盐酸艾司洛尔异丙酰胺化合物杂质的合成

目的合成盐酸艾司洛尔原料药中异丙酰胺化合物杂质。方法以3-[4-(2,3-环氧丙氧基)苯基]丙酸甲酯、异丙胺为原料,二甲苯为溶剂合成杂质异丙酰胺化合物。结果所合成的异丙酰胺化合物杂质的结构经红外、紫外、氢谱(H-NMR)和质谱(MS)确证,纯度经HPLC检测可达98.0%以上。结论合成了盐酸艾司洛尔中的异丙酰胺化合物杂质,可作为盐酸艾司洛尔原料药质量控制的杂质对照品。

二氯异丙虫酰胺的高效液相色谱分析

建立了二氯异丙虫酰胺的高效液相色谱分析方法。样品用乙腈溶解,采用Agilent TC-C18柱为色谱柱,V(乙腈)∶V(水)=50∶50为流动相,PDA检测器在245 nm对二氯异丙虫酰胺进行高效液相色谱分离和检测。方法在13.6~680μg/mL的浓度范围内线性关系良好,线性回归方程为y=22659x-15086,相关系数R^(2)=0.9999,变异系数为0.37,平均回收率为99.9%。该方法简单可靠,精密度及准确度符合定量分析要求,可用于二氯异丙虫酰胺的定量分析。

磺酸基甜菜碱共聚物的合成及其界面活性研究

以N-[3-(二甲氨基)丙基]丙烯酰胺与1,3-丙磺酸内酯为原料,制备了3-[(3-丙烯酰胺)丙基-二甲氨基]丙磺酸钠甜菜碱型单体,并将其与丙烯基聚乙二醇通过自由基聚合物反应合成了磺酸基甜菜碱和聚乙二醇的共聚物。利用红外光谱(FT-IR)和凝胶渗透色谱仪(GPC)对共聚物进行表征,并考察了在高浓度CaCl2条件下该共聚物作为转向剂的界面性质变化。结果表明,在高盐的水溶液中,该共聚物仍然具有很好的稠化能力,是一种潜在的抗Ca^2+稠化剂。

Preparation of Hollow Silica Microspheres via Poly（N-isopropylacrylamide）

Core-shell structured SiO2/poly（N-isopropylacrylamide） （SiO2/PNIPAM） microspheres were successfully fabricated through hydrolysis and condensation reaction of tertraethyl orthosilicate （TEOS） on the surface of PNIPAM template at 50 ~C. The PNIPAM template can be easily removed by water at room temperature so that SiO2 hollow microspheres were finally obtained. The transmission electron microscope and scanning electron microscope observations indicated that SiO2 hollow microspheres with an average diameter of 150 nm can be formed only if there are enough concentration of PNIPAM and TEOS, and the hy- drolysis time of TEOS. FTIR analysis showed that part of PNIPAM remained on the wall of SiO2 because of the strong interaction between PNIPAM and silica. This work provides a clean and efficient way to prepare hollow microspheres.

Rheological property and drying mechanism of thermoresponsive gelcasting of ZnO

To solve the problem of drying gelcast green body, the thermoresponsive gel system which contains macromonomer graft chains was used in gelcasting of ZnO. The effects of the amount and length of graft chains macromonomer PIPAAm, the total amount of organic matters, and the solid loading on the rheological properties of suspensions were investigated, and the drying mechanism of gelcast green body was analyzed. The results show that ZnO suspensions with the gel system still display shear- thinning rheological behavior, but its viscosity increases with increasing the addition amount and relative molecular mass of PIPAAm graft chain, and the total organic matter content. The PIPAAm graft chains inhibit or even eliminate the formation of the ＂dense layer” on the surface of gelcast ZnO green bodies, and accelerate the drying of green bodies. The introduction of PIPAAm graft chains facilitates the shrinkage of the gelcast ZnO green bodies, which is a feasible method to increase the relative density of green bodies.

Rheological behavior of ZnO suspension with thermosensitive poly(N-isopropylacrylamide) for colloidal processing of ceramics

Novel colloidal processing using thermosensitive poly（N-isopropylacrylamide） （PNIPAM） as a coagulating agent has beendeveloped to prepare complex-shaped ceramic components. In this work, the properties of PNIPAM aqueous solutions and therheological behavior of ZnO suspensions with PNIPAM were investigated. The results show that the PNIPAM solutions exhibitobvious thermosensitivity and its transition temperature is around 32℃. When the temperature is above 40℃ （Tc, the criticaltransition temperature of thermosensitive suspension）, the 50% ZnO （volume fraction） suspension with 8 mg/mL PNIPAM has asharp increase in viscosity and reaches up to 11.49 Pa·s at 50℃, displaying strong elasticity. The main reasons are the increase ofeffective volume fraction attributed to precipitation of PNIPAM segments and the flocculation between ZnO powder particles. Inaddition, the maximum solid loading （volume fraction） at 20 ℃ is higher than that at 40℃, which proves that the phase transition ofPNIPAM can induce the flocculation of suspension.

A Temperature-sensitive Hydrogel Refolding System: Preparation of Poly(N-isopropyl acrylamide) and Its Application in Lysozyme Refolding

Temperature-sensitive hydrogel—poly(N-isopropyl acrylamide) (PNIPA) was prepared and applied to protein refolding. PNIPA gel disks and gel particles were synthesized by the solution polymerization and inverse suspension polymerization respectively. The swelling kinetics of the gels was also studied. With these prepared PNIPA gels, the model protein lysozyme was renatured. Within 24h, PNIPA gel disks improved the yield of lysozyme activity by 49.3% from 3375.2U·mg^-1 to 5038.8U·mg^-1. With the addition of faster response PNIPA gel beads, the total lysozyme activity recovery was about 68.98% in 3h, as compared with 42.03% by simple batch dilution. The novel refolding system with PNIPA enables efficient refolding especially at high protein concentrations. Discussion about the mechanism revealed that when PNIPA gels were added into the refolding buffer, the hydrophobic interactions between denatured proteins and polymer gels could prevent the aggregation of refolding intermediates, thus enhanced the protein renaturation.

Effect of Graft Yield on the Thermo-Responsive Permeability Through Porous Membranes with Plasma-Grafted Poly(N-isopropylacrylamide)Gates

The effect of graft yield on both the thermo-responsive hydraulicpermeability and the therrno-responsive diffusional permeability through porous membranes withplasma-grafted poly(N-isopropylacrylamide) (PNIPAM) gates was investigated. Both thermo-responsiveflat membranes and core-shell microcapsule membranes with a wide range of graft yield of PNIPAM wereprepared using a plasma-graft pore-filling polymerization method. The grafted PNIPAM was formedhomogeneously throughout the entire thickness of both the flat polyethylene membranes and themicrocapsule polyamide membranes. Both the hydraulic permeability and the diffusional permeabilitywere heavily dependent on the PNIPAM graft yield. With increasing the graft yield, the hydraulicpermeability (water flux) decreases rapidly at 25℃ because of the decrease of the pore size;however, the water flux at 40℃ increases firstly to a peak because of the increase ofhydrophobicity of the pore surface, and then decreases and finally tends to zero because of the poresize becoming smaller and smaller. For the diffusional permeability, the temperature showsdifferent effects on the diffusional permeability coefficients of solutes across the membranes. Whenthe graft yield was low, the diffusional coefficient of solute across the membrane was higher attemperature above the lower critical solution temperature (LCST) than that below the LCST; however,when the graft yield was high, the diffusional coefficient was lower at temperature above the LCSTthan that below the LCST. It is very important to choose or design a proper graft yield of PNIPAMfor obtaining a desired thermo-responsive 'on/off' hydraulic or diffusional permeability.

Thermo-responsive functionalized PNIPAM@Ag/Ag3PO4/CN-heterostructure photocatalyst with switchable photocatalytic activity

It is extremely important for photocatalysts to exhibit intelligent responsiveness to their environment. Herein, a poly N-isopropyl acrylamide(PNIPAM)-modified Ag/Ag3PO4-20/CN hybrid material with excellent convertible photocatalytic activity is prepared. PNIPAM has good hydrophilicity below the lower critical solution temperature(LCST);this increases the capacity of the photocatalyst for adsorbing tetracycline(TC) molecules. In addition, the PNIPAM-modified Ag/Ag3PO4-20/CN can prevent the loss of Ag3PO4. The dispersity is improved by loading g-C3N4 nanosheets(CN) for enhancing the efficiency of photocatalytic activity. Furthermore, a Z-scheme heterostructure is formed between CN and Ag3PO4, accelerating the separation efficiency of the holes and electrons. Ag nanoparticles can be used as electron-shuttle mediators, and electrons receiving more energy are transferred via the localized surface plasmon resonance(LSPR) effect. Furthermore, the PNIPAM@Ag/Ag3PO4-20/CN photocatalyst exhibits an excellent degradation rate for the degradation of TC when the temperature is lower than the LCST. The photoluminescence spectra and photocurrent curves prove that the carrier-separation efficiency of PNIPAM@Ag/Ag3PO4-20/CN is higher than those of Ag/Ag3PO4/CN and CN. The main active species of ·O2-and h+ are detected to reveal the plausible mechanism of the PNIPAM@Ag/Ag3PO4-20/CN hybrid material system. This work provides a way to develop intelligent materials for switchable photocatalytic applications.

The Swelling Equilibria of N-isopropylacrylamide Based Hydrogel in Aqueous Solution of Ethanol

N-isopropylacrylamide (NIPAAm) was used to synthesize NIPAAm homopolymer (nonionized) and NIPAAm-sodium methacrylate copolymer (ionized). The swelling equilibria for both gels were obtained in aqueous solution of ethanol with concentration ranging from 0 to 100%(by mass) at 25℃. The swollen gel in water shrank first with the addition of a small amount of ethanol and then reswelled with further addition of ethanol showing not only a discontinuous volume phase transition but also a typical reentrant phenomenon. A thermodynamic model based on the UNIQUAC with the 'free-volume' contribution was applied to correlate and predict the swelling behavior of the poly(NIPAAM)-gels in ethanol-water mixture.

Surface Properties of the Microgels Based on N-isopropylacrylamide and Tert-butyl Acrylate by Using N,N′-methylene-bis(acrylamide) and Clay as Cross-linker

Adopting N, N＇-methylene-bis （aculamide） （MBA） and inorganic clay （hectorite） as chemical and physical crosslinking agent, respectively, a series temperature sensitive microgels, based on N-isopropylacrylamide （NIPAM） as a main monomer and tert-butyl acrylate （tBA） as a comonomer were synthesized by surfactant-free emulsion polymerization （SFEP）. The microgel particle size and morphology was investigated by means of Atomic Force Microscope （AFM）. The surface tension of latex particles was measured by OCA 40 Micro Video based contact angle measuring device. The results showed that the particle size of the microgels with clay as cross-linker was smaller than that using MBA as chemical cross-linker, but exterior morphology of physical microgels is not as clean and neat as chemical microgels. In general, surface tension decreases with increasing hydrophobic tBA content. These smart microgels varied with tetnperature have the potential applications in the field of drug delivery and intelligent gel fiber.

Thermosensitive Poly(N-isopropylacrylamide-co-acrylonitrile) Hydrogels with Rapid Response

Acrylonitrile (AN) was copolymerized with N-isopropylacrylamide (NIPA) to synthesize thermosensitive hy-drogels, and the on-off switch behavior of poly(NIPA-co-AN) hydrogels with different fraction of hydrophobic compo-nent (AN) was investigated. It is found that the lower critical solution temperature (LCST), the swelling ratio at certain temperature and the reswelling rate of poly(NIPA-co-AN) hydrogels decreased as AN unit fraction in copolymers in-creased. In order to improve the responsive rate of poly(NIPA-co-AN) hydrogels, they were further treated by surface crosslinking using N, N′-methylene bisacrylamide (BIS) as a crosslinking agent. The swelling and deswelling behaviors of these copolymers were compared with those of the untreated hydrogels. The results indicated that the responsive rate of poly(NIPA-co-AN) hydrogel was improved by surface crosslinking. The resulting hydrogels bearing cyano groups with fast response have potential applications in the field of drug-controlled release and immobilization of biomolecules.

Temperature-triggered Protein Adsorption and Desorption on Temperature-responsive PNIPAAm-grafted-silica:Molecular Dynamics Simulation and Experimental Validation

Poly(N-isopropylacrylamide)(PNIPAAm) grafted onto silica,which may be used for reverse phase chromatography(RPC),was simulated and synthesized for protein separation with temperature-triggered adsorption and desorption.Molecular dynamics simulation at an all-atom level was performed to illustrate the adsorption/desorption behavior of cytochrome c,the model protein,on PNIPAAm-grafted-silica,a temperature responsive adsorbent.At a temperature above the lower critical solution temperature(LCST),the PNIPAAm chains aggregate on the silica surface,forming a hydrophobic surface that is favorable for the hydrophobic adsorption of cytochrome c,which has a high exposure of hydrophobic patches.At temperatures below the LCST,the PNIPAAm chains stretch,forming hydrophilic surface due to hydrogen bonding between PNIPAAm and surrounding water.Desorption of cytochrome c on the PNIPAAm-grafted-silica surface occurs as a result of competition with water,which forms hydrogen bonds with the protein.The conformational transitions of both cytochrome c and PNIPAAm are monitored,providing molecular insight into this temperature-responsive RPC technique.PNIPAAm-grafted-silica beads were synthesized and used for the adsorption and desorption of cytochrome c at approximately 313 K and 290 K,respectively.The experimental results validate the molecular dynamics simulation.In comparison to conventional RPC,using temperature as a driving force for RPC reduces the risk of protein denaturation caused by exposure to chaotropic solvents.Moreover,it simplifies the separation process by avoiding the buffer exchange operations between the steps.

Halloysite Nanotube Composited Thermo-responsive Hydrogel System for Controlled-release

Halloysite nanotube-composited thermo-responsive hydrogel system has been successfully developed for controlled drug release by copolymerization of N-isopropylacrylamide （NIPAM） with silane-modified halloysite nanotubes （HNT） through thermally initiated free-radical polymerization. With methylene blue as a model drug, thermo-responsive drug release results demonstrate that the drug release from the nanotubes in the composited hy-drogel can^be well controlled by manipulating the environmental temperature. When the hydrogel network is swol- len at temperature below the lower critical solution temperature （LCST）, drug releases steadily from lumens of the embedded nanotubes, whereas the drug release stops when hydrogel shrinks at temperature above the LCST. The release of model drug from the HNT-composited hydrogel matches well with its thermo-responsive volume phasetransition, and shows characteristics of well controlled release. The design strategy and release results of the pro- posed novel HNT-composited thermo-responsive hydrogel system provide valuable guidance for designing respon- s_i_ve nanocomposites for controlled-release of active agents.

An easily recoverable thermo-sensitive polyelectrolyte as draw agent for forward osmosis process

As a potential solution to the crises of energy and resources, forward osmosis(FO) has been limited by the development of draw agents. An ideal draw agent should be able to generate high osmotic pressure and can be easily recovered. In this study, a thermo-sensitive polyelectrolyte of poly(N-isopropylacrylamide-co-acrylic acid)(PNA)is developed as an efficient draw agent, and two easy and simple methods are proposed to effectively recover the polyelectrolytes. After adjusting the pH value of polyelectrolyte solutions to around 6.0, the polyelectrolyte can generate relatively high osmotic pressure, and induce average water fluxes of 2.09 and 2.95 L·m^(-2)·h^(-1) during12 h FO processes when the polyelectrolyte concentrations are 0.20 and 0.38 g·ml^(-1) respectively. After acidifying and heating to 70 °C, the PNA-10 polyelectrolyte can aggregate together because of hydrophobic association and separate from water, so it can be easily recovered by either simple centrifugation or gravitational sedimentation. The recovery ratios of PNA-10 polyelectrolyte in both methods are as high as 89%, and the recovered polyelectrolytes can be reused with almost the same FO performance as fresh ones. The results in this study provide valuable guidance for designing efficient and easily recoverable draw agents for FO processes.

Swelling properties and molecular simulation of PNIPA porous hydrogels

A series of porous intelligent hydrogels, which exhibited appropriate lower critical solution temperature (LCST) and fast response behavior, were synthesized by radiation method. The structure and surface morphology of hydrogels were examined by the infrared radiation and the scanning electron microscopy, respectively. The influences of the content of crosslinking agent and relative molecular mass of polyethylene glycol (PEG) on the swelling properties of hydrogels were discussed. The molecular mechanics simulations were performed to investigate the phase transformation mechanism of poly(N-isopropyl acrylamide) (PNIPA) hydrogel. The results show that macropores are observed in hydrogels, whereas hydrogels prepared without using PEG have a dense surface. LCST of hydrogels increases with the increase of relative molecular mass of PEG. The swelling mechanism of PNIPA porous hydrogels follows non-Fickian diffusion model. The theoretical maximum water absorption S∞ is approximately consistent with experimental value according to the second-order kinetics model established by Schott. The molecule chains of PNIPA hydrogel begin folding and curling, resulting in volume shrinkage at 305 K. There are much intramolecular nonbonding interactions in molecule chains of hydrogels. The porous hydrogels are expected to be applied in the field of artificial intelligence material.

Transitional Process of Ploy（N-isopropylacrylamide） in Deuterated Solution

The fast phase-transitional process of ploy（N-isopropylacrylamide） （PNIPAM） in deuterated solution was studied by laser induced temperature jump technique combined with time-resolved mid-infrared absorbance difference spectroscopy on nanosecond level. The multi-peaks of amide I＇band of PNIPAM among the energy range of 1565-1700 cm^-1 was experimentally resolved to three groups （i, ii, iii） for the first time, while the distinct threestage procedure in the phase transitional process of long-chain PNIPAM was observed firstly too. Furthermore, proper assignments were also made for the three group peaks in amide I＇band and the three steps in the kinetics process of long-chain PNIPAM.

Temperature-, and pH-Responsiveness Properties of a Biopolymer Based on kC-g-poly （AA-co-NIPAM）

A novel thermo-sensitive superabsorbent hydrogel with salt- and pH-responsiveness properties was obtained by grafting of mixtures of acrylic acid （AA） and N-isopropylacrylamide （N1PAM） monomers onto kappa-carrageenan, kC, using ammonium persulfate （APS） as a free radical initiator in the presence of methylene bisacrylamide （MBA） as a crosslinker. Infrared spectroscopy was carried out to confirm the chemical structure of the hydrogel. Moreover, morphology of the samples was examined by scanning electron microscopy （SEM）. The effect of MBA concentration and AA/NIPAM weight ratio on the water absorbency capacity has been investigated. The swelling variations of hydrogels were explained according to swelling theory based on the hydrogel chemical structure. The hydrogels exhibited salt-sensitivity and cation exchange properties. The temperature- and pH-reversibility properties of the hydrogels make the intelligent polymers as good candidates for considering as potential carriers for bioactive agents, e.g. drugs.

Prediction of Swelling Behavior of AT-Isopropylacrylamide Hydrogels in Aqueous Solution of Sodium Chloride

In this paper, a model is presented to correlate and predict the swelling behavior of hydrogels in aqueous solutions of electrolytes. The model is a combination of VERS-model, 'phantom network' theory and 'free-volume' contribution. The VERS-model is used to calculate Gibbs excess energy; 'phantom network' theory to describe the elastic properties of polymer network, and 'free-volume' contribution to account for additional difference in the size of the species. To test the model, a series of N-isopropylacrylamide based hydrogels are synthesized by free radical polymerization in oxygen-free, deionized water at 25℃ under nitrogen atmosphere. Then, the degree of swelling of all investigated gels as well as the partition of the solute between the gel phase and the surrounding coexisting liquid phase are measured in aqueous solution of sodium chloride. The model test demonstrates that the swelling behavior correlated and predicted by the model agrees with the experimental data within the experimental uncertainty. The phase transition appeared in the experiment, and the influences of the total mass fraction of polymerizable materials ζgel as well as the mole fraction of the crosslinking agent yCR on the swelling behavior of IPAAm-gels can also be predicted correctly. All these show the potential of such model for correlation and prediction of the swelling behavior of hydrogels in aqueous solutions of electrolytes.

Phototactic Poly(N-isopropyl acrylamide)Microgels with Photoresponsive Property

Smart functional microgels hold great potential in a variety of applications,especially in drug transportation.However,current drug carriers based on physiological internal stimuli cannot efficiently orientate to designated locations.Therefore,it is necessary to introduce the self-propelled particles to the drug release of the microgels.In order to study self-propulsion of microgels induced by light,it is also a challenge to prepare micronsized microgels so that they can be observed directly under optical microscopes.In this work,phototactic microgels with photoresponsive properties are prepared.The microgel particles can be observed by confocal laser scanning microscopy.The photoresponsive properties of microgels are fully investigated by various instruments.Light can also regulate the state of the microgel solution,making it switch between turbidity and clarity.The phototaxis of particles irradiated by UV light was studied,which may be used for microgels enrichment and drug transportation and release.