Combined ATRP and 'click' chemistry for designing stable tumor-targeting superparamagnetic iron oxide nanoparticles

Important issues in the design of superparamagnetic iron oxide nanoparticles (SPIONs) for cancer diagnosis include stability under physiological conditions and specificity in targeting the cancer cells. In the present study, atom transfer radical polymerization (ATRP) was used to graft SPIONs with poly(glycidyl methacrylate-co-poly(ethylene glycol) methyl ether methacrylate) (SPIONs-P(GMA-co-PEGMA)). The PEGMA in the copolymer chain confers high stability to the nanoparticles in aqueous medium, and prevents recognition by macrophages with the aim of prolonging their in vivo circulation time. The GMA groups were used for conjugating the cancer targeting ligand, folic acid (FA), via 'click' chemistry. Using this method, the amount of FA conjugated to the nanoparticles (SPIONs-P(GMA-co-PEGMA)-FA) can be readily controlled. The specificity of cellular uptake of the nanoparticles by three different cell lines was investigated. The cellular iron uptake by KB cells (human epidermoid carcinoma) after 24 h of incubation is about thirteen and five times higher than those by 3T3 fibroblasts and macrophages, respectively. No significant cytotoxicity was observed with these three types of cells. The high targeting efficiency and biocompatibility of these nanoparticles are promising features for in vivo specific targeting and detection of tumor cells which overexpress the folate receptor.     

ATRP, subsequent azide substitution and 'click' chemistry: three reactions using one catalyst in one pot

This communication describes a novel and fast reaction to substitute the living chain end after Atom Transfer Radical Polymerization (ATRP) by an azide functionality. The reaction is catalyzed by the ATRP catalyst at room temperature in aqueous solution and can be followed by a 'click' reaction using again the same catalyst.     

Novel Hydrophobic Biodegradable Ester-Polymers Obtained via Azlactone Chemistry

Biodegradable polymers having a potential for constructing resorbable therapeutical micro- and nano-containers were synthesized by interaction of bis-azlactones with bis-(L-leucine)-1,6-hexylene diester/1,6-diamino hexane either separately or as comonomers. The thermograms (DSC) all of them showed a wide endothermal peak within 55–120 °C with a maximum ranged from 86 °C to 96 °C. The peak was assigned to the melting of hydrophobic domains formed by aromatic terephthalic acid fragments in the polymeric backbones. Preliminary in vitro study showed that the ester-bonds containing polymers obtained are biodegradable – α-chymotrypsin catalyzed ester bonds hydrolysis rates ranged within 0.02–0.34 µmole/min.     

Disintegration-controllable stimuli-responsive polyelectrolyte multilayer microcapsules via covalent layer-by-layer assembly

The disintegration-controllable stimuli-responsive polyelectrolyte multilayer microcapsules have been fabricated via the covalent layer-by-layer assembly between the amino groups of chitosan (CS) and the aldehyde groups of the oxidized sodium alginate (OSA) onto the sacrificial templates (polystyrene sulfonate, PSS) which was removed by dialysis subsequently. The covalent crosslinking bonds of the multilayer microcapsules were confirmed by FTIR analysis. The TEM analysis showed that the diameter of the multilayer microcapsules was <200nm. The diameter of the multilayer microcapsules decreased with the increasing of the pH values or the ionic strength. The pH and ionic strength dual-responsive multilayer microcapsules were stable in acidic and neutral media while they could disintegrate only at strong basic media.     

Heterocyclic monomers via reissert chemistry

An AA bisphenolic monomer ( 13 ), an AB activated fluoro‐phenolic monomer ( 14 ), and an AB₂ alcohol‐diester monomer precursor ( 17 ), all based on the isoquinoline nucleus, were prepared using Reissert compound chemistry. Additionally, model reactions established the efficiency of condensation of isoquinoline Reissert compounds with dihaloalkanes, providing evidence of the potential of this reaction to produce high molecular weight polymers, which was subsequently realized. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Metal-containing nanofibers via coordination chemistry

One-dimensional fibrous nanostructures may exhibit unique mechanical, optical, magnetic, and electronic properties as a result of their nanoscale dimensions. Various approaches have been used to prepare nanofibers (e.g., electrospinning, vapor deposition), but this review focuses on the research and development of self-assembled nanofibers formed through coordination chemistry. By employing metal–ligand interactions that extend along the backbone of the aggregates, nanofibrous, often gel-forming, materials with appealing properties have been formed. Other fibers formed through electrostatic interactions between charged coordination complexes are also discussed. The optical, electronic, and magnetic properties conferred upon the materials by the embedded coordination complexes render the nanofibers useful for applications in the fields of catalysis, sensors, and gas storage, and potentially for developing nanosized devices.     

Phosphatidylcholine-derived bolaamphiphiles via click chemistry

The copper-catalyzed azide alkyne cycloaddition is employed to modify phosphatidylcholine precursors with sn-2 acyl chains containing terminal alkyne or azide groups. Although the reactions are conducted as biphasic dispersions, the yields are essentially quantitative. Bolaamphiphiles are formed by simply clicking together two phosphatidylcholine alkyne precursors to a central bisazide scaffold. The chemistry introduces polar 1,4-triazole units into the lipophilic region of the bilayer membrane, and the bolaamphiphiles do not form stable vesicles. [structure: see text].     

Modular 'click' sensors for zinc and their application in vivo

Although the central role that zinc plays in many biological processes and important disease states is now well-established, there remains a pressing need to develop an absolute understanding of the underlying biology of zinc trafficking in terms of its dynamic and quantitative processing in specific organelles. Here we describe the modular synthesis of zinc sensors using a 'click' approach and demonstrate the applicability of our new sensors in vivo using a zebrafish model.     

Preparation of Biodegradable Polylactide Microparticles via a Biocompatible Procedure

PLA MPs are prepared via a novel and toxic‐chemical‐free fabrication route using ethyl lactate, a green solvent and FDA‐approved aroma. MPs are obtained by a solution jet break‐up and solvent displacement method. Adjusting flow parameters allows the tuning of MPs size between 60 and 180 µm, with reduced polydispersity. Morphological analysis shows microporous particles with Janus‐like surface. A fluorophore is successfully loaded into the MPs during their formation step. This versatile green solvent‐based procedure is proven to be suitable for drug encapsulation and delivery applications. The method may be extended to different droplet generation techniques.

     

熔融聚合法直接合成生物降解材料PLEG

以乳酸(LA)和分子量1000的聚乙二醇(PEG)为原料(mLA／mPEG=9),以氯化亚锡为催化剂(mc／mLA=0．005),165℃、70Pa下熔融聚合10h,合成生物降解材料聚乳酸-聚乙二醇(PLEG)。其[η]最高可达0．3398dL／g。直接熔融聚合法有利于降低其成本。     

pH-responsive protein microcapsules fabricated via glutaraldehyde mediated covalent layer-by-layer assembly

Bovine serum albumin (BSA) hollow microcapsules were fabricated through glutaraldehyde (GA) mediated covalent layer-by-layer assembly. The GA cross-linking of the adsorbed BSA on the colloidal particles enabled their surfaces to be covered by reactive aldehyde groups, which reacted with BSA molecules to result in another covalently linked layer. Repeating of this cycle could then yield particles coated with BSA multilayers. Hollow microcapsules well dispersed in water were obtained after core removal. The good integrity and morphology of the BSA capsules were confirmed and characterized by confocal laser scanning microscopy, scanning electron microscopy and scanning force microscopy. The obtained BSA microcapsules possess reversible pH response, i.e., the capsules are permeable to macromolecules below pH 4 or above pH 10, while impermeable in between. The mechanisms of permeability transition were discussed. Using this property, dextran, with a molecular weight of ~155 kDa, was successfully loaded.     

Thermally curable polyvinylchloride via click chemistry

Novel side‐chain benzoxazine functional polyvinylchloride (PVC‐Benzoxazine) was synthesized by using “Click Chemistry” strategy. First, approximately 10% of chloro groups of PVC were converted to azido groups by using NaN₃ in N,N‐dimethylformamide. Propargyl benzoxazine was prepared independently by a ring closure reaction between p‐propargyloxy aniline, paraformaldehyde, and phenol. Finally, azidofunctionalized PVC was coupled to propargyl benzoxazine with high efficiency by click chemistry. The spectral and thermal analysis confirmed the presence of benzoxazine functionality in the resulting polymer. It is shown that PVC containing benzoxazine undergoes thermally activated curing in the absence of any catalyst forming PVC thermoset with high thermal stability. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 3512–3518, 2008     

3,4,5-triarylisothiazoles via C-C coupling chemistry

The regiocontrolled preparation of triarylisothiazoles is presented. 3-Halo-5-phenylisothiazole-4-carbonitriles, 1 (hal=Cl) and 18 (hal=I), are converted into the corresponding 4-bromo derivatives 5 (3-hal=Cl) and 24 (3-hal=I) via a Hunsdiecker strategy while the 4-iodo analogues 7 (3-hal=Cl) and 22 (3-hal=I) are prepared via a Hoffmann and Sandmeyer strategy. Regioselective Suzuki, Stille and Negishi reactions occur at C-4 with both the 4-bromo- and 4-iodoisothiazoles 5 and 7 , the latter being more reactive than the former. 3-Iodoisothiazoles 22 and 24 fail to give regiocontrolled Suzuki, Stille or Negishi couplings, however, 4-bromo-3-iodo-5-phenylisothiazole 24 gives the regiospecific palladium catalysed Ullmann-type reaction product 3,3'-bi(4-bromo-5-phenylisothiazole) 25 . Alkali hydrolysis of 3-chloro-4,5-diphenylisothiazole 8 gives the 3-hydroxy analogue 12 which is converted into 3-bromo-4,5-diphenylisothiazole 13 with POBr(3). 3-Bromoisothiazole 13 reacts with phenylzinc chloride to give 3,4,5-triphenylisothiazole 17 but fails to undergo effective Suzuki or Stille couplings. 3,5-Diphenylisothiazole-4-carbonitrile 26 is converted into the 4-bromo- and 4-iodo-3,5-diphenylisothiazoles 30 and 34 both of which are effective for Suzuki and Stille couplings. A series of triarylisothiazoles are prepared in this manner and fully characterised.     

Biodegradable Poly(ester hydrazide)s via Enzymatic Polymerization

Summary: The reaction of hydrazine with ethyl glycolate results in 1,2‐bisglycoylhydrazine, a monomer that was used for the lipase‐catalyzed synthesis of biodegradable poly(ester hydrazide)s. The polymers derived from the hydrazide‐containing monomer and vinyl‐activated adipic, suberic, and sebacic acid, respectively, showed low melting temperatures of 136 to 141 °C and are thermally stable up to 300 °C. The aliphatic poly(ester hydrazide)s (PEHs) are highly crystalline, as proven by polarization microscopy and atomic force microscopy. Further, the PEHs represent the first described biodegradable poly(hydrazide)s. They degrade in the presence of lipase at 37 °C within a few weeks.

Synthetic route to poly(ester hydrazide)s.     

Amphiphilic silicone architectures via anaerobic thiol-ene chemistry

Despite broad application, few silicone-based surfactants of known structure or, therefore, surfactancy have been prepared because of an absence of selective routes and instability of silicones to acid and base. Herein the synthesis of a library of explicit silicone-poly(ethylene glycol) (PEG) materials is reported. Pure silicone fragments were generated by the B(C(6)F(5))(3)-catalyzed condensation of alkoxysilanes and vinyl-functionalized hydrosilanes. The resulting pure products were coupled to thiol-terminated PEG materials using photogenerated radicals under anaerobic conditions.     

Synthesis of heterocyclic monomers via Reissert chemistry

The chemistry of Reissert compounds has been used to synthesize activated difluorotetraketone monomers containing two coupled isoquinolyl moieties, linked at either the 1,1′‐ or 4,4′‐positions. These monomers offer routes to novel families of poly(heteroarylene ether)s. New 4,4′‐coupled bis(Reissert compound) 9 containing 4,4′‐diketo moieties failed to afford the desired difluorotetraketo monomer upon attempted rearrangement. However, analogous bis(Reissert compound) 19 containing 4,4′‐dibenzyl units did so, via aldehyde condensation, hydrolysis of the intermediate ester and oxidation of the four benzylic moieties to keto groups; thus the novel difluorotetraketone monomer 10 was prepared. Novel bis(Reissert compound)s 24 , 28 , and 35 were synthesized from diacid chlorides and 4‐(p‐fluorobenzyl)isoquinoline. Rearrangement of 24 to the diketone 29 , followed by oxidation of the 4‐benzyl moieties resulted in difluorotetraketone monomer 30 containing a 1,1′‐linked bisisoquinoline. The 1,1′‐linked bis(isoquinolylfluorodiketo) monomer 38 , isomeric with 10 , was prepared from 4‐(p‐fluorobenzyl) Reissert compound 36 by condensation with terephthaldehyde, ester hydrolysis to diol 37 , and oxidation. In the course of this effort, a number of new isoquinoline Reissert compounds were synthesized as model systems. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 3856–3867, 2010     

Shaping non-noble metal nanocrystals via colloidal chemistry

Non-noble metal nanocrystals with well-defined shapes have been attracting increasingly more attention in the last decade as potential alternatives to noble metals, by virtue of their earth abundance combined with intriguing physical and chemical properties relevant for both fundamental studies and technological applications. Nevertheless, their synthesis is still primitive when compared to noble metals. In this contribution, we focus on third row transition metals Mn, Fe, Co, Ni and Cu that are recently gaining interest because of their catalytic properties. Along with providing an overview on the state-of-the-art, we discuss current synthetic strategies and challenges. Finally, we propose future directions to advance the synthetic development of shape-controlled non-noble metal nanocrystals in the upcoming years.

This minireview describes the state-of-the-art of shape-controlled nanocrystals of third raw transition metals and discusses future directions to advance their synthetic development, which is important for many applications.     

Functional polyisobutylenes via a click chemistry approach

1‐(ω‐Azidoalkyl)pyrrolyl‐terminated polyisobutylene (PIB) was successfully synthesized both by substitution of the terminal halide of 1‐(ω‐haloalkyl)pyrrolyl‐terminated PIB with sodium azide and by in situ quenching of quasiliving PIB with a 1‐(ω‐azidoalkyl)pyrrole. Azide substitution of the terminal halide was carried out in 50/50 heptane/DMF at 90 °C for 24 h using excess azide. The 1‐(ω‐haloalkyl)pyrrolyl‐PIB precursors included 1‐(2‐chloroethyl)pyrrolyl‐PIB, 1‐(2‐bromoethyl)pyrrolyl‐PIB, and 1‐(3‐bromopropyl)pyrrolyl‐PIB. In situ quenching involved direct addition of 1‐(2‐azidoethyl)pyrrole to quasiliving PIB initiated from 5‐tert‐butyl‐1,3‐di(1‐chloro‐1‐methylethyl)benzene (bDCC)/TiCl₄ at ?70 °C in hexane/CH₃Cl (60/40, v/v). ¹H NMR analysis of the quenched product revealed mixed isomeric end groups in which PIB was attached at either C₂ or C₃ of the pyrrole ring (C₂/C₃ = 0.40/0.60). SEC indicated the absence of coupled PIB under optimized conditions, confirming exclusive mono‐substitution on each pyrrole ring. 1‐(3‐Azidopropyl)pyrrolyl‐PIB was reacted in modular fashion with various functional alkynes, propargyl alcohol, propargyl acrylate, glycidyl propargyl ether, and 3‐dimethylamino‐1‐propyne, via a Huisgen 1,3‐dipolar cycloaddition (Click) reaction, using Cu(I)Br/N,N,N′,N″,N″‐pentamethyldiethylenetriamine or bromtris(triphenylphosphine)Cu(I) as catalyst. The reactions were quantitative and produced PIBs bearing terminal hydroxyl, acrylate, glycidyl, or dimethylaminomethyl groups attached via exclusively four‐substituted triazole linkages. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 2533–2545, 2010