Co-reporter:Maria C. Arno, Maria Inam, Zachary Coe, Graeme Cambridge, Laura J. Macdougall, Robert Keogh, Andrew P. Dove, and Rachel K. O’Reilly
Journal of the American Chemical Society November 22, 2017 Volume 139(Issue 46) pp:16980-16980
Publication Date(Web):October 27, 2017
DOI:10.1021/jacs.7b10199
The fabrication of monodisperse nanostructures of highly controlled size and morphology with spatially distinct functional regions is a current area of high interest in materials science. Achieving this control directly in a biologically relevant solvent, without affecting cell viability, opens the door to a wide range of biomedical applications, yet this remains a significant challenge. Herein, we report the preparation of biocompatible and biodegradable poly(ε-caprolactone) 1D (cylindrical) and 2D (platelet) micelles in water and alcoholic solvents via crystallization-driven self-assembly. Using epitaxial growth in an alcoholic solvent, we show exquisite control over the dimensions and dispersity of these nanostructures, allowing access to uniform morphologies and predictable dimensions based on the unimer-to-seed ratio. Furthermore, for the first time, we report epitaxial growth in aqueous solvent, achieving precise control over 1D nanostructures in water, an essential feature for any relevant biological application. Exploiting this further, a strong, biocompatible and fluorescent hydrogel was obtained as a result of living epitaxial growth in aqueous solvent and cell culture medium. MC3T3 and A549 cells were successfully encapsulated, demonstrating high viability (>95% after 4 days) in these novel hydrogel materials.
Co-reporter:Guillaume Hedir, Christopher Stubbs, Phillip Aston, Andrew P. Dove, and Matthew I. Gibson
ACS Macro Letters December 19, 2017 Volume 6(Issue 12) pp:1404-1404
Publication Date(Web):December 1, 2017
DOI:10.1021/acsmacrolett.7b00905
Poly(vinyl alcohol) (PVA) is the most active synthetic mimic of antifreeze proteins and has extremely high ice recrystallization inhibition (IRI) activity. Addition of PVA to cellular cryopreservation solutions increases the number of recovered viable cells due to its potent IRI, but it is intrinsically nondegradable in vivo. Here we report the synthesis, characterization, and IRI activity of PVA containing degradable ester linkages. Vinyl chloroacetate (VClAc) was copolymerized with 2-methylene-1,3-dioxepane (MDO) which undergoes radical ring-opening polymerization to install main-chain ester units. The use of the chloroacetate monomer enabled selective deacetylation with retention of esters within the polymer backbone. Quantitative IRI assays revealed that the MDO content had to be finely tuned to retain IRI activity, with higher loadings (24 mol %) resulting in complete loss of IRI activity. These degradable materials will help translate PVA, which is nontoxic and biocompatible, into a range of biomedical applications.
Co-reporter:Ruairí P. Brannigan
Biomaterials Science (2013-Present) 2017 vol. 5(Issue 1) pp:9-21
Publication Date(Web):2016/12/20
DOI:10.1039/C6BM00584E
Polyester-based polymers represent excellent candidates in synthetic biodegradable and bioabsorbable materials for medical applications owing to their tailorable properties. The use of synthetic polyesters as biomaterials offers a unique control of morphology, mechanical properties and degradation profile through monomer selection, polymer composition (i.e. copolymer vs. homopolymer, stereocomplexation etc.) and molecular weight. Within this review, the synthetic routes, degradation modes and application of aliphatic polyester- and polycarbonate-based biomaterials are discussed.
Co-reporter:Laura J. Macdougall, Vinh X. Truong, and Andrew P. Dove
ACS Macro Letters 2017 Volume 6(Issue 2) pp:
Publication Date(Web):January 17, 2017
DOI:10.1021/acsmacrolett.6b00857
Synthetic hydrogel materials offer the ability to tune the mechanical properties of the resultant networks by controlling the molecular structure of the polymer precursors. Herein, we demonstrate that the nucleophilic thiol-yne click reaction presents a highly efficient chemistry for forming robust high water content (ca. 90%) hydrogel materials with tunable stiffness and mechanical properties. Remarkably, optimization of the molecular weight and geometry of the poly(ethylene glycol) (PEG) precursors allows access to materials with compressive strength up to 2.4 MPa, which can be repeatedly compressed to >90% stress. Beyond this, we demonstrate the ability to access hydrogels with storage moduli ranging from 0.2 to 7 kPa. Moreover, we also demonstrate that by a simple precursor blending process, we can access intermediate stiffness across this range with minimal changes to the hydrogel structure. These characteristics present the nucleophilic thiol-yne addition as an excellent method for the preparation of hydrogels for use as versatile synthetic biomaterials.
Co-reporter:Dr. Mathieu J.-L. Tschan;Dr. Nga Sze Ieong;Dr. Richard Todd;Jack Everson; Andrew P. Dove
Angewandte Chemie 2017 Volume 129(Issue 52) pp:16891-16895
Publication Date(Web):2017/12/22
DOI:10.1002/ange.201709934
AbstractPoly(ortho ester)s (POEs) are well-known for their surface-eroding properties and hence present unique opportunities for controlled-release and tissue-engineering applications. Their development and wide-spread investigation has, however, been severely limited by challenging synthetic requirements that incorporate unstable intermediates and are therefore highly irreproducible. Herein, the first catalytic method for the synthesis of POEs using air- and moisture-stable vinyl acetal precursors is presented. The synthesis of a range of POE structures is demonstrated, including those that are extremely difficult to achieve by other synthetic methods. Furthermore, application of this chemistry permits efficient installation of functional groups through ortho ester linkages on an aliphatic polycarbonate.
Co-reporter:Dr. Mathieu J.-L. Tschan;Dr. Nga Sze Ieong;Dr. Richard Todd;Jack Everson; Andrew P. Dove
Angewandte Chemie International Edition 2017 Volume 56(Issue 52) pp:16664-16668
Publication Date(Web):2017/12/22
DOI:10.1002/anie.201709934
AbstractPoly(ortho ester)s (POEs) are well-known for their surface-eroding properties and hence present unique opportunities for controlled-release and tissue-engineering applications. Their development and wide-spread investigation has, however, been severely limited by challenging synthetic requirements that incorporate unstable intermediates and are therefore highly irreproducible. Herein, the first catalytic method for the synthesis of POEs using air- and moisture-stable vinyl acetal precursors is presented. The synthesis of a range of POE structures is demonstrated, including those that are extremely difficult to achieve by other synthetic methods. Furthermore, application of this chemistry permits efficient installation of functional groups through ortho ester linkages on an aliphatic polycarbonate.
Co-reporter:Anthony W. Thomas;Paula K. Kuroishi;Maria M. Pérez-Madrigal;Andrew K. Whittaker
Polymer Chemistry (2010-Present) 2017 vol. 8(Issue 34) pp:5082-5090
Publication Date(Web):2017/08/30
DOI:10.1039/C7PY00358G
Thermally-responsive polymers have been widely studied, however access to materials in which both the thermal response can be tuned and in which the backbone is ultimately biodegradable is limited. To this end, a range of well-defined homopolymers of 2-allyloxymethyl-2-ethyltrimethylene carbonate (AOMEC) was prepared using a dual organocatalytic ring-opening polymerisation methodology. Post-polymerisation functionalisation of PAOMEC with thiols bearing a range of functional groups was optimised via photoinitated radical thiol–ene coupling reactions. The inclusion of thiol-terminated poly(ethylene glycol) (PEG) enabled the synthesis of polycarbonates that exhibit a lower critical solution temperature (LCST). This approach enables the facile modification of the cloud point of these materials to create a library of thermally-responsive polymers, achieved by simply varying the molecular weight of the PEG chains and grafting blends of PEG to PAOMEC.
Co-reporter:Qiutong Huang;Yijie Zou;Maria C. Arno;Shuai Chen;Tao Wang;Jingyi Gao;Jianzhong Du
Chemical Society Reviews 2017 vol. 46(Issue 20) pp:6255-6275
Publication Date(Web):2017/10/16
DOI:10.1039/C6CS00052E
Natural extracellular matrices (ECMs) have been widely used as a support for the adhesion, migration, differentiation, and proliferation of adipose-derived stem cells (ADSCs). However, poor mechanical behavior and unpredictable biodegradation properties of natural ECMs considerably limit their potential for bioapplications and raise the need for different, synthetic scaffolds. Hydrogels are regarded as the most promising alternative materials as a consequence of their excellent swelling properties and their resemblance to soft tissues. A variety of strategies have been applied to create synthetic biomimetic hydrogels, and their biophysical and biochemical properties have been modulated to be suitable for cell differentiation. In this review, we first give an overview of common methods for hydrogel preparation with a focus on those strategies that provide potential advantages for ADSC encapsulation, before summarizing the physical properties of hydrogel scaffolds that can act as biological cues. Finally, the challenges in the preparation and application of hydrogels with ADSCs are explored and the perspectives are proposed for the next generation of scaffolds.
Co-reporter:Wei Yu;Maria Inam;Joseph R. Jones;Rachel K. O'Reilly
Polymer Chemistry (2010-Present) 2017 vol. 8(Issue 36) pp:5504-5512
Publication Date(Web):2017/09/19
DOI:10.1039/C7PY01056G
Crystallisation-driven self-assembly (CDSA) has become an extremely valuable technique in the preparation of well-defined nanostructures using diblock copolymers. The use of triblock copolymers is considerably less well-known on account of more complex syntheses and assembly methods despite the functional advantages provided by a third block. Herein, we show the simple preparation of well-defined tuneable 1D and 2D structures based on poly(lactide) triblock copolymers of different block ratios synthesised by ring-opening polymerisation (ROP) and reversible addition–fragmentation chain transfer (RAFT) polymerisation, where a phase diagram based on a novel unimer solubility approach is proposed. Using a series of poly(L-lactide)-b-poly(N,N-dimethylacrylamide) (PLLA-b-PDMA) diblock copolymers and PDMA-b-PLLA-b-PDMA triblock copolymers with different core/corona ratios, single solvent CDSA processes revealed that comparatively hydrophilic polymers were liable to achieve 2D platelets, while the less hydrophilic counterparts yield ‘transition state’ wide cylinders and pure 1D cylinders. The length of crystalline core block is also shown to play an important role in fixed corona/core ratio systems, where a longer core block is prone to form cylindrical structures due to a lack of overall solubility, whereas a shorter block forms platelets. Importantly, this approach reveals contrary results to conventional theories, which state that longer solvophilic blocks relative to the core-forming block should favour more curved core/corona interfaces. Our morphological transitions are shown in both di- and tri-block copolymer systems, showing the generalisation of these assembly methods towards promising methodologies for the rational design of PLLA-based nanocarriers in the biomedical realm.
Co-reporter:Maria Inam;Graeme Cambridge;Anaïs Pitto-Barry;Zachary P. L. Laker;Neil R. Wilson;Robert T. Mathers;Rachel K. O'Reilly
Chemical Science (2010-Present) 2017 vol. 8(Issue 6) pp:4223-4230
Publication Date(Web):2017/05/30
DOI:10.1039/C7SC00641A
2D materials such as graphene, LAPONITE® clays or molybdenum disulfide nanosheets are of extremely high interest to the materials community as a result of their high surface area and controllable surface properties. While several methods to access 2D inorganic materials are known, the investigation of 2D organic nanomaterials is less well developed on account of the lack of ready synthetic accessibility. Crystallization-driven self-assembly (CDSA) has become a powerful method to access a wide range of complex but precisely-defined nanostructures. The preparation of 2D structures, however, particularly those aimed towards biomedical applications, is limited, with few offering biocompatible and biodegradable characteristics as well as control over self-assembly in two dimensions. Herein, in contrast to conventional self-assembly rules, we show that the solubility of polylactide (PLLA)-based amphiphiles in alcohols results in unprecedented shape selectivity based on unimer solubility. We use log Poct analysis to drive solvent selection for the formation of large uniform 2D diamond-shaped platelets, up to several microns in size, using long, soluble coronal blocks. By contrast, less soluble PLLA-containing block copolymers yield cylindrical micelles and mixed morphologies. The methods developed in this work provide a simple and consistently reproducible protocol for the preparation of well-defined 2D organic nanomaterials, whose size and morphology are expected to facilitate potential applications in drug delivery, tissue engineering and in nanocomposites.
Co-reporter:Dr. Guillaume G. Hedir;Dr. Maria C. Arno;Marvin Langlais;Jonathan T. Husb; Rachel K. O'Reilly; Andrew P. Dove
Angewandte Chemie International Edition 2017 Volume 56(Issue 31) pp:9178-9182
Publication Date(Web):2017/07/24
DOI:10.1002/anie.201703763
AbstractPolymers with a thermally triggered phase transition are important in the design of materials for biological applications, where their behavior can be used to trigger release or (dis)assembly events. Despite their advantages, a system with tunable thermal response, end-group reactive sites, low toxicity, and controlled main-chain degradability has not been realized, yet this would be a significant advance. The versatile new poly(oligo(ethylene glycol) vinyl acetate)s are presented with excellent control over their molecular properties obtained through RAFT/MADIX polymerization. Furthermore, we demonstrate structure-controlled thermal transitions, conjugation to human lysozyme through the retained end-group, and moreover show that this class of polymers can uniquely be copolymerized with 2-methylene-1,3-dioxepane (MDO) to generate polymers in which the degradability and cloud point can be independently tuned to create materials that display the same cloud point but degrade differently.
Co-reporter:Dr. Guillaume G. Hedir;Dr. Maria C. Arno;Marvin Langlais;Jonathan T. Husb; Rachel K. O'Reilly; Andrew P. Dove
Angewandte Chemie 2017 Volume 129(Issue 31) pp:9306-9310
Publication Date(Web):2017/07/24
DOI:10.1002/ange.201703763
AbstractPolymers with a thermally triggered phase transition are important in the design of materials for biological applications, where their behavior can be used to trigger release or (dis)assembly events. Despite their advantages, a system with tunable thermal response, end-group reactive sites, low toxicity, and controlled main-chain degradability has not been realized, yet this would be a significant advance. The versatile new poly(oligo(ethylene glycol) vinyl acetate)s are presented with excellent control over their molecular properties obtained through RAFT/MADIX polymerization. Furthermore, we demonstrate structure-controlled thermal transitions, conjugation to human lysozyme through the retained end-group, and moreover show that this class of polymers can uniquely be copolymerized with 2-methylene-1,3-dioxepane (MDO) to generate polymers in which the degradability and cloud point can be independently tuned to create materials that display the same cloud point but degrade differently.
Co-reporter:Panagiotis Bexis, Julien De Winter, Olivier Coulembier, Andrew P. Dove
European Polymer Journal 2017 Volume 95(Volume 95) pp:
Publication Date(Web):1 October 2017
DOI:10.1016/j.eurpolymj.2017.05.038
•Organocatalytic ring-opening polymerization of the O-carboxyanhydrides of l-lactic acid and l-malic acid.•Application of a single initiator/organocatalyst system leads to controlled ROP.•MALDI-TOF MS analysis provides understanding of all side-reactions.•The chiral polyesters are isotactic at high degrees of polymerization.The preparation of stereoregular isotactic P(l-BnMA) and PLLA by ring-opening polymerization (ROP) of 5-(S)-[(benzyloxycarbonyl)methyl]-1,3-dioxolane-2,4-dione (l-malOCA) and (S)-5-methyl-1,3-dioxolane-2,4-dione (l-lacOCA) is reported. The polymerization process was shown to be well controlled using two easily accessible single organocatalyst/initiator systems, pyridine/l-benzyl(Bn)malate and pyridine/lactic acid (Py·LA) ion pair adducts respectively. The obtained biodegradable polymers displayed narrow dispersity (ĐM) and excellent molar mass control. All ROP reactions were conducted at ambient temperature. The stereoregularity and thermal properties of the materials were thoroughly studied, demonstrating the retention of high levels of isotactic enrichment.Download high-res image (78KB)Download full-size image
Co-reporter:J. A. Wilson, S. A. Hopkins, P. M. Wright, and A. P. Dove
ACS Macro Letters 2016 Volume 5(Issue 3) pp:346
Publication Date(Web):February 18, 2016
DOI:10.1021/acsmacrolett.5b00940
The copolymerization of an ε-substituted ε-lactone, menthide (MI), and a range of nonsubstituted lactones (6-, 7-, 8-, and 9-membered rings) was investigated in order to determine the factors that affect the sequencing of the MI copolymers. Analysis by quantitative 13C NMR spectroscopy showed the copolymerization of MI with a nonsubstituted lactone of ring size 7 or less produced a randomly sequenced copolymer, as a consequence of the smaller lactone polymerizing first and undergoing rapid transesterification as MI was incorporated. Conversely, copolymerization with larger ring lactones (ring size 8 and above) produced block-like copolymers as a consequence of MI polymerizing initially, which does not undergo rapid transesterification side reactions during the incorporation of the second monomer. Terpolymerizations of a small ring lactone, macrolactone, and menthide demonstrated methods of producing lactone terpolymers with different final sequences, depending on when the small ring lactone was injected into the reaction mixture.
Co-reporter:Stefan Naumann, Anthony W. Thomas, and Andrew P. Dove
ACS Macro Letters 2016 Volume 5(Issue 1) pp:134
Publication Date(Web):January 6, 2016
DOI:10.1021/acsmacrolett.5b00873
In this work, the activity of N-heterocyclic olefins (NHOs), a newly emerging class of organopolymerization catalyst, is investigated to affect the metal-free polymerization of lactones and trimethylene carbonate (TMC). A decisive structure–activity relationship is revealed. While catalysts of the simplest type bearing an exocyclic ═CH2 moiety polymerize l-lactide (l-LA) and δ-valerolactone (δ-VL) in a non-living and non-quantitative manner, the introduction of methyl substituents on the exocyclic carbon radically changes this behavior. 2-Isopropylidene-1,3,4,5-tetramethylimidazoline is found to be highly active for a range of monomers such as l-LA, δ-VL, ε-caprolactone (ε-CL), and TMC, with quantitative conversion occurring within seconds with catalyst loadings of just 0.2 mol %. The high activity of this NHO further enables the ring-opening polymerization (ROP) of the macrolactone ω-pentadecalactone (PDL). However, this broad applicability is offset by a lack of control over the polymerizations, including side reactions as a consequence of its strong basicity. To overcome this, a saturated, imidazolinium-derived analogue was synthesized and subsequently demonstrated to possess a harnessed reactivity which enables it to polymerize both l-LA and TMC in a controlled manner (ĐM < 1.2). NMR spectroscopic and MALDI-ToF MS experiments highlight the differences in polymerization pathways for 2-methylene-1,3,4,5-tetramethylimidazoline, in which the exocyclic carbon is not substituted, in contrast to 2-isopropylidene-1,3,4,5-tetramethylimidazoline, with the former operating via its nucleophilicity and the latter acting as a base with enolizable δ-VL.
Co-reporter:Liang Sun, Anaïs Pitto-Barry, Anthony W. Thomas, Maria Inam, Kay Doncom, Andrew P. Dove and Rachel K. O'Reilly
Polymer Chemistry 2016 vol. 7(Issue 13) pp:2337-2341
Publication Date(Web):25 Feb 2016
DOI:10.1039/C5PY01970B
Sequential ring-opening and reversible addition–fragmentation chain transfer (RAFT) polymerization was used to form a triblock copolymer of tetrahydropyran acrylate (THPA), 5-methyl-5-allyloxycarbonyl-1,3-dioxan-2-one (MAC) and L-lactide. Concurrent deprotection of the THPA block and crystallization-driven self-assembly (CDSA) was undertaken and allowed for the formation of cylindrical micelles bearing allyl handles in a short outer core segment. These handles were further functionalized by different thiols using photo-initiated thiol–ene radical reactions to demonstrate that the incorporation of an amorphous PMAC block within the core does not disrupt CDSA and can be used to load the cylindrical nanoparticles with cargo.
Co-reporter:Stefan Naumann ;Andrew P Dove
Polymer International 2016 Volume 65( Issue 1) pp:16-27
Publication Date(Web):
DOI:10.1002/pi.5034
Abstract
This mini-review is intended to serve as a concise introduction to polymerizations that are catalysed by N-heterocyclic carbenes. The content is structured according to accessible monomer functionalities and type of polymerization. Both major achievements as well as the latest developments in this rapidly evolving field are presented. A broad range of different types of monomers is covered in this way, including among others lactones, epoxides, anhydrides, acrylates, siloxanes and lactams. Special emphasis is put on mechanistic understanding and structure–activity relationships. © 2015 Society of Chemical Industry
Co-reporter:Ruairí P. Brannigan, Anthony Walder, and Andrew P. Dove
Macromolecules 2016 Volume 49(Issue 7) pp:2518-2525
Publication Date(Web):March 22, 2016
DOI:10.1021/acs.macromol.5b02531
As a consequence of their mechanical properties, thermoplastic poly(ester–urethane)s (TPEUs) have been extensively examined for their potential applications in biomedical engineering. The incorporation of bio-derived small molecules, such as amino acid derivatives, as chain extenders may allow for more biodegradable hard segments, which result in nontoxic degradants. TPEUs were synthesized using modified 2-aminopropane-1,3-diol (serinol) extenders, ethyl (1,3-dihydroxypropan-2-yl)carbamate (C3c), and 1-(1,3-dihydroxypropan-2-yl)-3-ethylurea (C3u) in order to determine the effect of extender side-group functionality on the properties of the resultant materials. The TPEUs were synthesized with varying percentage “hard” segment (%HS) using poly(ε-caprolactone) (PCL) and 1-isocyanato-4-[(4-isocyanatocyclohexyl)methyl]cyclohexane (H12MDI) as the polyol and diisocyanate, respectively. It was found that by controlling the %HS and side group functionality, the thermal and mechanical properties of the materials could be tuned. Furthermore, the selection of extender was found to affect both the hydrophilicity and degradation profile of the materials.
Co-reporter:Rebecca J. Williams, Anaïs Pitto-Barry, Nigel Kirby, Andrew P. Dove, and Rachel K. O’Reilly
Macromolecules 2016 Volume 49(Issue 7) pp:2802-2813
Publication Date(Web):March 17, 2016
DOI:10.1021/acs.macromol.5b02710
The synthesis of cyclic amphiphilic graft copolymers with a hydrophobic polycarbonate backbone and hydrophilic poly(N-acryloylmorpholine) (PNAM) side arms via a combination of ring-opening polymerization (ROP), cyclization via copper-catalyzed azide–alkyne cycloaddition (CuAAC), and reversible addition–fragmentation chain transfer (RAFT) polymerization is reported. The ability of these cyclic graft copolymers to form unimolecular micelles in water is explored using a combination of light scattering, small-angle X-ray scattering (SAXS), and cryogenic transmission electron microscopy (cryoTEM) analyses, where particle size was found to increase with increasing PNAM arm length. Further analysis revealed differences in the solution conformations, loading capabilities, and morphologies of the cyclic graft copolymers in comparison to equivalent linear graft copolymer unimolecular micelle analogues. Furthermore, the cyclic and linear graft copolymers were found to exhibit significantly different cloud point temperatures. This study highlights how subtle changes in polymer architecture (linear graft copolymer versus cyclic graft copolymer) can dramatically influence a polymer’s nanostructure and its properties.
Co-reporter:Vinh X. Truong; Matthew P. Ablett; Stephen M. Richardson; Judith A. Hoyland
Journal of the American Chemical Society 2015 Volume 137(Issue 4) pp:1618-1622
Publication Date(Web):January 15, 2015
DOI:10.1021/ja511681s
The use of tough hydrogels as biomaterials is limited as a consequence of time-consuming fabrication techniques, toxic starting materials, and large strain hysteresis under deformation. Herein, we report the simultaneous application of nucleophilic thiol-yne and inverse electron-demand Diels–Alder additions to independently create two interpenetrating networks in a simple one-step procedure. The resultant hydrogels display compressive stresses of 14–15 MPa at 98% compression without fracture or hysteresis upon repeated load. The hydrogel networks can be spatially and temporally postfunctionalized via radical thiylation and/or inverse electron-demand Diels–Alder addition to residual functional groups within the network. Furthermore, gelation occurs rapidly under physiological conditions, enabling encapsulation of human cells.
Co-reporter:Stefan Naumann; Philip B. V. Scholten; James A. Wilson
Journal of the American Chemical Society 2015 Volume 137(Issue 45) pp:14439-14445
Publication Date(Web):October 27, 2015
DOI:10.1021/jacs.5b09502
Much work has been directed to the design of complex single-site catalysts for ring-opening polymerization (ROP) to enhance both activity and selectivity. More simply, however, cooperative effects between Lewis acids and organocatalytic nucleophiles/Lewis bases provide a powerful alternative. In this study we demonstrate that the combination of N-heterocyclic carbenes, 1,8-diazabicycloundec-7-ene (DBU) and 4-dimethylaminopyridine (DMAP) with simple Lewis acids enables the ROP of the macrolactone pentadecalactone in a rapid and efficient manner. Remarkably, regardless of the nature of the nucleophile, the order of activity was observed to be MgX2 ≫ YCl3 ≫ AlCl3 and MgI2 > MgBr2 > MgCl2 in every case. The minimal influence of the organobase on polymerization activity allows for the use of simple and inexpensive precursors. Furthermore, extension of the study to other cyclic (di)ester monomers reveals the choice of Lewis acid to lead to monomer selective ROP activity and hence control over copolymer composition by choice of Lewis acid. This approach could lead to the realization of complex polymer structures with tunable physical properties from simple catalyst combinations.
Co-reporter:Craig A. Bell, Guillaume G. Hedir, Rachel K. O'Reilly and Andrew P. Dove
Polymer Chemistry 2015 vol. 6(Issue 42) pp:7447-7454
Publication Date(Web):02 Sep 2015
DOI:10.1039/C5PY01156F
The copolymerization of vinyl acetate (VAc) and 2-methylene-1,3-dioxepane (MDO), as well as the homopolymerization of MDO in the presence of a p-methoxyphenyl xanthate chain transfer agent (CTA) is reported and comparison of the homopolymerization of MDO with other known xanthates was also investigated. In depth investigation showed loss of the xanthate functionality was a result of Z-group fragmentation leading to the formation of carbonodithioate groups, as confirmed by 13C NMR spectroscopy. The use of the xanthate with a substituted phenyl Z-group drastically reduces fragmentation through the Z-group and hence significantly increases chain-end retention during the polymerization using the RAFT/MADIX technique. Post-polymerization modification of the chain-end of poly(MDO) was achieved by in situ aminolysis and base-catalyzed Michael addition of propargyl methacrylate onto the terminal thiol to form alkyne functional poly(MDO).
Co-reporter:Stefan Naumann and Andrew P. Dove
Polymer Chemistry 2015 vol. 6(Issue 17) pp:3185-3200
Publication Date(Web):18 Mar 2015
DOI:10.1039/C5PY00145E
This review spotlights current areas of high interest for NHC-based polymerization research. A compact overview about the underlying mechanistic aspects is given, while the main focus is put on more recent developments and emerging new approaches in NHC-mediated polymerization chemistry. Contemporary frontiers in research, such as the preparation of macrocyclic polymers, the polymerization of activated olefins and new types of NHC delivery are discussed and put into perspective. Finally, an outlook is given on where future industrial applications might arise.
Co-reporter:Rebecca J. Williams, Andrew P. Dove and Rachel K. O'Reilly
Polymer Chemistry 2015 vol. 6(Issue 16) pp:2998-3008
Publication Date(Web):11 Mar 2015
DOI:10.1039/C5PY00081E
The self-assembly of block copolymers in solution is an expansive area of research as a consequence of the significant potential the resulting soft nanostructures possess in numerous applications (e.g. drug delivery, imaging and catalysis), as well as our desire to mimic nature's nanostructures (e.g. viruses and proteins). Of the various factors that affect self-assembly behaviour, the effect of polymer architecture is relatively unexplored despite the successful synthesis of a range of non-linear amphiphilic polymers. Indeed, recent synthetic breakthroughs have allowed the preparation of well-defined, high purity amphiphilic cyclic polymers and as a result the self-assembly of cyclic polymers is an area of increasing interest. This review will discuss the self-assembly of cyclic block copolymers, in addition to more complex cyclic architectures, as well as providing a comparison to the self-assembly of equivalent linear systems to elucidate the effect of cyclization on self-assembly.
Co-reporter:James A. Wilson, Sally A. Hopkins, Peter M. Wright, and Andrew P. Dove
Biomacromolecules 2015 Volume 16(Issue 10) pp:
Publication Date(Web):September 17, 2015
DOI:10.1021/acs.biomac.5b00862
We report the one-pot copolymerization of ω-pentadecalactone (PDL) to produce tri- and diblock-like copolymers with the ability to undergo postpolymerization modification. The ε-substituted ε-lactone (εSL), menthide (MI), was copolymerized with PDL to introduce side chain functionality into poly(ω-pentadecalactone) (PPDL) copolymers. The copolymerization was followed by quantitative 13C NMR spectroscopy, which revealed that the polymerization of MI occurred before the incorporation of PDL into the polymer chain to form a block-like copolymer. Transesterification side reactions were not found to occur interblock, although intrablock transesterification side reactions occurred only within the PPDL section. The same effect was demonstrated across a range of relative molar equivalents of monomers, and the generality of the approach was further demonstrated with the copolymerization of PDL with other εSL monomers. Finally, the copolymerization of PDL with an alkene-functionalized εSL was shown to produce one-pot PDL block-like copolymers that could undergo postpolymerization modification by thiol–ene addition to produce block copolymers with a range of characteristics in a simple procedure.
Co-reporter:James A. Wilson, Sally A. Hopkins, Peter M. Wright, and Andrew P. Dove
Macromolecules 2015 Volume 48(Issue 4) pp:950-958
Publication Date(Web):February 13, 2015
DOI:10.1021/ma5022049
ω-Pentadecalactone (PDL) was copolymerized with lactones of varying sizes (6-, 7-, 9-, and 13-membered rings) in order to characterize the properties of PDL copolymers throughout the lactone range for copolymerizations catalyzed by magnesium 2,6-di-tert-butyl-4-methylphenoxide (Mg(BHT)2(THF)2). Kinetics of the copolymerization reactions were studied using quantitative 13C NMR spectroscopy, which revealed that the polymerization of the smaller, strained lactone monomer occurred rapidly before the incorporation of PDL into the polymer. Furthermore, all polymers were randomly sequenced as a consequence of transesterification side reactions that occurred throughout polymerization. The copolymers were all shown to cocrystallize to produce polymers with melting and crystallization temperatures that displayed a linear relationship with respect to monomer ratio. Differences in degradation behavior of the smaller lactones enabled the synthesis of PDL copolymer materials that displayed independently controllable thermal and degradation properties.
Co-reporter:Guillaume G. Hedir, Craig A. Bell, Rachel K. O’Reilly, and Andrew P. Dove
Biomacromolecules 2015 Volume 16(Issue 7) pp:
Publication Date(Web):May 22, 2015
DOI:10.1021/acs.biomac.5b00476
The synthesis of vinyl bromobutanoate (VBr), a new vinyl acetate monomer derivative obtained by the palladium-catalyzed vinyl exchange reaction between vinyl acetate (VAc) and 4-bromobutyric acid is reported. The homopolymerization of this new monomer using the RAFT/MADIX polymerization technique leads to the formation of novel well-defined and controlled polymers containing pendent bromine functional groups able to be modified via postpolymerization modification. Furthermore, the copolymerization of vinyl bromobutanoate with 2-methylene-1,3-dioxepane (MDO) was also performed to deliver a range of novel functional degradable copolymers, poly(MDO-co-VBr). The copolymer composition was shown to be able to be tuned to vary the amount of ester repeat units in the polymer backbone, and hence determine the degradability, while maintaining a control of the final copolymers’ molar masses. The addition of functionalities via simple postpolymerization modifications such as azidation and the 1,3-dipolar cycloaddition of a PEG alkyne to an azide is also reported and proven by 1H NMR spectroscopy, FTIR spectroscopy, and SEC analyses. These studies enable the formation of a novel class of hydrophilic functional degradable copolymers using versatile radical polymerization methods.
Co-reporter:Francesca Ercole, Andrew E. Rodda, Laurence Meagher, John S. Forsythe and Andrew P. Dove
Polymer Chemistry 2014 vol. 5(Issue 8) pp:2809-2815
Publication Date(Web):12 Feb 2014
DOI:10.1039/C3PY01701J
The controlled ring-opening polymerisation (ROP) of an ε-caprolactone derivative that contains an ATRP initiator pendant to the ring, γ-(2-bromo-2-methyl propionyl)-ε-caprolactone (γ-BMPCL), and its copolymerisation with ε-caprolactone (CL) is reported. Functional PCL copolymers that contained pendant ATRP initiators were obtained with higher than previously reported molecular weights using diphenyl phosphate (DPP) as the catalyst at room temperature. Surface-initiated ATRP grafting of oligo(ethylene glycol) methacrylate was successfully carried out on the surface of two dimensional (2D) substrates comprising thin films of a functional PCL copolymer.
Co-reporter:James A. Wilson, Sally A. Hopkins, Peter M. Wright and Andrew P. Dove
Polymer Chemistry 2014 vol. 5(Issue 8) pp:2691-2694
Publication Date(Web):25 Feb 2014
DOI:10.1039/C4PY00034J
The ‘immortal’ ring-opening polymerization (iROP) of pentadecalactone (PDL), catalysed by magnesium 2,6-di-tert-butyl-4-methylphenoxide (Mg(BHT)2(THF)2) is reported for the first time. The polymerization was shown to occur without the requirement for extensive drying techniques or inert atmosphere whilst retaining end-group fidelity. The iROP technique is also further demonstrated to be applicable to ε-caprolactone (εCL).
Co-reporter:Anaïs Pitto-Barry, Nigel Kirby, Andrew P. Dove and Rachel K. O'Reilly
Polymer Chemistry 2014 vol. 5(Issue 4) pp:1427-1436
Publication Date(Web):29 Nov 2013
DOI:10.1039/C3PY01048A
We report the crystallization-driven self-assembly of diblock copolymers bearing a poly(L-lactide) block into cylindrical micelles. Three different hydrophilic corona-forming blocks have been employed: poly(4-acryloyl morpholine) (P4AM), poly(ethylene oxide) (PEO) and poly(N,N-dimethylacrylamide) (PDMA). Optimization of the experimental conditions to improve the dispersities of the resultant cylinders through variation of the solvent ratio, the polymer concentration, and the addition speed of the selective solvent is reported. The last parameter has been shown to play a crucial role in the homogeneity of the initial solution, which leads to a pure cylindrical phase with a narrow distribution of length. The hydrophilic characters of the polymers have been shown to direct the length of the resultant cylinders, with the most hydrophilic corona block leading to the shortest cylinders.
Co-reporter:Ian A. Barker, Matthew P. Ablett, Hamish T. J. Gilbert, Simon J. Leigh, James A. Covington, Judith A. Hoyland, Stephen M. Richardson and Andrew P. Dove
Biomaterials Science 2014 vol. 2(Issue 4) pp:472-475
Publication Date(Web):18 Dec 2013
DOI:10.1039/C3BM60290G
A new class of degradable aliphatic poly(carbonate) resins for use in microstereolithographic process is described. Using a biologically inert photo-inhibiting dye, exemplar 3-dimensional structures were produced using thiol–ene chemistry via microstereolithography. Fabricated constructs demonstrated good biological compatibility with cells and had tensile properties that render them suitable for use as tissue engineering scaffolds.
Co-reporter:Vinh X. Truong, Matthew P. Ablett, Hamish T. J. Gilbert, James Bowen, Stephen M. Richardson, Judith A. Hoyland and Andrew P. Dove
Biomaterials Science 2014 vol. 2(Issue 2) pp:167-175
Publication Date(Web):04 Oct 2013
DOI:10.1039/C3BM60159E
A water-soluble azide-functionalised chitosan was crosslinked with propiolic acid ester-functional poly(ethylene glycol) using copper-free click chemistry. The resultant hydrogel materials were formed within 5–60 min at 37 °C and resulted in mechanically robust materials with tuneable properties such as swelling, mechanical strength and degradation. Importantly, the hydrogels supported mesenchymal stem cell attachment and proliferation and were also non-toxic to encapsulated cells. As such these studies indicate that the hydrogels have potential to be used as injectable biomaterials for tissue engineering.
Co-reporter:Andrew P. Dove;Michael A. R. Meier
Macromolecular Chemistry and Physics 2014 Volume 215( Issue 22) pp:2135-2137
Publication Date(Web):
DOI:10.1002/macp.201400512
No abstract is available for this article.
Co-reporter:Ruairí P. Brannigan;Anthony Walder
Journal of Polymer Science Part A: Polymer Chemistry 2014 Volume 52( Issue 16) pp:2279-2286
Publication Date(Web):
DOI:10.1002/pola.27246
ABSTRACT
9-Phenyl-2,4,8,10-tetraoxaspiro[5,5]undecanone (PTO) was synthesized from pentaerythritol via the acid-catalyzed acetal formation reaction with benzaldehyde and subsequent ring closure with ethyl chloroformate. The cyclic carbonate monomer was subsequently polymerized by ring-opening polymerization (ROP) initiated from 1,4-butanediol (1,4-BDO) using the 1-(3,5-bis(trifluoromethyl)phenyl)-3-cyclohexylthiourea and 1,8-diazabicyclo[5.4.0]undec-7-ene dual organocatalytic system. It was found that the organocatalyst allowed for the synthesis of well-defined polymers with minimal adverse side reactions and low dispersities. This system was then employed in the ROP of PTO initiated from an α,ω-dihydroxy poly(caprolactone) (PCL) macroinitiator, with varying molecular weights, to yield a series of A-B-A block copolymers. These materials were characterized by 1H NMR spectroscopy, gel permeation chromatography, differential scanning calorimetry, thermogravimetric analysis and tensile analysis. It was found that the chain extension from PCL with poly(PTO) (PPTO) blocks yielded a thermoplastic material with superior tensile properties (elongation and Young's modulus) to that of the PCL homopolymer. Furthermore, it was noted that the addition of PPTO could be employed to alter the crystallization properties (crystallization temperature (Tc), and percentage crystallization) of the central PCL block. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014, 52, 2279–2286
Co-reporter:Guillaume G. Hedir, Craig A. Bell, Nga Sze Ieong, Emma Chapman, Ian R. Collins, Rachel K. O’Reilly, and Andrew P. Dove
Macromolecules 2014 Volume 47(Issue 9) pp:2847-2852
Publication Date(Web):April 23, 2014
DOI:10.1021/ma500428e
Herein we report the first example of the controlled synthesis of linear and hyperbranched copolymers of 2-methylene-1,3-dioxepane (MDO) with functional vinyl monomers to deliver a range of functional, degradable polymers by reversible deactivation radical polymerization. The copolymerization was able to be tuned to vary the incorporation of degradable segments to create degradable materials with predictable molar mass, low dispersity values while also featuring side-chain functionality. The formation of nanoparticles by the addition of divinyladipate to form degradable hyperbranched copolymers was proven by DLS and TEM analyses.
Co-reporter:Sarah Tempelaar, Laetitia Mespouille, Olivier Coulembier, Philippe Dubois and Andrew P. Dove
Chemical Society Reviews 2013 vol. 42(Issue 3) pp:1312-1336
Publication Date(Web):15 Nov 2012
DOI:10.1039/C2CS35268K
Owing to their low toxicity, biocompatibility and biodegradability, aliphatic poly(carbonate)s have been widely studied as materials for biomedical application. Furthermore, the synthetic versatility of the six-membered cyclic carbonates for the realization of functional degradable polymers by ring-opening polymerisation has driven wider interest in this area. In this review, the synthesis and ring-opening polymerisation of functional cyclic carbonates that have been reported in the literature in the past decade are discussed. Finally, the post-polymerisation modification methods that have been applied to the resulting homopolymers and copolymers and the application of the materials are also discussed.
Co-reporter:Richard Todd, Gabriel Rubio, Daniel J. Hall, Sarah Tempelaar and Andrew P. Dove
Chemical Science 2013 vol. 4(Issue 3) pp:1092-1097
Publication Date(Web):12 Dec 2012
DOI:10.1039/C2SC22053A
The synthesis and application of a dibenzyl-functionalized bispidine, in combination with 1-(3,5-bis(trifluoromethyl)phenyl)-3-cyclohexylthiourea (TU) co-catalyst, has been demonstrated to be an excellent catalyst for the controlled ring-opening polymerisation (ROP) of lactide and cyclic carbonate monomers. Notably, the polymerisation proceeds with negligible transesterification or epimerisation, with the polymerisation of stereopure L-lactide affording highly crystalline poly(lactide) with a Tm of 156 °C. ROP of racemic lactide results in the observation of a modest degree of stereocontrol such that the probability of isotactic enchainment, Pm = 0.74. Comparison of a range of alternative hydrogen bond donor co-catalysts revealed that TU displayed the highest polymerisation rates in combination with the dibenzyl-functionalized bispidine.
Co-reporter:Vinh X. Truong, Ian A. Barker, Milene Tan, Laetitia Mespouille, Philippe Dubois and Andrew P. Dove
Journal of Materials Chemistry A 2013 vol. 1(Issue 2) pp:221-229
Publication Date(Web):18 Oct 2012
DOI:10.1039/C2TB00148A
This work describes the preparation of a new class of in situ-forming poly(carbonate)-graft-poly(ethylene glycol) hybrid hydrogels using ‘thiol–ene’ photoclick chemistry. Morphological study by cryogenic Scanning Electron Microscopy (SEM) revealed that the hydrogels display characteristic macroporous and microporous distributions, the ratio of which can be tuned by varying the length of the poly(ethylene glycol) linker. Controlling the side-chain length of the poly(ethylene glycol) also allows tuning of the equilibrium water uptake, water diffusion, mechanical properties and degradability. Furthermore, we demonstrate that these hydrogels are robust materials with fracture compressive strength in the range of 27–468 kPa and are readily degraded under physiological conditions between 8 and 22 days. The swelling of the gels was also found to be thermoresponsive making them potential candidates for delivery applications.
Co-reporter:Ian A. Barker and Andrew P. Dove
Chemical Communications 2013 vol. 49(Issue 12) pp:1205-1207
Publication Date(Web):18 Dec 2012
DOI:10.1039/C2CC38114A
Triarylsulfonium hexafluorophosphate salts were shown to be effective catalysts for the ring-opening polymerisation of various cyclic monomers under UV irradiation. A dual basic/acidic catalytic system demonstrated the potential for UV-triggered formation of poly(δ-valerolactone)-b-poly(L-lactide)-b-poly(δ-valerolactone) in a ‘one-pot’ reaction.
Co-reporter:Sarah Tempelaar, Ian A. Barker, Vinh X. Truong, Daniel J. Hall, Laetitia Mespouille, Philippe Dubois and Andrew P. Dove
Polymer Chemistry 2013 vol. 4(Issue 1) pp:174-183
Publication Date(Web):17 Sep 2012
DOI:10.1039/C2PY20718D
The synthesis of well-defined propargyl-functional poly(carbonate)s was achieved via the organocatalytic ring-opening polymerization of 5-methyl-5-propargyloxycarbonyl-1,3-dioxan-2-one (MPC) using the dual catalyst system of 1-(3,5-bis(trifluoromethyl)phenyl)-3-cyclohexylthiourea (TU) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). The resulting homopolymers showed low dispersities and high end-group fidelity, with the versatility of the system being demonstrated by the synthesis of telechelic copolymers and block copolymers. The synthesized homopolymers with varying degree of polymerization were functionalized with a range of azides via copper-catalyzed Huisgen-1,3-dipolar addition or thiols via radical thiylation, to produce functional aliphatic poly(carbonate)s from a single polymeric scaffold.
Co-reporter:Liang Sun, Nikos Petzetakis, Anaïs Pitto-Barry, Tara L. Schiller, Nigel Kirby, Daniel J. Keddie, Ben J. Boyd, Rachel K. O’Reilly, and Andrew P. Dove
Macromolecules 2013 Volume 46(Issue 22) pp:9074-9082
Publication Date(Web):November 6, 2013
DOI:10.1021/ma401634s
A series of poly(l-lactide)-b-poly(acrylic acid) (PLLA-b-PAA) diblock copolymers with a range of hydrophobic or hydrophilic block lengths were designed in order to tune the size of the resultant cylindrical micelles using a crystallization-driven self-assembly (CDSA) approach. The precursor poly(l-lactide)-b-poly(tetrahydropyran acrylate) (PLLA-b-PTHPA) was synthesized by a combination of ring-opening polymerization (ROP) and reversible addition-fragmentation chain transfer (RAFT) polymerization. The CDSA process was carried out in a tetrahydrofuran/water (THF/H2O) mixture during the hydrolysis of PTHPA block at 65 °C using an evaporation method. A majority of PLLA-b-PAA diblock copolymers resulted in the formation of cylindrical micelles with narrow size distributions (Lw/Ln < 1.30) as determined by transmission electron microscopy (TEM) and dynamic light scattering (DLS). Furthermore, the length of PLLA block was found to control the length of the resultant cylindrical micelles while the length of PAA block governed their widths. Synchrotron small-angle X-ray scattering (SAXS) further proved that the length increase of these cylinders was a consequence of the decreasing PLLA block lengths. The crystalline core nature of these cylinders was characterized by wide-angle X-ray diffraction (WAXD), and the relative core crystallinity was calculated to compare different samples. Both the hydrophobic weight fraction and the relative core crystallinity were found to determine the geometry of the formed PLLA-b-PAA cylindrical micelles. Finally, changing the pH conditions of the CDSA process was found to have no significant effect on tuning the resultant dimensions of the cylinders.
Co-reporter:Dr. Vinh X. Truong ;Dr. Andrew P. Dove
Angewandte Chemie 2013 Volume 125( Issue 15) pp:4226-4230
Publication Date(Web):
DOI:10.1002/ange.201209239
Co-reporter:Dr. Vinh X. Truong ;Dr. Andrew P. Dove
Angewandte Chemie International Edition 2013 Volume 52( Issue 15) pp:4132-4136
Publication Date(Web):
DOI:10.1002/anie.201209239
Co-reporter:Simon J. Leigh, Hamish T. J. Gilbert, Ian A. Barker, Jan M. Becker, Stephen M. Richardson, Judith A. Hoyland, James A. Covington, and Andrew P. Dove
Biomacromolecules 2013 Volume 14(Issue 1) pp:
Publication Date(Web):November 20, 2012
DOI:10.1021/bm3015736
A novel method for the production of inhibitor- and solvent-free resins suitable for three-dimensional (3D) microstereolithography is reported. Using an exemplar poly(ethylene glycol)-based resin, the control of features in the X, Y, and Z planes is demonstrated such that complex structures can be manufactured. Human mesenchymal stem cells cultured on the manufactured scaffolds remained viable during the 7 day assessment period, with proliferation rates comparable to those observed on tissue culture polystyrene. These data suggest that this novel, yet simple, method is suitable for the production of 3D scaffolds for tissue engineering and regenerative medicine applications.
Co-reporter:Rebecca J. Williams, Ian A. Barker, Rachel K. O’Reilly, and Andrew P. Dove
ACS Macro Letters 2012 Volume 1(Issue 11) pp:1285
Publication Date(Web):October 18, 2012
DOI:10.1021/mz300496q
Well-defined norbornene-functional poly(carbonate)s were prepared by ring-opening polymerization and utilized as multireactive polymeric scaffolds in a range of postpolymerization modifications. The norbornene-functional handles were shown to undergo facile reaction with azides via a 1,3-dipolar cycloaddition, tetrazines in the inverse electron demand Diels–Alder reaction and thiols via radical thiol-ene coupling. Furthermore, the above-mentioned chemistries were demonstrated in a sequential one-pot, three-step modification reaction illustrating the potential of these polymers as scaffolds to access multifunctionalized materials in an undemanding manner.
Co-reporter:Andrew P. Dove
ACS Macro Letters 2012 Volume 1(Issue 12) pp:1409
Publication Date(Web):December 5, 2012
DOI:10.1021/mz3005956
Organic catalysis in ring-opening polymerization (ROP) has become a powerful alternative to more traditional metal-based catalysts. The field has developed to a point at which there are not only excellent low cost and easy to use organocatalysts for day-to-day polymerizations, but the ability to precisely control the synthesis of advanced polymer architectures and ROP monomers that are extremely challenging to polymerize with other catalysts now exists. This viewpoint article will highlight the key advances in organocatalyst design with the aim of encouraging the wider application of organic catalysts in ROP.
Co-reporter:David M. Stevens, Sarah Tempelaar, Andrew P. Dove, and Eva Harth
ACS Macro Letters 2012 Volume 1(Issue 7) pp:915
Publication Date(Web):July 3, 2012
DOI:10.1021/mz300179r
Advanced organocatalytic synthesis methods were employed to prepare linear poly(carbonate)s with control over functional group incorporation and molecular weight. Pendant allyl or epoxide groups served as reaction partners in thiol–ene click or epoxide–amine reactions with ethylene oxide-containing cross-linking groups to form a panel of six novel poly(carbonate) nanosponges with cross-linking densities ranging from 5, 10, and 20% via an intermolecular chain cross-linking approach.
Co-reporter:Nikos Petzetakis, David Walker, Andrew P. Dove and Rachel K. O'Reilly
Soft Matter 2012 vol. 8(Issue 28) pp:7408-7414
Publication Date(Web):14 Jun 2012
DOI:10.1039/C2SM25247C
The aqueous crystallization-driven sphere-to-rod transition of poly(lactide)-b-poly(acrylic acid), PLA-b-PAA block copolymers, with a short homochiral PLA core forming block and a 10 times longer (in terms of degree of polymerization) PAA corona forming block is presented. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) is utilized to follow the kinetics of the transition and wide angle X-ray diffraction (WAXD) to confirm the correlation between degree of crystallinity and morphology. Studies at different concentrations and solvent mixtures provide valuable information regarding the nucleation and growth mechanism of the system, showing that the micelle dynamics are a key aspect of the assembly process. Furthermore, the in situ crystallization-driven cylinder formation during the acrylate ester hydrolysis reaction is demonstrated. Finally, we report that the micelle morphology can be switched between cylinders and spheres by facilitating or blocking the crystallization of the core block, demonstrating a simple method to control the morphology of the resultant assembly.
Co-reporter:Sebla Onbulak, Sarah Tempelaar, Ryan J. Pounder, Ozgul Gok, Rana Sanyal, Andrew P. Dove, and Amitav Sanyal
Macromolecules 2012 Volume 45(Issue 3) pp:1715-1722
Publication Date(Web):January 17, 2012
DOI:10.1021/ma2019528
Co-reporter:Nikos Petzetakis, Andrew P. Dove and Rachel K. O'Reilly
Chemical Science 2011 vol. 2(Issue 5) pp:955-960
Publication Date(Web):15 Feb 2011
DOI:10.1039/C0SC00596G
The synthesis and self-assembly of poly(lactide)-b-poly(acrylic acid) and poly(lactide)-b-poly(dimethylaminoethylacrylate) block copolymers by a combination of ring-opening polymerization and reverse-addition fragmentation chain transfer (RAFT) polymerization is reported. Self-assembly of block copolymers containing enantiopure homochiral poly(lactide), PLA, by a simple direct dissolution methodology results in core-crystallization to afford micelles with a cylindrical morphology. Amorphous atactic PLA cores and conditions that did not promote crystallization resulted in spherical micelles. Cylindrical micelles were characterized by transmission electron microscopy (TEM) with cryo-TEM, small angle neutron scattering (SANS) and angular dependent dynamic light scattering (DLS) proving that the cylindrical morphology was persistent in solution. Manipulation of the assembly conditions enabled the length and dispersity of the resultant cylindrical micelles to be controlled.
Co-reporter:Ryan J. Pounder, David J. Fox, Ian A. Barker, Michael J. Bennison and Andrew P. Dove
Polymer Chemistry 2011 vol. 2(Issue 10) pp:2204-2212
Publication Date(Web):19 Jul 2011
DOI:10.1039/C1PY00254F
The synthesis and ring-opening polymerization (ROP) of an O-carboxyanhydride (OCA) monomer derived from L-malic acid (L-malOCA) is reported. Application of 4-dimethylaminopyridine as catalyst led to the observation of a number of undesirable side products. Investigation of different para-substituted pyridines as catalysts identified 4-methoxypyridine to have the ideal balance of activity and selectivity to enable the controlled ROP of L-malOCA. Deprotection of the benzyl ester side groups of the resultant polymers was achieved by hydrogenolysis and the resulting hydrophilic poly(α-malic acid) was observed to fully degrade within 7 days in aqueous solution.
Co-reporter:Helen Middleton, Sarah Tempelaar, David M. Haddleton and Andrew P. Dove
Polymer Chemistry 2011 vol. 2(Issue 3) pp:595-600
Publication Date(Web):20 Dec 2010
DOI:10.1039/C0PY00227E
The synthesis of astaxanthin-containing poly(lactide)s is reported by the ring-opening polymerization of lactide initiated from residual alcohol groups on astaxanthin using a previously reported thiourea/tertiary amine catalyst. Polymers with molecular weights between 2500 and 30000 g mol−1 are obtained with excellent levels of control, astaxanthin incorporation being confirmed by UV/Vis detected GPC, 1H NMR, MALDI-TOF MS and IR spectroscopic analysis. Study of the polymerizations at extended time periods revealed greatly increased levels of transesterification in comparison to polymerizations initiated by 4-pyrene-1-butanol, attributed to increased intramolecular transesterification side reactions.
Co-reporter:Ian A. Barker;Daniel J. Hall;Claire F. Hansell;Filip E. Du Prez;Rachel K. O'Reilly
Macromolecular Rapid Communications 2011 Volume 32( Issue 17) pp:1362-1366
Publication Date(Web):
DOI:10.1002/marc.201100324
Co-reporter:Ryan J. Pounder, Helen Willcock, Nga Sze Ieong, Rachel K. O′Reilly and Andrew P. Dove
Soft Matter 2011 vol. 7(Issue 22) pp:10987-10993
Publication Date(Web):27 Sep 2011
DOI:10.1039/C1SM06164J
The ring-opening polymerization of 5-(S)-[(benzyloxycarbonyl)methyl]-1,3-dioxolane-2,4-dione (L-malOCA) and 5-(R)-[(benzyloxycarbonyl)methyl]-1,3-dioxolane-2,4-dione (D-malOCA) from poly(ethylene oxide), PEO, macroinitiators using 4-methoxypyridine as the catalyst is reported. The self-assembly of these polymeric amphiphiles was shown to proceed most efficiently by a solvent switch methodology from THF to nanopure H2O. Variation of the block lengths revealed that, as expected, larger block copolymers led to increased micelle dimensions as determined by dynamic light scattering (DLS) and transmission electron microscopy (TEM) and longer hydrophobic blocks led to increased micelle stabilities as determined by measurement of the critical micelle concentration (CMC). Furthermore, the self-assembly of equimolar mixtures of PEO-b-P(L-BMA) and PEO-b-P(D-BMA) resulted in micelles of increased sizes by both DLS and TEM analysis. These micelles also have a CMC value of 5.53 × 10−3 g L−1 which is markedly lower than micelles formed from either enantiopure block copolymer (CMC values = 1.23 × 10−2 g L−1 and 9.78 × 10−3 g L−1 for micelles formed from PEO-b-P(L-BMA) and PEO-b-P(D-BMA) respectively).
Co-reporter:Daniel J. Hall;Helene M. Van Den Berghe
Polymer International 2011 Volume 60( Issue 8) pp:1149-1157
Publication Date(Web):
DOI:10.1002/pi.3121
Abstract
This mini-review provides an introduction to the key work in the area of synthesis and post-polymerization functionalization of maleimide-functional polymers. The versatility and utility of the maleimide group in the efficient functionalization of polymers by both ‘thiol-ene’ Michael addition and Diels–Alder cycloaddition chemistries are highlighted. Copyright © 2011 Society of Chemical Industry
Co-reporter:Sarah Tempelaar, Laetitia Mespouille, Philippe Dubois, and Andrew P. Dove
Macromolecules 2011 Volume 44(Issue 7) pp:2084-2091
Publication Date(Web):March 15, 2011
DOI:10.1021/ma102882v
Well-defined allyl-functional poly(carbonate)s were synthesized via the organocatalytic ring-opening polymerization of 5-methyl-5-allyloxycarbonyl-1,3-dioxan-2-one using the dual 1-(3,5-bis(trifluoromethyl)phenyl)-3-cyclohexylthiourea and (−)-sparteine catalyst system. The resulting allyl-functional poly(carbonate)s obtained showed low polydispersities and high end-group fidelity, with the versatility of the system being demonstrated by the synthesis of block copolymers and telechelic polymers. Further functionalization of homopolymers with degrees of polymerization of 11 and 100 were realized via the radical addition of thiols to the pendant allyl functional groups, resulting in a range of functional aliphatic poly(carbonate)s.
Co-reporter:Matthew J. Stanford and Andrew P. Dove
Chemical Society Reviews 2010 vol. 39(Issue 2) pp:486-494
Publication Date(Web):01 Oct 2009
DOI:10.1039/B815104K
The important advances and current trends in the stereocontrolled ring-opening polymerisation of lactide are discussed in this tutorial review. Microstructures, structural characterisation methods and the properties of stereoregular poly(lactide)s are examined. The application of metal-based catalysts dominates this area although simple anionic polymerisation and organocatalytic routes that demonstrate control of the polymer tacticity are discussed.
Co-reporter:Ryan J. Pounder and Andrew P. Dove
Polymer Chemistry 2010 vol. 1(Issue 3) pp:260-271
Publication Date(Web):05 Jan 2010
DOI:10.1039/B9PY00327D
The recent trends in the synthesis of functional poly(ester)s by ring-opening polymerization (ROP) are reviewed. While the use of ROP processes for the synthesis of poly(lactide), poly(lactide-co-glycolide) and several poly(lactone)s has been well studied, the paucity of functional groups available for further reaction limits their application. Recent efforts to expand this available functionality are reviewed focusing on the application of renewable resources in the synthesis of new monomers and the utilization of click chemistry to provide common intermediate polymers in the manipulation of poly(ester) functionality. In turn these advances are leading to a new generation of precisely controlled nanoparticles comprised entirely of poly(ester)s.
Co-reporter:Jan M. Becker;Ryan J. Pounder
Macromolecular Rapid Communications 2010 Volume 31( Issue 22) pp:1923-1937
Publication Date(Web):
DOI:10.1002/marc.201000088
Co-reporter:Matthew J. Stanford, Robin L. Pflughaupt and Andrew P. Dove
Macromolecules 2010 Volume 43(Issue 16) pp:6538-6541
Publication Date(Web):July 28, 2010
DOI:10.1021/ma101291v
Co-reporter:Ryan J. Pounder and Andrew P. Dove
Biomacromolecules 2010 Volume 11(Issue 8) pp:
Publication Date(Web):July 22, 2010
DOI:10.1021/bm1004355
The synthesis of 3-(S)-[(benzyloxycarbonyl)methyl]-1,4-dioxane-2,5-dione (BMD) and 3,6-(S)-[di(benzyloxycarbonyl)methyl]-1,4-dioxane-2,5-dione (malide) from commercially available l-malic acid is reported. Ring-opening polymerization (ROP) studies of BMD are reported showing that the controlled ROP of this monomer is possible in the absence of transesterification side reactions, despite the presence of side-chain esters, using 1-(3,5-bis(trifluoromethyl)phenyl)-3-cyclohexylthiourea and (−)-sparteine to catalyze the polymerization. The ROP of malide with this system was ineffective. Investigation of the effect of initiating species revealed that the electronic nature of the alcohol had a greater effect on the ultimate molecular weight and hence initiator efficiency than steric considerations. Deprotection of the resultant poly(BMD) using H2 and Pd/C resulted in hydrophilic poly(glycolic-co-malic acid)s (PGMAs) that were able to undergo autocatalytic degradation in dilute H2O solution such that complete degradation was observed within 6 days.
Co-reporter:JanM. Becker Dr.;Sarah Tempelaar;MatthewJ. Stanford;RyanJ. Pounder;JamesA. Covington Dr.;AndrewP. Dove Dr.
Chemistry - A European Journal 2010 Volume 16( Issue 20) pp:6099-6105
Publication Date(Web):
DOI:10.1002/chem.200902518
Abstract
The ring-opening polymerisation of lactide by a range of amino–oxazoline and amino–thiazoline catalysts is reported. The more electron-rich derivatives are demonstrated to be the most highly active and polymerisation is well controlled, as evidenced by the linear relationship between the molecular weight and both the monomer conversion and the monomer-to-initiator ratio. Mechanistic studies reveal significant interactions between the monomer, initiator and catalyst and that the polymerisation is first order with respect to each of these components. These observations indicate that the polymerisation operates by a general base/pseudo-anionic mechanism.
Co-reporter:Matthew J. Stanford and Andrew P. Dove
Macromolecules 2009 Volume 42(Issue 1) pp:141-147
Publication Date(Web):December 11, 2008
DOI:10.1021/ma801977e
The synthesis of stereoregular α,ω-chain end functional linear, telechelic, and star-shaped polymers and copolymers is reported using a one-pot chain end functionalization methodology. Aluminum methyl complexes are applied in combination with functional and multifunctional initiating species to synthesize stereoregular poly(lactide)s by the stereospecific ring-opening polymerization of rac-lactide. The quenching of the reactions with an excess of acid chloride functional molecules has enabled the in situ quantitative modification of the ω-chain ends of the polymers such that primary and secondary alkyl and aryl groups can be incorporated. This methodology has been extended to the synthesis of linear, telechelic, and star-shaped polymers with “click” functional handles for both copper-catalyzed Huisgen 1,3-dipolar cycloaddition and thiol−ene Michael additions and block copolymers through the application of a trithiocarbonate, suitable for mediating RAFT polymerization. This tolerant and mild method is used in the synthesis of star-shaped block copolymers with a biodegradable poly(lactide) core and results in poly(lactide)s that display increased resistance to degradation.
Co-reporter:Ryan J. Pounder, Matthew J. Stanford, Paul Brooks, Stephen P. Richards and Andrew P. Dove
Chemical Communications 2008 (Issue 41) pp:5158-5160
Publication Date(Web):29 Sep 2008
DOI:10.1039/B809167F
The stoichiometric reaction between thiols and maleimide-functional poly(ester)s is demonstrated to be a quantitative, tolerant, mild and efficient method for polymer modification.
Co-reporter:Richard Todd, Gabriel Rubio, Daniel J. Hall, Sarah Tempelaar and Andrew P. Dove
Chemical Science (2010-Present) 2013 - vol. 4(Issue 3) pp:NaN1097-1097
Publication Date(Web):2012/12/12
DOI:10.1039/C2SC22053A
The synthesis and application of a dibenzyl-functionalized bispidine, in combination with 1-(3,5-bis(trifluoromethyl)phenyl)-3-cyclohexylthiourea (TU) co-catalyst, has been demonstrated to be an excellent catalyst for the controlled ring-opening polymerisation (ROP) of lactide and cyclic carbonate monomers. Notably, the polymerisation proceeds with negligible transesterification or epimerisation, with the polymerisation of stereopure L-lactide affording highly crystalline poly(lactide) with a Tm of 156 °C. ROP of racemic lactide results in the observation of a modest degree of stereocontrol such that the probability of isotactic enchainment, Pm = 0.74. Comparison of a range of alternative hydrogen bond donor co-catalysts revealed that TU displayed the highest polymerisation rates in combination with the dibenzyl-functionalized bispidine.
Co-reporter:Ryan J. Pounder, Matthew J. Stanford, Paul Brooks, Stephen P. Richards and Andrew P. Dove
Chemical Communications 2008(Issue 41) pp:NaN5160-5160
Publication Date(Web):2008/09/29
DOI:10.1039/B809167F
The stoichiometric reaction between thiols and maleimide-functional poly(ester)s is demonstrated to be a quantitative, tolerant, mild and efficient method for polymer modification.
Co-reporter:Sarah Tempelaar, Laetitia Mespouille, Olivier Coulembier, Philippe Dubois and Andrew P. Dove
Chemical Society Reviews 2013 - vol. 42(Issue 3) pp:NaN1336-1336
Publication Date(Web):2012/11/15
DOI:10.1039/C2CS35268K
Owing to their low toxicity, biocompatibility and biodegradability, aliphatic poly(carbonate)s have been widely studied as materials for biomedical application. Furthermore, the synthetic versatility of the six-membered cyclic carbonates for the realization of functional degradable polymers by ring-opening polymerisation has driven wider interest in this area. In this review, the synthesis and ring-opening polymerisation of functional cyclic carbonates that have been reported in the literature in the past decade are discussed. Finally, the post-polymerisation modification methods that have been applied to the resulting homopolymers and copolymers and the application of the materials are also discussed.
Co-reporter:Ruairí P. Brannigan and Andrew P. Dove
Biomaterials Science (2013-Present) 2017 - vol. 5(Issue 1) pp:NaN21-21
Publication Date(Web):2016/11/14
DOI:10.1039/C6BM00584E
Polyester-based polymers represent excellent candidates in synthetic biodegradable and bioabsorbable materials for medical applications owing to their tailorable properties. The use of synthetic polyesters as biomaterials offers a unique control of morphology, mechanical properties and degradation profile through monomer selection, polymer composition (i.e. copolymer vs. homopolymer, stereocomplexation etc.) and molecular weight. Within this review, the synthetic routes, degradation modes and application of aliphatic polyester- and polycarbonate-based biomaterials are discussed.
Co-reporter:Vinh X. Truong, Ian A. Barker, Milene Tan, Laetitia Mespouille, Philippe Dubois and Andrew P. Dove
Journal of Materials Chemistry A 2013 - vol. 1(Issue 2) pp:NaN229-229
Publication Date(Web):2012/10/18
DOI:10.1039/C2TB00148A
This work describes the preparation of a new class of in situ-forming poly(carbonate)-graft-poly(ethylene glycol) hybrid hydrogels using ‘thiol–ene’ photoclick chemistry. Morphological study by cryogenic Scanning Electron Microscopy (SEM) revealed that the hydrogels display characteristic macroporous and microporous distributions, the ratio of which can be tuned by varying the length of the poly(ethylene glycol) linker. Controlling the side-chain length of the poly(ethylene glycol) also allows tuning of the equilibrium water uptake, water diffusion, mechanical properties and degradability. Furthermore, we demonstrate that these hydrogels are robust materials with fracture compressive strength in the range of 27–468 kPa and are readily degraded under physiological conditions between 8 and 22 days. The swelling of the gels was also found to be thermoresponsive making them potential candidates for delivery applications.
Co-reporter:Maria Inam, Graeme Cambridge, Anaïs Pitto-Barry, Zachary P. L. Laker, Neil R. Wilson, Robert T. Mathers, Andrew P. Dove and Rachel K. O'Reilly
Chemical Science (2010-Present) 2017 - vol. 8(Issue 6) pp:
Publication Date(Web):
DOI:10.1039/C7SC00641A
Co-reporter:Nikos Petzetakis, Andrew P. Dove and Rachel K. O'Reilly
Chemical Science (2010-Present) 2011 - vol. 2(Issue 5) pp:NaN960-960
Publication Date(Web):2011/02/15
DOI:10.1039/C0SC00596G
The synthesis and self-assembly of poly(lactide)-b-poly(acrylic acid) and poly(lactide)-b-poly(dimethylaminoethylacrylate) block copolymers by a combination of ring-opening polymerization and reverse-addition fragmentation chain transfer (RAFT) polymerization is reported. Self-assembly of block copolymers containing enantiopure homochiral poly(lactide), PLA, by a simple direct dissolution methodology results in core-crystallization to afford micelles with a cylindrical morphology. Amorphous atactic PLA cores and conditions that did not promote crystallization resulted in spherical micelles. Cylindrical micelles were characterized by transmission electron microscopy (TEM) with cryo-TEM, small angle neutron scattering (SANS) and angular dependent dynamic light scattering (DLS) proving that the cylindrical morphology was persistent in solution. Manipulation of the assembly conditions enabled the length and dispersity of the resultant cylindrical micelles to be controlled.
Co-reporter:Vinh X. Truong, Matthew P. Ablett, Hamish T. J. Gilbert, James Bowen, Stephen M. Richardson, Judith A. Hoyland and Andrew P. Dove
Biomaterials Science (2013-Present) 2014 - vol. 2(Issue 2) pp:NaN175-175
Publication Date(Web):2013/10/04
DOI:10.1039/C3BM60159E
A water-soluble azide-functionalised chitosan was crosslinked with propiolic acid ester-functional poly(ethylene glycol) using copper-free click chemistry. The resultant hydrogel materials were formed within 5–60 min at 37 °C and resulted in mechanically robust materials with tuneable properties such as swelling, mechanical strength and degradation. Importantly, the hydrogels supported mesenchymal stem cell attachment and proliferation and were also non-toxic to encapsulated cells. As such these studies indicate that the hydrogels have potential to be used as injectable biomaterials for tissue engineering.
Co-reporter:Matthew J. Stanford and Andrew P. Dove
Chemical Society Reviews 2010 - vol. 39(Issue 2) pp:NaN494-494
Publication Date(Web):2009/10/01
DOI:10.1039/B815104K
The important advances and current trends in the stereocontrolled ring-opening polymerisation of lactide are discussed in this tutorial review. Microstructures, structural characterisation methods and the properties of stereoregular poly(lactide)s are examined. The application of metal-based catalysts dominates this area although simple anionic polymerisation and organocatalytic routes that demonstrate control of the polymer tacticity are discussed.
Co-reporter:Ian A. Barker and Andrew P. Dove
Chemical Communications 2013 - vol. 49(Issue 12) pp:NaN1207-1207
Publication Date(Web):2012/12/18
DOI:10.1039/C2CC38114A
Triarylsulfonium hexafluorophosphate salts were shown to be effective catalysts for the ring-opening polymerisation of various cyclic monomers under UV irradiation. A dual basic/acidic catalytic system demonstrated the potential for UV-triggered formation of poly(δ-valerolactone)-b-poly(L-lactide)-b-poly(δ-valerolactone) in a ‘one-pot’ reaction.
Co-reporter:Ian A. Barker, Matthew P. Ablett, Hamish T. J. Gilbert, Simon J. Leigh, James A. Covington, Judith A. Hoyland, Stephen M. Richardson and Andrew P. Dove
Biomaterials Science (2013-Present) 2014 - vol. 2(Issue 4) pp:NaN475-475
Publication Date(Web):2013/12/18
DOI:10.1039/C3BM60290G
A new class of degradable aliphatic poly(carbonate) resins for use in microstereolithographic process is described. Using a biologically inert photo-inhibiting dye, exemplar 3-dimensional structures were produced using thiol–ene chemistry via microstereolithography. Fabricated constructs demonstrated good biological compatibility with cells and had tensile properties that render them suitable for use as tissue engineering scaffolds.
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