Thermally reversible polymer gels for biohybrid artificial pancreas

As an approach to replacing islets of Langerhans in an implanted biohybrid artificial pancreas, thermally reversible polymers based on N-isopropylacrylamide were synthesized and then evaluated as an extracellular matrix for islets in an immunoprotecting membrane pouch. A high molecular weight poly(N-isopropylacrylamide-co-acrylic acid (2 mole % in feed)) demonstrated gelation at 37°C and became a solution below 30°C. This polymer exhibited minimum syneresis (water separation) upon gelation from a solution state when the temperature was raised from room temperature to 37°C, while poly(N-isopropylacrylamide) exhibited considerable syneresis under the same conditions. These properties influence the efficiency of islet entrapment. The copolymer was able to entrap rat islets almost 100%, but the homopolymer entrapped less than 50%. The static insulin secretion of the islets in the copolymer matrix at high glucose concentration (16.5 mM) was comparable to that of control islets, however, the entrapped islets showed prolonged viability in vitro. These results indicate the potential of developing a rechargeable biohybrid pancreas using thermally reversible polymer gels.     

Thermally reversible polymer linkages. II. Linear addition polymers

The stepwise addition polymerization reactions of bisazlactones [bis(2-oxazolin-5-one)s] and a variety of 4,4′-bisphenols have been studied for the purpose of making thermally reversible linear polymers. Thus polymerization occurs at or near room temperature, while depolymerization yielding the two monomer species occurs at elevated temperatures. The synthesis of oligomers in solution without the use of catalyst occurs for the reaction of bisazlactones with bisphenols containing an electron-withdrawing moiety between the two phenol groups of the bisphenol. These oligomers regenerate the bisphenol and bisazlactone monomers upon heating to 165–200°C for several hours under dry box conditions. In many cases, these reactions follow the same patterns of reactivity observed in model studies. This chemistry may be useful for forming degradable or recyclable polymers, where shortchain prepolymers, or macromonomers, endcapped with azlactone and phenol moieties could be used to form high molecular weight polymers that are thermoreversible. Such a reaction system might also be used for preventing reactions of bisphenols and/or bisazlactones at low temperatures, with the desired reaction initiated by formation of the reactive species at elevated temperatures. Envisioned uses in this case might be thermally triggered crosslinking or polymerization reactions, or temperature controlled drug release. © 1993 John Wiley & Sons, Inc.     

Tuning reversible supramolecular polymer properties through co-monomer addition

Unlike most low molar mass organogelators, which form strong gels due to the entanglement of strong molecular aggregates such as crystalline fibres, a few reversible supramolecular polymers form viscoelastic solutions due to the formation of both rigid and dynamic filaments. By using three different bisureas which self-assemble according to the same hydrogen-bonding pattern and form such rigid reversible supramolecular polymers, we have shown that it is possible to finely tune the properties of the resulting solutions. The critical temperature below which viscoelastic solutions are obtained and the viscosity of the dilute solutions can be adjusted by changing the co-monomer content. This clearly facilitates gel formulation, which is an important step as far as applications are concerned.

By using three different bis-ureas which self-assemble according to the same hydrogen bonding pattern and form rigid reversible supramolecular polymers, we show that it is possible to finely tune the properties of the resulting viscoelastic solutions.     

Thermally reversible polymer systems by cyclopentadienylation. II. The synthesis of cyclopentadiene-containing polymers

The synthesis of polymers containing either terminal or pendant cyclopentadiene (CPD) groups has been studied. Using information obtained from model studies, the synthesis of polyisobutylenes containing a CPD terminus was accomplished by the use of the tert-butylchloride–dimethylcyclopentadienylaluminum initiator system. Isobutylene polymerization by this system under carefully chosen conditions is essentially transfer free, and termination occurs by cyciopentadienylation. The presence of CPD end group has been established by UV spectroscopy and reaction with maleic anhydride. Selectivity toward termination by cyclopentadienylation increases with decreasing temperatures; at ?41°C and low conversion (<10%) ca. 72% of the polymer chains terminate in this manner. The synthesis of polymers containing randomly distributed pendant CPD groups along the chain has been accomplished by cyclopentadienylating with dimethylcyclopentadienylaluminum chlorobutyl rubber and chlorinated poly(ethylene-co-propylene) (Cl-EPM). Pendant CPD groups undergo Diels-Alder/retro-Diels-Alder condensations yielding thermally reversible networks; e.g., a cyclopentadienylated Cl-EPM was remolded three times to elastic sheets.     

Thermally reversible,covalently crosslinked polyphosphazenes

The concept of thermally reversible crosslinking was investigated by using poly[bis(trifluoroethoxy)phosphazenes] with different percentages of cyclopentadienylethoxy and dicyclopentadienyldiethoxy substituent groups. The resultant structures of these polymers are discussed and the phenomenon of reversible crosslinking is demonstrated by means of a DSC study and solubility behavior.     

Reactive, multifunctional polymer films through thermal cross-linking of orthogonal click groups

The ability to produce robust and functional cross-linked materials from soluble and processable organic polymers is dependent upon facile chemistries for both reinforcing the structure through cross-linking and for subsequent decoration with active functional groups. Generally, covalent cross-linking of polymeric assemblies is brought about by the application of heat or light to generate highly reactive groups from stable precursors placed along the chains that undergo coupling or grafting reactions. Typically, these strategies suffer from a general lack of control of the cross-linking chemistry as well as the fleeting nature of the reactive species that precludes secondary chemistry. We have addressed both of these issues using orthogonal chemistries to effect both cross-linking and subsequent functionalization of polymer films by mild heating, which results in exacting control of the cross-link density as well as the density of the residual stable functional groups available for subsequent, stepwise functionalization. This methodology is exploited to develop a strategy for the independent and orthogonal triple-functionalization of cross-linked polymer thin-films through microcontact printing.     

Thermally reversible C60-based donor-acceptor ensembles

Diels-Alder cycloaddition of anthracene derivatives--bearing fused pi-extended TTFs--to C60 yielded thermally reversible donor-acceptor materials which function as fluorescence switches.     

Ultrathin polymer film formation by collision-induced cross-linking of adsorbed organic molecules with hyperthermal protons

A new synthetic approach for the formation of ultrathin polymer films with customizable properties was developed. In this approach, the kinematic nature of proton collisions with simple organic molecules condensed on a substrate is exploited to break C-H bonds preferentially. The subsequent recombination of carbon radicals gives a cross-linked polymer thin film, and the selectivity of C-H cleavage preserves the chemical functionalities of the precursor molecules. The nature and validity of the method are exemplified with theoretical results from ab initio molecular dynamics calculations and experimental evidence from a variety of characterization techniques. Its applicability is demonstrated by the synthesis of ultrathin polymer films with precursor molecules such as dotriacontane, docosanoic acid, poly(acrylic acid) oligomer, and polyisoprene. The approach is fundamentally different from conventional chemical synthesis as it involves an unusual mix of physical and chemical processes including charge exchange, projectile penetration, kinematics, collision-induced dissociation, inelastic energy transfer, chain transfer, and chain cross-linking.     

Thermally reversible polymer systems by cyclopentadienylation. I. A model for termination by cyclopentadienylation of olefin polymerization

The reaction between tert-butylchloride (t-BuCl) and dimethylcyclopentadienylaluminum (Me₂AlCPD) was studied as a model for initiation by the tert-butyl cation (t-Bu^⊕) and termination by cyclopentadienylation by the Me₂Al(CPD)Cl^? counteranion of isobutylene polymerization. All reaction products formed in this model system have been identified and quantitatively determined. A comprehensive scheme that indicates pathways to these products was developed (scheme III). It is proposed that the predominant product, tert-butylcyclopentadiene (t-BuCPD), arises in the collapse of the t-Bu^⊕-Me₂Al(CPD)Cl^? ion pair, mainly by CPD^? transfer to the tert-butyl cation. The minor products are neopentane (t-BuMe) and isobutylene (i-C₄H₈), which are probably formed, respectively, by Me^? transfer to and proton loss from the t-butyl cation. Cyclopentadienylation selectivity increases by lowering the temperature and extrapolation of results suggests 100% cyclopentadienylation at ?55°C. The t-BuCl/Me₂AlCPD ratio strongly influences the overall reaction pathway. The reaction is first order in t-BuCl with ΔE_a of ca. 7 kcal/mole (1,2-dichloroethane or chlorobenzene solvents, +24 to ?29°C). Indirect evidence indicates that the kinetic product of cyclopentadienylation is 5-t-BuCPD and that this isomer cannot be tert-butylated; that is, the initiation of 5-t-BuCPD polymerization by t-Bu^⊕ is sterically unfavorable. Detailed analysis of the chemistry and kinetics of the t-BuCl/Me₂AlCPD model system holds important clues to the controlled polymerization of olefins leading to macromolecules with cyclopentadiene (CPD) termini.     

Synthesis of multimetallic dendrimers through non-covalent interactions

Hexa-ammonium functionalized Dendriphos ligands and mono-sulfonate functionalized metal complexes have been used as building blocks for the preparation of multimetallic dendritic assemblies. These metallodendrimers consist of a single metal centre surrounded by an oligocationic shell formed by the coordinated Dendriphos ligands and multiple associated anionic organometallic complexes.     

Investigation of thermo-reversibility of polymer crosslinked by reversible covalent bonds through torque measurement

Brominated butyl rubber (BIIR) was crosslinked through an esterification reaction using the sodium salt of dicyclopentadiene dicarboxylic acid (DCPDCA) as crosslinking agent. The crosslinked BIIR could de-crosslink upon heating and re-crosslink upon cooling due to Diels-Alder type reversible de-dimerization/re-dimerization of dicyclopentadiene moieties in the rubber networks. Torque measurement of the crosslinked rubber was conducted at various temperatures using a typical curemeter to investigate the thermo-reversibility. It was revealed that proper temperature for thermal processing of the crosslinked BIIR would be around 174 °C, at which the crosslinked polymer exhibits good flowability and is not too high to induce unexpected side reactions. The torque measurement was also carried out to investigate the efficiency of antioxidant on retarding the loss of the thermo-reversibility of the crosslinked polymer during heating-cooling cycles. It was found that addition of antioxidant 2246 [2,2′-methylenebis(6-tert-butyl-4-methylphenol)] into BIIR could significantly improve the thermo-reversibility of DCPDCA crosslinked BIIR. Torque measurement provides a convenient and sensitive method to understand the thermal behavior of reversible covalent crosslinked polymer.     

Thermally reversible linking of halide-containing polymers by potassium dicyclopentadienedicarboxylate

A novel crosslinker for thermally reversible covalent (TRC) linking of halide-containing polymers is suggested. Chlorine-containing polymers such as chloromethylstyrene copolymers, chlorinated polypropylene, polyvinylchloride, chlorinated polyisoprene, and polyepichlorohydrin were crosslinked with potassium dicyclopentadienedicarboxylate (KDCPDCA). The crosslinker was prepared by reacting potassium ethoxide with dicyclopentadienedicarboxylic acid. Because of the low solubility of KDCPDCA in organic solvents, a phase transfer catalyst, benzyltrimethyl-ammonium bromide, was employed for the crosslinking reaction. The crosslinking reaction occurred at a higher rate in a polar solvent, such as dimethylformamide, than in a nonpolar one, such as toluene, and was affected by the nature of the chlorine-containing polymer. Some of the polymers crosslinked even at room temperature. The chain-extending reaction between KDCPDCA and a α,ω-dihalide compound such as α,α′-dichloro-p-xylene, 1,4-dichlorobutane, or 1,4-dibromobutane also was carried out to obtain linear oligomers. The IR spectra indicated that the crosslinking and chain-extending reactions were based on the esterification between the halide carbon bonds of the polymer and the COOK groups of KDCPDCA. The flowability at 195 °C and solubility on heating in a dichlorobenzen-maleic compound mixture of the crosslinked polymers indicated that the TRC crosslinking occurred via the reversible Diels–Alder cyclopentadiene/dicyclopentadiene conversion as long as the polymer was thermally stable and did not contain olefinic CC bonds. The TRC linking also was confirmed by the rapid decrease of the specific viscosity of the obtained linear oligomers on heating. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 4390–4401, 1999     

Preparation of polymer microspheres from solutions

Polymer microspheres are obtained by the dropwise addition of a precipitant, containing a polymeric stabilizer, into a polymer solution, containing a polymeric stabilizer. The polymer and stabilizer concentrations, the stirring speed, and the precipitation temperature determine the size and size uniformity of the microspheres. Seven polymer microspheres of polyimide, poly(ether imide), poly(ether ketone), poly(phenylene oxide), polysulfone, poly(vinylidene fluoride), and cellulose diacetate have been prepared with dimethylacetamide as the solvent, with water as the precipitant, and with poly(vinyl alcohol) as the stabilizer. The size and size uniformity of the obtained microspheres are d = 2.3–25.7 μm and ? = 0.15–0.50, respectively (? = σ/d, where ? is the dispersion coefficient, d is the average diameter, and σ is the standard deviation of the diameter). © 2002 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 41: 159–165, 2003     

Supramolecular self-assembly of dendronized polymers: reversible control of the polymer architectures through acid-base reactions

Acid-base switchable supramolecular dendronized polyacetylenes (DPAs) with increasing steric bulk on going from generation one [G1] to three [G3], were constructed using multiple self-assembly processes between Fréchet-type [G1]-[G3]-dendritic dialkylammonium salts and a dibenzo[24]crown-8-containing polymer. The formation of the supramolecular systems is acid-base switchable to either an ON (rodlike dendronized polymers) or an OFF (flexible polymers) state. Thus, by controlling the superstructures of the supramolecular polymers with the [G1]-[G3] dendrons, it is possible to induce conformational changes within the polymer backbones. The supramolecular dendronized polymers, as well as their threading-dethreading properties, were characterized by (1)H NMR and UV absorption spectroscopies, gel permeation chromatography (GPC) and light scattering (LS). Independent measures of molecular weight (GPC, LS) indicate that DPAs behave as increasingly rigid macromolecules with each generation in solution. Molecular dynamics simulations of each DPA suggest that the lengths of the polymer backbones increase accordingly. Atomic force microscopy of the [G3]-dendronized polystyrene (DPS), as well as the DPAs, reveal surface morphologies indicative of aggregated superstructures.     

Preparation of thermosensitive polymer nanoparticles by protein-mimetic cross-linking

Thermosensitive nanoparticles were prepared by mimicking protein folding where polymer aggregates were formed by precipitation of thermosensitive polymer chains followed by disulfide formation of their thiol groups. N-Isopropylacrylamide (NIPAM) and methacryloxy succinimide (SuMA) were co-polymerized and then cysteamine was allowed to react with succinimide moieties of the polymer to render thiol moieties. A polymer aqueous solution precipitated to form nano-sized aggregates by increasing temperature above its lower critical solution temperature (LCST), and their sizes were monodispersed and tunable by the polymer concentration. The aggregates were cross-linked to produce nanoparticles by oxidation of thiol groups in a manner similar to formation of a disulfide bond of protein. As a result, the cross-linked nanoparticles exhibited swelling by decreasing temperature below the LCST of the copolymer. Fluorescein and bovine serum albumin (BSA) were chosen as a small and a large substance, respectively, and were encapsulated into the swollen nanoparticles at 25?°C. Fluorescein was rapidly released from both swollen and shrunken nanoparticles. Although BSA exhibited little release at any temperatures, it was released from nanoparticles by adding the reducing agent to dissociate the disulfide cross-linking and incubating below the LCST.