers.74 Such properties were

assigned to ordered domains acting as pseudo-crosslinks helping

in freezing the transient shape due to increased intermolecular

interactions, which depended on the number of hydroxyl groups

of the bile acid moieties.75 Both the mechanical properties and

glass transition temperatures (Tg) were tuned by copolymeriza-

tion of the macrocycles with another cyclic monomer, ricinoleide,

derived from castor oil.26,74 These features provide anFig. 3 Demonstrating the shape recovery of bile acid main chain poly-

mer films (reprinted with permission from ref. 74, Copyright 2010

American Chemical Society).74

This journal is The Royal Society of Chemistry 2011

Scheme 11 Enzyme-catalyzed recycling of polyesters, here an example

of poly(butylene adipate).51opportunity for designing natural compound-based biomaterials

with controllable mechanical and chemical properties as well as

biocompatibility and bioresponsiveness.

3.5. Enzymatic polymerization

Increasing environmental concerns have turned researchers to

explore greener alternatives for materials synthesis. Enzymes

have been utilized as a non-toxic alternative for metal catalysts

since the beginning of the 1990s, and particularly lipases have

been studied in the syntheses and hydrolyses of polyesters and

polycarbonates.52,77,78 The active site of lipases is CH2OH of the

serine residue, and lipase-catalyzed reactions proceed via an

acylenzyme intermediate, enzyme-activated monomer (EM,

Scheme 10).79 As discussed above, an enzymatic approach has

been shown to be particularly suitable for ED-ROP of macro-

lides, such as 11-undecanolide,80 12-dodecanolide,80 15-penta-

decanolide,81 and 16-hexadecanolide55 (1217-membered rings).

Heise and co-workers have demonstrated the biocompatibility of

polymers of 1517-membered lactones synthesized by an enzy-

matic method.82 Lipase-catalyzed ROP can be carried out in bulk

or in organic solvents (e.g. toluene, heptane, or 1,4-dioxane) but

also greener alternatives (e.g. water, ionic liquids, or supercritical

carbon dioxidescCO2) have often been employed.52

Enzyme-catalyzed ED-ROP of cyclic oligomers has been

considered as a simple and green method towards high molar

mass dioldiacid polyesters, such as poly(butylene adipates) and

poly(butylene succinates).9b,38 Direct enzyme-catalyzed poly-

condensation of adipic acid and butane-1,4-diol has been

successful, but molar masses have generally been low and the

removal of condensation product methanol is difficult, which can

be avoided by the ring-opening polymerization.38,83 In addition,

large ring monomers and oligomers for ED-ROP can be

produced either by enzymatic cyclization reactions or by lipase-

catalyzed cyclodepolymerization of synthetic or microbial poly-

esters thus enabling recycling of polymers (Scheme 11).9b,8486

Recently, Hodge and co-workers87 explored the scope of

polymer-supported Candida antarctica (CA) lipase B in ED-ROP

of 1284-membered macrocycles bearing lithocholic acid moie-

ties. Although CA lipase-catalyzed oligocondensation of cholic

acid was reported earlier,88 Hodge and co-workers did not detect

any polymer in the case of unsubstituted lithocholic acid or its

cyclic dimers and trimers. However, the lipase-catalyzed ED-

ROP of larger lithocholic acid-based macrocycles in anhydrous

toluene at 70 C gave polymers and copolymers (Scheme 12) in

high yields, and molar masses of 910025 400 g mol1 (Mn).87Scheme 10 Principle of lipase-catalyzed ring-opening polymerization.79

This journal is The Royal Society of Chemistry 2011This suggests that even large cyclics are accessible to the active

site of the enzyme.4. Future perspectives and concluding remarks

To summarize, entropy-driven ring-opening polymerizations

exploiting the well-known phenomenon of ring-chain equilib-

rium can be carried out by various mechanisms to yield

high-molar-mass main-chain functionalized polymers and

copolymers. In recent years, studies on ED-ROP have focused on

the development of novel functional materials as well as envi-

ronmentally friendly processes and products. The advantages of

ED-ROP lie in its lack of byproducts or released heat, and the

possibility of carrying out the synthesis under solvent-free

conditions. Since the reaction is reversible, cyclo-

depolymerization can be employed for recycling of polymers by

different mechanisms and continuous enzyme-catalyzed

processes have already been developed for recycling of poly-

esters.51 The production of macrocycles, however, requires large

amounts of solvents, whether they are produced by ring-closing

reactions or by cyclodepolymerization, and a great deal of effort

is put on developing ring-closing and ROP processes in green

solvents such as water, ionic liquids or supercritical CO2,

particularly in enzymatic catalysis.51,66

As metathesis reactions proceed via double bonds of olefins,

processing of compounds from renewable resources such as

vegetable oils could provide means towards environmentally

friendly products.24 Metathesis catalysts are still expensive and

need developing for further synthetic control over ring-opening

polymerizations. In addition, the potential toxicity of catalystsScheme 12 Copolymer of a bile-acid based macrocycle by lipase-cata-

lyzed ED-ROP.87

Polym. Chem., 2011, 2, 791799 | 797

and their difficult removal bring serious limitations for food

industry and biomedical applications. Enzymatic methods are

a highly promising alternative for polymerizing macrocyclic

compounds in the absence of metal catalysts, some of which are

difficult to polymerize by chemical means.50 Although the first

steps have already been taken towards chemical versatility

through enzymatic ED-ROP, the obtained molar masses are still

relatively low and the reactions proceed slowly.

So far, the range of polymers and materials produced by ED-

ROP has been encouraging, from polyethers and high-perfor-

mance polymers to polypseudorotaxanes and shape-memory

elastomers. Without doubt this scope will expand hand-in-hand

with further advances in enthalpy-driven ring-opening poly-

merizations.Acknowledgements

We wish to acknowledge the Natural Sciences and Engineering

Research Council (NSERC) of Canada, Fonds Quebecois de

Recherche sur la Nature et les Technologies (FQRNT) and the

Canada Research Chair program for financial support. We are

members of Centre for Self-Assembled Chemical Structures

(CSACS) funded by FQRNT and Groupe de Recherche en

Sciences et Technologies Biomedicales (GRSTB) funded by

FRSQ. S.S. thanks FQRNT for a postdoctoral scholarship

(Programme de Bourses dExcellence pour Etudiants Etrangers).References

1 (a) G. Odian, Principles of Polymerization, John Wiley & sons,Hoboken, 4th edn, 2004; (b) Handbook of Ring-OpeningPolymerization, ed. P. Dubois, O. Coulembier, and J. M. Raquez,Wiley-VCH Verlag GmbH & Co., Weinheim, 2009.

2 A. J. Hall and P. Hodge, React. Funct. Polym., 1999, 41, 133.3 P. Hodge and H. M. Colquhoun, Polym. Adv. Technol., 2005, 16, 84.4 I. Goodman and B. F. Nesbitt, Polymer, 1960, 1, 384.5 R. Nomura, A. Ueno and T. Endo, Macromolecules, 1994, 27, 620.6 (a) M. F. Teasley, D. Q. Wu and R. L. Harlow, Macromolecules, 1998,

31, 2064; (b) M. Chen and H. W. Gibson, Macromolecules, 1996, 29,5502.

7 (a) D. Zhang, M. A. Hillmyer and W. B. Tolman, Macromolecules,2004, 37, 8198; (b) T. Fey, H. Keul and H. Hocker,Macromolecules, 2003, 36, 3882; (c) D. Zhang, J. Xu, L. Alcazar-Roman, L. Greenman, C. J. Cramer, M. A. Hillmyer andW. B. Tolman, Macromolecules, 2004, 37, 5274; (d) R. Slivniak andA. J. Domb, Biomacromolecules, 2005, 6, 1679.

8 (a) Y. F. Wang, K. P. Chan and A. S. Hay, Macromolecules, 1995, 28,6371; (b) M. G. Zolotukhin, S. Fomine, H. M. Colquhoun, Z. Zhu,M. G. B. Drew, R. H. Olley, R. A. Fairman and D. J. Williams,Macromolecules, 2004, 37, 2041; (c) H. M. Colquhoun,M. G. Zolotukhin, Z. Zhu, P. Hodge and D. J. Williams,Macromol. Rapid Commun., 2004, 25, 808.

9 (a) Y. Hori, H. Hongo and T. Hagiwara, Macromolecules, 1999, 32,3537; (b) S. Okajima, R. Kondo, K. Toshima and S. Matsumura,Biomacromolecules, 2003, 4, 1514.

10 P. Hodge and S. D. Kamau, Angew. Chem., Int. Ed., 2003, 42, 2412.11 C. W. Bielawski and R. H. Grubbs, Prog. Polym. Sci., 2007, 32, 1.12 Z. Xue and M. F. Mayer, Soft Matter, 2009, 5, 4600.13 A. Gradillas and J. Perez-Castells, Angew. Chem., Int. Ed., 2006, 45,

6086.14 (a) G. Galli, G. Illuminati and L. Mandolini, J. Am. Chem. Soc., 1973,

95, 8374; (b) G. Galli, G. Illuminati, L. Mandolini and P. Tamborra,J. Am. Chem. Soc., 1977, 99, 2591; (c) L. Mandolini, J. Am. Chem.Soc., 1978, 100, 550; (d) G. Ercolani, L. Mandolini, P. Mencarelliand S. Roelens, J. Am. Chem. Soc., 1993, 115, 3901.

15 S. Monfette and D. E. Fogg, Chem. Rev., 2009, 109, 3783.16 J. E. Gautrot and X. X. Zhu, J. Mater. Chem., 2009, 19, 5705.798 | Polym. Chem., 2011, 2, 79179917 S. D. Kamau, P. Hodge, A. J. Hall, S. Dad and A. Ben-Haida,Polymer, 2007, 48, 6808.

18 C. Y. Tastard, P. Hodge, A. Ben-Haida and M. Dobinson, React.Funct. Polym., 2006, 66, 93.

19 C. W. Bielawski, D. Benitez and R. H. Grubbs, J. Am. Chem. Soc.,2003, 125, 8424.

20 D. Xie, Q. Ji and H. W. Gibson, Macromolecules, 1997, 30, 4814.21 (a) For example: D. J. Brunelle and T. G. Shannon, Macromolecules,

1991, 24, 3035; (b) P. Hubbard, W. J. Brittain, W. J. SimonsickJr andC. W. Ross III, Macromolecules, 1996, 29, 8304.

22 C. L. Ruddick, P. Hodge, A. Cook and A. J. McRiner, J. Chem. Soc.,Perkin Trans. 1, 2002, 629.

23 A. Cook, P. Hodge, B. Manzini and C. L. Ruddick, Tetrahedron Lett.,2007, 48, 6496.

24 R. H. Grubbs, Angew. Chem., Int. Ed., 2006, 45, 3760.25 J. E. Gautrot and X. X. Zhu, Angew. Chem., Int. Ed., 2006, 45, 6872.26 J. E. Gautrot and X. X. Zhu, Chem. Commun., 2008, 1674.27 Y. Yang and T. M. Swager, Macromolecules, 2007, 40, 7437.28 S. Kang, B. M. Berkshire, Z. Xue, M. Gupta, C. Layode, P. A. May

and M. F. Mayer, J. Am. Chem. Soc., 2008, 130, 15246.29 M. S. Sanford, J. A. Love and R. H. Grubbs, J. Am. Chem. Soc., 2001,

123, 6543.30 E. W. Spanagel and W. H. Carothers, J. Am. Chem. Soc., 1935, 57,

929.31 J. W. Hill and W. H. Carothers, J. Am. Chem. Soc., 1933, 55, 5031.32 A. Ben-Haida, P. Hodge and H. M. Colquhoun, Macromolecules,

2005, 38, 722.33 S. D. Kamau and P. Hodge, React. Funct. Polym., 2004, 60, 55.34 H. M. Colquhoun, D. F. Lewis, P. Hodge, A. Ben-Haida,

D. J. Williams and I. Baxter, Macromolecules, 2002, 35, 6875.35 I. Baxter, A. Ben-Haida, H. M. Colquhoun, P. Hodge, F. H. Kohnke

and D. J. Williams, Chem. Commun., 1998, 2213.36 A. Ben-Haida, H. M. Colquhoun, P. Hodge and D. J. Williams,

Macromolecules, 2006, 39, 6467.37 E. Thorn-Csanyi and K. Ruhland, Macromol. Chem. Phys., 1999, 200,

1662.38 S. Sugihara, K. Toshima and S. Matsumura, Macromol. Rapid

Commun., 2006, 27, 203.39 H. Jakobson and W. H. Stockmeyer, J. Chem. Phys., 1950, 18, 1600.40 Z. R. Chen, J. P. Claverie, R. H. Grubbs and J. A. Kornfield,

Macromolecules, 1995, 28, 2147.41 Handbook of Polyolefins, ed. C. Vasile, Marcel Dekker Inc., New

York, 2nd edn, 2000, pp. 124125.42 Y. A. Ibrahim, J. Mol. Catal. A: Chem., 2006, 254, 43.43 L. Reif and H. Hocker, Macromolecules, 1984, 17, 952.44 C. W. Bielawski and R. H. Grubbs, Angew. Chem., Int. Ed., 2000, 39,

2903.45 M. Scholl, S. Ding, C. W. Lee and R. H. Grubbs, Org. Lett., 1999, 1,

953.46 M. R. Buchmeiser, Chem. Rev., 2009, 109, 303.47 J. Lu and P. H. Toy, Chem. Rev., 2009, 109, 815.48 D. E. Bergbreiter, J. Tian and C. Hongfa, Chem. Rev., 2009, 109, 530.49 C. Hongfa, J. Tian, H. S. Bazzi and D. E. Bergbreiter, Org. Lett.,

2007, 9, 3259.50 I. K. Varma, A. C. Albertsson, R. Rajkhowa and R. K. Srivastava,

Prog. Polym. Sci., 2005, 30, 949.51 S. Matsumura, Adv. Polym. Sci., 2006, 194, 95.52 S. Kobayashi, Proc. Jpn. Acad., Ser. B, 2010, 86, 338.53 A. Duda, A. Kowalski, S. Penczek, H. Uyama and S. Kobayashi,

Macromolecules, 2002, 35, 4266.54 L. van der Mee, F. Helmich, R. de Brujin, J. A. J. M. Vekemans,

A. R. A. Palmans and E. W. Meijer, Macromolecules, 2006, 39, 5021.55 S. Namekawa, H. Uyama and S. Kobayashi, Proc. Jpn. Acad., Ser. B,

1998, 74, 65.56 B. J. B. Folmer, R. P. Sijbesma and E. W. Meijer, J. Am. Chem. Soc.,

2001, 123, 2093.57 A. C. Albertsson and I. K. Varma, Biomacromolecules, 2003, 4, 1466.58 Y. F. Wang, K. P. Chan and A. S. Hay, J. Polym. Sci., Part A: Polym.

Chem., 1996, 34, 375.59 Q. Z. Guo, H. H. Wang, J. Y. Wu, D. Guo and T. L. Chen, Polym.

Adv. Technol., 2010, 21, 290.60 H. M. Colquhoun, D. F. Lewis, R. A. Fairman, I. Baxter and

D. J. Williams, J. Mater. Chem., 1997, 7, 1.61 Y. F. Wang, K. P. Chan and A. S. Hay, Macromolecules, 1996, 29,

3717.This journal is The Royal Society of Chemistry 2011

62 Y. Z. Meng, S. C. Tjong and A. S. Hay, Polymer, 2001, 42, 5215.63 H. M. Colquhoun, M. G. Zolotukhin, L. G. Sestiaa, F. Arico, Z. Zhu,

P. Hodge, A. Ben-Haida and D. J. Williams, J. Mater. Chem., 2003,13, 1504.

64 K. M. Stridsberg, M. Ryner and A. C. Albertsson, Adv. Polym. Sci.,2002, 157, 41.

65 S. D. Kamau, P. Hodge, R. T. Willimans, P. Stagnaro andL. Conzatti, J. Comb. Chem., 2008, 10, 644.

66 A. Leitgeb, J. Wappel and C. Slugovc, Polymer, 2010, 51, 2927.67 (a) M. J. Marsella, H. D. Maynard and R. H. Grubbs, Angew. Chem.,

Int. Ed. Engl., 1997, 36, 1101; (b) H. D. Maynard and R. H. Grubbs,Macromolecules, 1999, 32, 6917.

68 U. Luning, F. Fahrenkrug and M. Hagen, Eur. J. Org. Chem., 2001,2161.

69 P. A. Chase, M. Lutz, A. L. Spek, G. P. M. van Klink and G. vanKoten, J. Mol. Catal. A: Chem., 2006, 254, 2.

70 W. Gao, R. Hagver, V. Shah, W. Xie, R. A. Gross, M. F. Ilker,C. Bell, K. A. Burke and E. B. Coughlin, Macromolecules, 2007, 40,145.

71 I. N. A. Van Bogaert, K. Saerens, C. DeMuynck, D. Develter,W. Soetaert and E. J. Vandamme, Appl. Microbiol. Biotechnol.,2007, 76, 23.

72 S. K. Singh, A. P. Felse, A. Nunez, T. A. Foglia and R. A. Gross, J.Org. Chem., 2003, 68, 5466.

73 E. Zini, M. Gazzano, M. Scandola, S. R. Wallner and R. A. Gross,Macromolecules, 2008, 41, 7463.This journal is The Royal Society of Chemistry 201174 J. E. Gautrot and X. X. Zhu, Macromolecules, 2009, 42, 7324.75 H. Therien-Aubin, J. E. Gautrot, Y. Shao, J. Zhang and X. X. Zhu,

Polymer, 2010, 51, 22.76 R. Mohr, K. Kratz, T. Weigel, M. Lucka-Gabor, M. Moneke and

A. Lendlein, Proc. Natl. Acad. Sci. U. S. A., 2006, 103, 3540.77 R. A. Gross, A. Kumar and B. Kalra, Chem. Rev., 2001, 101, 2097.78 R. A. Gross, B. Kalra and A. Kumar, Appl. Microbiol. Biotechnol.,

2001, 55, 655.79 S. Kobayashi, H. Uyama and S. Kimura, Chem. Rev., 2001, 101, 3793.80 H. Uyama, K. Takaya, N. Hoshi and S. Kobayashi, Macromolecules,

1995, 28, 7046.81 (a) K. S. Bisht, L. A. Henderson, R. A. Gross, D. L. Kaplan and

G. Swift, Macromolecules, 1997, 30, 2705; (b) A. Kumar, B. Kalra,A. Dekhterman and R. A. Gross, Macromolecules, 2000, 33, 6303.

82 I. van der Meulen, M. de Geus, H. Antheunis, R. Deumens,E. A. J. Joosten, C. E. Koning and A. Heise, Biomacromolecules,2008, 9, 3404.

83 H. Uayama, K. Inada and S. Kobayashi, Polym. J., 2000, 32, 440.84 C. Berkane, G. Mezoul, T. Lalot, M. Brigodiot and E. Marechal,

Macromolecules, 1997, 30, 7729.85 Y. Takahashi, S. Okajima, K. Toshima and S. Matsumura,

Macromol. Biosci., 2004, 4, 346.86 Y. Osanai, K. Toshima and S. Matsumura, Macromol. Biosci., 2004,

4, 936.87 B. Manzini, P. Hodge and A. Ben-Haida, Polym. Chem., 2010, 1, 339.88 O. Noll and H. Ritter, Macromol. Rapid Commun., 1996, 17, 553.Polym. Chem., 2011, 2, 791799 | 799

Recent advances in entropy-driven ring-opening polymerizationsRecent advances in entropy-driven ring-opening polymerizationsRecent advances in entropy-driven ring-opening polymerizationsRecent advances in entropy-driven ring-opening polymerizationsRecent advances in entropy-driven ring-opening polymerizationsRecent advances in entropy-driven ring-opening polymerizations

Recent advances in entropy-driven ring-opening polymerizationsRecent advances in entropy-driven ring-opening polymerizationsRecent advances in entropy-driven ring-opening polymerizationsRecent advances in entropy-driven ring-opening polymerizationsRecent advances in entropy-driven ring-opening polymerizationsRecent advances in entropy-driven ring-opening polymerizations

Recent advances in entropy-driven ring-opening polymerizationsRecent advances in entropy-driven ring-opening polymerizations