Self-assembling diblock copolymers of poly[N-(2-hydroxypropyl)methacrylamide] and a beta-sheet peptide

The self-assembly of hybrid diblock copolymers composed of poly(HPMA) and beta-sheet peptide P11 (CH(3)CO-QQRFQWQFEQQ-NH(2)) blocks was investigated. Copolymers were synthesized via thiol-maleimide coupling reaction, by conjugation of semitelechelic poly(HPMA)-SH with maleimide-modified beta-sheet peptide. As expected, CD and CR binding studies showed that the peptide block imposed its beta-sheet structural arrangement on the structure of diblock copolymers. TEM and AFM proved that peptide and these copolymers had the ability to self-assemble into fibrils.     

Release of prostaglandin E(1) from N-(2-hydroxypropyl)methacrylamide copolymer conjugates by bone cells

Bone-targeting N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-PGE(1) conjugates, containing cathepsin K sensitive spacers, were incubated with induced osteoclasts and osteoblasts, their precursors, and control non-skeletal cells. The release of PGE(1) was monitored by an HPLC assay. In both murine and human cell lines, osteoclasts appeared to be the most active cells in the cleavage (PGE(1) release). Incubation with osteoblasts also resulted in fast PGE(1) release, whereas precursor and control cells released PGE(1) with a substantially slower rate than bone cells (apparently through ester bond cleavage). Experiments in the presence of inhibitors revealed that other enzymes, in addition to cathepsin K, were participating in the cleavage of the conjugate. Confocal fluorescence studies exposed internalization of the conjugate by endocytosis with ultimate localization in the lysosomal/endosomal compartment.     

Synthesis and biological evaluation of disulfide-linked HPMA copolymer-mesochlorin e6 conjugates

Novel polymeric delivery systems for the photosensitizer mesochlorin e6 (Mce6) were synthesized to overcome problems of systemic toxicity. A disulfide bond was included to allow for quick release of Mce6 from the N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer backbone once internalized in tumor tissue. The synthesized conjugates demonstrated a time-dependent reductive cleavage with an accompanying increase in the quantum yield of singlet oxygen generation on exposure to DTT. Quicker release kinetics and a higher cytotoxicity in SKOV-3 human ovarian carcinoma cells were obtained as compared to polymer conjugate with a proteolytically cleavable GFLG spacer. These novel conjugates hold promise as clinically relevant drug delivery systems for photodynamic therapy of cancer.     

A series of poly[N-(2-hydroxypropyl)methacrylamide] copolymers with anthracene-derived fluorophores showing aggregation-induced emission properties for bioimaging

A series of new poly[N-(2-hydroxypropyl)methacrylamide]-based amphiphilic copolymers were synthesized through a radical copolymerization of a monomeric/hydrophobic fluorophore possessing aggregation-induced emission (AIE) property with N-(2-hydroxypropyl)methacrylamide. Photophysical properties were investigated using UV-Vis absorbance and fluorescence spectrophotometry. Influences of the polymer structures with different molar ratios of the AIE fluorophores on their photophysical properties were studied. Results show that the AIE fluorophores aggregate in the cores of the micelles formed from the amphiphilic random copolymers and polymers with more hydrophobic AIE fluorophores facilitate stronger aggregations of the AIE segments to obtain higher quantum efficiencies. The polymers reported herein have good water solubility, enabling the application of hydrophobic AIE materials in biological conditions. The polymers were endocytosed by two experimental cell lines, human brain glioblastoma U87MG cells and human esophagus premalignant CP-A, with a distribution into the cytoplasm. The polymers are non-cytotoxic to the two cell lines at a polymer concentration of 1 mg/mL.     

N-(2-hydroxypropyl) methacrylamide copolymers containing pendant saccharide moieties: Synthesis and bioadhesive properties

A new route for the synthesis of bioadhesive water soluble polymeric drug carriers has been developed. Novel monomers, namely, N-methacryloylglycylglycylgalactosamine (MA-Gly-Gly-GalN) [ 8 ], MA -Gly-Gly-FucN [ 9 ], MA -Gly-Gly-GlcN [ 10 ], and MA-Gly-Gly-ManN [ 11 ], and copolymers [ 12–16 ] based on N-(2-hydroxypropyl) methacrylamide (HPMA) containing different content of pendant saccharide moieties (galactosamine, fucosylamine, glucosamine, or mannosamine), were synthesized. Copolymerization parameters for the copolymerization of HPMA [M₁] and MA-Gly-Gly-GalN [M₂] have been determined (r₁ = 0.82, r₂ = 0.38). Bioadhesion studies with everted sacs of guinesa pig small intestine and colon in vitro demonstrated that HPMA copolymers containing side-chains terminated in fucosylamine bind selectively to the colonic tissue. The extent of binding was dependent on the fucosylamine content of copolymers.     

Poly[N-(2-hydroxypropyl)methacrylamide]—I. Radical polymerization and copolymerization

The radical polymerization of N-(2-hydroxypropyl)methacrylamide was investigated kinetically. The hydrophilic character of the polymerization medium was found to affect the rate of decomposition of the initiator [2,2′-azobis(methyl isobutyrate)] and the course of primary radical termination. The presence of the -OH group in the alkyl group attached to the nitrogen atom leads to an increase in the molecular weight of the polymer in comparison with polymers of N-alkyl methacrylamides. This phenomenon was interpreted in terms of the possibility of a polymeranalogous transesteramidation and of an increased possibility of transfer to monomer and polymer. The copolymerization parameters of N-(2-hydroxypropyl)methacrylamide (M₁) with methyl methacrylate and styrene were determined; in the first case, r₁ = 0·84 ± 0·05, r₂ = 0·66 ± 0·07; in the second case, r₁ = 0·53 ± 0·08, r₂ = 1·72 ± 0·19.     

N‐(2‐Hydroxypropyl)methacrylamide (HPMA) Copolymer‐Linked Nitroxides: Potential Magnetic Resonance Contrast Agents

N‐(2‐Hydroxypropyl)methacrylamide (HPMA) copolymer‐linked nitroxides were synthesized as macromolecular contrast agents for MR imaging. Molar relaxivities of HPMA copolymer‐linked nitroxides increased linearly in proportion to the number of nitroxides attached per gram of copolymer. HPMA copolymer‐linked nitroxides with 15, 20 and 30 mol‐% nitroxide exhibited higher relaxivities than gadolinium diethylenetriaminepentaacetic acid (Gd‐DTPA). These results demonstrate the potential of HPMA copolymer‐linked nitroxides as MR contrast agents for solid tumors.

Structure of HPMA copolymer‐linked nitroxides.     

Synthesis,characterization, and electroluminescence properties of poly(fluorenevinylene benzobisthiazoles)

A series of vinylene‐linked copolymers based on electron‐deficient benzobisthiazole and electron‐rich fluorene moieties were synthesized via Horner–Wadsworth–Emmons polymerization. Three different polymers P1 , P2 , and P3 , were prepared bearing octyl, 3,7‐dimethyloctyl, and 2‐(2‐ethoxy)ethoxyethyl side chains, respectively. The polymers all possessed moderate molecular weights, good solubility in aprotic organic solvents, and high fluorescence quantum efficiencies in dilute solutions. P2 , which bore branched 3,7‐dimethyloctyl side chains, exhibited better solubility than the other polymers, but also exhibited the lowest thermal decomposition temperature of all polymers. Overall, the impact of the side chains on the polymers optical properties in solution was negligible as all three polymers gave similar absorption and emission spectra in both solution and film. Guest‐host light‐emitting diodes using dilute blends of the polymers in a poly(N‐vinylcarbazole) host gave blue‐green emission with P2 exhibiting the highest luminous efficiency, 0.61 Cd/A at ～500 nm. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013     

Assembly of poly[N‐(2‐hydroxypropyl)methacrylamide] having cholesteryl moiety as terminal groups

Poly[N‐(2‐hydroxypropyl)methacrylamide]s (PHPMAs) with one pendant cholesteryl moiety at the polymer end and two pendant cholesteryl moieties at both polymer ends as terminal groups (PHPMA‐Chol and PHPMA‐2Chol) were prepared by the radical polymerization of N‐(2‐hydroxypropyl)methacrylamide initiated with 4,4′‐azobis‐[(3‐cholesteryl) 4‐cyanopentanoate] in the presence of 2‐mercaptoethanol and thiocholesterol as chain‐transfer reagents, respectively. The self‐organization of the PHPMAs was analyzed by fluorescence and ¹H NMR measurements. The critical micelle concentration (CMC) decreases with a decreasing PHPMA degree of polymerization. The CMC of PHPMA‐Chol is much larger than that of PHPMA‐2Chol. PHPMA exhibits an excellent blood compatibility, as determined from the Michaelis constant for the enzymatic reaction of thrombin and a synthetic substrate, S‐2238, in the presence of PHPMA‐2Chol. According to a small‐angle X‐ray scattering measurement, PHPMA‐2Chol can hold the cholesterol molecule as a lipophilic drug model in a hydrophobic layer formed by terminal‐located cholesteryl groups in PHPMA‐2Chol. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 3369–3377, 2000     

Aminosalicylate-based biodegradable polymers: Syntheses and in vitro characterization of poly(anhydride-ester)s and poly(anhydride-amide)s

Poly(anhydride-ester)s and poly(anhydride-amide)s derived from both 4- and 5-aminosalicylate acids (4- and 5-ASA) were synthesized and characterized by physicochemical methods. Thermal and solubility characteristics directly correlated to the polymer backbone composition; polymers based on 5-ASA had greater solubilities in organic solvents than polymers based on 4-ASA, and the poly(anhydride-ester)s thermally decomposed at temperatures nearly 100 °C higher than the corresponding poly(anhydride-amide)s. The polymers were self-contained, controlled-release systems that combine the drug and controlled-release mechanism into the polymer backbone. The erosion and degradation characteristics of the polymers were measured in physiologically relevant media. All polymer matrices fully degraded in media buffered to pH 7.4, whereas in acidic media (pH 1.2), all polymer matrices maintained greater than 50% mass over a 90-day time period. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 3667–3679, 2003     

HPMA copolymer-doxorubicin-gadolinium conjugates: synthesis, characterization, and in vitro evaluation

This study describes the synthesis, characterization, and in vitro evaluation of N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-gadolinium (Gd)-doxorubicin (Dox) conjugates. Copolymers of HPMA were derivatized to incorporate side chains for Gd chelation and Dox conjugation. The conjugates were characterized by their side chain contents, T(1) relaxivity (r(1)), stability, and in vitro cytotoxicity. High stability and relaxivity of these conjugates coupled with low toxicity show their potential for monitoring the in vivo fate of HPMA-based drug delivery systems by magnetic resonance imaging techniques.     

Poly[N-(2-hydroxypropyl)methacrylamide]—II: Hydrodynamic properties of dilute solutions

The results of viscosity and light scattering measurements on fractions of poly[N-(2-hydroxypropyl)methacrylamide] in several solvents were used for the determination of the parameters of the Mark-Houwink equation, characteristic ratio and its temperature coefficient and the parameters of the polymer-solvent interaction. The solutions in water and in aq. NaCl are exothermal, in dimethylformamide approx. athermal, and in ethanol endothermal. The effect of the solvent on the short-range interactions between the polymer chain units was also demonstrated.     

Synthesis and characterization of eumelanin‐inspired poly(indoylenearylenevinylene)s and poly(indoylenearyleneethynylene)s

Four novel conjugated polymers containing the eumelanin‐inspired indole core have been successfully synthesized using common cross coupling reactions. These polymers differed by the arylene and the carbon–carbon bond linkage. Optoelectronic experiments of these polymers suggest that the ethynylene linkage contributed to the red‐shifted absorption spectra and blue‐shifted emission spectra when compared to the vinylene linkage polymers. Furthermore, the optical bandgaps of the poly(indoylenearyleneethynylene)s (PIAEs) were smaller compared to the poly(indoylenearylenevinylene)s (PIAVs). Surprisingly, the HOMOs of these polymers were less affected by the nature of the carbon–carbon linkage. However, the LUMOs of the PIAEs were lower in comparison to the PIAVs. These eumelanin‐inspired PIAEs and PIAVs are good fluorophores with fluorescence quantum yields ranging from 0.12 to 0.67 and have good thermal stability for applications such as in organic light‐emitting diodes. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55, 457–463     

Synthesis and characterization of poly(phenylacetylene)s carrying oligo(ethylene oxide) pendants

A group of new amphiphilic poly(phenylacetylene)s bearing polar oligo(ethylene oxide) pendants, poly{4‐[2‐(2‐hydroxyethoxy)ethoxy]phenylacetylene} ( 1 ), poly(4‐{2‐[2‐(2‐hydroxyethoxy)‐ethoxy]ethoxy}phenylacetylene) ( 2p ), poly(3‐{2‐[2‐(2‐hydroxyethoxy)ethoxy]ethoxy}phenylacetylene) ( 2m ), poly(4‐{2‐[2‐(2‐methanesulfonyloxyethoxy)ethoxy]ethoxy}phenylacetylene) ( 3 ), poly(4‐{2‐[2‐(p‐toluenesulfonyloxyethoxy)ethoxy]ethoxy}phenylacetylene) ( 4 ), poly(4‐{2‐[2‐(2‐trimethylsilyloxy‐ethoxy)ethoxy] ethoxy}phenylacetylene) ( 5 ), and poly(4‐{2‐[2‐(2‐chloroethoxy)ethoxy]ethoxy}phenylacetylene) ( 6 ), were synthesized with organorhodium complexes as the polymerization catalysts. The structures and properties of the polymers were characterized with IR, UV, NMR, and thermogravimetric analysis. 1 , 2p , and 2m , the three polymers containing pendants with hydroxyl groups, were oligomeric or insoluble. The organorhodium complexes worked well for the polymerization of the monomers without hydroxyl groups, giving soluble polymers 3 – 6 with a weight‐average molecular weight up to ～160 × 10³ and a yield up to 99%. Z‐rich polymers 3 – 6 could be prepared by judicious selections of the catalyst under optimal conditions. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 1153–1167, 2006     

Synthesis and aggregation of poly(valine)‐poly (ethylene glycol) block copolymers

The solubility nature of many medicines presents a challenge for successful delivery of these drugs to the body. Polymeric carriers are potentially viable as vessels for both the protection and transport of these medicinal substances. In an effort to generate polymeric materials for this desired application, A‐B‐A triblock copolymers have been synthesized with a central block composed of hydrophilic poly (ethylene glycol) (PEG) and flanking hydrophobic sequences composed of five valine units terminated with end groups of varying hydrophobicity. These copolymers were constructed by adding amino acids stepwise to the hydrophilic block using solution phase chemistry. The self‐assembly behavior of all polymers was investigated using fluorimetry with a pyrene probe. In general, copolymers with more hydrophobic end groups exhibited lower critical aggregation concentrations (CACs). Fmoc‐terminated copolymers displayed the lowest CAC of 0.032 mg/mL and demonstrated little cytotoxicity when exposed to SW620 colorectal cancer cells. Transmission electron micrographs show the presence of multiple compartments within these spherical assemblies, which may prove useful in encapsulating medicinal substances. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 5381–5389, 2008     

N-（p-羟基苯基）甲基丙烯酰胺的合成与表征

N-芳基取代的甲基丙烯酰胺(结构式如图1所示)是一类非常有用的共聚单体,它们可以与甲基丙烯酸酯或N-取代马来酰亚胺等单体共聚,使共聚物的一些性能,如耐热性、耐水性、透明度、硬度等都有不同程度的改进[1-4].关于N-芳基取代的甲基丙烯酰胺的制备,文献[5-8]曾有报道,通常采用甲基丙烯酰氯与芳基胺在乙醚、苯等溶剂中反应,并加入适当的缚酸剂来完成.而N-(p-羟基苯基)甲基丙烯酰胺(此处R＝OH)是N-芳基取代甲基丙烯酰胺中一种比较特殊的单体,它即含有碳碳双键,又含有酚羟基,属于双官能团物质.关于它的制备及用途,尚未见有文献报道.文献[5]曾报道说,采用对胺基苯酚与甲基丙烯酰氯反应仅能得到甲基丙烯酸(N-(p-甲基丙烯酰胺基)苯酚酯(即酰胺-酯化合物).本文合成出了这种物质,并对其进行了表征和证实;我们推测它与一些单体(如N-取代马来酰亚胺等)的共聚物可以溶于碱性水溶液,并且有好的耐热性,因此在紫外光刻胶中可能有比较大的应用潜力[9-11],有关这方面的内容我们将另文报道.     

Synthesis of poly(ester‐amide) dendrimers based on 2,2‐Bis(hydroxymethyl) propanoic acid and glycine

Water‐soluble, biodegradable, and biocompatible poly(ester‐amide) dendrimers with hydroxyl functional groups are synthesized from previously prepared AB₂ adduct of 2,2‐bis(hydroxymethyl) propanoic acid (bis‐MPA) and glycine as a repeating unit. Two esterification procedures using different coupling reagent/catalyst systems (DCC/DPTS or EDC/DMAP) are studied with respect to efficiency, ease of products purification, and quality of the final products. Both procedures have their own benefits and drawbacks, depending on dendrimer generation. The synthesized poly(ester‐amide) dendrimers as well as commercially available bis‐MPA dendrimers, poly(ester‐amide) hyperbranched polymer, and poly(vinyl alcohol) are used for preparation of solid dispersions of sulfonylurea antidiabetic drug glimepiride to improve its poor water‐solubility. In vitro dissolution studies show in comparison with pure glimepiride in crystalline or amorphous form, to the same extent improved glimepiride solubility for solid dispersions based on dendritic polymers, but not for poly(vinyl alcohol). The amount of glimepiride complexed with both dendrimer types increases with dendrimer generation. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 3292–3301     

Synthesis and characterization of star oligo/poly(2,2‐dimethyltrimethylene carbonate)s containing cholic acid moieties

Star oligo/poly(2,2‐dimethyltrimethylene carbonate)s containing cholic acid moieties were synthesized through the ring‐opening polymerization of 2,2‐dimethyltrimethylene carbonate (DTC) initiated by cholic acid with hydroxyl groups. Through the control of the feed ratio of the initiator cholic acid to the monomer DTC, a series of star oligomers/polymers with different molecular weights were obtained. The star oligomers/polymers were characterized with Fourier transform infrared spectroscopy, proton nuclear magnetic resonance spectroscopy, combined size exclusion chromatography/multi‐angle laser light scattering analysis, wide‐angle X‐ray scattering, polarizing light microscopy, and differential scanning calorimetry. Compared with linear poly(2,2‐dimethyltrimethylene carbonate), these star oligo/poly(2,2‐dimethyltrimethylene carbonate)s had much faster hydrolytic degradation rates. With one of the star oligomers/polymers, a microsphere drug‐delivery system of a submicrometer size was fabricated with a very convenient ultrasonic dispersion method that did not involve toxic organic solvents. The in vitro drug release was studied. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 6688‐6696, 2006     

Immobilization of aminothiols on poly(oxyethylene H‐phosphonate)s and poly(oxyethylene phosphate)s—An approach to polymeric protective agents for radiotherapy of cancer

This study describes the synthesis and characterization of polymer complexes constructed from the radioprotective agent S‐2(3‐aminopropylamino) ethylphosphorothioic acid dihydrate (amifostine or WR‐2721), applied in the radiation cancer treatment, and biodegradable poly(oxyethylene H‐phosphonate), poly(hydroxyoxyethylene phosphate), or poly(methyloxyethylene phosphate). The immobilization of another radioprotector, used in cancer radiotherapy, 1‐(3‐aminopropyl)aminoethanethiol (WR‐1065) on the same polymers is also achieved through a covalent bond (Atherton‐Todd reaction coupling), ionic bond, and physical complexation, respectively. The structure of the complexes formed is elucidated by ¹H‐ ¹³C‐, ³¹P NMR and FTIR spectroscopy. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 1349–1363, 2007