H NMR study of temperature-induced phase transitions in D2O solutions of poly(N-isopropylmethacrylamide)/poly(N-isopropylacrylamide) mixtures and random copolymers

¹H NMR spectroscopy was used to investigate temperature-induced phase transitions in D₂O solutions of poly(N-isopropylmethacrylamide) (PIPMAm)/poly(N-isopropylacrylamide) (PIPAAm) mixtures and P(IPMAm/IPAAm) random copolymers of various composition on molecular level. While two phase transitions were detected for PIPMAm/PIPAAm mixtures, only single phase transition was found for P(IPMAm/IPAAm) copolymers. The phase transition temperatures of PIPAAm component (appears at lower temperatures) are not affected by the presence of PIPMAm in the mixtures; on the other hand, the temperatures of the phase transition of PIPMAm component (appears at higher temperatures) are affected by the phase separation of the PIPAAm component and depend on concentration of the solution. For P(IPMAm/IPAAm) random copolymers, a departure from the linear dependence of the transition temperatures on the copolymer composition was found for a sample with 75 mol% of IPMAm monomeric units.     

Synthesis and characterization of biresponsive graft copolymer gels

Graft copolymer gels with different compositions were prepared by the radical polymerization of N-isopropylacrylamide (NIPAAm) and poly(2-vinylpyridine) (P2VP) macromonomers in dioxane with 1 mol% N,N′-methylenebisacrylamide (BIS) as the crosslinking agent. The graft copolymer gels were analyzed at different temperatures and pH values. They demonstrated the typical swelling behavior for poly(N-isopropylacrylamide) (PNIPAAm) gels with changing temperature. In addition to the temperature dependent measurements, the graft copolymer with a high P2VP content showed a pronounced swelling transition with changing pH value. By separating the temperature and the pH sensitive component, it was possible to obtain a gel which could be swelled independently in response to temperature and pH.     

Preparation and evaluation of thermo-reversible copolymer hydrogels containing chitosan and hyaluronic acid as injectable cell carriers

Poly(N-isopropylacrylamide) end-capped with a carboxyl group (PNIPAM-COOH) was grafted to chitosan for synthesizing thermo-reversible chitosan-g-poly(N-isopropylacrylamide) (CPN), which was further grafted with hyaluronic acid (HA) to form hyaluronic acid-g-CPN (HA-CPN). PNIPAM-COOH, CPN and HA-CPN formed injectable free-flowing aqueous solutions and exhibited reversible sol-to-gel phase transition (above 5% polymer concentration) at 30 °C. Chemical properties and temperature-dependent physical properties of the polymer hydrogels, such as rheological behavior, phase transition kinetics, and water content were characterized in detail. The mechanical stiffness of hydrogels increased with the presence of chitosan in the copolymer, but decreased after conjugation with HA. Chitosan and HA grafting also endowed higher water content and resistance to volume contraction during phase change of the copolymer solution. In vitro cell culture experiments with chondrocytes and meniscus cells in HA-CPN hydrogel showed beneficial effects on the cell phenotypic morphology, proliferation, and differentiation. Progressive tissue formation was demonstrated by monotonic increases in extracellular matrix contents and mechanical properties.     

Photo cross-linkable poly(N-isopropylacrylamide) copolymers III: micro-fabricated temperature responsive hydrogels

Micro-fabricated temperature responsive poly(N-isopropylacrylamide) (PNIPAAm) hydrogels were produced by photolithographic patterning of photo cross-linkable polymers. These polymers were synthesized by copolymerization of N-isopropylacrylamide (NIPAAm) and 2-(dimethyl maleimido)-N-ethyl-acrylamide (DMIAAm). The patterning process of polymers with 9.2 mol% DMIAAm and film thickness below 5 μm in the dry state was able to depict a lateral resolution of 4 μm with insignificant shape change. In order to increase the adhesion of the swollen hydrogels, and thus, the resolution of a particular pattern, a special adhesion promoter based on a monochlorosilane anchor group and a chromophore head group was synthesized. If a silicon wafer surface was pretreated with the adhesion promoter, the structures were stable and well adhered even at lower cross-linking densities. The hydrogels are suitable as working substances for micro-actuators because of their thermally induced volume changes. The swelling ratio of the pattern at low temperatures increased with a decreased cross-linking density. As expected from the chemical composition of the gels, the phase transition temperature (T_c) decreased with increasing DMIAAm content. The swelling of microstructures in water in comparison to macroscopic objects occured significantly faster. This behavior was attributed to the small gel dimension but it was even more pronounced because of the sponge-like nanostructure of the hydrogels characterized by high-resolution field emission scanning electron microscopy. Suitable applications of these hydrogels are adjusting limbs in fluid micro-systems such as micro-pumps and micro-valves.     

Thermo-, and pH dual-responsive poly(N-vinylimidazole): Preparation,characterization and its switchable catalytic activity

A monomer, 2-(isobutyramido)-3-methylbutyl methacrylate (IMMA) was synthesized through a two-step reaction. When a few of IMMA (less than 4 mol%) was copolymerized with N-vinylimidazole (VIm) under free radical polymerization condition, water-soluble P(VIm-co-IMMA) copolymers were obtained. Their structural information was verified and interpreted from ¹H NMR, FTIR and GPC. Kinetic analyses from ¹H NMR demonstrated that one-batch addition of IMMA into the polymerization system led to an inhomogeneous distribution of IMMA units in the copolymers, whereas homogeneous distribution of IMMA units in the copolymers could be obtained through the portion-wise addition of IMMA monomer. The thermal properties of such copolymers were measured by DSC. Compared with PVIm homopolymer, the few IMMA units in the P(VIm-co-IMMA) copolymer had little influence on the T_g values. The obtained P(VIm-co-IMMA) copolymers were thermoresponsive in water, and their phase transition temperatures could be efficiently raised through reducing the IMMA content in the copolymers, raising the addition times of IMMA monomers or lowering the pH of media. Dynamic light scattering analysis showed that unlike the traditional thermoresponsive linear polymers, obvious size shrinkage around the phase transition temperature could not be observed in such P(VIm-co-IMMA) copolymers. Such copolymers could be used as smart organocatalysts in the hydrolysis of p-nitrophenyl acetate. Below the phase transition temperature the reaction rate followed the Arrhenius law, but above the phase transition temperature the reaction rate increased much slower than the prediction from the Arrhenius law. Moreover, the catalytic transition temperature could be tuned through utilizing the P(VIm-co-IMMA) copolymers with different phase transition temperature. The mechanism was discussed accordingly.     

Solid-state phase transition induced by ordering of flexible chain alkylamine in N-ethyl-n-butylammonium 3, 5-dinitrobenzoate monohydrate

A new molecule-based compound, N-ethyl-n-butylammonium 3, 5-dinitrobenzoate monohydrate, which undergoes a reversible solid-state phase transition at 197 K (T_c), has been successfully constructed based on long-chain alkylamine. Specific heat capacity and differential scanning calorimetry (DSC) measurements confirm that it is first-order phase transition with a 5 K thermal hysteresis between heating and cooling scans. Dielectric constants exhibit distinct anomalies around T_c accompanied with step-like responses between low and high dielectric states, which further confirm the phase transition. Variable-temperature single-crystal X-ray diffraction analyses illustrate that the phase transition was elucidated from ordering of the flexible N-ethyl-n-butylammonium cations coupled with reorientational motion of the alkylamine chain.     

Synthesis and thermo-responsive behavior of fluorescent labeled microgel particles based on poly(N-isopropylacrylamide) and its related polymers

Poly(N-isopropylacrylamide) (PNIPAM) microgel particles labeled with 3-(2-propenyl)-9-(4-N,N-dimethylaminophenyl)phenanthrene (VDP) as an intramolecular fluorescent probe were prepared by emulsion polymerization. The thermo-responsive behavior of the VDP-labeled PNIPAM microgel particles dispersed in water was studied by turbidimetric and fluorescence analyses. The transition temperature of the VDP-labeled PNIPAM microgel particles in water determined by turbidimetric analysis was ca. 32.5 °C. The wavelength at the maximum fluorescence intensity of the VDP units linked directly to the microgel particles dramatically blue-shifted around the transition temperature. In addition it gradually blue-shifted even below the transition temperature where there was no change observed in the turbidity. These findings suggest that the gradual shrinking of microgel particles occurs with increasing temperature and the subsequent dramatic shrinking results in the increasing in the turbidity. The transition temperatures of VDP-labeled poly(N-n-propylacrylamide) and poly(N-isopropylmethacrylamide) microgel particles determined by turbidimetric analysis were ca. 23 and ca. 42.5 °C, respectively, and their thermo-responsive behavior was similar to that for the VDP-labeled PNIPAM system. In these three systems the microenvironments around the fluorescent probes above the transition temperatures became more hydrophobic than those below the transition temperature, and the estimated values of microenvionmental polarity around the VDP units on their collapsed states were almost the same.     

Temperature-induced reversible isostructural phase transition in N-isopropylbenzylammonium trifluoromethanesulfonate

A novel organic molecular phase transition material, N-isopropylbenzylamine trifluoromethanesulfonate (1), which displays the reversible tunable dielectric behavior, has been successfully assembled by the intermolecular hydrogen-bonds. It undergoes a first-order solid-to-solid state phase transition at 189.7 K (T_c), being confirmed by thermal analyses including differential scanning calorimetry (DSC), specific heat (C_p) and dielectric measurements. The dielectric constant and dielectric loss of 1 exhibit obvious anomalies and slight tunabilities triggered by heating when the temperature increases approaching to T_c. Variable-temperature single crystal X-ray diffraction demonstrates that the origin of its phase transition may be ascribed to the order–disorder transformation of trifluoromethanesulfonate anions, together with the slight twisting motions of the isopropyl groups in N-isopropylbenzylammonium cation. All the findings make us believe that 1 might be a potential phase transition material.     

Flow and aggregation characteristics of thermo-responsive poly(N-isopropylacrylamide) spheres during the phase transition

To date, a great many researches were focused on improving stimuli-responsive and controlled-release properties of thermo-responsive hydrogel carriers, whereas for the research on flow characteristics during the phase transition, prior reports have not been found. In this paper, poly(N-isopropylacrylamide) (PNIPAM) spheres with thermo-responsive phase transition characteristics were prepared by cross-linked polymerization. In a transparent Pyrex glass pipe with hydrophilic inner wall, flow and aggregation characteristics of PNIPAM spheres during the phase transition from low temperature which was lower than the lower critical solution temperature (LCST) to high temperature (T>LCST) was studied for the first time. Many interesting phenomena about the flow and aggregation behaviors of PNIPAM spheres were found. The velocity of PNIPAM spheres in horizontal pipe decreased from 1.07 cm/s before the phase transition to 0.65 cm/s or even became zero after the phase transition, which is what targeting drug delivery systems desired. When the initial distance was about 5.5 mm at the entrance of testing pipe section, the PNIPAM spheres could aggregate together after the phase transition and subsequently roll forward; but when the initial distance was as large as 8.5 mm, the distance became close at first during the phase transition and then far after the phase transition. Similar results were also found as mentioned above in vertical pipe. When 10 spheres aggregated together, they stopped at a certain position just after the phase transition in horizontal pipe. If the flowrate was more than 40 ml/min, the aggregation configurations such as triangle, tetrahedron, hexahedron and octahedron which formed after the phase transition at flowrate of 20 ml/min disappeared. The results provided valuable information for future applications of thermo-responsive PNIPAM spheres.     

Adsorption of N,N′-dimethylthiourea at a mercury/aqueous solution of NaClO4 interface; dependence on the supporting electrolyte concentration

Adsorption of N,N′-dimethylthiourea (DMTU) on mercury electrode from 0.1, 1 and 5 M NaClO₄ was studied as the function of electrode charge density and adsorbate bulk concentration. In the study, the experimental data obtained from the measurements of differential capacity of double layer were used, the measurements of zero charge potential and surface tension at the zero charge potential. In each system studied the values of the relative surface excess increase with an increase of the concentration of N,N′-dimethylthiourea and NaClO₄. The adsorption parameters were obtained from the Frumkin, virial and modified Flory-Huggins isotherms. It was found that the values of free adsorption energy, interactions constants and integral capacity depends on the supporting electrolyte concentration. The strength of the surface bond formed between N,N′-dimethylthiourea and the electrode surface and the influence of water present on the electrode surface in the obtained results of calculations were discussed.     

pH-Controlled association of PEG-containing terpolymers of N-isopropylacrylamide and 1-vinylimidazole

Temperature- and pH-controlled association of terpolymers of N-isopropylacrylamide (NIPA) with 1-vinylimidazole (VI) and polyethylene glycol (PEG) has been investigated by light scattering and atomic force microscopy (AFM) in situ. The polymers contained 0-15 mol% VI and 0-2 mol% PEG. The phase transition temperatures (T_p) have been in the range of 32-45 °C and exhibited significant dependence on the pH of solution in the pH range between 5 and 8. The T_p of the polymers increased with increasing VI content and with decreasing pH, confirming major effect of VI ionization status on T_p. The presence of PEG grafts in the polymer structure had augmenting effect on the magnitude of pH-responsiveness and on the pH-independent colloidal stability of the polymer particles formed above T_p. Incorporation of VI into the polymer structure had similar, but pH-dependent effect on colloidal stabilization of the polymer particles. The size of the particles formed after the phase transition is driven by the association of the collapsed NIPA segments in the globule conformation and it decreased with decreasing pH. The phase transition temperature of the polymers could be adjusted to increase from temperatures below, to temperatures above body temperature upon decreasing pH from 7 to 6, suggesting that such polymers could provide a material platform for a variety of biomedical applications. AFM analysis in situ showed a fully reversible formation of particles in the solutions of the polymers above their T_p.     

H NMR study of thermotropic phase transitions in D2O solutions of poly(N-isopropylmethacrylamide)/poly(vinyl methyl ether) mixtures

¹H NMR spectroscopy was used to investigate thermotropic phase transitions in D₂O solutions of poly(N-isopropylmethacrylamide) (PIPMAm)/poly(vinyl methyl ether) (PVME) mixtures. In all studied solutions (polymer concentrations c=0.1-10 wt%) two phase transitions were detected at temperatures roughly corresponding to different lower critical solution temperatures of PIPMAm and PVME. While the phase transition of PVME component (located at lower temperatures) is not affected by the presence of PIPMAm in the mixture, the phase transition temperatures of PIPMAm component (located at higher temperatures) are affected by the phase separation of the PVME component. Measurements of ¹H spin-spin relaxation of residual water (HDO) molecules revealed that above the phase transition, a certain portion of water molecules is bound to polymer globular structures. A major part of bound water is present in globular structures of predominating polymer component in the mixture.     

Influence of the acidity level on the electropolymerization of N-vinylcarbazole: Electrochemical study and characterization of poly(3,6-N-vinylcarbazole)

Poly(3,6-N-vinylcarbazole) films were prepared by electrochemical oxidation of N-vinylcarbazole on a Pt electrode using acetonitrile as solvent and tetraethylammonium tetrafluoroborate as electrolyte. The electrosynthesis was carried out by electrical potential cycling in the presence of two different bases: tetraethylammonium benzoate (Bz⁻) and tetraethylammonium phthalate (Ph⁻). These salts were expected to modify the acidity level of the electrolyte since they can act as scavengers for the protons released during the polymerization, when the reaction takes place in the carbazole unit.Products were characterized by cyclic voltammetry, scanning electron microscopy, FTIR spectroscopy, thermogravimetric analysis, differential scanning calorimetry, absorption spectroscopy and four-probe electrical conductivity measurements. Both bases influenced significantly the chemical structure and morphology of the deposited materials. The presence of Ph⁻ in the electrolyte decreases the cross-linking of the electrodeposited polymer, leading to a poly(3,6-N-vinylcarbazole) bearing a more uniform morphology, higher thermal stability and electrical conductivity compared to those of the polymers obtained in the presence of Bz⁻ and without acidity control.     

Toward an understanding of thermoresponsive transition behavior of hydrophobically modified N-isopropylacrylamide copolymer solution

Poly(N-isopropylacrylamide-co-vinyl laurate)(PNIPAAm-co-VL) copolymers were prepared at various feed ratios via conventional radical random copolymerization. The formation, composition ratios and molecular weight of copolymers were examined. The thermoresponsive behaviors of PNIPAAm and PNIPAAm-co-VL solutions at low and high concentrations were intensively investigated by turbidity measurement, Micro-DSC, temperature-variable state fluorescence, ¹H NMR and dynamic light scattering (DLS). Several important results were obtained that (1) incorporation of PVL results in much lower and broader LCST regions of the copolymer solutions, and facilitates the formation of hydrophobic microdomains far below LCST, causing a pronounced aggregation in solutions (2) temperature-variable ¹H NMR spectra shows that during the phase transition, the ‘penetration’ of PNIPAAm into the hydrophobic core is a process accompanied with a transition of isopropyl from hydration to dehydration as well as a self-aggregation of hydrophobic chains at different temperature stages (3) according to the ¹H NMR spectra of polymer solutions obtained at varied temperatures, the microdomains from hydrophobic VL moieties have a different accessibility for isopropyl groups and the entire chains during phase transition (4) temperature-variable DLS demonstrates that the temperature-induced transition behavior of copolymers is supposedly divided into three stages: pre-LCST aggregation (<20 °C), coil-globule transition at LCST (20-25 °C) and post-LCST aggregation (>25 °C).     

N-1-alkylitaconamic acids-co-styrene copolymers. Surface characterization

A serie of six N-1-alkylitaconamic acids-co-styrene copolymers with alkyl groups varying in side chain length from 3 to 12 was used in this study. The surface behaviour of the copolymers has been studied as function of the side chain length. Contact angle data for two of these copolymer surfaces were obtained in water and several liquids. From this information the surface energy was determined. Differences in the wettability of N-1-alkylitaconamic acid-co-styrene are found. The results are discussed in terms of hydrophobic and polar effect of the copolymers. Results on spread monolayers characteristics of these copolymers on water surfaces are also reported. Surface pressure-area (π-A) isotherms on a pure water subphase exhibit a transition region depending on the length of the alkyl side chain of the itaconamic acid moiety. It was also analyzed the phase transition in the monolayer at the air/water interface by brewster angle microscopy (BAM). Molecular mechanics approach was used to obtain predictions about the local interaction energies between segments. It was possible to conclude that the local interaction energies of propyl and decyl derivatives are quite similar while the hexyl derivative has higher interaction energy. The analysis of the coulombic energies together with the dispersion van der Waals energies (VDW) would be indicative, in first approximation, that carbonyl groups are more exposed in the case of propyl than in the other copolymers studied.     

Small angle neutron scattering studies on structural inhomogeneities in polymer gels: irradiation cross-linked gels vs chemically cross-linked gels

A comparison of network structure in a solvent was made for two types of poly(N-isopropylacrylamide) gels cross-linked by chemical reaction with N,N′-methylenebisacrylamide (BIS) (chemical gels) and by γ-ray irradiation (γ-ray gels). The cross-linking density dependence for these gels was examined by small angle neutron scattering (SANS). The SANS results indicated an increase of frozen inhomogeneities with an introduction of cross-links for both chemical and γ-ray gels. However, it was found that the effect of cross-linking is much stronger in the chemical gels than in the γ-ray gels. The differences in the structure were successfully interpreted by a statistical-mechanical theory of gels proposed by Panyukov-Rabin (Phys. Rep. 269 (1996) 1). The degree of polymerization between cross-links, N, was a decreasing function of cross-linking content for both types of gels, while that for the γ-ray gels was a weak function of irradiation dose. Quantitative analyses on BIS concentration and γ-ray dose dependence led to an experimental evidence of the existence of cross-linking saturation threshold.     

Property of diblock copolymer having extremely narrow molecular weight distribution

Molecular weight distribution effect on the morphological behavior of polystyrene-block-polyisoprene (PS-b-PI) diblock copolymers was investigated. PS-b-PI samples were prepared by anionic polymerization and further fractionated by HPLC to obtain the fractions of similar average molecular weight and composition but of narrower distributions in both molecular weight and composition. The strategy is to use reversed-phase LC to fractionate the PI block and normal phase LC to fractionate the PS block with a minimal effect on the other blocks. The interfacial thickness, grain size and the phase transition behavior of the unfractionated and fractionated PS-b-PI were compared by X-ray reflectivity, small angle X-ray scattering, transmission electron microscopy and rheological measurements. The fractionated PS-b-PI with more homogeneous molecular weight and composition exhibits a narrower interface, larger grain size and a sharper morphological transition compared to the unfractionated PS-b-PI.     

Phase diagram of a cellulose solvent: N-methylmorpholine-N-oxide-water mixtures

The phase diagram of the N-methylmorpholine-N-oxide-H₂O mixtures from 0 to 100% has been determined. Three crystalline hydrates have been identified, the already known monohydrate, a dihydrate and a hydrate composed of 8 water molecules per NMMO. The melting temperature of the 8H₂O-NMMO hydrate is −47 °C with a melting enthalpy of about 80 J/g. The region between 25 and 55% of water does not show any crystallisation, but a glass transition around −60 to −100 °C.     

N,N′-alkylated Imidazolium-Derivatives Act as Quorum-Sensing Inhibitors Targeting the Pectobacterium atrosepticum-Induced Symptoms on Potato Tubers

Bacteria belonging to the Pectobacterium genus are the causative agents of the blackleg and soft-rot diseases that affect potato plants and tubers worldwide. In Pectobacterium, the expression of the virulence genes is controlled by quorum-sensing (QS) and N-acylhomoserine lactones (AHLs). In this work, we screened a chemical library of QS-inhibitors (QSIs) and AHL-analogs to find novel QSIs targeting the virulence of Pectobacterium. Four N,N′-bisalkylated imidazolium salts were identified as QSIs; they were active at the μM range. In potato tuber assays, two of them were able to decrease the severity of the symptoms provoked by P. atrosepticum. This work extends the range of the QSIs acting on the Pectobacterium-induced soft-rot disease.     

Micellization and phase transition behavior of thermosensitive poly(N-isopropylacrylamide)-poly(?-caprolactone)-poly(N-isopropylacrylamide) triblock copolymers

Thermosensitive triblock copolymers with two hydrophilic poly(N-isopropylacrylamide) blocks flanking a central hydrophobic poly(?-caprolactone) block were synthesized by atom transfer radical polymerization. Core-shell micellization of the triblock copolymers was inferred from the ¹H NMR spectra derived in two different solvent environments (CDCl₃ and D₂O). The micellar characteristics of these amphiphilic triblock copolymers were studied by pyrene fluorescence techniques, dynamic light scattering and transmission electron microscopy. The critical micelle concentrations of the triblock copolymers were in the range of 4-16 mg/L and the partition coefficients were in the range of 3.10 × 10⁴ to 2.46 × 10⁵. The mean diameters of the micelles, measured by light scattering, were between 90 and 120 nm. The temperature sensitivity of the triblock copolymers was demonstrated by the phase transition of a 250 mg/L aqueous polymer solution at the lower critical solution temperature (LCST). The enthalpy of the phase transition was determined by differential scanning calorimetry. PM3 quantum mechanical calculation method was used to understand the intermolecular interactions between the copolymer and the water molecules. A modular approach was used to simulate the phase transition observed at the LCST.