Structural insights in Dy3+‐doped β‐Tricalcium phosphate and its multimodal imaging characteristics

A series of Dysprosium (Dy³⁺) doped β‐Tricalcium phosphate [β‐TCP, β‐Ca₃(PO₄)₂] were developed for applications in magnetic resonance imaging (MRI) and computed tomography (CT). Characterization studies confirmed the Dy³⁺ occupancy at Ca²⁺(1), Ca²⁺(2), and Ca²⁺(3) lattice sites of β‐Ca₃(PO₄)₂ and its substitution limit was determined as 4.35 mol%. The transitions from the ⁶H_15/2 ground state to various excited energy levels is validated by the characteristic absorption peaks of Dy³⁺. Luminescence studies inferred two intense bands at 480 and 572 nm due to ⁴F_9/2→⁶H_15/2 (blue) and ⁴F_9/2→⁶H_13/2 (yellow) transitions of Dy³⁺. The paramagnetic and nontoxic behavior of Dy³⁺‐doped β‐Ca₃(PO₄)₂ were confirmed from magnetic and MTT tests, respectively. Dy³⁺ in the host induces a high X‐ray absorption ability for X‐ray computed tomography (CT) and showed efficient contrast T₂‐enhancing modality. Thus the proposed system could be used as a promising probe for multimodality with optical imaging, computed tomography and magnetic resonance imaging.     

磷酸钙生物降解陶瓷的研究现状与发展

磷酸钙类陶瓷其成分与骨矿物组成类似,生物相容性好,被视为典型的生物陶瓷。它们在生理环境下能发生不同程度的降解,被组织吸收。这种特性与材料的化学成分、结晶相、结构形态等材料学因素有关,同时也与宿主个体差异、植入部位、与骨接触方式等生物学因素有关。目前主要的研究方法有体外模拟实验及体内埋植实验,通过观测材料结构、性能及成分的变化,与骨界面结合状态、细胞学、组织学等,探讨陶瓷的生物降解机理及控制降解的途径,以寻找新型骨修复材料。     

Facile Synthesis of Element‐Substituted Hydroxyapatite Whiskers Using α‐Tricalcium Phosphate as Precursors

In the absence of any surfactants, organic solvents or structure‐directing reagents, the cation‐ and anion‐substituted HAp whiskers, and cation‐/anion‐co‐substituted HAp whiskers with controllable substitution amounts were successfully synthesized via hydrothermal treatment of the same precursor of α‐TCP in an aqueous solution containing the objective substituted elements. Through regulating the initial ion concentrations of the aqueous solutions, the element substitution level could be well facilely tailored. The cytocompatibility of the products was confirmed by Cell Counting Kit‐8 (CCK‐8) assay using the osteoblast cell line MC3T3‐E1. This study provided a facile strategy for the synthesis of element‐substituted HAp materials.     

Ruthenium(II)‐Catalyzed Protocol for Preparation of Diverse α,β‐ and β,β‐Dihaloenones from Diazodicarbonyls

Efficient one‐step syntheses of α,β‐ and β,β‐dihaloenones were achieved by ruthenium(II)‐catalyzed reactions between cyclic or acyclic diazodicarbonyl compounds and oxalyl chloride or oxalyl bromide in moderate to good yields. This methodology offers several significant advantages, which include ease of handling, mild reaction conditions, one‐step reaction, and the use of an effective and non‐toxic catalyst. The synthesized compounds were further transformed into highly functionalized novel molecules bearing aromatic rings on the enone moiety using the Suzuki reaction.

     

超临界CO_2微孔发泡制备聚乳酸/磷酸三钙多孔材料

利用超临界二氧化碳(sc-CO2)微孔发泡方法制备聚乳酸/磷酸钙(PLA/TCP)多孔材料,通过扫描电子显微镜(SEM)观察TCP颗粒分散和泡孔形态。结果表明,TCP质量分数为1 wt%和3 wt%时,微米级TCP颗粒均匀分布在PLA基体中,在发泡过程中起到异相成核的作用,减小泡孔尺寸同时增加泡孔密度。当TCP含量为5 wt%时,TCP颗粒出现团聚,异相成核作用减弱,泡孔密度下降。随着发泡温度升高,泡孔尺寸增大的同时泡孔壁变薄甚至破裂,发泡温度对泡孔密度影响不大。增加发泡压力,泡孔的数量急剧增加,同时泡孔的尺寸减少,泡孔壁变厚。     

Chemoenzymatic Preparation of Enantiopure Homoadamantyl β‐Amino Acid and β‐Lactam Derivatives

Racemic cis‐10‐azatetracyclo[7.2.0.1^2,6.1^4,8]tridecan‐11‐one was prepared from homoadamant‐4‐ene by chlorosulfonyl isocyanate addition. The transformation of the β‐lactam to the corresponding β‐amino ester followed by Candida antarctica lipase A‐catalyzed enantioselective (E>>200) N‐acylation with 2,2,2‐trifluoroethyl butanoate afforded methyl (1R,4R,5S,8S)‐5‐aminotricyclo[4.3.1.1^3,8]undecane‐4‐carboxylate and the (1S,4S,5R,8R)‐butanamide with>99% ee at 50% conversion. Alternatively, transformation of the β‐lactam to the corresponding N‐hydroxymethyl‐β‐lactam and the following Pseudomonas cepacia (currently Burkholderia cepacia) lipase‐catalyzed enantioseletive O‐acylation provided the (1S,4S,6R,9R)‐alcohol (ee=87%) and the corresponding (1R,4R,6S,9S)‐butanoate (ee>99%). In the latter method, competition for the enzyme between the (1R,4R,6S,9S)‐butanoate, 2,2,2‐trifluoroethyl butanoate and the hydrolysis product, butanoic acid, tended to stop the reaction at about 45% conversion and finally gave racemization in the (1S,4S,6R,9R)‐alcohol with time.     

An Efficient and Simple Procedure for the Preparation of α‐Keto‐β‐lactams

The methods for the preparation of α‐keto‐β‐lactams described in the literature are generally specific for a particular target molecule and lack generality. A short route to several of these compounds has been developed and is described in this communication. The protocol based on an efficient cyclization procedure followed by hydrolysis and oxidation allows preparation of α‐keto‐β‐lactams 5a—g with sensitive substituents.     

Synthesis of (E)‐α,β‐Unsaturated Carbonyls via Silver‐Catalyzed Tandem Epoxide Rearrangement/Intermolecular Carbonyl‐ Heteroalkyne Metathesis

A regio‐ and stereoselective method for the synthesis of (E)‐α,β‐unsaturated carbonyls has been developed via a silver‐catalyzed tandem epoxide rearrangement/intermolecular carbonyl‐heteroalkyne metathesis. Various heteroalkynes including ynol ethers, ynamides, and thioalkynes work well for this transformation, leading to the production of (E)‐α,β‐unsaturated esters, amides, and thioesters in moderate to excellent yields with good functional group compatibility. It represents one of the rare examples of regio‐ and stereoselective intermolecular alkyne‐carbonyl metathesis (ACM).

     

Preparation of polyethylene oxide/LixV2‐δO4‐δ nanocomposites

Polyethylene oxide (PEO)/LixV_2‐δO_4‐δ nanocomposites were prepared in aqueous solution. Characterization of the nanocomposites using thermal gravimetric analysis (TGA), differential scanning calorimetry (DSC), powder X‐ray diffraction (XRD), and Fourier transform infrared spectrum (FTIR) shows that polymer chains intercalate inorganic host lamella and exhibit lattice expansion along the stacking direction of 4.2 Å. A possible model for the structure of the nanocomposite is also provided. © 2001 John Wiley & Sons, Inc. J Appl Polym Sci 80: 2162–2166, 2001     

Nano‐Hydroxyapatite Improves the Properties of β‐tricalcium Phosphate Bone Scaffolds

β‐Tricalcium phosphates have been widely used as biomaterials for bone substitutes; however, the poor mechanical properties limit the application in bearing loading bones. In this study, nano‐hydroxyapatite has been introduced to improve the mechanical properties for porous bioceramic scaffolds. Nanocomposites containing 0–10 wt% needle‐like nano‐hydroxyapatite were prepared for investigation. It has been found that needle‐like nano‐hydroxyapatite improves the toughness, hardness, and compressive strength of the porous β‐tricalcium phosphates scaffolds, as well as the microstructure properties. The study provides a reference for the development of safe, excellent bone scaffolds for bone tissue engineering.     

Preparation and characterization of β‐cyclodextrin‐linked chitosan microparticles

Hydrophobically modified chitosan containing β‐cyclodextrin (CD) units was synthesized by using tosylated β‐CD. The final product was characterized by Fourier transform infrared (FTIR) spectroscopy, elemental analysis and TGA, and rheometry. The polymer bearing β‐CD moieties was used to obtain crosslinked microparticles by spray‐drying which could then be used in a controlled release system for drugs. FTIR confirmed the formation of an amide linkage between cyclodextrin and chitosan. As fluorescence spectroscopy demonstrated, hydrophobic microenvironments were formed by chitosan bearing cyclodextrin in solution at lower concentrations than for chitosan. Rheometry and FTIR showed the crosslinking of the new polymer using genipin, a molecule of natural origin. Microspheres (MS) obtained by spray‐drying showed narrow size distribution when β‐CD was grafted onto chitosan and ξ‐potential of MS was slightly lower although it remained positive. In conclusion, β‐CD linked chitosan polymer can be considered as a very promising controlled drug delivery system for drugs. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Low‐Temperature Preparation of β‐Si3N4 Porous Ceramics with a Small Amount of Li2O–Y2O3

Porous β‐Si₃N₄ ceramics are sintered at 1600°C in N₂ and postheat treated at 1500°C under vacuum using Li₂O and Y₂O₃ as the sintering additives. The partial sintering and phase transformation are promoted at low temperature by the addition of Li₂O. The addition of Y₂O₃ is advantageous for the formation of high aspect ratio β‐Si₃N₄ grains. After postheat treatment, a large amount of intergranular glassy phase is removed, and the Li content in the samples is decreased. By this method, the β‐Si₃N₄ porous ceramic with a porosity of 54.1% and high flexural strength of 110 ± 8.1 MPa can be prepared with a small amount of sintering additives, 0.66 wt% Li₂O and 0.33 wt% Y₂O₃, and it is suitable for high‐temperature applications.     

Preparation and Use of Polystyryl‐DABCOF2: An Efficient Recoverable and Reusable Catalyst for β‐Azidation of α,β‐Unsaturated Ketones in Water

Novel solid fluorides were prepared to optimize the β‐azidation of α,β‐unsaturated ketones. The higher loading of these catalysts compared to that of commercially available fluorides has allowed the use of a smaller mass of catalyst helping the mixing of the reaction mixture. Porous polymeric supports have proved to be more efficient in the presence of water as reaction medium. Water has played a crucial role showing a beneficial effect on the reactivity by improving dispersion of the reaction mixture and also by avoiding organic fouling caused by the retention of the reaction mixture within the polymeric matrix. This has facilitated the recovery of the products from the catalyst. The protocol reported has allowed a significant reduction in the organic solvent required for the complete recovery of the pure product whilst leaving the catalyst clean and reusable. E‐factors are in the range of 5.9–10.5 and therefore ca. 3 times smaller than previous procedures operating under solvent‐free conditions. To further improve the efficiency of our approach we have developed a protocol operating in a continuous‐flow manner that has allowed us to achieve an E‐factor of 1.7–1.9, with a reduction of ca. 80% of the corresponding batch conditions. The continuous‐flow protocol has allowed us to minimize the use of trimethylsilyl azide making the recovery and reuse of water and catalyst 5f very efficient and simple. Finally, a novel reduction system using palladium on alumina (5 mol%) and equimolar amount of formic acid has been used in the presence of 1 equivalent of di‐tert‐butyl pyrocarbonate to set a multistep protocol operating in continuous‐flow conditions for the preparation of two representative N‐Boc‐β‐amino ketones starting from the corresponding enones with E‐factors of 3.2 and 2.7, respectively.     

Preparation and permeation characterization of β‐zeolite‐incorporated composite membranes

In this work, several β‐zeolite‐incorporated polymer composite membranes were fabricated with the solution‐casting method. The zeolite loadings were 10, 20, and 30 wt %, respectively. Scanning electron microscopy characterization showed that the zeolite particles could be uniformly distributed in the whole polymer matrix. Gas permeation results demonstrated that after the incorporation of the same β‐zeolite, the polyimide exhibited a significant increase in gas permeability but a decrease in permselectivity, and both were quite pronounced at high zeolite loadings; this resulted from the loose structure that formed. The poly(ether sulfone) composite membranes showed obvious increases in both permeability and selectivity, and the permeability increase was considerably greater at higher zeolite loadings. The permselectivity increase could possibly be attributed to the pore sieving and preferential adsorption of β‐zeolite entities for the test gases as the heat treatment may have resulted in the formation of a defect‐free microstructure. However, breakthrough of the upper‐bound line was not achieved for these composite membranes, as reflected by Robeson plots. Our results suggest that changes in membrane performance not only are attributable to the properties and content of β‐zeolite particles but also depend on the heterogeneous microstructure created by zeolite entities. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Synthesis of γ‐Fluoro‐α, β‐unsaturated Carboxylic Esters from Saturated α‐Fluoro Aldehydes

γ‐Fluoro‐α, β‐unsaturated carboxylic esters 7a, 7b and 7d and 4‐fluoro‐4‐phenylbut‐3‐enoic ester ( 8 ) are obtained by two alternative pathways from 2‐fluoro aldehydes 5a—d , either by Horner—Wadsworth—Emmons reaction or by Wittig reaction. The aldehydes 5a—d are prepared by Swern oxidation of the corresponding fluorohydrins 4a—d . These are available from α‐olefins by bromofluorination, bromineby‐acetate replacement and subsequent hydrolysis.     

Synthesis of α‐Arylphosphonates using Copper‐Catalyzed α‐Arylation and Deacylative α‐Arylation of β‐Ketophosphonates

Efficient methods for the direct arylation and deacylative arylation of β‐ketophosphonates with iodoarenes in presence of a copper(I) or a copper(II) salt as the catalysts have been developed. The corresponding α‐arylphosphonates were obtained in high yields. A tentative mechanism for the deacylative arylation reaction was proposed on the basis of the experimental data.     

Highly Efficient Suzuki Coupling Reaction of α‐Chloroalkylidene‐β‐lactones and β‐Lactams with Organoboronic Acids

The activation of C Cl bond of (Z)‐α‐chloroalkylidene‐β‐lactones and (E)‐α‐chloroalkylidene‐β‐lactams via the Suzuki cross‐coupling reaction is reported in this paper. Alkyl, heteroaromatic, substituted phenyl‐ and alkenylboronic acids can be coupled with a wide variety of α‐chloroalkylidene‐β‐lactones and β‐lactams in excellent yields within a short period of time. The cross‐coupling reaction of optically active substrates leads to the optically active compounds without racemization of the corresponding chiral center.     

Asymmetric α‐Hydroxylation of β‐Indanone Esters and β‐Indanone Amides Catalyzed by C‐2′ Substituted Cinchona Alkaloid Derivatives

The highly catalytic asymmetric α‐hydroxylation of β‐indanone esters and β‐indanone amides using peroxide as the oxidant was realized with a new C‐2′ substituted Cinchona alkaloid derivatives. The two enantiomers of α‐hydroxy‐β‐indanone esters could be obtained by simply changing the oxidant. This protocol allows a convenient access to the corresponding α‐hydroxy‐β‐indanone esters and α‐hydroxy‐β‐indanone amides with up to 99% yield and 98% ee.

     

β‐Aminopeptidase‐Catalyzed Biotransformations of β2‐Dipeptides: Kinetic Resolution and Enzymatic Coupling

We have previously shown that the β‐aminopeptidases BapA from Sphingosinicella xenopeptidilytica and DmpA from Ochrobactrum anthropi can catalyze reactions with non‐natural β³‐peptides and β³‐amino acid amides. Here we report that these exceptional enzymes are also able to utilize synthetic dipeptides with N‐terminal β²‐amino acid residues as substrates under aqueous conditions. The suitability of a β²‐peptide as a substrate for BapA or DmpA was strongly dependent on the size of the C_α substituent of the N‐terminal β²‐amino acid. BapA was shown to convert a diastereomeric mixture of the β²‐peptide H‐β²hPhe‐β²hAla‐OH, but did not act on diastereomerically pure β²,β³‐dipeptides containing an N‐terminal β²‐homoalanine. In contrast, DmpA was only active with the latter dipeptides as substrates. BapA‐catalyzed transformation of the diastereomeric mixture of H‐β²hPhe‐β²hAla‐OH proceeded along two highly S‐enantioselective reaction routes, one leading to substrate hydrolysis and the other to the synthesis of coupling products. The synthetic route predominated even at neutral pH. A rise in pH of three log units shifted the synthesis‐to‐hydrolysis ratio (v_S/v_H) further towards peptide formation. Because the equilibrium of the reaction lies on the side of hydrolysis, prolonged incubation resulted in the cleavage of all peptides that carried an N‐terminal β‐amino acid of S configuration. After completion of the enzymatic reaction, only the S enantiomer of β²‐homophenylalanine was detected (ee>99 % for H‐(S)‐β²‐hPhe‐OH, E>500); this confirmed the high enantioselectivity of the reaction. Our findings suggest interesting new applications of the enzymes BapA and DmpA for the production of enantiopure β²‐amino acids and the enantioselective coupling of N‐terminal β²‐amino acids to peptides.     

Preparation and swelling behavior of biodegradable hydrogels based on α,β‐poly(N‐2‐hydroxyethyl‐DL‐aspartamide)

Biodegradable polymers and the hydrogels have been increasingly applied in a variety of biomedical fields and pharmaceutics. α,β‐Poly(N‐2‐hydroxyethyl‐DL ‐aspartamide), PHEA, one of poly(amino acid)s with hydroxyethyl pendants, are known to be biodegradable and biocompatible, and has been studied as an useful biomaterial, especially for drug delivery, via appropriate structural modification. In this work, hydrogels based on PHEA were prepared by two‐step reaction, that is, the crosslinking of polysuccinimide, the precursor polymer, with oligomeric PEG or PEI‐diamines and the following nucleophilic ring‐opening reaction by ethanolamine. Soft hydrogels possessing varying degrees of gel strength could be prepared easily, depending on the amount of different crosslinking reagents. The swelling degrees, which were in the range of 10–40 g–water/dry gel, increased somewhat at higher temperature, and also at alkaline pH of aqueous solution. A typical hydrogel remained almost unchanged for 1 week, at 37°C in phosphate buffer of pH 7.4, and then seemed to degrade slowly as time. A porous scaffold could be fabricated by the freeze drying of water‐swollen gel. The PHEA‐based hydrogels have potential for useful biomaterial applications including current drug delivery system. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 3741–3746, 2003