Studies on the effect of polylactide in-situ grafting during melt processing on poly(ʟ-lactide)/graphene oxide composite films.

The present work tried to solve the compatibility and dispersion problems of industrial grade graphene oxide (GO) mixing with polylactide (PLA) by melt processing for practical application. PLA was grafted on the GO using the silane coupling agent (KH560) as "bridge" by in-situ melting reaction to improve the compatibility. For better compatibility and dispersion, poly(ᴅ-lactide) (PDLA) was grafted on GO (D-G) to form stereocomplex crystallites with poly(ʟ-lactide) (PLLA) to enhance the interaction between GO and PLLA matrix. By biaxial stretching, the PLLA and GO composite films were prepared. Results show that GO was seriously aggregated in the film containing GO without PLA grafting (PLLA/L/G0.05) and the average size of aggregated GO was about 19.5 µm. PLA grafting decreased the aggregated GO size, so that the films containing L-G or D-G presented better dispersion. The film containing 5 % D-G (PLLA/D-G0.05) exhibited the smallest average size of aggregated GO, about 12.7 µm. Compared with neat PLLA film, PLLA/L/G0.05 film presented worse tensile properties due to serious aggregation of GO. While, PLLA/D-G0.05 film presented the best tensile performance that tensile strength and elongation at break reached 120 MPa and 107 %, respectively.

A biodegradable CO2-based polymeric antitumor nanodrug via a one-pot surfactant- and solvent-free miniemulsion preparation.

In the present study, low molecular weight poly(propylene carbonate) (PPC, Mn = 3500), a biodegradable liquid polymer easily prepared from carbon dioxide (CO2), was modified into poly(propylene carbonate)diacrylate (PPC-DA) by acylation, and methoxy poly(ethylene glycol) (mPEG) was modified into methoxy poly(ethylene glycol) acrylate (mPEG-A). Using PPC-DA as the dispersant to dissolve hydrophobic doxorubicin (DOX) and the initiator, and with mPEG-A as the co-monomer and polymerisable surfactant, a biodegradable nanodrug with excellent biocompatibility was prepared by shear emulsification polymerization without surfactants or organic solvent residues. The nanodrug can be efficiently endocytosed by tumor cells and can rapidly release doxorubicin triggered by the acidic endosomal pH. As evidenced by experiments in tumor-bearing mice, such a nanodrug is stealthy during blood circulation, and targets tumor sites with high efficiency. Moreover, this nanodrug is more effective and less toxic than free doxorubicin. This study provides a green and versatile approach for preparing biodegradable nanodrugs via a simple and efficient process. Moreover, this study extends the applications of CO2 based polymers in the biomedical field, promoting the development of CO2 polymerization fixation.

A shear-thinning electrostatic hydrogel with antibacterial activity by nanoengineering of polyelectrolytes.

Injectable shear-thinning hydrogels can be prepared by the non-covalent interactions between hydrophilic polymers. Although electrostatic force is a typical non-covalent interaction, direct mixing of two oppositely charged polyelectrolytes usually leads to a complex coacervate rather than an injectable hydrogel. Herein, a facile approach is proposed to prepare a shear-thinning hydrogel by nanoengineering of polyelectrolytes. Nanosized cationic micelles with electroneutral shells were prepared by mixing methoxyl poly(ethylene glycol)-block-poly(ε-caprolactone) and poly(ε-caprolactone)-block-poly(hexamethylene guanidine) hydrochloride-block-poly(ε-caprolactone) in an aqueous solution. When sodium carboxymethyl cellulose was added into the micellar solution, the outer poly(ethylene glycol) shell of mixed micelles prevented the instant electrostatic interaction between poly(hexamethylene guanidine) hydrochloride segments and sodium carboxymethyl cellulose, resulting in a homogenous shear-thinning electrostatic (STES) hydrogel. Because of the cationic poly(hexamethylene guanidine) hydrochloride segments, this hydrogel exhibits strong antibacterial activity against both Gram-positive and Gram-negative bacteria. Furthermore, the poly(ε-caprolactone) core of the mixed micelles can efficiently encapsulate a hydrophobic drug. In this work, curcumin-loaded STES hydrogel prepared by this method was used as wound dressing material that can promote wound healing even in infected wounds by further reducing bacterial infection via releasing curcumin. The present study provides a facile strategy to prepare shear-thinning antibacterial hydrogels from polyelectrolytes, which has great potential in biomedical application.

Facile and Versatile Modification of Cotton Fibers for Persistent Antibacterial Activity and Enhanced Hygroscopicity.

Natural fibers with functionalities have attracted considerable attention. However, developing facile and versatile strategies to modify natural fibers is still a challenge. In this study, cotton fibers, the most widely used natural fibers, were partially oxidized by sodium periodate in aqueous solution, to give oxidized cotton fibers containing multiple aldehyde groups on their surface. Then poly(hexamethylene guanidine) was chemically grafted onto the oxidized cotton fibers forming Schiff bases between the terminal amines of poly(hexamethylene guanidine) and the aldehyde groups of oxidized cotton fibers. Finally, carbon-nitrogen double bonds were reduced by sodium cyanoborohydride, to bound poly(hexamethylene guanidine) covalently to the surface of cotton fibers. These functionalized fibers show strong and persistent antibacterial activity: complete inhibition against Escherichia coli and Staphylococcus aureus was maintained even after 1000 consecutive washing in distilled water. On the other hand, cotton fibers with only physically adsorbed poly(hexamethylene guanidine) lost their antibacterial activity entirely after a few washes. According to Cell Counting Kit-8 assay and hemolytic analysis, toxicity did not significantly increase after chemical modification. Attributing to the hydrophilicity of poly(hexamethylene guanidine) coatings, the modified cotton fibers were also more hygroscopic compared to untreated cotton fibers, which can improve the comfort of the fabrics made of modified cotton fibers. This study provides a facile and versatile strategy to prepare modified polysaccharide natural fibers with durable antibacterial activity, biosecurity, and comfortable touch.

Synthesis and Properties of Networks Based on Thiol-ene Chemistry Using a CO2 -Based δ-Lactone.

3-Ethylidene-6-vinyltetrahydro-2H-pyran-2-one, a divinyl δ-lactone derived from CO2 and 1,3-butadiene, is used for the synthesis of networks with various compositions through the thiol-ene click reaction with di- and tri-thiol compounds. Thermal, mechanical, and optical properties of the networks are characterized. The networks have sharp and uniform glass transitions and show good thermal stability with T d from 287 to 332 °C. Mechanical properties of the networks can be adjusted by the cross-link density; 6.18 MPa of tensile strength, 574% break elongation and 1.84 of tan δ at maximum are reached. Metal complexation makes the networks tougher due to additional cross-links. The highly homogeneous networks are transparent with average 90% transmittance of visible light, and of decent refractive indices around 1.55. Swelling-induced twist shape transformation and visible QR code under UV light is realized by pattern of the network.

Dispersible lanthanide organic hybrid nanoparticles: synthesis, morphology and application.

Novel nanoparticles of coordination polymers (CPs) with various morphologies are successfully prepared. The obtained products can be well-dispersed to make films on glass substrates by the colloidal deposition method and introduced into methyl cellulose to produce transparent and luminescent films.

An injectable drug-loaded hydrogel based on a supramolecular polymeric prodrug.

We reported a novel injectable doxorubicin-loaded hydrogel based on host-guest interaction and Schiff's base reaction. A supramolecular polymeric prodrug was prepared through the inclusion of adamantane-modified doxorubicin into the ß-cyclodextrin cavity on the polyaldehyde dextran chain, which was in situ crosslinked by carboxymethyl chitosan.

Research into europium complexes as magnetic resonance imaging contrast agents (Review).

Europium (Eu) is a paramagnetic lanthanide element that possesses an outstanding luminescent property. Eu complexes are ideal fluorescence imaging (FI) agents. Eu2+ has satisfactory relaxivity and optical properties, and can realize magnetic resonance (MRI)-FI dual imaging applications when used with appropriate cryptands that render it oxidatively stable. By contrast, based on the chemical exchange saturation transfer (CEST) mechanism, Eu3+ complexes can provide enhanced MRI sensitivity when used with optimal cryptands, incorporated into polymeric CEST agents or blended with Gd3+. Eu complexes are promising in MRI-FI dual imaging applications and have a bright future.

Carbon bridged triphenolate lanthanide complexes: synthesis, characterization, DFT studies and catalytic activities for isoprene polymerization.

The dinuclear lanthanide complexes [Ln2(L)2(THF)n] (Ln = Nd (1) n = 4, Gd (2) n = 3, Lu (3) n = 2) supported by carbon bridged triphenolate ligands [LH3 = tris(3,5-di-tert-butyl-2-hydroxyphenyl)methane] were synthesized via a salt metathesis reaction between lanthanide trichlorides and LNa3 in THF. All complexes were characterized by elemental analysis and X-ray crystallography, and complex 3 was characterized by (1)H and (13)C NMR spectroscopy. Agostic interactions were found in these complexes and were further substantiated by DFT calculations of complex 3. These lanthanide complexes in combination with aluminum alkyls and [Ph3C](+)[B(C6F5)4](-) generated efficient homogeneous catalysts for the cis-1,4 polymerization of isoprene, with complex 1 having the best catalytic activity.

Reduction-triggered release of paclitaxel from in situ formed biodegradable core-cross-linked micelles.

Paclitaxel-loaded reduction-responsive core-crosslinked micelles were prepared in situ in aqueous media via"click" chemistry. An amphiphilic block copolymer with multiple pendant azide groups was first synthesized through the controlled ring-opening copolymerization of ε-caprolactone (CL) and 5,5-dibromomethyl trimethylene carbonate (DBTC) in the presence of methoxy poly(ethylene glycol) (mPEG) as a macroinitiator, followed by azidation. This amphiphilic block copolymer could self-assemble into micelles and paclitaxel (PTX) could be encapsulated into the micellar core to form PTX-loaded micelles, which were core-crosslinked in situ by propargyl dithiopropionate via"click" chemistry, to develop a reduction-responsive polymeric drug delivery system. The in vitro release studies revealed the minimized release of PTX under physiological conditions, whereas a burst release of PTX was observed in response to reductive conditions. The core-crosslinked micelles displayed efficient cell-uptake and reduction-responsive drug release due to the nanoscale diameter and splitting of disulfide bonds under a reductive environment, which was confirmed by confocal laser scanning microscopy using Nile red as a fluorescent probe. This kind of polymeric nano-carrier with excellent biocompatibility and quick reduction-response opens a new avenue to intracellular anticancer drug delivery.

Chiroptical inversion induced by rotation of a carbon-carbon single bond: an experimental and theoretical study.

We propose a new strategy to construct chiral molecular switches with highly reversible and sensitive chiroptical responses to variations in the external environment. Its fundamental concept involves a stimuli-triggered exchange of two conformations presenting significantly different chiroptical properties through the rotation of a carbon-carbon single bond, as demonstrated by chiral Schiff bases s-1, s-2, and a salicylamide analogue s-3. Upon addition of base in solution, the circular dichroism (CD) spectra of these molecular switches displayed unique changes featuring an inversion of the Cotton effect's signs, and the original CD profiles can be recoverd by acidification. Various spectroscopic studies as well as the conformational analysis combining with TDDFT computations allowed clear elucidation of the chiroptical inversion mechanism. It is expected that this kind of chiroptical switches is of great interest for molecular recognition, chemosensing, and the construction of molecular-scale devices. Furthermore, the present study indicates that the use of the conformational transition about a single bond may serve as the basis for designing chiroptical inversion systems.

A facile strategy to prepare redox-responsive amphiphilic PEGylated prodrug with high drug loading content and low critical micelle concentration.

A redox-responsive amphiphilic polymeric prodrug was synthesized in a facile way by polycondensation of oligo(ethylene glycol) with dicarboxylic acids including malic acid and 3,3'-dithiodipropionic acid , followed by esterification with ibuprofen, which was used as a model drug. Because of its amphiphilic nature and relatively high molecular weight, this polymeric prodrug can form stable micelles in aqueous media with a low critical micellar concentration (CMC). Free ibuprofen molecules can be steadily incorporated into the core of these micelles with a surprisingly high loading content (38.9 wt%), owing to hydrophobic interaction and π-π stacking with the ibuprofen moieties in the copolymer. The in vitro release results indicate that there was a relatively slow and sustained release of the conjugated ibuprofen moieties, while encapsulated ibuprofen molecules showed a rapid release. Furthermore, for both the conjugated ibuprofen and the encapsulated ibuprofen there was an accelerated release in the presence of 10 mM dl-dithiothreitol due to cleavage of the disulfide bonds, which lead to disassociation of the micelles. Notably, this prodrug was revealed to have excellent cell compatibilities via a cell counting kit-8 (CCK-8) assay. Confocal laser scanning microscope observations indicated that the micelles based on the polymeric prodrug can be taken up quickly by cells and present a redox-responsive drug release in cytoplasm. This kind of polymeric nanocarrier with a high drug loading content, low CMC, excellent biocompatibility and rapid response to a reductive environment may have tremendous scope in the area of controlled drug delivery.

Acid-triggered drug release from micelles based on amphiphilic oligo(ethylene glycol)-doxorubicin alternative copolymers.

We report a facile strategy to synthesize pH-sensitive amphiphilic oligo(ethylene glycol) (OEG)-doxorubicin (DOX) alternative conjugates. Poly[oligo(ethylene glycol) malicate] (POEGM) with numerous pendent hydroxyl groups was first synthesized by the direct polycondensation of oligo(ethylene glycol) (OEG) with malic acid under mild conditions. Then, benzaldehyde groups were introduced into the POEGM backbone via esterification between the pendant hydroxyl groups and 4-formylbenzoic acid. DOX moieties were finally attached to the polymeric backbone via benzoic imine linkages to obtain the OEG-DOX conjugates. Because of the high molecular weight and alternate architecture, this type of amphiphilic OEG-DOX alternative conjugates can form stable micelles in aqueous solution with a high DOX loading content (38.2 wt%) and low critical micelle concentrations (0.021 mg mL-1). Due to the pH-sensitive benzoic imine linkages between the DOX moieties and polymeric backbone, DOX could be rapidly released from the micelles at pH 5.8, whereas only a minimal amount of DOX was released at pH 7.4 under the same conditions. The cytotoxicity assay indicates that the OEG-DOX conjugates show cytotoxic effects to MCF-7 tumor cells, while the corresponding polymer material POEGM-CHO exhibits a great biocompatibility for MCF-7 tumor cells. These pH-sensitive and high drug loading nano-carriers based on the OEG-DOX alternative conjugates provide a promising platform for targeted cancer therapy.

A polymeric film probe with a turn-on fluorescence response to hydrogen sulfate ions in aqueous media.

A new kind of hydrophilic copolymer poly(HEMA-co-VNP) was designed and synthesized by the radical copolymerization of 2-hydroxyethylmethacrylate (HEMA) and 2-{[2-(4-vinylbenzyloxy)naphthalen-1-yl]methyleneamino}-(S)-2-phenylethanol (VNP). The desired copolymer showed a highly selective red-shifted emission and a unique chiroptical response upon HSO4 - binding in organic solution. UV-vis and 1H NMR spectroscopic studies revealed that the hydrogen bonding between the imine moiety in the VNP repeating units and HSO4 - is crucial for the high selectivity of the receptor to this anion. As expected, the incorporation of HEMA into the polymer matrix endowed the copolymer excellent hydrophilicity, flexibility and good film-forming properties. Thus, high-quality film sensors could be easily fabricated on quartz plates through spin-casting techniques. The resultant polymeric films can recognize HSO4 - ions among a series of common anions in aqueous solution with high selectivity and sensitivity. The promising new film probe for HSO4 - has distinct characteristics such as a rapid response, enough stability in an aqueous media and practicality.

Well-defined novel fluorene-containing polymers: synthesis, fluorescent properties, and micellar nanoparticles.

We report the synthesis of a new monomer, 9,9-diethylfluoren-2-yl methyl methacrylate (FMMA) and its controlled reversible addition-fragmentation chain transfer (RAFT) homopolymerization to give PFMMA with narrow polydispersity indices (PDIs). The corresponding copolymerization with 2-(N,N-dimethylamino)ethyl methacrylate (DMAEMA) also gave well-defined block and random copolymers with controlled molecular weights and narrow PDIs. Their thermal behavior, UV-Vis absorption, and photoluminescent properties were studied. The PDMAEMA-b-PFMMA amphiphilic block copolymers showed self-assembly into aqueous spherical micellar nanoparticles with uniform size. The PFMMA core showed photoluminescence when carrying dichloromethane "guest" molecules and its emission was shown to be quenched after the release of the guest.

Direct cyclodextrin-mediated ring opening polymerization of ϵ-caprolactone in the presence of yttrium trisphenolate catalyst.

Unmodified ß-cyclodextrin has been directly used to initiate ring-opening polymerization of ϵ-caprolactone in the presence of yttrium trisphenolate. Well-defined cyclodextrin (CD)-centered star-shaped poly(ϵ-caprolactone)s have been successfully synthesized containing definite average numbers of arms (N(arm) = 4-6) and narrow polydispersity indexes (below 1.10). The number-average molecular weight (M(n,NMR)) and average molecular weight per arm (M(n,arm)) are controlled by the feeding molar ratio of monomer to initiator. The prepared star-PCL with M(n,NMR) of 2.7 × 10(3) is in fully amorphous and that with M(n,NMR) of 13.3 × 10(3) is crystallized. In addition, the obtained poly(e-caprolactone) (PCL) stars with various molecular weights have different solubilities in methanol and tetrahydrofuran, which can be applied for further modifications.

Synthesis and characterization of benzoxazine-functionalized amine bridged bis(phenolate) lanthanide complexes and their application in the ring-opening polymerization of cyclic esters.

The synthesis and structures of lanthanide complexes supported by benzoxazine-functionalized amine bridged bis(phenolate) ligand 6,6'-(2-(8-tert-butyl-6-methyl-2H-benzo[e][1,3]oxazin-3(4H)-yl)ethylazanediyl)bis(methylene)bis(2-tert-butyl-4-methylphenolato) (L(2-)) are described. Salt metathesis reaction between lanthanide trichloride and 2 eq of LNa(2) in THF at room temperature afforded the corresponding "ate" complexes [L(2)LnNa(THF)(2)] (Ln[double bond, length as m-dash]Y (1), Nd (2), Er (3), Yb (4)). Further treatment of the product with 18-crown-6 afforded discrete ion-pair complexes [L(2)Ln][(18-crown-6)Na(THF)(2)] (Ln[double bond, length as m-dash]Y (5), Yb (6)). The single-crystal structural analyses of 1 and 3-6 revealed that the lanthanide cation and the sodium cation were bridged by two phenolate oxygen atoms in complexes 1, 3 and 4, while in complexes 5 and 6, the anion comprises a lanthanide cation coordinated by two L(2-) and the cation is comprised of a sodium cation surrounded by an 18-crown-6 and two THF molecules. These complexes were found to exhibit distinct activities towards the ring-opening polymerization of ε-caprolactone and l-lactide.

Synthesis, self-assembly, and drug-loading capacity of well-defined cyclodextrin-centered drug-conjugated amphiphilic A(14)B(7) Miktoarm star copolymers based on poly(epsilon-caprolactone) and poly(ethylene glycol).

Novel drug-conjugated amphiphilic A(14)B(7) miktoarm star copolymers composed of 14 poly(epsilon-caprolactone) (PCL) arms and 7 poly(ethylene glycol) (PEG) arms with beta-cyclodextrin (beta-CD) as core moiety were synthesized by the combination of controlled ring-opening polymerization (CROP) and "click" chemistry. (1)H NMR, FT-IR, and SEC-MALLS analyses confirmed the well-defined A(14)B(7) miktoarm star architecture. These amphiphilic miktoarm star copolymers could self-assemble into multimorphological aggregates in aqueous solution, which were characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Moreover, the drug-loading efficiency and drug-encapsulation efficiency of the drug-conjugated miktoarm star copolymers were higher than those of the corresponding non-drug-conjugated miktoarm star copolymers.

Copolymerization of CO2 and cyclohexene oxide using a lysine-based (salen)Cr(III)Cl catalyst.

A new, natural lysine-based (salen)Cr(III)Cl ((lys-salen)Cr(III)Cl) complex was prepared and its catalytic activity for the copolymerization of CO(2) and cyclohexene oxide (CHO) was described in the presence of PPNCl (PPN(+) = bis(triphenylphosphoranylidene)ammonium) as cocatalyst. The influence of the reaction time, operating temperature and the molar ratio of the catalyst components on the copolymerization was investigated in detail. The results showed that the (lys-salen)Cr(III)Cl, synthesized from non-ortho-diamine, could effectively catalyze the alternating copolymerization (carbonate linkages = 94.6-99.0%). The selectivity was >95%, and was less sensitive to the temperature and the molar ratio of catalyst components, compared to that of the copolymerization catalyzed by traditional salen-metal complexes. The ESI-MS analyses of oligomer and (lys-salen)Cr(III)Cl indicated that a possible chain-transfer reaction had taken place, which might be induced by the water coordinating to the central metal ion.

Characterization of impurities in the bulk drug lisinopril by liquid chromatography/ion trap spectrometry.

Two trace impurities in the bulk drug lisinopril were detected by means of high-performance liquid chromatography coupled with mass spectrometry (HPLC/MS) with a simple and sensitive method suitable for HPLC/MSn analysis. The fragmentation behavior of lisinopril and the impurities was investigated, and two unknown impurities were elucidated as 2-(6-amino-1-(1-carboxyethylamino)-1-oxohexan-2-ylamino)-4-phenylbutanoic acid and 6-amino-2-(1-carboxy-3-phenylpro-pylamino)-hexanoic acid on the basis of the multi-stage mass spectrometry and exact mass evidence. The proposed structures of the two unknown impurities were further confirmed by nuclear magnetic resonance (NMR) experiments after preparative isolation.