Near-infrared polyfluorene encapsulated in poly(ε-caprolactone) nanoparticles with remarkable large Stokes shift

Near-infrared (NIR) fluorescent dyes have attracted increasing attention as fluorescent probes in biomedical applications due to their low biological autofluorescence as well as high tissue penetration depth. However, their being hydrophobic in nature limits their clinical use as they are prone to aggregate in the physiological environment. Herein, we have designed and synthesized a novel polymeric NIR fluorescent dye and then encapsulated it into a poly(ε-caprolactone) (PCL) matrix by way of an emulsion–diffusion technique. The effect of the structure of the surfactant on the nanoparticle properties is investigated. Results show that polymeric surfactant, Kolliphor® P188, allows the formation of a high fluorescence intensity of the nanoparticles with the highest level homogeneity and stability. The synthesized nanoparticles show significant advantages in terms of a remarkable large stokes shift (276 nm) in the aqueous solution and excellent biocompatibility. The fabrication process is not limited to encapsulation of polymeric fluorescent dye. The synthesized NIR polymeric nanoparticles would be potentially applicable for biomedical applications.

A near-infrared dye encapsulated in poly(ε-caprolactone) nanoparticles have been synthesized. Using Kolliphor® P188 as a surfactant, the stable nanoparticles exhibit strong fluorescence intensity and remarkable large Stokes shift.     

Effects of shear on epitaxial crystallization of poly(ε-caprolactone) on reduced graphene oxide

Epitaxial crystallization of poly(ε-caprolactone) (PCL) on reduced graphene oxide (RGO) was investigated by shearing at different shear rates of 3 s⁻¹ and 75 s⁻¹ and different shear temperatures of 65 °C, 70 °C and 75 °C, respectively. Two dimensional wide angle X-ray diffraction (2D WAXD) results show that the crystallinity and the orientation degrees of the (110) plane of PCL/RGO nanocomposites with shear are higher than those without shear, but the imposed shear field has no obvious effect on the crystal structure of the PCL matrix. Two dimensional small angle X-ray scattering (2D SAXS) results suggest that the imposed shear field makes PCL chains epitaxially crystallize on RGO surfaces to form thicker lamellae. Thereby the melt points of PCL/RGO nanocomposites with shear are higher than that without shear from the differential scanning calorimetry (DSC) results. These results indicate that the imposed shear field can enhance the orientation of the PCL matrix, and promote epitaxial crystallization of PCL chains on RGO surfaces. Higher shear temperature is the requirement for PCL chains to epitaxially crystallize well on RGO at low shear rate, although it is not required for the samples at high shear rate.

Epitaxial crystallization of poly(ε-caprolactone) (PCL) on reduced graphene oxide (RGO) was investigated by shearing at different shear rates of 3 s⁻¹ and 75 s⁻¹ and different shear temperatures of 65 °C, 70 °C and 75 °C, respectively.     

Crystallization,rheology and mechanical properties of the blends of poly(l-lactide) with supramolecular polymers based on poly(d-lactide)–poly(ε-caprolactone-co-δ-valerolactone)–poly(d-lactide) triblock copolymers

In this study, we investigated the blending of poly(l-lactide) (PLLA) with supramolecular polymers based on poly(d-lactide)–poly(ε-caprolactone-co-δ-valerolactone)–poly(d-lactide) (PDLA–PCVL–PDLA) triblock copolymers as an efficient way to modify PLLA. The supramolecular polymers (SMP) were synthesized by the terminal functionalization of the PDLA–PCVL–PDLA copolymers with 2-ureido-4[1H]-pyrimidinone (UPy). The structure, thermal properties and rheological behavior of the synthesized supramolecular polymers were studied; we found that the formation of the UPy dimers expanded the molecular chain of the polymer and the incorporation of the UPy groups suppressed the crystallization of polymers. In addition, the synthesized supramolecular polymers had a low glass transition temperature of about −50 °C, showing the characteristics of elastomers. On this basis, superior properties such as a fast crystallization rate, high melt strength, and toughness of fully bio-based, i.e., PLA-based materials were achieved simultaneously by blending PLLA with the synthesized supramolecular polymers. In the PLLA/SMP blends, PLLA could form a stereocomplex with its enantiomeric PDLA blocks of supramolecular polymers, and the stereocomplex crystals with the cross-linking networks reinforced the melt strength of the PLLA/SMP blends. The influences of the SMP composition and the SMP content in the PLLA matrix on crystallization and mechanical properties were analyzed. The supramolecular polymers SMP0.49 and SMP1.04 showed a reverse effect on the crystallization of PLLA. Tensile tests revealed that the lower content of the synthesized supramolecular polymers could achieve toughening of the PLLA matrix. Therefore, the introduction of supramolecular polymers based on PDLA–PCVL–PDLA is an effective way to control the crystallization, rheology and mechanical properties of PLLA.

Supramolecular polymer based on PDLA–PCVL–PDLA triblock copolymer was used for the modification of PLLA, and the results showed that it is an effective way to control the crystallization, rheology and mechanical properties of PLLA.     

Effect of polyvinyl acetals on non-isothermal crystallization behaviour and mechanical properties of poly(ε-caprolactone)

Polyvinyl acetaldehyde (PVAC) and polyvinyl butyral (PVB), as nucleating agents, were melt mixed with poly(ε-caprolactone) (PCL), and the non-isothermal crystallization behavior and crystalline morphology of PCL was characterized using differential scanning calorimetry (DSC) and polarizing microscopy (POM). It was found that melt shearing made the crystallinity of control PCL increase from 37.94% (as-received) to 41.15% and the crystallization temperature raised by 7.7 °C. As the mass fraction of polyvinyl acetals increased from 0.1 wt% to 10 wt%, both crystallization temperature and crystallinity of PCL were decreased; the spherulite size of PCL was increased from a few microns to 200 μm and a fast cooling procedure facilitated the homogeneity of spherulite size. When the content of nucleating agent was less than 1 wt%, no obvious microphase separation was observed under scanning electron microscopy; the tensile strength, yield strength and elongation at break of PCL increased slightly; and the Young''s modulus of PCL was improved by 67% at a 0.1 wt% mass fraction of PVB which is beneficial to PCL in high load bearing applications. When the contents of nucleating agents were higher than 1 wt%, the microphase separation occurred obviously and a large amount of fine spherulites appeared with the deterioration of mechanical properties. The modified Avrami and Tobin models could well describe the non-isothermal crystallization kinetics.

Melt shearing made the crystallinity of as-received PCL increased and the crystallization temperature raised by 7.7 °C. Polyvinyl acetals increased the spherulite size of PCL from a few microns to 200 μm and PVB improved the Young’s modulus of PCL by 67%.     

Synthesis and characterization of 4-arm star-shaped amphiphilic block copolymers consisting of poly(ethylene oxide) and poly(ε-caprolactone)

Star-shaped polymers exhibit lower hydrodynamic volume, glass transition temperature, critical micelles concentration (CMC), and higher viscosity and drug-loading capacity compared to their linear counterparts. In the present study, amphiphilic biodegradable 4-arm star-shaped block copolymers, based on poly(ethylene oxide) (PEO) as a hydrophilic part and poly(ε-caprolactone) (PCL) as a hydrophobic segment, are synthesized by ring-opening polymerization of ε-caprolactone employing pentaerythritol as an initiator and stannous octoate as a catalyst, followed by the coupling reaction with carboxyl-functionalized monomethoxy poly(ethylene oxide) (MeO-PEO-COOH). The structures of intermediates were deduced through ¹H-NMR and FT-IR spectroscopy. Average chemical composition of the star block copolymer is determined by proton NMR. Information related to molar mass distribution of targeted products and their precursors is obtained by size exclusion chromatography (SEC). However, due to its inherent poor resolution SEC could not reveal whether all the parent homopolymers are coupled to each other or remained unattached to the other segment. In order to comprehensively characterize the synthesized star-block copolymers, liquid chromatography at critical conditions of both blocks is employed. The study allowed for separation of homopolymer precursors from targeted star-block copolymers. The study exposed heterogeneity of star block copolymers that was not possible by conventional techniques.

LCCC on RP columns proves to be efficient for separation of precursors from targeted star block copolymers in a single run.     

Sustainable xanthophylls-containing poly(ε-caprolactone)s: synthesis,characterization, and use in green lubricants

Three xanthophylls [(3R,3′R,6′R)-lutein (1), (3R,3′S)-zeaxanthin (2), and (3R,3′S)-astaxanthin (3)] were used for the first time as initiators in the ring-opening polymerization (ROP) of ε-caprolactone (CL) catalyzed by tin(ii) 2-ethylhexanoate [Sn(Oct)₂] for the synthesis of novel sustainable xanthophyll-containing poly(ε-caprolactone)s (xanthophylls-PCL). The obtained polyesters were characterized by ¹H and ¹³C NMR, FT-IR, DSC, SEC, and MALDI-TOF MS, and their use as additives in green lubricants was evaluated using a sliding friction test under boundary conditions. Xanthophylls-PCL were obtained with good conversions and with molecular weights determined by SEC to be between 2500 and 10 500 Da. The thermal properties of xanthophyll-polyesters showed a crystalline domain, detected by DSC. Lastly, the green lubricant activity of these polymers was evaluated and the results showed that xanthophylls-PCL could be employed as additives for biodegradable lubricant applications since they have better tribological behavior than current additives, which demonstrates their potential as future commercial materials with interesting eco-friendly properties for diverse applications.

Sustainable polyesters initiators from renewable resources and additives in green lubricants.     

Binary catalytic system for homo- and block copolymerization of ε-caprolactone with δ-valerolactone

The combined interaction of 2,3,6,7-tetrahydro-5H-thiazolo[3,2-a] pyrimidine (ITU) as the organocatalytic nucleophile with YCl₃ as Lewis acid cocatalyst, generating ITU/YCl₃, was employed for homo- and copolymerization of ε-caprolactone (CL) with δ-valerolactone (VL). Poly(caprolactone) (PCL) and poly(caprolactone)–poly(ethylene glycol)–poly(caprolactone) (PCL–PEG–PCL) triblock copolymer and poly(valerolactone)–poly(caprolactone)–poly(ethylene glycol)–poly(caprolactone)–poly(valerolactone) (PVL–PCL–PEG–PCL–PVL) pentablock copolymer were successfully prepared by ring-opening polymerization (ROP) of CL employing ITU/YCl₃ as catalyst in the presence of benzyl alcohol (BnOH) or poly(ethylene glycol) (PEG) as initiator, respectively. The reaction was systematically optimized, and the architecture, molecular weight and thermal properties of the polymers were characterized by NMR, FTIR, SEC and DSC analyses. Finally, a plausible polymerization mechanism was proposed.

The combined interaction of 2,3,6,7-tetrahydro-5H-thiazolo[3,2-a] pyrimidine (ITU) as the organocatalytic nucleophile with YCl₃ as Lewis acid cocatalyst, generating ITU/YCl₃, was employed for homo- and copolymerization of CL with VL.     

Star-poly(ε-caprolactone) as the stationary phase for capillary gas chromatographic separation

This work presents the separation performance of star-poly(ε-caprolactone) (star-PCL) as the stationary phase for capillary gas chromatography (GC). The statically coated star-PCL column showed a column efficiency of 3345 plates per m and moderate polarity. Importantly, the star-PCL column exhibited high selectivity and resolving capability for more than a dozen mixtures covering a wide-ranging variety of analytes and isomers. Among them, the star-PCL column displayed advantageous resolving capability over the commercial DB-1701 column for aromatic amine isomers such as toluidine, chloroaniline and bromoaniline. Moreover, it was applied for the determination of isomer impurities in real samples, showing good potential in GC applications.

This work presents the separation performance of star-poly(ε-caprolactone) (star-PCL) as the stationary phase for capillary gas chromatography (GC).     

An electrospun poly(ε-caprolactone) nanocomposite fibrous mat with a high content of hydroxyapatite to promote cell infiltration

Electrospun polymer/inorganic biomimetic nanocomposite scaffolds have emerged for use in a new strategy for bone regeneration. In this study, a poly(ε-caprolactone) (PCL)/hydroxyapatite (HAp) nanocomposite mat with a HAp content as high as 60% was prepared via one-step electrospinning using trifluoroethanol as the solvent, and it has superior dispersibility and spinnability. The structure and physicochemical properties of the scaffolds were studied using scanning electron microscopy and spectroscopic techniques. X-ray diffraction and Fourier transformed infrared spectroscopy confirmed the presence of HAp in the composite PCL fibers. The results of cell culturing suggested that the incorporation of HAp with PCL could regulate the cytoskeleton and the differentiation of cells. More interestingly, the high content of HAp was also found to be conducive to the infiltration of MC-3T3 cells into the mat. The results indicated the potential of PCL/HAp scaffolds as a promising substitute for bone regeneration.

PCL nanofibers with 60% HAp content were fabricated, and the presence of HAp regulated cell morphology to enhance cell infiltration.     

Salivary SARS-CoV-2 antibody detection using S1-RBD protein-immobilized 3D melt electrowritten poly(ε-caprolactone) scaffolds

Sensitive detection of immunoglobulin antibodies against SARS-CoV-2 during the COVID-19 pandemic is critical to monitor the adaptive immune response after BNT162b2 mRNA vaccination. Currently employed binding antibody detection tests using 2D microplate-based enzyme-linked immunosorbent assays (ELISA) are limited by the degree of sensitivity. In this study, a 3D antibody test was developed by immobilizing the receptor-binding domain on Spike subunit 1 (S1-RBD) of SARS-CoV-2 onto engineered melt electrowritten (MEW) poly(ε-caprolactone) (PCL) scaffolds (pore: 500 μm, fiber diameter: 17 μm) using carbodiimide crosslinker chemistry. Protein immobilization was confirmed using X-ray photoelectron spectroscopy (XPS) by the presence of peaks corresponding with nitrogen. Self-developed indirect ELISA was performed to assess the functionality of the 3D platform in comparison with a standard 2D tissue culture plate (TCP) system, using whole unstimulated saliva samples from 14 non-vaccinated and 20 vaccinated participants (1- and 3- weeks post-dose 1; 3 days, 1 week and 3 weeks post-dose 2) without prior SARS-CoV-2 infection. The three-dimensional S1-RBD PCL scaffolds, while demonstrating a kinetic trend comparable to 2D TCP, exhibited significantly higher sensitivity and detection levels for all three immunoglobulins assayed (IgG, IgM, and IgA). These novel findings highlight the potential of MEW PCL constructs in the development of improved low-cost, point-of-care, and self-assessing diagnostic platforms for the detection and monitoring of SARS-CoV-2 antibodies.

Our work developed a 3D SARS-CoV-2 antibody detection platform in non-invasive saliva samples using S1-RBD protein-immobilized 3D melt electrowritten poly(ε-caprolactone) scaffolds.     

Fabrication of fibrillated and interconnected porous poly(ε-caprolactone) vascular tissue engineering scaffolds by microcellular foaming and polymer leaching

This paper provides a method combining eco-friendly supercritical CO₂ microcellular foaming and polymer leaching to fabricate small-diameter vascular tissue engineering scaffolds. The relationship between pore morphology and mechanical properties, and the cytocompatibility, are investigated with respect to the effects of poly(ε-caprolactone)/poly(ethylene oxide) (PCL/PEO) phase morphologies and PEO leaching. When PEO content increases, the pore size decreases and the pore density increases. After the leaching process, highly interconnected and fibrillated porous structures are detected in the foamed PCL70 blend with droplet-matrix morphologies. Moreover, the leaching process had a greater contribution to improve the open-cell content in the PCL50 blend, which has a co-continuous morphology and easily obtained open-cell content of more than 80%. Small-diameter tubular PCL70 and PCL50 porous scaffolds with an average pore size of 48 ± 1.4 μm and 30 ± 1.0 μm respectively, are fabricated successfully. Prominent orientated pores are found in the PCL70 scaffold, and a mixed microstructure combining interconnected channels and open cells occurs in PCL50 scaffold. The PCL70 scaffold has a greater longitudinal tensile strength, longer toe region, and larger cyclical recoverability. HUVECs tend to align along the direction of the pore orientation in the PCL70 scaffold, whereas HUVECs have a higher density and spreading area in the PCL50 scaffold. The results gathered in this paper may provide a theoretical basis and data support for fabricating small-diameter porous tissue engineering vascular scaffolds.

This paper provides a method combining eco-friendly supercritical CO₂ microcellular foaming and polymer leaching to fabricate small-diameter vascular tissue engineering scaffolds.     

Enhanced osteogenesis of mesenchymal stem cells on electrospun cellulose nanocrystals/poly(ε-caprolactone) nanofibers on graphene oxide substrates

Cellulose nanocrystals (CNCs) have received a great amount of attention to the production of micro/nano-platforms for tissue engineering applications. CNCs were extracted from rice husk biomass and characterized by different spectroscopic techniques. The biocompatibility of the extracted CNCs was revealed by the WST-1 assay technique in the presence of human mesenchymal stem cells (hMSCs) after different time intervals. An improvement in the mechanical properties was observed in the fabricated scaffolds (PCL/CNC) compared to PCL scaffolds. Graphene oxide (GO)-coated (PCL/CNC) electrospun scaffolds (GPC) were prepared by the deposition of PCL/CNC composite nanofibers on the surface of GO for tissue engineering. Notably, better cell proliferation and differentiation were observed in the presence of the fabricated scaffolds. This enhancement of the properties of the fabricated scaffolds was due to the presence of conductive GO moieties which facilitated the cellular response. Therefore, the fabricated materials have the potential to be used as a biomaterial for enhanced cell proliferation and osteogenic differentiation.

Cellulose nanocrystals (CNCs) have received a great amount of attention to the production of micro/nano-platforms for tissue engineering applications.     

Sodium alginate/collagen composite multiscale porous scaffolds containing poly(ε-caprolactone) microspheres fabricated based on additive manufacturing technology

Biocompatible porous scaffolds with adjustable pore structures, appropriate mechanical properties and drug loading properties are important components of bone tissue engineering. In this work, biocompatible sodium alginate (SA)/collagen (Col) multiscale porous scaffolds containing poly(ε-caprolactone) microspheres (Ms-PCL) have been facilely fabricated based on 3D extrusion printing of the pre-crosslinked composite hydrogels. The prepared composite hydrogels can be 3D extrusion printed into porous scaffolds with different designed shapes and adjustable pore structures. The hydroxyapatite (HAP) nanoparticles have been added into the SA/Col hydrogels to achieve stress dispersion and form double crosslinking networks. SA-Ca²⁺ crosslinking networks and Col–genipin (GP) crosslinking networks have been constructed to improve the mechanical properties of the scaffolds (about 2557 kPa of compressive stress at 70% strain), and reduce the swelling rate and degradation rate of SA/Col scaffolds. Moreover, the SA/Col hydrogels contain hydrophobic antibacterial drug enrofloxacin loaded Ms-PCL, and in vitro drug release research shows a sustained-release function of porous scaffolds, indicating the potential application of SA/Col porous scaffolds as drug carriers. In addition, the antibacterial experiments show that the composite scaffolds display a distinguished and long-term antibacterial activity against Escherichia coli and Staphylococcus aureus. Furthermore, mouse bone mesenchymal stem cells (mBMSCs) are seeded on the SA/Col composite scaffolds, and an in vitro biocompatibility experiment shows that the mBMSCs can adhere well on the composite scaffolds, which indicate that the fabricated composite scaffolds are biocompatible. In short, all of the above results suggest that the biocompatible SA/Col composite porous scaffolds have enormous application and potential in bone tissue engineering.

Biocompatible porous scaffolds with adjustable pore structures, appropriate mechanical properties and drug loading properties are important components of bone tissue engineering.     

A novel application of electrospun silk fibroin/poly(l-lactic acid-co-ε-caprolactone) scaffolds for conjunctiva reconstruction

Electrospun hybrid nanofibers prepared using combinations of natural and synthetic polymers have been widely investigated in tissue engineering. In this study, silk fibroin (SF) and poly(l-lactic acid-co-ε-caprolactone) (PLCL) hybrid scaffolds were successfully prepared by electrospinning. Scanning electron micrographs (SEM) showed that SF/PLCL scaffolds were composed of defect-free nanofibers with a smooth and homogeneous fiber morphology. Water contact angle measurements demonstrated that the scaffolds were hydrophilic. To assess the cell affinity of SF/PLCL scaffolds, rabbit conjunctival epithelial cells (rCjECs) were cultured on the electrospun scaffolds. Scanning electron micrographs and in vitro proliferation assays showed that the cells adhered and proliferated well on the scaffolds. The quantitative polymerase chain reaction (qPCR) results showed excellent expression of CjEC genes, with reduced expression of inflammatory mediators. Hematoxylin and eosin (H&E) staining showed that the engineered conjunctiva constructed with SF/PLCL scaffolds consisted of 2–4 layers of epithelium. Furthermore, SF/PLCL scaffolds transplanted subcutaneously exhibited excellent biocompatibility. Therefore, SF/PLCL scaffolds may find biomedical applications in conjunctival reconstruction in the near future.

We present a promising scaffold with favorable mechanical and biological properties for conjunctival regeneration.     

Copolyesters of ε-caprolactone and l-lactide catalyzed by a tetrabutylammonium phthalimide-N-oxyl organocatalyst

Aliphatic polyesters are biocompatible materials that can be used in biomedical applications. We report here the use of tetrabutylammonium phthalimide-N-oxyl catalyst (TBAPINO), as a thermally stable organocatalyst for the ring-opening polymerization (ROP) of cyclic esters under mild conditions. In the solution ROP of ε-caprolactone (ε-CL), quantitative conversion and M_n of ∼20 000 g mol⁻¹ are achieved in a wide temperature range from −15 to 60 °C. Under bulk condition, the conversion of ε-CL reaches over 85% at 120 °C within 2 h. The living ROP character of l-lactide (l-LA) catalyzed over TBAPINO is proved by multiple additions of monomer in the bulk polymerization. The catalyst shows comparable selectivity towards the ring-opening polymerization of l-LA and ε-CL. Their copolymerization over TBAPINO is carried out in one-pot bulk condition in terms of the reaction time, monomer feed ratio, and sequence of addition. The colorless poly(ε-caprolactone-co-lactide) (PCLA) is obtained with considerable conversion of both monomers with the M_n over 22 000 g mol⁻¹.

By utilizing tetrabutylammonium phthalimide-N-oxyl organocatalyst, copolymer PCLA with M_n over 20 000 g mol⁻¹ was synthesized by sequential ring-opening polymerization of ε-caprolactone and l-lactide under bulk conditions.     

Novel biodegradable and non-fouling systems for controlled-release based on poly(ε-caprolactone)/Quercetin blends and biomimetic bacterial S-layer coatings

Quercetin is a strong antioxidant with low bioavailability due to its high crystallinity. A further drawback is that Quercetin has potentially toxic effects at high concentrations. To improve this low water solubility, as well as control the concentration of the flavonoid in the body, Quercetin is incorporated into a polymeric matrix to form an amorphous solid dispersion (ASD) stable enough to resist the recrystallization of the drug. For this purpose, miscible poly(ε-caprolactone) (PCL) and Quercetin (Q) blends are prepared, provided that they have complementary interacting groups. For compositions in which the flavonoid remains in an amorphous state thanks to the interactions with polymer chains, various PCL/Q drug release platforms are fabricated: micrometric films by solvent casting, nanometric films by spin coating, and nanofibers by electrospinning. Then, the potential use of bacterial S-layer proteins as release-preventive membranes is tested on PCL–Quercetin blends, due to their ability to construct a biomimetic coating including nanometric pores. For all the platforms, the SbpA coating can maintain a stable release under the toxicity level of Quercetin. Accordingly, a PCL/Q system with an S-layer coating allows the design of versatile bioavailable Quercetin eluting devices that prevent toxicity and biofouling issues.

S-Layer coating on PCL–Quercetin miscible blends acts as a release controller from films and scaffolds, as well as antifouling agent.     

T Cell Development in Mice Lacking All T Cell Receptor ζ Family Members (ζ, η, and FcεRIγ)

The ζ family includes ζ, η, and FcεRIγ (Fcγ). Dimers of the ζ family proteins function as signal transducing subunits of the T cell antigen receptor (TCR), the pre-TCR, and a subset of Fc receptors. In mice lacking ζ/η chains, T cell development is impaired, yet low numbers of CD4⁺ and CD8⁺ T cells develop. This finding suggests either that pre-TCR and TCR complexes lacking a ζ family dimer can promote T cell maturation, or that in the absence of ζ/η, Fcγ serves as a subunit in TCR complexes. To elucidate the role of ζ family dimers in T cell development, we generated mice lacking expression of all of these proteins and compared their phenotype to mice lacking only ζ/η or Fcγ. The data reveal that surface complexes that are expressed in the absence of ζ family dimers are capable of transducing signals required for α/β–T cell development. Strikingly, T cells generated in both ζ/η^−/− and ζ/η^−/−–Fcγ^−/− mice exhibit a memory phenotype and elaborate interferon γ. Finally, examination of different T cell populations reveals that ζ/η and Fcγ have distinct expression patterns that correlate with their thymus dependency. A possible function for the differential expression of ζ family proteins may be to impart distinctive signaling properties to TCR complexes expressed on specific T cell populations.     

Oxygen Equilibrium Characteristics of Abnormal Hemoglobins: Hirose (α2β237Ser), L Ferrara (α247Glyβ2), Broussais (α290Asnβ2), and Dhofar (α2β258Arg)

The oxygen equilibrium characteristics of four structural variants of hemoglobin A were correlated with their amino acid substitutions.Hemoglobin Dhofar, in which the proline at E2(58)beta is replaced by arginine, had normal oxygen equilibrium characteristics.Hemoglobin L Ferrara. in which the aspartic acid at CD5(47)alpha is replaced by glycine, and hemoglobin Broussais, in which the lysine at FG2(90)alpha is replaced by asparagine, both showed a slightly elevated oxygen affinity; nevertheless both demonstrated a normal heme-heme interaction and a normal Bohr effect.Hemoglobin Hirose, in which the tryptophan at C3 (37)beta is replaced by serine, showed abnormalities of all oxygen equilibrium characteristics; i.e., increased oxygen affinity, diminished heme-heme interaction, and reduced Bohr effect.These results suggest that aspartic acid at CD5(47)alpha and lysine at FG2(90)alpha are involved in the function of the hemoglobin molecule, despite the fact that these positions are not located directly in the heme or the alpha-beta-contact regions.Tryptophan at C3(37)beta is located at contact between alpha(1)- and beta(2)-subunits. It is suggested that the substitution by serine might disturb the quarternary structure of the mutant hemoglobin molecule during transition from oxy-form to deoxy-form resulting in an alteration of the heme function.     

LiCl-promoted amination of β-methoxy amides (γ-lactones)

An efficient and mild method has been developed for the amination of β-methoxy amides (γ-lactones) including natural products michelolide, costunolide and parthenolide derivatives by using lithium chloride in good yields. This reaction is applicable to a wide range of substrates with good functional group tolerance. Mechanism studies show that the reactions undergo a LiCl promoted MeOH elimination from the substrates to form the corresponding α,β-unsaturated intermediates followed by the Michael addition of amines.

The amination of β-methoxy amides (γ-lactones) including natural products michelolide, costunolide and parthenolide derivatives were first developed by using lithium chloride.

The formation of carbon–nitrogen bonds remains one of the most fundamental and widely practiced reactions in organic synthesis, due to the prevalence of this functionality in the preparations of functional molecules in pharmaceutical chemistry, biochemistry and material sciences.¹ Various synthetic methodologies have been developed to form C(sp²)-N bonds, including the Goldberg reaction,² Buchwald–Hartwig reaction,³ imine reduction⁴ and the nucleophilic addition of carbon-nucleophiles to imine derivatives.⁵ Meanwhile, the formations of C(sp³)-N bonds can be achieved by reductive amination, which involves the conversion of a carbonyl group to an amine via an imine intermediate, such as Eschweiler–Clarke reaction⁶ and Borch reductive amination.⁷ Nucleophilic substitution of alkyl(pseudo)halides with amines (amine alkylation) serves as one direct strategy for the preparation of alkylamines, while the necessity of pre-installation of the halogen atoms and the production of stoichiometric inorganic salt wastes are considered as two main drawbacks for its application in large scale industrial synthesis.⁸Methoxy as the leaving group in the amination reactions has recently attracted the attention of organic chemists. For instance, Chiba and coworkers reported a method for the nucleophilic amination of methoxy arenes,⁹ which was achieved by using sodium hydride (NaH) in the presence of lithium iodide (LiI) through a concerted nucleophilic aromatic substitution pathway (Fig. 1a).¹⁰ Kondo and coworkers demonstrated that the organic superbase t-Bu-P4 efficiently catalyzes the amination of methoxy(hetero)arenes with the amine nucleophiles (Fig. 1b).¹¹ The t-Bu-P4 is also suitable to catalyze the amination of β-(hetero)arylethyl ethers with amines to synthesize β-(hetero)arylethylamines (Fig. 1c).¹² Sun and coworkers reported that C–S bond cleavage to access N-substituted acrylamide and β-aminopropanamide(Fig. 1d).¹³Open in a separate windowFig. 1Amination reactions of methyl ethers.Recently, we described the application of a CuBr–LiCl composite for the short-chain alkoxylation of aryl bromides.¹⁴ During that course of study, the single-shell lithium ion was found to embrace a unique affinity for oxygen and can be used as an additive to activate C–O bond and facilitate the nucleophilic reaction. On the basis of this study, we herein present the synthesis of β-amino amides (γ-lactones) via the elimination of methoxy group followed by Michael addition of an amine, that was promoted by LiCl in good yields under conventional conditions.We initiated our study with the reaction of 3-methoxy-N-phenylpropanamide 1a and piperidine 2a in the presence of lithium salts (

Ring opening polymerization of d,l-lactide and ε-caprolactone catalysed by (pyrazol-1-yl)copper(ii) carboxylate complexes

1,2-Bis{(3,5-dimethylpyrazol-1-yl)methyl}benzene (L) reacts with [Cu(OAc)₂] and C₆H₅COOH, 4-OH-C₆H₄COOH, 2-Cl-C₆H₄COOH and (3,5-NO₂)₂-C₆H₃COOH to afford the copper complexes [Cu₂(C₆H₅COO)₄(L)₂] (1), [Cu₂(4-OH-C₆H₄COO)₄(L)₂] (2), [Cu₂(2-Cl-C₆H₄COO)₄(L)₂]_n (3) and [Cu{(3,5-NO₂)₂-C₆H₃COO}₂L]_n (4) which are characterised by IR, mass spectrometry, elemental analyses, and X-ray crystallography. The structural data revealed two geometries that are adopted by the complexes: (i) paddle wheel in 1, 2·7H₂O, 3 and (ii) regular chains in 3 and 4. Magnetic studies show strong antiferromagnetic couplings in the paddle wheel complexes and a weak antiferromagnetic coupling in the monometallic chain one. Catalysis studies performed with these complexes (1–4) showed that they initiate ring opening polymerization (ROP) of ε-caprolactone (ε-CL) under solvent-free conditions and d,l-lactide in toluene at elevated temperatures. Polycaprolactone (PCL) and poly(d,l-lactide) (PLA) obtained from the polymerization reactions are of low molecular weights (858 for PCL and 602 Da for PLA for initiator 1) and polydispersity indices (typically 2.16 for PCL and 1.64 for PLA with 1 as the initiator). End group analysis of the polymers, determined by MALDI-ToF MS, indicates that the polymers have benzoate, hydroxyl, methoxy and cyclic end groups.

We report the synthesis, structure and complete characterization of four new pyrazolyl carboxylate-based copper(ii) complexes that catalyze the ring opening polymerization of ε-caprolactone under solvent-free conditions and of d,l-lactide in toluene.