Phase transition of aqueous solutions of poly(N,N-diethylacrylamide-co-acrylic acid) by differential scanning calorimetric and spectrophotometric methods

 The phase transition of aqueous solutions of poly(N,N-diethylacrylamide-co-acrylic acid) (DEAAm–AA) is studied by differential scanning calorimetry (DSC) and UV–vis spectrophotometry. The copolymer aqueous solutions are shown to have well-defined lower critical solution temperatures (LCSTs). The LCST values obtained from the maximum of the first derivatives of the DSC and optical transition curves agree well. DSC can be used to measure the phase-transition temperature of more dilute polymer solutions. On increasing the AA composition in the copolymers, the LCST values of the copolymer increase, then decrease at higher AA composition. For the aqueous solution of the copolymers, the transition curve obtained by the spectrophotometric method is highly wavelength dependent. The LCST values are found to be concentration-dependent. The changes in the heat of the phase transition of the copolymer solutions measured from DSC are lower than that of the homopolymer PDEAAm solution. This is consistent with the suggestion that the polymer chains of the copolymers collapsed only partially at temperatures above the LCST. The added salt (sodium chloride) decreases the transition temperature of the polymer solution. Received: 14 November 2000 Accepted: 15 January 2001     

Random copolymers of N-isopropylacrylamide and methacrylic acid monomers with hydrophobic spacers: pH-tunable temperature sensitive materials

Two series of random copolymers of N-isopropylacrylamide (NIPAAm) and comonomers derived from methacrylic acid with a different number of methylene units as hydrophobic spacers (n=4, 7 and 10) were synthesized via free radicals. The first series was prepared having the acid groups methoxy-protected while the second series have the acid groups free. The NIPAAm-copolymers of both series were prepared varying the comonomer content from 5 to 20 mol%. All the copolymers were characterized by FTIR, DSC, ¹H NMR and SLS. The aqueous solution behaviour of the copolymers having methoxy-protected acid groups shows that the comonomer increases the hydrophobicity of the copolymer chain and decreases its lower critical solution temperature (LCST). For the copolymers having free acid groups, hydrogen-bonding is responsible for a further decrease in the LCST of these copolymers in pure water. In buffer solutions, every acid comonomer have a critical ionization degree (α_crit) above which the LCST increases with increasing comonomer content while at an ionization degree lower than α_crit the LCST decreases with increasing comonomer content. In dependence of comonomer content, number of methylene units in the spacer and the pH of the buffer solution, the LCST of the copolymers can be varied widely, showing that these random copolymers have pH-tunable temperature sensitivity.     

N‐Isopropylacrylamide Copolymers with Acrylamide and Methacrylamide Derivatives of Cholic Acid: Synthesis and Characterization

By free radical polymerization, we have prepared a series of water‐soluble, thermosensitive copolymers based on N‐isopropylacrylamide and (meth)acrylamide derivatives of cholic acid, one of the bile acids. The copolymers contained 1–7 mol‐% of the (meth)acrylamide derivatives of cholic acid. The chemical composition in the copolymers was studied by NMR spectroscopy and was found to be close to the original composition of the comonomers in the feed prior to polymerization. The lower critical solution temperatures (LCST) of the polymer solutions were measured by means of differential scanning calorimetry and turbidimetry. The resulting copolymers exhibit systematic changes in their LCSTs as a function of their chemical composition, as the incorporation of hydrophobic comonomers leads to a lower LCST.     

Controlled synthesis of poly(acetone oxime acrylate) as a new reactive polymer: Stimuli-responsive reactive copolymers

Acetone oxime acrylate has been synthesized as a new active ester monomer. Free radical polymerization yielded a reactive polymer soluble in various organic solvents, such as chloroform, dioxane, DMSO, acetone, methanol, dichloromethane, DMF, and ethanol. Controlled radical polymerization of acetone oxime acrylate was successfully conducted using the RAFT, NMP and Iniferter method. Partly polymer analogous reaction with N-isopropylamine resulted in the reactive copolymer poly(N-isopropylacrylamide-co-acetone oxime acrylate), which featured a lower critical solution temperature (LCST) of 61 °C in water. Further, the reactivity of the copolymer was exemplary proven by complete reaction with ammonia yielding poly(N-isopropylacrylamide-co-acrylamide), which does not possess a LCST.     

Influence of crosslinker and ionic comonomer concentration on glass transition and demixing/mixing transition of copolymers poly(N-isopropylacrylamide) and poly(sodium acrylate) hydrogels

Hydrogels based on N-isopropylacrylamide and sodium acrylate as ionic comonomer were synthesized by free radical polymerization in water using N,N′-methylenebisacrylamide as crosslinker and ammonium persulfate as initiator. The glass transition of dried copolymers poly(N-isopropylacrylamide) (PNIPA) and poly(sodium acrylate) (SA) gels and demixing/mixing transition of PNIPA-SA hydrogels swollen with increasing amounts of water were studied using conventional differential scanning calorimetry. In the crosslinked polymers, the glass transition linearly increases, and the transition range becomes broader, with increasing crosslinker content. Increasing content of ionic comonomer also produces an increase of glass transition temperature, which moves to higher temperatures with higher sodium acrylate fraction. The influence of chemical structure of PNIPA-SA hydrogels on the lower critical solution temperature (LCST) of PNIPA-SA/water mixtures during heating and cooling was quantified as function of the content of the crosslinker and the ionic comonomer, as well as water content of the hydrogel in the range from 95 to 70 wt%. At parity of water content, the LCST occurs at higher temperatures for gels containing higher amounts of sodium acrylate. Similarly, the introduction of N,N′-methylenebisacrylamide causes an increase of the LCST, which grows with increasing of crosslinking degree of the hydrogel.     

Temperature‐induced aggregation of the copolymers of N‐isopropylacrylamide and sodium 2‐acrylamido‐2‐methyl‐1‐propanesulphonate in aqueous solutions

A series of random copolymers of N‐isopropylacrylamide (NIPAM) and sodium 2‐acrylamido‐2‐methyl‐1‐propanesulphonate (AMPS) was synthesized by free‐radical copolymerization. The content of AMPS in the copolymers ranged from 1.1 to 9.6 mol %. The lower critical‐solution temperature (LCST) of copolymers in water increased strongly with an increasing content of AMPS. The influence of polymer concentration on the LCST of the copolymers was studied. For the copolymers with a higher AMPS content, the LCST decreased faster with an increasing concentration than for copolymers with a low content of AMPS. For a copolymer containing 1.1 mol % of AMPS the LCST dropped by about 3 °C when the concentration increased from 1 to 10 g/L, whereas for a copolymer containing 9.6 mol % of AMPS the LCST dropped by about 10 °C in the concentration range from 2 to 10 g/L. It was observed that the ionic strength of the aqueous polymer solution very strongly influences the LCST. This effect was most visible for the copolymer with the highest content of AMPS (9.6 mol %) for which an increase in the ionic strength from 0.2 to 2.0 resulted in a decrease in the LCST by about 27 °C (from 55 to 28 °C), whereas for the copolymer containing 1.1 mol % of AMPS the LCST decreased only by about 6 °C (from 37 to 31 °C) when the ionic strength increased from 0.005 to 0.3. The reactivity ratios for the AMPS and NIPAM monomer pairs were determined using different methods. The values of r_AMPS and r_NIPAM obtained were 11.0–11.6 and 2.1–2.4, respectively. © 2001 John Wiley & Sons, Inc. J Polym Sci Part A: Polym Chem 39: 2784–2792, 2001     

ATRP synthesis and association properties of temperature responsive dextran copolymers grafted with poly(N-isopropylacrylamide)

Temperature responsive copolymers of dextran grafted with poly(N-isopropylacrylamide) (Dex-g-PNIPAAM) were prepared by atom transfer radical polymerization (ATRP) in homogeneous mild conditions without using protecting group chemistry. Dextran macroinitiator was synthesized by reaction of dextran with 2-chloropropionyl chloride at room temperature in DMF containing 2% LiCl. ATRP was carried out in DMF:water 50:50 (v/v) mixtures at room temperature with CuBr/Tris(2-dimethylaminoethyl)amine (Me₆TREN) as catalyst. Several grafted copolymers with well defined number and length of low polydispersity grafted chains were prepared. Temperature induced association properties in aqueous solution were studied as a function of temperature and polymer concentration by dynamic light scattering, fluorescence spectroscopy and atomic force microscopy (AFM). LCST, ranging from 35 to 41 °C, was significantly affected by number and length of grafted chains. The fine tuning of LCST around body temperature is an important characteristic not obtainable by conventional radical grafting of PNIPAAM. Well defined spherical nanoparticles were formed above the LCST of PNIPAAM. Hydrodynamic diameter was in the range 73-98 nm.     

Preparation of hydrophobically-modified acrylamide copolymers using poly(ethylene imine) as a photoinitiator and its performance evaluation in Bohai oilfield

This paper presents copolymers of acrylamide, N,N-dimethyl-N-vinylnonadecan-1-ammonium chloride and N-(2,4-dimethylpentan-2-yl) acrylamide synthesized by photopolymerization using modified poly(ethylene imine) as initiator in water. These hydrophobically modified acrylamide copolymers were dissolved in the brine that was used in enhanced oil recovery in Bohai oilfield. It was found that when the content of N-(2,4-dimethylpentan-2-yl) acrylamide and N,N-dimethyl-N-vinylnonadecan-1-ammonium chloride were 0.1 mol % and 0.3 mol %, respectively, the resulting polymer could meet the demand of solution time and the polymer mechanical shear stability required in Bohai oilfield. The solution properties of synthesized copolymers were compared with the hydrophobically modified polymer currently used in enhanced oil recovery in Bohai oilfield.     

Copolymer of poly(4-vinylpyridine)-g-poly(ethylene oxide) respond sharply to temperature, pH and ionic strength

The stimuli-responsive copolymers with poly(ethylene oxide) (PEO) as side chain were prepared by free-radical copolymerization of methacrylamide end-capped PEO macromonomer and 4-vinylpyridine (4VP). Phase transition behavior of these copolymers of poly(4-vinylpyridine)-g-poly(ethylene oxide) (P4VP-g-PEO) was investigated as a function of polymer concentration, temperature, pH and ionic strength by monitoring the turbidity of the polymer solutions. The copolymers displayed sharp response to temperature and pH. The LCST of P4VP-g-PEO copolymer increased with the increase of PEO content and decreased with increasing pH due to the deprotonation of the pyridine ring, indicating well-tunable LCST. In addition, the LCST of P4VP-g-PEO9 presented a unique phase transition behavior with varying salt concentration, showing a minimum with 1 M NaCl solution at pH 6.0.     

Synthesis and self‐assembly of thermosensitive double‐hydrophilic poly(N‐vinylcaprolactam)‐b‐poly(N‐vinyl‐2‐pyrrolidone) diblock copolymers

We report on novel diblock copolymers of poly(N‐vinylcaprolactam) (PVCL) and poly(N‐vinyl‐2‐pyrrolidone) (PVPON) (PVCL‐b‐PVPON) with well‐defined block lengths synthesized by the MADIX/reversible addition‐fragmentation chain transfer (RAFT) process. We show that the lower critical solution temperatures (LCST) of the block copolymers are controllable over the length of PVCL and PVPON segments. All of the diblock copolymers dissolve molecularly in aqueous solutions when the temperature is below the LCST and form spherical micellar or vesicular morphologies when temperature is raised above the LCST. The size of the self‐assembled structures is controlled by the molar ratio of PVCL and PVPON segments. The synthesized homopolymers and diblock copolymers are demonstrated to be nontoxic at 0.1–1 mg mL^?1 concentrations when incubated with HeLa and HEK293 cancer cells for various incubation times and have potential as nanovehicles for drug delivery. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 2725–2737     

Synthesis and characterization of temperature‐sensitive block‐graft PNiPAAm‐b‐(PαN3CL‐g‐alkyne) copolymers by ring‐opening polymerization and click reaction

This study synthesized thermo‐sensitive amphiphilic block‐graft PNiPAAm‐b‐(PαN₃CL‐g‐alkyne) copolymers through ring‐opening polymerization of α‐chloro‐ε‐caprolactone (αClCL) with hydroxyl‐terminated macroinitiator poly(N‐isopropylacrylamide) (PNiPAAm), substituting pendent chlorides with sodium azide. This was then used to graft various kinds of terminal alkynes moieties by means of the copper‐catalyzed Huisgen's 1,3‐dipolar cycloaddition (“click” reaction). ¹H NMR, FTIR, and gel permeation chromatography (GPC) was used to characterize these copolymers. The solubility of the block‐graft copolymers in aqueous media was investigated using turbidity measurement, revealing a lower critical solution temperature (LCST) in the polymers. These solutions showed reversible changes in optical properties: transparent below the LCST, and opaque above the LCST. The LCST values were dependant on the composition of the polymer. With critical micelle concentrations (CMCs) in the range of 2.04–9.77 mg L^?1, the block copolymers formed micelles in the aqueous phase, owing to their amphiphilic characteristics. An increase in the length of hydrophobic segments or a decrease in the length of hydrophilic segments amphiphilic block‐graft copolymers produced lower CMC values. The research verified the core‐shell structure of micelles by ¹H NMR analyses in D₂O. Transmission electron microscopy was used to analyze the morphology of the micelles, revealing a spherical structure. The average size of the micelles was in the range of 75–145 nm (blank), and 105–190 nm (with drug). High drug entrapment efficiency and drug loading content were observed in the drug micelles. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

The synthesis and solution behaviors of novel amphiphilic block copolymers based on d-galactopyranose and 2-(dimethylamino)ethyl methacrylate

A series of novel stimuli-responsive AB, ABA, and BAB type block copolymers based on 6-O-methacryloyl-1,2:3,4-di-O-isopropylidene-d-galactopyranose (MAIpGP:A block) and 2-(N,N-dimethylamino)ethyl methacrylate (DMAEMA: B block) were synthesized via ATRP techniques using ethyl 2-bromoisobutyrate (EBiB) as monofunctional ATRP initiator in the case of diblock copolymer and diethyl meso-2,5-dibromoadipate (DEDBA) as bifunctional ATRP initiator in the case of triblock copolymers. The PMAIpGP blocks of the AB, ABA, and BAB type linear block copolymers were converted to water soluble PMAGP blocks via deprotection process under mild acidic conditions. Both proton NMR and DLS studies demonstrated that block copolymers were temperature-sensitive, whereby the lower critical solution temperature (LCST) of polymers varied with the polymerization degrees of comonomers in the block copolymers. LCST was determined to be between ∼35 °C and 55 °C depending on the type and the comonomer compositions of the block copolymers. It was observed that an increase on the percentage of hydrophilic PMAGP block in block copolymer caused an increase on the LCST value as expected.     

Nonlinear depression of the lower critical solution temperatures in aqueous solutions of thermo-sensitive random copolymers

We develop a theoretical model of cooperative hydration to clarify the molecular origin of the observed nonlinear depression of the lower critical solution temperature (LCST) in the aqueous solutions of thermosensitive random copolymers and find the monomer composition at which LCST shows a minimum. Phase diagrams of poly(N-isopropylacrylamide-co-N,N-diethylacrylamide) copolymer solutions are theoretically derived on the basis of the theory of cooperative hydration by introducing the microscopic structure parameter η which characterizes the distribution of the monomer sequences along the chains. We compared them with the experimental data of LCST of random copolymers with various monomer compositions and also of the diblock copolymers with equimolar monomer composition. The transition temperature shifts to lower than those of homopolymer counterparts when the monomer sequence of the chains has an alternative tendency. On the contrary, for the blocky polymers such as diblock copolymers, the transition temperature remains almost the same as those of the homopolymers. Thus, the nonlinear effect in phase separation appears when the average block length of the copolymers is shorter than the average sequence length of the cooperative hydration. The degree of hydration is calculated as a function of the temperature and polymer concentration for varied distribution of the copolymer compositions. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2013, 51, 1112–1123     

Dual stimuli‐responsive polyamines derived from modified N‐vinylpyrrolidones through CuAAC click chemistry

The synthesis via copper(I)‐catalyzed azide alkyne cycloaddition (CuAAC) of three new monomer derivatives of N‐vinyl‐2‐pyrrolidone (VP) carrying cyclic pyrrolidine, piperidine, and piperazine groups and the corresponding copolymers with unmodified VP is shown. The systems bearing pyrrolidine and piperidine displayed both thermo‐ and pH‐response, which has not been reported previously for a polymer with polyvinylpyrrolidone (PVP) backbone. A broad modulation of the LCST with the copolymer composition and pH was observed in a temperature range 0–100 °C. The polymers carrying piperazine exhibited broad buffering regions and no thermosensitivity. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 1098–1108     

Synthesis of N,N-dimethylaminoethyl methacrylate copolymers with N-vinyl caprolactam and their complexing and flocculating behavior

Thermosensitive copolymers of N-vinyl carprolactam with N,N-dimethylaminoethyl methacrylate have been synthesized via free-radical polymerization, and reactivity ratios in dioxane have been estimated as 2.44 and 0.07, respectively. It has been shown that temperatures of phase separation for 1% aqueous solutions of homopolymers are close and remain virtually unchanged with the copolymer composition. The efficiency of flocculating behavior of copolymers with respect to a polystyrene latex has been estimated from the initial rate of flocculation as a function of the polyelectrolyte concentration in an acidic medium.     

Thermo and pH sensitive fluorescent polymer sensor for metal cations in aqueous solution

A new monomeric fluorophore N‐acryl‐N'‐(quinolin‐8‐yl)thiourea (AQT) was synthesized. Free radical copolymerization was carried out in order to prepare a water‐soluble fluorescent copolymer, based on N‐isopropylacrylamide. The fluorescent characteristic of the aqueous solutions of copolymers was investigated both in varied pH and in the presence of metal cations. The polymer‐ contained AQT was found to be a selective chemosensor for Ni, Pb, Co ions especially for Co ion. The obtained copolymers show thermo‐sensitive lower critical solution temperature (LCST) ranging from 32.5 to 37.5°C with varied ratios of AQT, N, N‐dimethylacrylamide and N‐isopropylamide. Copyright © 2007 John Wiley & Sons, Ltd.     

A polymer regulator of enzyme activity

The reaction of the amino group of α-chymotrypsin with poly(N,N-diethylacrylamides) bearing terminal carboxyl groups which have the degree of polymerization ranging from 30 to 180 and which possess an LCST of 34–29°C affords polymer derivatives of the enzyme. It is found that, upon an increase in the temperature of the aqueous solution of the resulting derivatives to 40°C, the derivative with a degree of polymerization of 180 precipitates at 34°C, while the derivatives with a degree of polymerization of 30–80 remain in solution. The activity of α-chymotrypsin as a part of the derivatives with a degree of polymerization of 30 does not change with increasing temperature, whereas the activity of the enzyme as a part of the derivatives with degrees of polymerization of 60 and 80 decays almost to zero near the LCST of the initial polymers. Such a change in the enzyme activity is reversible (the activity fully recovers with a decrease in temperature).     

Tailor‐made biomimetic random copolymers for medical applications

Biospecific copolymers were synthesized by random substitution of a preformed polymer with suitable chemical groups or by random copolymerization of suitable functional monomers. Such polymers contain arrangements of the chemical functions that mimic natural biospecific sites. The probability of occurrence of such arrangements will depend on the average composition of the copolymer. Two examples of such bioactive copolymers are presented. Some O‐[(N‐benzylcarbamoyl)methyl]dextrans (DMCB) exhibit an inhibitory effect on the growth of human breast cancer cell lines. Its derivatives, associated or conjugated to sodium phenylacetate (NaPA), were found to have a strong antitumoral activity on malignant human melanoma 1205LU. Preliminary in vivo tests on nude mice are performed. Adhesion of Staphylococcus aureus to biospecific random polystyrene derivatives or acrylic terpolymers carrying sulfate and carboxylate groups is hindered in a composition‐dependent way. In addition, a correlation between the bacterial adhesion and proliferation has been evidenced. As a result, biospecific random copolymers endowed with both bacteriophobic and bacteriostatic activities were synthesized.     

Preparation of fast response superabsorbent hydrogels by radiation polymerization and crosslinking of N-isopropylacrylamide in solution

Macroporous temperature-responsive poly(N-isopropylacrylamide) (PNIPAAm) hydrogels with high equilibrium swelling and fast response rates were obtained by a ⁶⁰Co γ- and electron beam (EB) irradiation of aqueous N-isopropylacrylamide (NIPAAm) monomer solutions. The effect of irradiation temperatures, the dose, the addition of a pore-forming agent on the swelling ratio, and the kinetics of swelling and shrinking of the PNIPAAm gels was studied. The gels synthesized above the LCST exhibited the highest equilibrium swelling (300–400) and fastest response rate measured by minutes. Scanning electron microscope (SEM) pictures revealed that the gels synthesized above the LCST have larger pores than those prepared at temperatures below the LCST. The gels showed a reversible response to cyclical changes in temperature and might be used in a pulsed drug delivery device. The gels synthesized above the LCST exhibited the highest testosterone propionate release.     

Synthesis and Characterization of Catechol-Containing Polyacrylamides with Adhesive Properties

In this study, a row of four analogous dopamine acryl- and methacrylamide derivatives, namely N-(3,4-dihydroxyphenyethyl) acrylamide, N-(3,4-dihydroxyphenyethyl) meth acrylamide, N-phenethyl methacrylamide, N-(4-hydroxyphenethyl) methacrylamide were synthesized and characterized by ¹H-NMR and ¹³C-NMR, followed by further solvent-based radical polymerization with N-hydroxyethyl acrylamide. All copolymers were characterized by ¹H-NMR, dynamic differential calorimetry, and gel permeation chromatography. The dependency of the used comonomer ratios to the molecular mass of the corresponding copolymers has been described. The synthesis of the various polymers serves as a feasibility study and provides important data for a future biometric application in the medical field. We synthesized N-(3,4-dihydroxyphenyethyl) acrylamide copolymer up to 80 mol% by free radical polymerization without using any protecting groups. All polymers show identical perfect adhesive properties by a simple scratch test. Further, the monomers were used as a photo reactive glue formulation to test its adherence to a medical titanium surface sample by tensile shear test.