Highly efficient synthesis of β-amino esters via Mannich-type reaction under solvent-free conditions using ZnCl_2 catalyst

β-Amino esters were synthesized via ZnCl2-catalyzed Mannich-type reaction of imines and malonate esters under solvent-free conditions in 6 min. The β-amino ester was converted into the corresponding aspartic acid derivatives.

Apoptosis of A549 cells by small interfering RNA targeting survivin delivery using poly-β-amino ester/guanidinylated O-carboxymethyl chitosan nanoparticles

Gene-based therapeutics has emerged as a promising approach for human cancer therapy. Among a variety of non-viral vectors, polymer vectors are particularly attractive due to their safety and multivalent groups on their surface. This study focuses on guanidinylated O-carboxymethyl chitosan(GOCMCS) along with poly-β-amino ester(PBAE) for si RNA delivery. Binding efficiency of PBAE/si RNA/GOCMCS nanoparticles were characterized by gel electrophoresis. The si RNA-loaded nanoparticles were found to be stable in the presence of RNase A, serum and BALF respectively. Fine particle fraction(FPF) which was determined by a two-stage impinger(TSI) was 57.8% ± 2.6%. The particle size and zeta potential of the nanoparticles were 153.8 ± 12.54 nm and + 12.2 ± 4.94 m V. In vitro cell transfection studies were carried out with A549 cells. The cellular uptake was significantly increased. When the cells were incubated with si Survivin-loaded nanoparticles, it could induce 26.83% ± 0.59% apoptosis of A549 cells and the gene silencing level of survivin expression in A549 cells were 30.93% ± 2.27%. The results suggested that PBAE/GOCMCS nanoparticle was a very promising gene delivery carrier.

Direct Colorimetric Detection of Hydrogen Peroxide Using 4-Nitrophenyl Boronic Acid or Its Pinacol Ester

A colorimetric method for the direct determination of hydrogen peroxide in aqueous solution is described. H2O2 stoichiometrically converts 4-nitrophenyl boronic acid or 4-nitrophenyl boronic acid pinacol ester into 4-nitrophenol, which can be quantified by measuring the absorption at 400 nm in neutral or basic media. The reactions proceed fast under basic conditions and complete in 2 minutes to at pH 11 and 80?C. The linear range for the colorimetric method extends beyond 1.0 to 40 μM H2O2, and the limit of detection is ~1.0 μM H2O2. This method offers a convenient and practical process for rapid determination of hydrogen peroxide in aqueous media. Compared to many other techniques in H2O2 detection, this process is a direct measurement of H2O2, and is relatively unaffected by the presence of various salts, metal ions and the chelator EDTA.

In vitro polymerization of the dopamine-borate melanin precursor:A proof-of-concept regarding^(10)boron neutron-capture therapy for melanoma

The^(10)boron neutron-capture therapy(BNCT)is an emerging antitumoral method that shows increasing biomedical interest.BNCT is based on the selective accumulation of the^(10)boron isotope within the tumor,which is then irradiated with low-energy thermal neutrons,generating nuclear fission that produces 7lithium,4helium,andγrays.Simple catechol-borate esters have been rather overlooked as precursors of melanin biosynthesis,and therefore,a proof-of-concept approach for using dopamine-borate(DABO)as a suitable boron-containing candidate for potential BNCT is presented here.DABO can spontaneously oxidize and autopolymerize in vitro,giving a soluble,eumelaninlike brown-black poly-DABO product.Melanotic melanoma cell cultures treated with 1 mM DABO for 24 and 48 h were viable and showed no signs of damage or cell death.The stability and possible trans-esterification of DABO is shortly discussed.Chemical calculations and quantitative structure-activity relationships(QSAR)analysis of DABO and the BNCT agent BPA indicated that they should be cell permeant and accumulate within lysosomes and melanosomes.Molecular modeling allows visualization of both the DABO precursor and the structure of a borate derivative of the proposed catechol-porphycene model for eumelanin,showing interesting features from molecular orbital calculations.The main difference between DABO and other agents,such as BPA,is that it is not a boronic acid nor a boron cluster.This simple catechol-borate ester(protected from oxidation and blackening)could be administrated to living cells and organisms,in which biosynthesis of boron-melanin in melanoma melanocytes can lead to improved BNCT.

Preparation and Characterization of Poly(β-Amino Ester) Capsules for Slow Release of Bioactive Material

Network structures from poly(β-amino ester) (PAE) were synthesized for applying as drug delivery matrix via a simplified addition polymerization method. It can hold an active organic compound (drug) that has an effect as antitumor activity in order to control its release. PAE was prepared from piperazine and 1,4-butandiol diacrylate with different molar ratios. The active compound was mixed with the prepared polymer while warming for 15 minutes to obtain the capsule product. The resulting polymer structures and the surface morphology of the PAE capsules before and after encapsulation with the active drug were characterized by FT-IR and SEM, respectively. Swelling and degradation behavior of PAE were studied. The characterization showed that the obtained network structure of PAE depends on the molar ratio between the reactants. The optimum ratio of the reactants was found to be 1:1. Therefore, stable and white product as well as good holding capability for drug produced. The SEM studies illustrate good dispersion and holding properties of the drug into the network structure of the prepared polymer. In vitro, the release results of the drug from the PAE capsules indicated that the capsules were able to give sustained release of drug in DMF up to 10 days at 25°C.

Fluorinated amphiphilic Poly(β-Amino ester)nanoparticle for highly efficient and specific delivery of nucleic acids to the Lung capillary endothelium

Endothelial cell dysfunction occurs in a variety of acute and chronic pulmonary diseases including pulmonary hypertension,viral and bacterial pneumonia,bronchopulmonary dysplasia,and congenital lung diseases such as alveolar capillary dysplasia with misalignment of pulmonary veins(ACDMPV).To correct endothelial dysfunction,there is a critical need for the development of nanoparticle systems that can deliver drugs and nucleic acids to endothelial cells with high efficiency and precision.While several nanoparticle delivery systems targeting endothelial cells have been recently developed,none of them are specific to lung endothelial cells without targeting other organs in the body.In the present study,we successfully solved this problem by developing non-toxic poly(β-amino)ester(PBAE)nanoparticles with specific structure design and fluorinated modification for high efficiency and specific delivery of nucleic acids to the pulmonary endothelial cells.After intravenous administration,the PBAE nanoparticles were capable of delivering non-integrating DNA plasmids to lung microvascular endothelial cells but not to other lung cell types.IVIS whole body imaging and flow cytometry demonstrated that DNA plasmid were functional in the lung endothelial cells but not in endothelial cells of other organs.Fluorination of PBAE was required for lung endothelial cell-specific targeting.Hematologic analysis and liver and kidney metabolic panels demonstrated the lack of toxicity in experimental mice.Thus,fluorinated PBAE nanoparticles can be an ideal vehicle for gene therapy targeting lung microvascular endothelium in pulmonary vascular disorders.

Improving gene transfection efficiency of highly branched poly(β-amino ester)s through the in-situ conversion of inactive terminal groups

Highly branched poly(β-amino ester)s(HPAEs)have emerged as a safe and efficient type of non-viral gene delivery vectors.However,the presence of inactive terminal secondary amine groups compromises their gene transfection capability.In this study,HPAEs with similar topological structures and chemical compositions but varying numbers of terminal secondary 4-amino-1-butanol(S4)and secondary/tertiary 3-morpholinopropylamine(MPA)groups were synthesized.The results demonstrate that an increased number of secondary/tertiary MPA groups in-situ significantly enhances the DNA binding capability of HPAEs,leading to the formation of smaller HPAE/DNA polyplexes with higher zeta potential,ultimately resulting in superior gene transfection efficiency in bladder epithelial cells.This study establishes a sim-ple yet effective strategy to maximize the gene transfection potency of HPAEs by converting the inactive terminal groups in-situ without the need for complex modifications to their topological structure and chemical composition.

Free amino group-directed C(sp^(2))-H arylation ofα-amino-β-aryl esters by palladium catalysis

Native amino-directed palladium-catalyzed C(sp^(3))-H activation/functionalization has been developed for modification ofα-amino acids and peptides.Herein a palladium(Ⅱ)-catalyzed C(sp^(2))-H arylation ofα-amino-β-aryl esters has been disclosed,using the native amino as the directing group.A variety of chiralα-amino-β-aryl esters can be functionalized to give the corresponding ortho-substituted mono-and di-arylated products.

气相色谱法测定吡唑硼酸频哪酯及方法学验证

(目的)建立了测定吡唑硼酸频哪酯的气相色谱法方法,并进行了方法学验证。(方法)采用5%苯基-甲基聚硅氧烷色谱柱(30 m×∅0.25 mm,0.25μm)检测器:氢离子火焰检测器;载气:氮气;流速:1.0 mL/min;进样器温度:215℃;检测器温度:295℃;分流比:3∶1;进样量:0.1μL;柱箱温度:初始50℃,维持2 min,按10℃/min升温至150℃,维持0 min,按30℃/min升温至260℃,维持5 min;氢气流速:30 mL/min;空气流速:300 mL/min;氮气流速:25 mL/min。结果表明,方法的专属性、重复性、线性、中间精密度及溶液稳定性试验结果均符合要求。(结论)本法操作简单,方法准确,可用于吡唑硼酸频哪酯的测定。

Study of ATP borate ester effects on cell sensitization to radiation emitted by a nuclear reactor

Adenosine triphosphate(ATP)borate ester as a new boron agent for boron neutron capture therapy was tested.It was synthesized via a dehydration reaction induced by heating adenosine triphosphate disodium with boric acid.Next,ATP borate ester pretreatments were assessed to study their effects on cell sensitization from exposure to thermal neutron irradiation emitted by a nuclear reactor.Using cell viability assays(CCK8),survival rates of A549 cells pretreated with or without boroncontaining agents,including ATP borate ester and 4-dihydroxyborylphenylalanine(BPA),were measured.One week after feeding an ATP borate ester solution to tumorbearing nude mice,elemental B content values of tumor muscle and blood were measured using inductively coupled plasma mass spectrometry(ICP-MS).Meanwhile,other tumor tissue samples were placed in a culture medium,subjected to a 3-min neutron irradiation exposure,and then fixed in formalin 24 h later for the terminaldeoxynucleotidyl transferase(TDT)-mediated d UTP nick end labeling(TUNEL)immunohistochemical staining analysis.Results showed that A549 cell irradiation sensitization(irradiation dose of 0.33 Gy)varied with pretreatment.Sensitization values of the ATP borate ester pretreatment group were 1.3–14.1 with boron agent concentrations of 0.3–4.5 mM.Within 1.1–3.4 mM,ATP borate ester showed significantly higher sensitization values than BPA.Meanwhile,TUNEL results demonstrated that apoptosis rates of tumor tissue cells exposed to irradiation after ATP borate ester pretreatment significantly exceeded the corresponding rates for BPA-pretreated cells.In animal experiments,although the distribution ratio of ATP borate ester(tumor tissue/normal muscle,T/N)of 1.2 was not significantly different compared with that of BPA(1.3),the total ATP borate ester concentration in the tumor tissue(0.79±0.05μg/g)significantly exceeded that of BPA(0.58±0.05μg/g).Thus,compared with BPA,the greater enrichment of ATP borate ester in tumor tissues permits preferential targeting toward tumor cells for radiation sensitization.Therefore,ATP borate ester is superior to BPA for use in boron neutron capture therapy.

一种具有光热转化能力的光愈合聚氨酯的制备及性能

本文以具有光热转化能力的对苯醌二肟(BQDO)为聚氨酯扩链剂,2,2-(1,4-亚苯基)-二[4-巯基-1,3,2-二恶硼烷](BDB)为交联剂,利用硼酸酯键的动态效应,通过一步法制备了具有光热转化能力的光愈合聚氨酯(PHPU)。系统研究了材料的化学结构、热稳定性、光热转化能力以及光愈合性能。结果表明,交联剂用量的增加可以有效地使材料的拉伸强度从13.4 MPa提高到23.06 MPa,但对材料的热稳定性影响不大,BQDO以共聚的形式引入到聚氨酯主链可以提高其对光的吸收能力。当交联剂BDB用量为1%时,实验样品在红外光照射8 h条件下达到99%的愈合效率,显示出良好的综合性能和光愈合能力。

Highly branched poly(β-amino ester)s with narrow molecular weight distribution: Fractionation and gene transfection activity

Highly branched poly(β-amino ester)s(HPAEs) have shown their great promise in gene delivery. However, their broad molecular weight distribution(MWD) poses an additional challenge to the mechanistic understanding of the influence of molecular weight(MW) on their gene transfection activity. Using a stepwise precipitation strategy, HPAEs were fractionated. It is shown that MW has a significant effect on the transfection activity and cytotoxicity of HPAEs. The intermediate MW mediates higher transfection efficiency while maintaining high cell viability. Mechanistic studies show that the intermediate MW confers stronger DNA binding affinity to HPAEs, leading to the formulation of polyplexes with a relatively smaller size and more positive zeta potential. This study not only suggests a simple strategy to fractionate HPAEs with narrow MWD but also provides new insights into understanding the structure-property relationship, which would facilitate the clinical translation of HPAEs in gene therapy.

Efficient gene transfection of suspension cells by highly branched poly(β-amino ester)

Suspension cells play a crucial role in many biological processes. However, compared to adherent cells, it is particularly challenging to introduce exogenous genes into suspension cells to regulate their biological functions with non-viral gene vectors, mainly due to the low cellular uptake and endosomal escape of polyplexes. Herein, to improve the interactions of polyplexes with cellular membranes, we design and synthesize highly branched poly(β-amino ester)(HPAE) via an “A2 + B4 + C2” Michael addition strategy.Results show that branching significantly increases DNA condensation of HPAE, cellular uptake and endosomal escape of HPAE/DNA polyplexes. In mast cells(MCs), HPAE exhibits up to 80-fold higher gene transfection efficiency compared to the corresponding linear poly(β-amino ester)(LPAE) and the leading commercial gene transfection reagents PEI25k, jetPEI, and Lipofectamine 3000, without causing obvious cytotoxicity. Our study establishes a reliable non-viral platform for efficient gene transfection of suspension cells.

介孔SBA-15增强硼酸酯交换基环氧类玻璃高分子

研究了改性介孔SBA-15的添加量对复合材料的性能影响,尤其是机械性能,热稳定性,再回收,自修复以及形状记忆的能力。首先利用γ-缩水甘油醚氧丙基三甲氧基硅烷(KH560)对介孔SBA-15进行改性,使其表面具有可反应的环氧官能团,然后用于对邻甲酚醛环氧类玻璃的增强。以端基二硫醇的2,2′-(1,4-亚苯基)-双[4-硫醇1,3,2-二氧杂戊烷(BDB)为交联剂,邻甲酚醛环氧树脂为预聚体,改性后的介孔SBA-15为增强剂,通过“巯基-环氧”点击反应得到高强度环氧类玻璃复合材料。研究表明当增强剂添加量为环氧树脂的1.0%(质量分数)时,环氧类玻璃复合材料的拉伸强度最高可达54.9 MPa,断裂应变为12.7%。

基于传统化学键/动态硼酸酯键构建的超支化柠檬酸聚酯体系的研究及其应用初步探索

以生物质材料柠檬酸和丙三醇为原料,通过控制反应条件合成了两种不同分子量的端基为羟基的超支化柠檬酸聚酯(HBPE),采用FT-IR、1H-NMR和GPC对HBPE的分子结构、支化度以及分子量进行了表征,其支化度为85%,分子量分别为4115和6011g/mol。再以上述两种HBPE为原料进一步制备了两种不同化学键交联的水溶性聚酯:与丁二酸以传统化学键交联得到的HBPE-SA和与硼砂以动态硼酸酯键交联的络合物HBPE-borax。流变学实验表明,HBPE-borax的力学强度和黏度受含水量和HBPE分子量影响,整体而言,HBPE-borax和HBPE-SA表现为黏度很大的液体,其黏度在剪切速率为30s-1时仍保持在3200Pa·s左右。由于HBPE-borax中含有动态硼酸酯键,赋予HBPE-borax自愈性和pH响应性。吸湿性实验表明两种聚酯在相对湿度为68%的条件下20min即可恢复黏性,基于上述特性初步表明可用作水溶性生物质“不干胶”,并初步探索了黏接性能。

Thermally Conductive,Healable Glass Fiber Cloth Reinforced Polymer Composite based onβ-Hydroxyester Bonds Crosslinked Epoxy with Improved Heat Resistance

To simultaneously endow thermal conductivity,high glass transition temperature(Tg)and healing capability to glass fiber/epoxy(GFREP)composite,dynamic crosslinked epoxy resin bearing reversibleβ-hydroxyl ester bonds was reinforced with boron nitride nanosheets modified glass fiber cloth(GFC@BNNSs).The in-plane heat conduction paths were constructed by electrostatic self-assembly of polyacrylic acid treated GFC and polyethyleneimine decorated BNNSs.Then,the GFC@BNNSs were impregnated with the mixture of lower concentration(3-glycidyloxypropyl)trimethoxysilane grafted BN micron sheets,3,4-epoxycyclohexylmethyl 3,4-epoxycyclohexanecarboxylate and hexahydro-4-methylphthalic anhydride,which accounted for establishing the through-plane heat transport pathways and avoiding serious deterioration of mechanical performances.The resultant GFREP composite containing less boron nitride particles(17.6 wt%)exhibited superior in-plane(3.29 W·m^(-1)·K^(-1))and through-plane(1.16 W·m^(-1)·K^(-1))thermal conductivities,as well as high Tg of 204℃(Tg of the unfilled epoxy=177℃).The reversible transesterification reaction enabled closure of interlaminar cracks within the composite,achieving decent healing efficiencies estimated by means of tensile strength(71.2%),electrical breakdown strength(83.6%)and thermal conductivity(69.1%).The present work overcame the disadvantages of conventional thermally conductive composites,and provided an efficient approach to prolong the life span of thermally conductive GFREP laminate for high-temperature resistant integrated circuit application.

Rh^(III)-Catalyzed heteroarylation of N-2,6-difluoro-phenyl arylamides with heteroaryl boronate esters

Herein,an efficient strategy to achieve aryl-heteroaryl formation via Rh^(III)-catalyzed ortho-C(sp^(2))–H heteroarylation of(hetero)arenes with heterocyclic boronates using a readily removable N-2,6-difluoro-phenyl arylamide directing group has been disclosed.A variety of heteroaromatic boronates as the coupling partners were shown to be able to participate in this protocol,providing the desired hetero-arylated products with high reactivity and good tolerance of functional groups.

基于有机硼化合物的氟离子化学探针

本文综述了有机硼化合物在氟离子探针领域的研究进展。介绍了基于三芳基硼化合物、硼酸和硼酸酯的有机硼化合物在氟离子检测中的应用,评述了这些化合物的结构和检测性能之间的关系,讨论了检测机理,即有机硼化合物中硼原子空的pπ轨道使其作为路易斯酸能够选择性地结合氟离子,硼原子与氟离子的结合破坏了硼中心与芳香取代基的pπ-π共轭,引起有机硼化合物光物理性质的变化,从而实现对氟离子的高选择性检测。最后提出了有机硼化合物作为氟离子探针存在的一些问题,并展望了有机硼化合物在氟离子探针领域的研究和发展方向。

聚乙二醇硼酸酯的合成

以硼酸和聚乙二醇为原料,苯为水的共沸剂,合成了一种聚乙二醇硼酸酯。考察了反应温度、反应时间、共沸剂、物料摩尔比等因素对合成工艺的影响,用热重法考察了硼酸的脱水反应,分析反应过程中可能存在的副反应,用红外光谱对聚乙二醇硼酸酯进行结构表征。最佳反应条件为:反应温度130℃,反应时间60 m in,n(PEG)∶n(硼酸)=3∶1,共沸剂V(苯)/V(水)=1.25,硼酸的酯化率可达98.89%。聚乙二醇硼酸酯在工作电解液中添加质量分数为5%时,可提高闪火电压近65 V。

基于动态共价键的pH响应自修复水凝胶的制备与评价

以α-甲基丙烯酸(MAA)和2-丙烯酰胺-2-甲基丙磺酸(AMPS)的共聚物P(MAA/AMPS)及聚乙烯醇(PVA)为单体、十水合四硼酸钠为交联剂合成了P(MAA/AMPS)-PVA二重互穿网络的p H响应水凝胶。通过SEM、FTIR、GPC、TGA-DTG和流变仪等表征了水凝胶的表面形貌和化学状态;测定了水凝胶的溶胀性﹑p H响应性﹑自修复性和流变性。结果表明,水凝胶形成了稳定的互穿网络结构且具有pH敏感性、自修复性;PVA羟基与硼酸根离子形成的共价配位硼酸酯键使水凝胶具备自修复性并受介质酸碱性的控制;力学性能测定结果显示,自修复水凝胶(SB用量为2.5%,水凝胶溶胀度为4)拉伸强度668 kPa,断裂伸长率可达665%,修复效率可达81%。