The effect of covalent immobilization of sialic acid on the removal of lipopolysaccharide and reactive oxygen species for polyethylene terephthalate

Polyethylene terephthalate (PET) was aminolyzed with 1,6‐diaminohexane (DAH) and then sialic acid (NANA) was immobilized via amidation onto the surface. The surface concentration of NANA was determined by 2‐thiobarbituric acid (TBA) test. The hemocompatibility of the resulting PET fabrics was evaluated based on complete blood count (CBC), coagulating times, and protein adsorption. The ability to remove lipopolysaccharide (LPS) was also determined. In addition, the effect of contacting NANA‐immobilizing PET on the suppression of reactive oxygen species (ROS) production was measured by the chemiluminescence (CL) method. The results show that by immobilizing NANA onto PET, the adhesion of platelet (PLt) was reduced, and oxidative stress was suppressed. The level of LPS was also greatly reduced. Copyright © 2010 John Wiley & Sons, Ltd.     

四氟乙烯齐聚体的反应 III: 四氟乙烯四聚体与脂族胺以及烷氧亲核试剂的反应

3, 4-Bis (trifluoromethyl)-perfluorohexene-(3) (1) reacted with diethylamine to give the 1-N, N-diethylamino-2-pentafluoroethyl -3-trifluoromethyl-perfluoropentene-(1)(2), which was easily hydrolyzed to the corresponding N, N-diethyl-2-penta-fluoroethyl- 3-trifluoromethyl-perfluoropenteno-(2)-amide (3). When compound 1 was allowed to react with n-butyl amine at 40-50`C, the 2,3,4-tris(trifluoromethyl)-4-pentafluoroethyl-1-n-butyl-aza- cyclobutene-(2) (5) was obtained as the main product and at-30-40`C, 3,4-bis(trifluoromethyl)-4-n-butylamino-perfluorohexene-(2) (4) as the main product. The isomers 3, 4-bis(trifluoromethyl)-4-allyloxy-perfluoro-hexen-(2) (6) and 2-pentafluoroethyl-3-trifluoromethyl-3-allyloxy-perfluoropentene-(1)(7) were formed when 1 was reacted with sodium allyl alcoholate.     

Development of piezoelectric immunosensors for measurement of albuminuria

The development of piezoelectric immunosensors for human serum albumin (HSA) is reported. The piezoelectric crystals were modified either with monoclonal antibody AL-01 (direct assay) or with HSA (competitive assay). Measurements were carried out in the flow-through mode. Affinity interaction between albumin and the antibody was characterised. With immobilised antibody and HSA in solution, the kinetic association rate constant k(a) was 18 100 l mol(-1) s(-1) and the dissociation constant k(d) was 0.00369 s(-1). For the opposite arrangement (immobilised HSA), a slower dissociation was observed, k(d) was 0.00085 s(-1). A competitive assay for HSA was developed with working range of 1-5 mug ml(-1) and a total time for one analysis equal to 17 min. Samples of urine were analysed after tenfold dilution. The developed system was successfully evaluated on real samples from diabetic patients and the obtained results correlated well with the standard reflectometric assay of proteins in urine.     

Tabletting of solid dispersion particles consisting of indomethacin and porous silica particles

We attempted to make the rapidly dissolving tablet (Tab) containing solid dispersion particles (SD) with indomethacin (IMC) and porous silica (Sylysia350) as carrier prepared by using spray-drying technique. Rapidly dissolving tablet was formulated with mannitol as a diluent and low substituted hydroxypropylcellulose (L-HPC) or partly pre-gelatinized starch (PCS) as a disintegrant. The percent dissolved from Tab (SD) was higher than that of tablet containing physical mixture (PM) at 20 min. Nearly 100% of drug in Tab (SD) was dissolved within 60 min, while the drug dissolution of Tab (PM) was not completed at the same time period. In addition, the tensile strength of Tab (SD) was much higher than that of Tab (PM). Adding L-HPC in Tab (SD) (Tab (SD-L-HPC)), the percent dissolved from Tab (SD-L-HPC) at 5 min became much higher than that from Tab (SD). The dissolution profile of IMC from Tab (SD-L-HPC) was almost the same irrespective of the compression pressure, while the tensile strength of tablet increased with increasing the compression pressure. In comparing the compaction property of these tablets by observing the ratio of residual die wall pressure (RDP) to maximum die wall pressure (MDP) (RDP/MDP), it was found that addition of L-HPC in the tablet formulation improved compactibility. In case that PCS was formulated as disintegrant, Tab (SD-PCS), similar improvement in the dissolution profile and tensile strength was observed, though the dissolution rate of IMC from Tab (SD-PCS) was slightly lower than that from Tab (SD-L-HPC) irrespective of the compression pressure.     

Chemometric study of selected polychlorinated biphenyls in ambient air of Madrid (Spain)

The formation of Fe(III) and Fe(II) chelates with pyridylazo and thiazolylazo reagents was examined. Optimum conditions for the formation of Fe(III) and Fe(II) chelates with 2-(5-bromo-2-pyridylazo)-5-diethylaminophenol (5-Br-PADAP) were in detail evaluated. The LC method for simultaneous separation of Fe(III) and Fe(II) ions as 5-Br-PADAP chelates was evaluated using the PEEK column with C18 e.c. stationary phase and acetonitrile+water (90:10, v/v) eluent containing the 1x10(-3) mol l(-1) C(12)H(25)SO(3)Na, the ion-pairing reagent, pH 3.4-3.6. The simultaneous determination of 20-500 mug l(-1) Fe(II) ions (detection at 555 nm) and 20-500 mug l(-1) Fe(III) ions (detection at 585 nm) as 5-Br-PADAP chelates (for both ions, detection limit, 18 mug l(-1) for 20 mul loop) was established. The chromatographic method was applied to the water analysis. Although the present method is able to determine both Fe(III) and Fe(II) ions, the Fe(III) ion was not detected in all water samples. The Fe(II) was detected only in fresh gathered oligocene water at the level of 135 mug l(-1). The present method was used to the investigation of the distribution of Fe(III)/Fe(II) ions in aqueous and micellar solutions after action of external, ultrasonic field.     

Chiral capillary electrophoresis-mass spectrometry of tetrahydroisoquinoline-derived neurotoxins: observation of complex stereoisomerism

Previous studies have shown that certain 1,2,3,4-tetrahydroisoquinoline derivatives (TIQs) are neurotoxins inducing Parkinsonism. Further, individual enantiomers of these toxins such as (R/S)-N-methylsalsolinol ((R/S)-NMSal) possess distinct neurotoxicological properties. In this work, a chiral capillary electrophoresis (CE) method with electrospray ionization-tandem mass spectrometric (ESI-MS/MS) detection was developed for the quantification of TIQ enantiomers. Enantioseparation was achieved with sulfated β-cyclodextrin (sulfated β-CD) as chiral selector. To avoid any potential contamination of MS ionization source by the non-volatile chiral selector, partial filling technique was deployed in the CE separation. TIQ derivatives, including (R/S)-6,7-dihydroxy-1-methy-TIQ (salsolinol, Sal), (R/S)-1-benzyl-TIQ (BTIQ), and (R/S)-NMSal, were base-line resolved with resolution values (R) ranging from 3 (for Sal) to 4.5 (for BTIQ), which were much better than those reported previously by HPLC methods. ESI-MS/MS detection of the resolved TIQ enantiomers was specific and sensitive (LOD=1.2 μM for Sal enantiomers). The proposed chiral CE-MS/MS method was used to study in vitro formation of (R/S)-NMSal. It was found that NMSal was formed from the incubation of epinine (a dopamine metabolite) with acetaldehyde (a metabolite of alcohol). More interestingly, four isomers of NMSal were separated and detected in the incubation solution. They were identified as (R)-e.e-NMSal, (R)-e.a-NMSal, (S)-e.e-NMSal, and (S)-e.a-NMSal. This was the first lab evidence that this Parkinsonian neurotoxin exists in multiple isomeric forms.     

对苯乙烯磺酸在水滑石层间的柱撑及聚合

对苯乙烯磺酸在水滑石层间的柱撑及聚合;水滑石;对苯乙烯磺酸;柱撑;聚合     

Synthesis of a dimeric Lewis antigen and the evaluation of the epitope specificity of antibodies elicited in mice

The Lewis(y)-Lewis(x) heptasaccharide, modified by an artificial aminopropyl spacer, was synthesized by an approach that employed two orthogonally protected lactosamine building blocks. A p-(benzoyl)-benzyl glycoside was used as a novel anomeric protecting group, which could be selectively removed at a late stage in the synthesis, thus offering the benefit of enhanced flexibility. The artificial aminopropyl moiety was modified by a thioacetyl group, which allowed an efficient conjugation to keyhole limpet hemocyanin (KLH) that had been activated with electrophilic 3-(bromoacetamido)-propionyl groups. Mice were immunized with the Le(y)Le(x)-BrAc-KLH antigen. Analysis of the sera by ELISA established that a strong helper T-cell immune response was raised against the Le(y)Le(x) saccharide. Further ELISA analysis showed that the titer for monomeric Le(y) tetrasaccharide was tenfold lower whereas recognition of the Le(x) trisaccharide was negligible.     

Chemiluminescence of cobalt(II)-hydrogen peroxide-hydrogencarbonate in the absence of luminescent reagents

A novel chemiluminescence (CL) system, cobalt(II)-hydrogen peroxide-hydrogencarbonate without luminescent reagents, was described. When cobalt(II) was injected into mixed solution of 0.4 mol l(-1) hydrogencarbonate and 0.01 mol l(-1) hydrogen peroxide in a flow injection system, CL occurred, which was significantly enhanced when rhodamine B coexisted. The CL emission intensity was found correlation with the concentration of cobalt(II) in the range of 2.0x10(-9)-1.0x10(-5) mol l(-1) with a detection limit of 1.2x10(-9) mol l(-1) cobalt(II). The relative standard derivative (RSD) for 5.0x10(-7) mol l(-1) cobalt(II) was 1.6% based on nine repetitive measurements. In addition to cobalt(II), other metal ions were also investigated, and only chromium(III) gave out measurable CL emission. The possible mechanism was discussed based on the CL emission spectrum.     

Synthesis of a novel fluorescent probe based on acridine skeleton used for sensitive determination of DNA

In this study, a novel fluorescent probe of acridine derivative N-((N-(2-dimethylamino)ethyl)acridine-4-carboxamide)-alpha-alanine (N-(ACR-4-CA)-alpha-ALA) was synthesized. The structure of the new compound was characterized by (1)H NMR, MS, elemental analysis, fluorescent and ultraviolet spectra. It was found that DNA had the ability to quench the fluorescence of N-(ACR-4-CA)-alpha-ALA, and the quenched intensity of fluorescence was proportional to the concentration of DNA. A method for DNA determination based on the quenching fluorescence (lambda(ex) = 260 nm, lambda(em) = 451 nm) of N-(ACR-4-CA)-alpha-ALA was established. Under optimal conditions, the linear range is 0.05-2.0 microg mL(-1) for both fish semen (fsDNA) and calf thymus DNA (ctDNA). The corresponding determination limits are 9.1 ng mL(-1) for fsDNA and 8.7 ng mL(-1) for ctDNA, respectively. The results suggested that the interaction mode between N-(ACR-4-CA)-alpha-ALA and DNA was intercalative binding. The intrinsic binding constant was determined and the result showed a large binding constant of N-(ACR-4-CA)-alpha-ALA with DNA.     

温度对掺杂球形Ni(OH)_2质子扩散的影响

应用微电极恒电位阶跃法研究了在Ni(OH) 2 电极的阳极及阴极过程反应中 ,温度对球形Ni(OH) 2 的质子扩散系数和表观扩散活化能的影响 .研究表明 ,于Ni(OH) 2 中掺杂Co和Co +Zn后可降低其阳极和阴极过程的表观扩散活化能 ,增大质子扩散系数 ,掺Co的效果更加明显 ,而掺Zn则增大表观扩散活化能 ,降低了扩散系数 .这说明前者的掺入其作用是降低了质子扩散阻力使电极的反应活性增加、而后者的掺入则是增大了质子的扩散阻力而使电极反应活性降低 .     

Use of a chiral surfactant for enantioselective reduction of a ketone

The influence of a chiral surfactant and a polymer-supported chiral additive on reduction of ketones using sodium borohydride will be described. Initial preparations involved methylation of (S)-leucinol to give (2S)-N , N-dimethyl-2-amino-4-methyl-1-pentanol (1) (67%). The chiral surfactant (2) was synthesized by reacting (1) with bromohexadecane (71%). The functionalized styrene for the polymer-supported chiral additive (5) was synthesized by reacting (1) with 4-vinylbenzyl chloride. Polymerization was carried out with 10% of the functionalized monomer (4), 5% cross-linking agent divinylbenzene, and 85% styrene with AIBN as the initiator. The activity of the chiral surfactant and polymeric additive were examined by using them as additives in a standard reduction of 2-pentanone with sodium borohydride to yield (R)- and (S)-2-pentanol (3) (20%). The resulting alcohol was analyzed by polarimetry (ee 9.5%) and also esterified with (2S)-methylbutyric acid prior to characterization by NMR. 13C NMR indicated an enantiomeric excess of 5.2% when the chiral surfactant was used, and 7% when the polymeric additive was used.     

Investigation of the pharmacokinetics of celecoxib by liquid chromatography-mass spectrometry

A new method for the quantification of celecoxib in human plasma based on reversed-phase high-performance liquid chromatography (HPLC) coupled to atmospheric pressure chemical ionization (APCI) mass spectrometry (MS) after liquid-liquid extraction is presented. The method is rapid, sensitive and highly selective. The retention time of celecoxib was 2.3 min. The limit of quantification was 5 microg/L. Rofecoxib was used as internal standard. After validation, the method was used to study the pharmacokinetic profile of celecoxib following administration of a single oral dose (200 mg) in 12 healthy volunteers. Since celecoxib should be metabolized primarily by cytochrome 2C9 (CYP2C9), a poor metabolizer (PM) for this cytochrome P450 enzyme was included in the study. Pharmacokinetic characteristics (mean +/- SD) of extensive metabolizers (EM) were t(max) 2.9+/-1.2h, c(max) 842+/-280 microg/L, AUC(infinity) 6246+/-2147 microg h/L and t(1/2) 7.8+/-2.7h. The area under the curve (AUC(infinity)) for the PM was 12561 microg h/L. However, we found no noticeable increase in half life in the PM (11.5 h) after a single dose of celecoxib.     

丁酸氯维地平降解杂质的合成

以4-(2,3-二氯苯基)-1,4-二氢-2,6-二甲基-3,5-吡啶二羧酸(2-氰基乙基)（甲基）酯(5)为起始原料,合成了丁酸氯维地平的5种降解杂质：4-(2,3-二氯苯基)-1,4-二氢-2,6-二甲基-3,5-吡啶二羧酸单甲酯(A), 4-(2,3-二氯苯基)-1,4-二氢-2,6-二甲基-3-吡啶羧酸甲酯(B), 4-(2,3-二氯苯基)-2,6-二甲基-3,5-吡啶二羧酸单甲酯(C), 4-(2,3-二氯苯基)-2,6-二甲基-3,5-吡啶二羧酸（丁酰氧基甲基）（甲基）酯(D)和4-(2,3-二氯苯基)-2,6-二甲基-3-吡啶羧酸甲酯(E)。其中A由5水解制得;B由A脱羧制得;C由5氧化后再经水解制得;D由C和丁酸氯甲酯缩合制得;E由C脱羧制得,化合物结构经¹H NMR和MS（ESI）确证。     

Experimental and theoretical study of the electronic spectrum of BeAl

The electronic structure of BeAl was investigated by laser induced fluorescence and resonance enhanced multiphoton ionization spectroscopy. BeAl was formed by pulsed laser ablation of a Be/Al alloy in the presence of helium carrier gas, followed by a free jet expansion into vacuum. In agreement with recent ab initio studies, the molecule was found to have a (2)Pi(1/2) ground state. Transitions to two low lying electronic states, (2)(2)Pi(1/2)(v') <-- X (2)Pi(1/2) (v' = 0) and (1)(2)Delta(v') <-- X (2)Pi(1/2) (v' = 0,1), were observed and rotationally analyzed. An additional band system, identified as (4)(2)Sigma(+)(v') <-- X (2)Pi(1/2), was found in the 28 000-30 100 cm(-1) energy range. This transition exhibited an unusual pattern of vibrational levels resulting from an avoided crossing with the (5)(2)Sigma(+) electronic state. New multi-reference configuration interaction calculations were carried out to facilitate the interpretation of the UV bands.An ionization energy of 48 124(80) cm(-1) was determined for BeAl from photoionization efficiency (PIE) measurements. Fine structure in the PIE curve was attributed to resonances with Rydberg series correlating with vibrationally excited states of the BeAl(+) ion. Analysis of this structure yielded a vibrational frequency of 240(20) cm(-1) for the cation.     

Structural Characterization and Toxicity Prediction of Some Organic Compounds

A new molecular structural characterization(MSC)method called molecular vertexes correlative index(MVCI)was constructed in this paper.The index was used to describe the structures of 45 compounds and a quantitative structure-activity relationship(QSAR)model of toxicity(–lgEC50)was obtained through multiple linear regression(MLR)and stepwise multiple regression(SMR).The correlation coefficient(R)of the model was 0.912,and the standard deviation(SD)of the model was 0.525.The estimation stability and prediction ability of the model were strictly analyzed by both internal and external validations.The Leave-One-Out(LOO)Cross-Validation(CV)correlation coefficient(RCV)was 0.816 and the standard deviation(SDCV)was 0.739,respectively.For the external validation,the correlation coefficient(Rtest)was 0.905 and the standard deviation(SDtest)was 0.520,respectively.The results showed that the index was superior in molecular structural representation.The stability and predictability of the model were good.     

Isolation of highly pure erlotinib hydrochloride by recrystallization after nucleophilic substitution of an impurity with piperazine

Optimized synthesis and purification of erlotinib hydrochloride (N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)quinazoline-4-amine hydrochloride) were studied. Highly polar piperazine was used in a nucleophilic substitution reaction with the chlorinated intermediate byproduct N-(3-ethynylphenyl)-6(2-chloroethoxy)-7-(2-methoxyethoxy)quinazolin-4-amine hydrochloride. As a result, N-(3-ethynylphenyl)-6(2-chloroethoxy)-7-(2-methoxyethoxy)quinazolin-4-amine hydrochloride was completely transformed to N-(3-ethynylphenyl)-6(2-piperzinoethoxy)-7-(2-methoxyethoxy)quinazolin-4-amine hydrochloride. The polarity of N-(3-ethynylphenyl)-6(2-piperzinoethoxy)-7-(2-methoxyethoxy)quinazolin-4-amine hydrochloride was changed, and its molecule was enlarged. It was easy to remove this larger, more polar, compound by recrystallization. Highly pure erlotinib hydrochloride was obtained with low impurity content (<1 %). The purity of erlotinib hydrochloride was >99.9 %.     

(乙酸乙烯酯-co-丙烯酸)共聚物的合成、醇解及产物水溶性研究

用乙酸乙烯酯(VAc)和丙烯酸(AA)进行溶液聚合制备(乙酸乙烯酯-co-丙烯酸)共聚物[P(VAc-co-AA)],研究了不同单体投料比时的聚合反应速率,结果表明:反应时间一定,随AA含量增加,聚合反应速率降低,转化率降低;反应5小时后,不同AA含量体系的转化率差别减小;傅里叶变换红外吸收光谱(FTIR)和核磁共振氢谱(1H-NMR)测试结果表明AA与VAc发生共聚.用氢氧化钠(NaOH)作为催化剂对P(VAc-co-AA)进行醇解制得产物聚乙烯醇(PVA),通过X-射线衍射(XRD)测定了醇解产物结晶度,进一步考察了醇解产物在70℃水中的溶解性.结果表明:与聚乙酸乙烯酯(PVAc)的醇解产物相比,P(VAc-co-AA)的醇解产物结晶度有所下降,在水中的溶解性提高.     

Advantages of deuterium-labelled mixed triacylglycerol in studies of intraluminal fat digestion

The (13)C-mixed triacylglcerol (MTG, 1,3-distearyl, 2-[1-(13)C]octanoyl glycerol) breath test is a non-invasive measure of intraluminal fat digestion. Recovery of (13)C in breath CO(2) is incomplete (<50%) owing to sequestration of (13)C into organic molecules via the tricarboxylic acid (TCA) cycle. In addition lack of knowledge of CO(2) production rate (VCO(2)) during the test leads to errors in the calculated percentage dose recovered (PDR). (2)H sequestration into organic molecules is low ( approximately 4%) and is not influenced by factors that affect VCO(2) such as food intake or physical activity. After oxidation of (2)H-labelled macromolecules, the label appears in body water, which can be sampled non-invasively in urine or saliva. After an overnight fast, two healthy adults consumed [(2)H]MTG (1,3-distearyl, 2-[(2)H(15)]octanoyl glycerol) and [(13)C]MTG (1,3 distearyl, 2-[1-(13)C]octanoyl glycerol) simultaneously. Total body water (TBW) was measured by (18)O dilution and also estimated from height and weight. Urine and saliva were sampled at baseline and for 10 h after consumption of the test meal. The abundance of (2)HOH and H(2) (18)O in urine and saliva was measured by continuous-flow isotope-ratio mass spectrometry. Cumulative PDR of (2)H and (18)O was calculated from the plateau enrichment, which was reached by 6 h in both saliva and urine. Recovery of (2)H calculated using measured TBW was compared with that using an estimated value of TBW. Mean recovery of (2)H in saliva was 99.3% and in urine was 96.4%. Errors introduced by estimating TBW were <5%. [(2)H]MTG could provide a simpler, more robust, indirect test of intraluminal fat digestion compared with the (13)C-breath test. Further studies are required in pancreatic insufficient patients.     

Liquid-liquid distribution of ion-associates of dichlorocuprate(I) with quaternary ammonium counter-ions

The dichlorocuprate(I) anion CuCl(-)(2) can be extracted as its ion-associates Q(+).CuCl(-)(2) with quaternary ammonium cations (Q(+)) into chloroform. The extraction constants K(ex) have been determined, and the log K(ex) values found for the various counter-ions used are 1.93 for (C(3)H(7))(4)N(+), 4.10 for (C(4)H(9))(4)N(+), 6.57 for (C(5)H(11))(4)N(+), 1.57 for C(8)H(17)N(+) (CH(3))(3), 2.83 for C(10)H(21)N(+) (CH(3))(3) 4.12 for C(12)H(25)N(+) (CH(3))(3) and 5.21 for C(14)H(29)N(+)(CH(3))(3), respectively. A linear relationship was found between log K(ex) and the total number of carbon atoms in Q(+); from the slope of the line, the contribution of a methylene group to log K(ex) was calculated to be 0.59. The extractability with alkyltrimethylammonium cations was larger than that with symmetrical tetra-alkylammonium cations and the difference in log K(ex) for two cations (one of each type) with the same number of carbon atoms was about 0.4. From the extraction constants obtained, the extractability of CuCl(-)(2) was found to lie between that of ReO(-)(4) and ClO(-)(4).