Synthetic thermally reversible gel systems. VI

Forming and conditioning thermally reversible aqueous gels of polyacrylyglycinamide (PAG) at various temperatures has little effect on either the melting point (T_m) of the gels or the heat of crosslinking (ΔH_c) except at temperatures where partial hydrolysis can occur. This is added evidence that unlike with gelatin, crystallite formation does not play a role in gel formation. For unfractioned PAG, the linear relationship between the logarithm of molecular weight and 1/T_m predicted and observed for gelatin gels, does not hold. With mixed gelatin-PAG gels, a gelatin/PAG ratio of ≥4 completely inhibits the formation of a PAG gel network. At lower gelatin/PAG ratios, the PAG network forms, and if gelatin is considered as an inert diluent, normal values for the melting points and ΔH_c for PAG gels are observed. At a gelatin/PAG ratio of 4, the presence of PAG reduces the ΔH_c for the gelatin gel by inhibiting the formation of as large or as ordered crystallite crosslinks. To reconcile the problem of aggregation preceding gelation one can assume that M?_w of an aggregate is a linear function of C². If this is done, the same relationship which normally relates C with T_m is obtained. The equilibrium swelling of PAG films in water at 25°C is markedly molecular weight-de-pendent and can vary from below 5 to about 40 wt-% polymer at equilibrium. It has been found that long-term dark storage of dry samples of PAG under ambient temperature conditions results in pronounced decreases in the intrinsic viscosities of their aqueous solutions. It is speculated that this results from weak links, perhaps peroxy, in the polymer backbone. The possible relationship of this phenomenon to the slow stage of the viscosity deterioration of aqueous polyacrylamide solutions is pointed out. The higher viscosity of low DP PAG in 2M NaCNS compared to H₂O and the larger percentage increse of [η] with increasing temperature in the latter, verify the greater solvent power of 2M aqueous thiocyanate for PAG. At a concentration level of 3%, aqueous PAG solutions are almost Newtonian whereas at higher concentrations (5%), the viscosity decreases appreciably with increasing rates of shear. The copolymerization of AG with isopropylacrylamide has been studied and the somewhat unusual results discussed. Copolymers containing an AG mole fraction greater than 0.40 do not exhibit a cloud point up to 100°C. If the isopropylacrylamide mole fraction approaches 0.60, the solutions do not gel down to 0°C. This ability to prepare copolymers over a narrow composition range that neither gel or undergo phase separation in the temperature range 0–100°C is probably related to the random distribution of monomer units in the copolymer backbone.     

Synthetic thermally reversible gel systems. III

Polyacrylylglycinamide (PAG) and its thermally reversible aqueous gels have been investigated and comparisons made with gelatin. For unfractionated PAG homopolymers in 2M NaCNS at 25°C, the Mark-Houwink-Sakurada equation is [η] = 1.16 × 10^?3 M?_n^0.52. The Huggins k′ value is found to be about 0.9 and the Flory-Huggins polymer-solvent interaction parameter, 0.49. A theoretically calculated value of K_θ is very close to the experimental one and it is for this reason and the observed μ and M?_n exponent values that 2M NaCNS at 25°C approaches being a θ solvent for PAG. A thermodynamic approach based on equilibrium swelling and modulus measurements indicates that a single thermally reversible crosslink in a gelatin gel involves numerous peptide backbone units, whereas in PAG gels a crosslink perhaps involves only one residue from each of two chains. These results complement the very high exothermic heat of gelation crosslinking, δH_c, for gelatin compared to PAG. ΔH_c has been measured on PAG samples of different DP and found to be independent of chain length. Similar measurements on acrylylglycinamide copolymers and terpolymers containing basic and acidic groups produce no change in δH_c so that coulombic forces do not appear to be significant. Data are also included relating to the density of PAG, its glass transition and thermal decomposition temperature, the tensile modulus of equilibrium-swelled PAG films in water and the chain-transfer constant of methanol with the acrylylglycinamide free radical.     

Synthetic thermally reversible gel systems. VII

Polymethacrylylglycinamides (PMG), like polyacrylylglycinamides (PAG), form thermally reversible aqueous gels, but higher molecular weights and/or concentrations are required and the melting points of the gels are lower. The heats of crosslinking for aqueous PMG gels fall in the range of ?5 to ?10 kcal/mole of crosslinks, the same as for aqueous PAG gels, implying that the crosslinks are chemically similar. PMG and PAG are incompatible with each other but both are individually compatible with some types of gelatin. The solubilities of PMG and PAG are similar. Various reagents, however, affect PMG and PAG gels in quite different manners. Aqueous PMG solutions, just outside conditions required for gelation, are rheopectic. Intrinsic viscosities [η] of PMG in 2M NaCNS are about 2.5 times those in water. The Huggins' k′ value for PMG in 2M NaCNS has a value of 0.39–0.40, and both it and [η] are essentially temperature-independent over the range 25–45°C. In water at 25°C for PMG, k′ has an average value of about 1.4. With increasing temperature, for H₂O, there is a considerable increase in [η] which is accompanied by a decrease in the value of k′. Osmotic molecular weight measurements on unfractionated PMG in H₂O at 40°C yield π/c versus c plots having essentially zero slope, implying a value of close to zero for the second virial coefficient, a value of about 0.5 for the polymer–solvent interaction parameter, and a condition close to a θ condition. An approximate viscosity–M _n relationship for polydisperse PMG is [η]_{2M NaCNS, 25deg;C} = 1.7 × 10^?8 M _n^1.5. The low value of K and high value of the exponent do not result from large differences in polydispersity but rather from a stiff, rodlike configuration in solution. This steric hindrance to rotation also manifests itself in the extreme brittleness of PMG films and in a ΔH_p for homopolymerization of only ?6 kcal/-mole. The infrared spectra of MG monomer and PMG are recorded as well as the density and refractive index for PMG. PMG has a glass transition at 226°C by DTA and by TGA, thermal decomposition sets in at about 300°C. From copolymerization with acrylic acid, values of 1.66 and +0.06, respectively, were obtained for the resonance factor Q and the electrical factor e for MG monomer.     

Synthetic thermally reversible gel systems. IV

The polymerization kinetics in water of acrylylglycinamide (AG) initiated by K₂S₂O₈ was studied over the temperature range 40.0 to 60.0°C. Monomer concentration was varied from 7.8 × 10^?3 to 31.2 × 10^?3M and catalyst from 1.85 × to 11.10 × 10^?5M. The rate expression is ?d[M]/dt = R_p, = k_1.22[K₂S₂O₈]^0.5[M]^1.22, and the overall empirical rate constant, k_1.22 = 1.14 × 10¹¹e^?15,800/RT 1.^0.72 mole^?0.72 min^?1. To explain the dependence on monomer, a kinetic scheme which includes a bimolecular reaction (k₂) between monomer and initiator is suggested. The simplified expression which describes the initial rate of polymerization is: ?d[M]/dt = R_p, = k₄(2[I]/k₅)^1/2[M](k₁ + k₂[M])^1/2, where k₁, k₂, k₄ and k₅ are rate constants for S₂O₈ = decomposition, a bimolecular reaction between monomer and initiator, propagation, and termination, respectively. Individual bimolecular rate constants are expressed in liter/mole-min. The equation predicts a dependence on monomer concentration between 1.0 and 1.5 with 1.5 being approached a t high monomer concentrations. Plots of R_P²/[M]² versus [M] are linear, as predicted by the postulated reaction route and values for k₂ and k₄/k₅^1/2 were obtained from the slopes and intercepts of these plots. The temperature dependence of the bimolecular monomer-initiator reaction is k₂ = 5.19 × 10²¹e^?36,000/RT. Instead of the usual behavior, the k₄/k₅^1/2 ratio was found to decrease with temperature and the difference of activation energies, (E₄ ? E₅/2), is ?1.50 kcal. The temperature dependence of the propagation to square root of the termination rate constant ratio is k₄/k₅^1/2 = 6.16e^1500/RT. These rather unusual results may be related to the ability of AG polymers in water to form thermally reversible gels; even above the gel melting points, the polymers are considerably aggregated in solution. This would tend to make the bimolecular termination reaction more temperature dependent and also account for the high values (59–69) for the k₄/k₅^1/2 ratios. For similar temperatures, the overall rate constants for AG are approximately four times those for acrylamide.     

Synthetic thermally reversible gel systems. V

Differential thermal analysis has been used to study the fusion of aqueous thermally reversible gels of gelatin and polyacrylylglycinamide (PAG). In the case of gelatin gels, endotherms close to the melting point are readily observed and these are sometimes preceeded by a small exothermic heat of gel reorganization. Calculations are presented to show that breaking of the gelatin gel network requires only a small fraction of the observed endothermic heat of fusion and that most of the heat is required for melting larger crystallites within gelatin aggregates and for perhaps a helix → coil transition. Failure to observe endotherms by DTA over the known temperature range of fusion of PAG gels is consistent with prior measurements and conclusions. The noncrystallinity of PAG gels and soluble aggregates together with a heat of crosslinking of only ?5 to ?10 kcal/mole of crosslinks places the heat of fusion of PAG gels outside the lower limits of DTA sensitivity.     

Synthetic thermally reversible gel systems. VIII. Poly(vinyl chloride)–dioxane

When interpreted by network theory, equilibrium swelling measurements on poly-(vinyl chloride) (PVC) film in dioxane and moduli measurements on the equilibrium swelled films yield values for the approximate molecular weight between thermally reversible crosslinks and for the number of these crosslinks per polymer chain. These values are in reasonable agreement with the thermodynamic analysis of PVC–dioxane gels by Takahashi, Nakamura, and Kagawa and with the premise that three-dimensional network formation in these gels occurs by crystallization of a very limited number of syndiotactic sequences per chain having a sequence length of between 8 and 10. Failure to observe fusion endotherms by DTA on PVC–dibutyl phthalate gels supports the view that PVC gels have a low crystalline crosslink density and a low heat of crosslinking. The heat of crosslinking obtained by the method of Eldridge and Ferry shows only moderate agreement with expectations based on the heat of fusion of PVC and the number of repeating units per PVC chain passing through a crystalline crosslink in a PVC–dioxane gel.     

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.     

Melting temperatures of thermally reversible gels IV. Methyl cellulose-water gels

Summary The gel/sol transition temperatures (T _m ^g ) were measured by cooling of thermally reversible methyl cellulose (MC)-water gels using the ten MC samples. A linear relationship between 1/T _g ^m and the logarithm ofv ₂ x was found for each MC gel, wherev ₂ is the volume fraction of MC andx the degree of polymerization. The X-ray diffraction patterns of both MC films and gels revealed that the network junction points of the MC gels are crystalline and consist of trimethyl glucose units. The heat of fusion of trimethyl cellulose was estimated as 2.6 × 10³ J/mol, and entropy of dilution parameter = –1.6 and = 320 K were also evaluated. Using these values, the gel/sol transition temperature was analysed according to our previous theory. It is concluded that the network junction points of MC gels are between 4 and 8 units long and also that the length is in good agreement with the sequence length estimated from the methoxy content of MC.

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Zusammenfassung Die Umwandlungstemperaturen (T _g ^m ) Gel/Sol von zehn Methylzelluloseproben (MC) wurden an dem Abkühlungsverhalten von reversiblen Methylzellulose-Wasser-Gelen untersucht. Ein linearer Zusammenhang zwischen 1/T/ _g ^m und den logarithmischenv ² x-Werten wurde für jedes MC-Gel gefunden, worinv ² die Volumenfraktion von MC undx den Polymerisationsgrad bedeuten. Die Röntgendiagramme von beiden, MC-Film und MC-Gel, weisen darauf hin, daß die Verzweigungspunkte vom MC-Gel Kristallite sind und diese aus Trimethylglukosegrundbausteinen aufgebaut werden. Die Schmelzwärme der Trimethylglukose wurde zu 2.6 × 10³ J/mol geschätzt, und der Wechselwirkungsparameter sowie die Theta-Temperatur wurden als = –1.6 und = 320 K berechnet. Nimmt man diese Werte an, so kann man die Gel/Sol-Übergangstemperaturen nach unserer früheren Theorie bestimmen. Daraus läßt sich folgern, daß die Verzweigungspunkte von MC-Gel zwischen 4 und 8 Bausteinen lang sind und daß dies auch mit der bezüglichen Sequenzlänge, die aus dem Methoxygehalt abgeschätzt werden kann, übereinstimmt.

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With 5 figures and 4 tables     

Photochemically reversible and thermally stable axially chiral diarylethene switches

A series of dithienylcyclopentenes containing axially chiral 1,1'-binaphthyl units were successfully synthesized by a Suzuki-Miyaura protocol. All these compounds exhibited photochemically reversible isomerization with thermal stability in both organic solvent and a liquid crystal (LC) host. When doping into an achiral LC host, some of them exhibited very high helical twisting powers. Reversible reflection wavelength tuning in the visible region and LC phase switching between nematic and cholesteric upon light irradiation were demonstrated.     

Radiation preparation and diffusion behavior of thermally reversible hydrogels

Temperature sensitive PolyNIPAAm hydrogels in the form of rod were prepared from the binary system of NIPAAm/water and ternary system of NIPAAm/Bis/water by γ-irradiation with ⁶⁰Co source at room temperature, respectively. The prepared hydrogels had obvious temperature sensitivity (LCST is about 35.0 °C) and suitable mechanical properties. The incorporation of cross-linking agent, N, N′-methylene-bisacrylamide (Bis), into the binary system of monomer/water reduced the gelation dose. The maximum swelling ratio of hydrogels was decreased with the increasing of dose or the incorporation of Bis. The diffusion behavior of water in hydrogels obtained in this work was investigated. In addition, the drug delivery of fluoro uracili (Fu-5) from the hydrogels was investigated.     

Emulsion procedures for thermally reversible covalent crosslinking of polymers

Quaternization and dequaternization of tertiary amine compounds were employed to obtain thermally reversible ionene networks from aqueous colloidal polymer dispersions prepared via emulsion polymerization. Chlorine‐functionalized polymers prepared via the emulsion copolymerization of styrene (St), butylacrylate (BA), or both with chloromethylstyrene, and amino‐functionalized polymers prepared via the emulsion copolymerization of St, BA, or both with 2‐(dimethylamino)ethylacrylate or 4‐vinylpyridine, were reacted without polymer separation, with a ditertiaryamine crosslinker and a dihalide crosslinker, respectively, to obtain crosslinked polymers. Crosslinked polymers were also obtained via the reaction of a chlorine‐functionalized polymer dispersion with an amino‐functionalized polymer dispersion or via the drying of the polymer blend prepared from the two kinds of dispersions. Reactive solubility experiments, flowability investigations (by thermocompression at ca. 215 °C), IR, and ¹H NMR analyses of the obtained crosslinked polymers indicated that the generated ionene bridges dequaternized on heating and requaternized on cooling. In comparison with solution crosslinking, no organic solvent was employed, and simple procedures were required for the preparation of the thermally reversible covalent crosslinked polymers. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 4373–4384, 2000     

Synthetic studies toward pectenotoxin 2. Part II. Synthesis of the CDE and CDEF ring systems

A convergent synthesis of the CDE and CDEF ring systems of pectenotoxin-2 from C and F ring precursors is described.     

Relaxation of a viscoelastic gel bar: II. Silica gel

Silica gel is shown to be elastic in the presence of dry alcohol, but viscoelastic (VE) in aqueous media; the rate of VE relaxation increases with the concentration of water. At 25 vol% water in ethanol, the rate of viscoelastic relaxation decreases with pH, approaching zero (i.e., elastic behavior) at pH 1.5. Elastic behavior is also seen in methanol, but VE relaxation is rapid upon addition of 1% triethylamine. It is concluded that VE relaxation results from attack by the liquid on siloxane bonds in the gel network. The kinetics of relaxation are well described by the theory presented in Part I.     

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.     

Synthetic approaches to cularines. II. Ullmann condensation

The first total syntheses of O-methylcularicine 9b and sarcocapnine 9c are described together with a new synthesis of cularine 9a using the Ullmann condensation reaction of the appropriate 2′-bromo-8-hydroxy-tetrahydrobenzylisoquinoline formed by phase-transfer alkylation of Reissert compound 2. When this strategy was combined with the lead tetraacetate treatment of the tetrahydrobenzylisoquinoline it yielded 4-hydroxycularines, from which highly oxidized members of the family can be obtained. This is exemplified by the first synthesis of 4-hydroxysarcocapnine 19 and its transformation to the 3,4-dioxoisocularine yagonine 20 , rearrangement of which afforded the aristoisocularine aristoyagonine 21.     

Density gradient electrophoresis of cells in a reversible gel

Density gradient electrophoresis permits the separation of cell types according to surface charge density with high resolution. Any source of flow compromises the resolving power of density gradient electrophoresis. Although procedures have been devised to successfully counteract electroosmotic and convective flows, the final collection of separands requires that they be pumped out of the electrophoresis column. Experiments were therefore designed to test the hypothesis that this flow could also be eliminated by trapping the separated bands in a gel, from which they could be collected by slicing the gel cylinder. Glutaraldehyde-fixed rat and rabbit erythrocytes were used as test particles in a phosphate-buffered isotonic Ficoll-sucrose density gradient in a 2.2 cm diameter, thermostated vertical glass column that could be opened at both ends. Two types of agarose were used as gel polymers: Electrophoresis grade agarose (J.T. Baker Chemical Co.) at final concentrations of 0.1 to 0.25% and SeaPrep ultralow gelling agarose (Marine Colloids Div., FMC Corp.) at a final concentration of 1.0%. Electrophoretic separability of the test particles and fluid stability were tested independently at 55 degrees C and 32 degrees C at which the two agaroses were, respectively, liquid. The experiments demonstrated that the higher temperatures required and the presence of agarose compromised neither the stability of the density gradient nor the migration properties of the cells, and cells can be separated in a sol at a temperature that is compatible with cell viability.     

Synthesis and characterization of thermally reversible macroporous poly(N-isopropylacrylamide) hydrogels

Macroporous hydrogels are characterized by large pore sizes, high pore volumes, and high specific surface area. Besides these characteristics, macroporous hydrogels based on thermally reversible polymers respond to temperature changes much faster than hydrogels prepared by a conventional method. Crosslinked poly(N-isopropylacrylamide) (polyNIPAAm) forms a thermally reversible hydrogel which shows a lower critical solution temperature (LCST) ca. 33°C in aqueous solutions. We have synthesized thermally reversible polyNIPAAm hydrogels having macroporous structures by a new method. These macroporous hydrogels have large pore volumes, large average pore sizes, and faster macromolecule permeation rates in comparison to conventional polyNIPAAm hydrogels synthesized by a conventional method. Compared with conventional polyNIPAAm hydrogels, the macroporous polyNIPAAm hydrogels have higher swelling ratios at temperatures below the LCST and exhibit faster deswelling and reswelling rates. The deswelling rates are especially rapid. These thermally reversible macroporous hydrogels may be very useful in controlled active agent delivery and toxin removal, as well as dewatering of solutions. Peptides or proteins may behave as if they were in bulk solution within the large aqueous pores, and this may reduce their inactivation when such gels are used for their storage and later release. The gels may also be useful in microrobotic devices due to their fast response to temperature. © 1992 John Wiley & Sons, Inc.     

Nonoscillation in closed reversible chemical systems

For a closed reversible chemical system obeying mass action kinetics, we prove that structurally stable closed orbits do not exist if there are no more reaction steps than reactants. We derive this using an appropriate Lyapunov function for a special case in which the number of reaction steps equals the number of reactants and a stationary point is shown to be unique and asymptotically stable.