Synthetic Polyphosphonates,Polyphosphates, and Phosphonocarboxylates as Allosteric Effectors of Hemoglobin

Abstract

Synthetic phosphonocarboxylates, diphosphonates, polyphosphates, and some triphosphonic acids were studied as effectors in the binding of dioxygen to human hemoglobin. Ethane-1,2-diphosphonic acid, and triphosphate anion were strong effectors.     

Preparation and characterization of new hybrid organic/inorganic systems derived from calcium (alpha-aminoalkyl)-phosphonates and -phosphonocarboxylates

We have studied the phenomenon of calcium complexation by lab synthesized amphiphilic (alpha-aminoalkyl)-phosphonocarboxylic or -phosphonic acids. The electrical conductivity of aqueous solutions of sodium salts of all these acids was measured versus the volume of a calcium salt solution added. It appeared that calcium complexes are formed in a Ca/P atomic ratio close to 1. Calcium phosphonocarboxylates and calcium phosphonates were also precipitated by mixing aqueous solutions of disodium salts of phosphorus amphiphiles and calcium nitrate solutions. Before chemical analysis, these complexes were calcined to remove the organic part. In the mineralized products, calcium and phosphate were assayed: the Ca/P atomic ratio was equal to 1. X-ray diffraction and IR spectroscopy showed that they are made entirely of beta pyrophosphate (Ca2P2O7), a result in agreement with previous chemical analysis. The chemical formula of the starting calcium complexes could be written as CaL2H2O (L=ligand). The SEM micrographs of these complexes show plate-like structures. XRD patterns are characteristic of layered structures. These facts suggest that calcium complexes are composed of alternating bimolecular layers of calcium alkylphosphonocarboxylates or calcium alkylphosphonates, the chains being tilted and partially interdigitated.     

Metal complexes as templates: syntheses, structures, and luminescent properties of two zinc phosphonocarboxylates with ABW-zeolite topology

Two novel zinc phosphonocarboxylates, Zn(3)(pbc)(2)(bpy)(H(2)O)·H(2)O (1) and Zn(2)(pbc)(2)·Zn(bpy)(H(2)O)(4)·2H(2)O (2) (pbc = 4-phosphono-benzoic acid, bpy = 2,2'-bipyridine), were hydrothermally synthesized and structurally characterized. Both of them exhibit zeolitic ABW topology in which double-zigzag inorganic chains are cross-linked by the organic parts. It is notable that the metal complex Zn(bpy)(H(2)O)(x) plays different roles in the two compounds. In 1, the Zn(bpy)(H(2)O) units coordinate with the phosphonate and carboxylate oxygen atoms and participate in the construction of the three-dimensional framework. In 2, the in situ generated [Zn(bpy)(H(2)O)(4)](2+) cation acts as a template, which directs the ABW-type open-framework by strong hydrogen bonds. It is the first example where a metal complex is used as a template in the synthesis of metal phosphonates. The luminescent properties of 1 and 2 are also investigated.     

A Zeolite‐Like Zinc Phosphonocarboxylate Framework and Its Transformation into Two‐ and Three‐Dimensional Structures

Three zinc phosphonocarboxylates, Zn₂(pbc)₂?Hdma?H₃O?2H₂O ( 1 ), Zn(pbc)?Hdma ( 2 ), and Zn_4.5(pbc)₃(OH)(H₂O)_0.5?Hdma ( 3 ) (H₃pbc=4‐phosphonobenzoic acid, dma=dimethylamine) were synthesized by the mixed solvothermal reaction of Zn(Ac)₂?2H₂O and 4‐phosphonobenzoic acid in N,N‐dimethylformamide (DMF) and water. The zigzag and ladderlike chains completely constructed by triply fused 4‐membered rings (denoted SBU‐1) are linked by the organic moieties to form the 3D zeolite‐like structure 1 and the layered structure 2 , respectively. As for structure 3 , a new second building unit (SBU‐2) formed by the inset of the [Zn₃O₁₂] trimer into the 4‐membered ring as well as SBU‐1 is observed. The connections between the two types of SBUs lead to a “zinc phosphate” layer, which is linked by the organic groups to generate a 3D pillar‐layered structure. Both solution‐mediated and solid‐state transformations of 1 to 2 and 3 were observed. A possible mechanism for the transformation is proposed. Gas sorption studies show that 1 has accessible pores for methanol and water and exhibits size selectivity for alcohols.     

Synthesis of Isomeric Aminomethyl Derivatives of Furylmethanephosphonates

By chloromethylation of diethyl 2- and 3-furylmethanephosphonates 5-chloromethylfur-2(3)-ylmethanephosphonates were synthesized. The other four isomers of chloromethyl derivatives of furylmethanephosphonates were prepared by substitution of hydroxy groups in the corresponding phosphorylated furylmethanols via the reaction with thionyl chloride in the presence of pyridine. Thermal stability of these chlorides was sufficiently high, and they were involved in nucleophilic substitution of chlorine with azido group by treating with sodium azide in boiling acetonitrile in the presence of potassium iodide. No decomposition of substrates was observed. The azides obtained were reduced to amines with triphenylphosphine in ethanol.     

Effects of surface processing of lactose carrier particles on dry powder inhalation properties of salbutamol sulfate

The effects of the surface processing of lactose carrier particles on the dry powder inhalation properties of salbutamol sulfate were investigated. Lactose carrier particles were processed using a high-speed elliptical-rotor-type powder mixer (Theta-Composer). In the present study, drug/carrier powder mixtures were prepared, consisting of micronized salbutamol sulfate and coarse lactose carriers with various particle surface conditions prepared by surface processing. These powder mixtures were aerosolized by a Jethaler, and the in vitro inhalation properties of salbutamol sulfate were evaluated with a twin impinger. Compared with those of the powder mixed with unprocessed lactose carriers, the in vitro inhalation properties of the powder mixture prepared using the surface processed lactose carriers were significantly different, showing that the in vitro inhalation properties of salbutamol sulfate were improved. The in vitro inhalation properties increased with the rotor rotation rate. Using this surface processing system would thus be valuable for increasing the inhalation properties of dry powder inhalation with lactose carrier particles.     

Effects of sublethal doses of gamma rays on the accumulation of zinc in mice fed the higher concentration diets

This paper reports preliminary studies on the mechanism of the mortality reduction effects in sublethally irradiated mice by administration of zinc at the high concentration. At first, accumulations of 65Zn in non-irradiated mice, which were orally administered with the artificial diet containing the radio-tracer and the stable metal at the high concentration (1,000 ppm), were investigated, and compared with those in mice which were administered with the artificial basal diet containing the tracer (control). Then the irradiation effects of 60Co gamma-ray at the sublethal dose on the accumulation were studied. The concentrations of zinc in whole body, tissues and organs of non-irradiated mice which were administered with the former diet were 2-fold higher than in the mice which were administered with the latter diet (control). But the accumulation of the tracer was affected by the irradiation, i.e. the concentrations in tissues and organs (except for blood and bone) of irradiated mice were lower than those in non-irradiated mice. However, the concentration in spleen of irradiated mice was remarkably higher than in the other tissues.     

Evaluation of process conditions and characterization of particle size and stability of oil-in-water nanoemulsions

This article reports on the oil in water (o/w) nanoemulsions, which were prepared using a mixture of solvents (decane, toluene and cyclohexane) as oils and the mixtures of ethoxylated lauryl alcohols with various concentrations as surfactants with HLB values ranged from 10 to 12. The Ultra-Turrax (rotor-stator type) stirring and/or ultrasound processing were applied for varied processing times. The data show that the particle sizes in nanoemulsions prepared with ultrasound were smaller than those produced by stirring. The stability of these emulsions was, however, enhanced, when the mixtures were preliminary processed with the shearing agitator. The most stable nanoemulsions were obtained in 10 wt % surfactant mixture of the alcohols with HLB 11 in the shearing agitator.     

Effect of solvents on the electrochemistry of olefins and aromatic molecules

Cyclic voltammetry and electrolysis studies were carried out in dimethyl sulfoxide, diglyme and liquid ammonia. The depolarizers were diethyl fumarate, ethyl cinnamate, stilbene and anthracene. The reduction reactions were carried out in the presence of organic halides, phenol, acids and water. The rates of the reactions were measured. The main solvent effect was noticed with water which reacts 100 times faster in diglyme than in liquid ammonia or DMSO. The results of electrolytic experiments with two reactants simultaneously were compared with those predicted from the kinetic data.     

Dependence of structure of dehydrated PVA on the crystallinity of the original PVA

Poly(vinyl alcohol) (PVA) films having different crystallinities were prepared by elongating PVA films to different degrees and heating the films with and without elongation treatment at several temperatures between 60 and 200°C. Then, they were dehydrated by heating from 80°C to 230 or 330°C in hydrogen chloride gas. Infrared spectral measurements were made on the dehydrated PVA films obtained. Absorbances of the absorption bands due to several groups seen in the infrared spectra depended only on the density of original PVA films, regardless of its degree of elongation. From these dependences, it was found that the dehydration reaction progressed more easily in the crystalline region than in the amorphous region, that the aromatic rings with four or five adjacent hydrogen atoms were formed mainly in the amorphous region and those with two adjacent hydrogen atoms in the crystalline region, and that the aromatic rings with two isolated hydrogen atoms were formed in both the amorphous and crystalline regions. Relative concentrations of the groups of which the dehydrated PVA were composed were estimated. Comparison of the numbers of carbon atoms among the composing groups indicated that the main groups were the methylene group and the aromatic ring.     

Reaction of Lithium Cellulosate with Episulfides

The reactions of propylene, ethylene, and styrene sulfide with cotton fabrics in the form of their lithium cellulosate derivative, obtained by metallation with lithium methoxide, were studied. Both graft and homo-polymerization took place and in the reaction with propylene and ethylene sulfide, cotton fabrics with high polysulfide content were obtained. With propylene sulfide 50% of the monomer polymerized was grafted. The effects of monomer concentration, cellulosate degree of substitution, reaction time, and solvent on the polymerization were investigated. In contrast with propylene and ethylene sulfide, only small conversions were obtained in the reaction with styrene sulfide. The results were attributed to steric effects.     

苦瓜成分的提取工艺探索

考察了溶剂用量(1-10mL)、浸泡时间(1～24h)、超声时间(0～20min)对0．2g苦瓜的籽、果实、叶子中成分提取的影响,利用均匀设计(3因素5水平)与固定单因素的方法相结合(9个实验)获取14个不同实验条件,通过多元线性回归得到相关系数大于0．95的4因素表达式。结果表明,超声波对同一个样品中不同的组分有效果相反的作用,即对有些组分降解破坏的同时却会提高另外一些组分的提取率。实验验证了MATLAB预测的最佳实验条件和实验结果,预测准确率大于97％。对于所研究的苦瓜籽、果实、叶子样品0．2g,最佳提取溶剂体积10mL,浸泡时间24h,超声时间0min(果实)或20min(籽、叶子)。     

Dynamic modification of the capillary wall for electrophoretic separations of small ions

Separations of small ions were carried out under nonequilibrated conditions using capillaries treated with NaOH, HCl, or tris(hydroxymethyl)aminomethane (Tris) prior to analysis. For separations of benzoic acid isomers or acids and amines under weakly acidic conditions, capillaries flushed with 0.1 M NaOH and subsequently with running buffers prior to analysis were used. Separations of six benzoic acid isomers were accomplished in 4 min in 1 mM phosphate buffers, pH 4.01, containing 2.5 mM hydroxypropyl-beta-cyclodextrin. Without additives, the separation of biological amines and acids were also achieved in 10 min at pH 4.01. Capillaries treated with 0.1 M HCl prior to analysis were tested in separations of six phenols in 5 mM Tris solutions at pH 7.0. As a result of small electrophoretic mobilities of phenols against a small electroosmotic flow, resolution was optimized. We also found that reproducibility was improved using capillaries treated with HCl. The relative standard deviations of migration mobility of phenols were less than 1%, which were smaller than those obtained using capillaries treated with 0.1 M NaOH or Tris.     

In vitro determination of the release kinetics of peptides and free amino acids during the digestion of food proteins

The kinetics of peptide release during in vitro digestion of 4 protein sources (casein, cod protein, soy protein, and gluten) were investigated. Samples were sequentially hydrolyzed with pepsin (30 min) and pancreatin (2, 4, or 6 h) in a dialysis cell with continuous removal of digestion products. Nondialyzed digests were fractionated by ion-exchange chromatography and ultrafiltration. Animal proteins were digested at a greater rate than plant proteins. Target amino acids of specific enzymes appeared more rapidly in the dialyzed fractions when compared to other amino acids. Throughout the hydrolysis, nondialyzed digests contained a higher proportion of peptide mixtures with basic-neutral properties. Except for gluten, peptide fractions with molecular weights that exceeded 10 kDa (basic-neutral, BN > 10) were rapidly hydrolyzed during the first 2 h of pancreatin digestion. The kinetics of release and the composition of peptide fractions were different when the protein sources were compared. The analysis of amino acids revealed that threonine and proline proportions were relatively high in BN > 10 and in peptide fractions with molecular weight between 10-1 kDa (BN 10-1), while tyrosine, phenylalanine, lysine, and arginine predominated in the low molecular weight (<1 kDa) fractions. More resistant peptides were generally rich in proline and glutamic acid. The role of in vitro digestion assays in dietary protein quality evaluation is discussed.     

Effect of surface covering of lactose carrier particles on dry powder inhalation properties of salbutamol sulfate

The effect of the surface covering of lactose carrier particles on the dry powder inhalation properties of salbutamol sulfate was investigated. Lactose carrier surfaces were covered with sucrose tristearate (J-1803F) by a high-speed elliptical-rotor-type powder mixer (Theta-Composer). In the present study, drug/carrier powder mixtures were prepared consisting of micronized salbutamol sulfate and lactose carriers with various particle surface conditions prepared by surface covering. These powder mixtures were aerosolized by a Jethaler), and the in vitro inhalation properties of salbutamol sulfate were evaluated by a twin impinger. Compared with the powder mixed with uncovered lactose carrier, the in vitro inhalation properties of the powder mixture prepared using the surface covering lactose carrier were significantly different, showing that the in vitro inhalation properties of salbutamol sulfate were improved. In vitro inhalation properties increased with the percentage of J-1803F added. Using this surface covering system would thus be valuable for increasing the inhalation properties of dry powder inhalation with lactose carrier particles.     

Polymerization of allyl(vinyl phenyl) ethers and reactions of the resulting polymers

Solution polymerizations of allyl(o-vinyl phenyl)ether and allyl(p-vinyl phenyl)ether with cationic and radical initiators were investigated. Soluble polymers were formed in polymerizations with boron trifluoride etherate and with benzoyl peroxide. In polymerization with azobisisobutyronitrile the polymerization in dilute solution gave a soluble polymer, whereas that in concentrated solution gave a crosslinked, insoluble one. For informationon the polymerization behavior some infrared and ultraviolet spectroscopic investigations of the soluble polymers were made. From these results it appears that polymers with pendant allyl groups are formed in polymerization with boron trifluoride etherate at low temperature, and polymers containing pendant vinyl groups and allyl groups are obtained with the two types of radical initiator. Copolymerizations of these monomers with ethyl vinyl ether and styrene with the use of boron trifluoride etherate were sucessfully effected. Such reactions as Claisen rearrangement, crosslinking induced with radical initiators, and epoxidation with perbenzoic acid were examined for the polymers prepared in the polymerization with boron trifluoride etherate. Good results were obtained for the former two reactions. However, the latter was unsuccessful.     

血液透析联合血液灌流治疗急性肾功能衰竭的临床效果分析

目的分析急性肾功能衰竭采取血液透析联合血液灌流治疗的临床效果。方法选取2010年1月—2015年1月期间惠州市中医医院收治的24例急性肾功能衰竭患者作为研究对象,按治疗方法的不同将本组患者分为两组,对照组12例患者接受单纯血液透析治疗,观察组12例患者接受血液透析联合血液灌流治疗,治疗2个月后,对两组患者的临床指标及临床效果进行统计对比。结果观察组治疗后CRP、Cr、BUN、MMS指标优于对照组,差异有统计学意义(P0.05);观察组治疗有效率为91.67%(11/12),高于对照组75.00%(9/12),差异有统计学意义(P0.05)。结论对急性肾功能衰竭患者的治疗,采取血液透析联合血液灌流治疗的临床效果显著,促进患者康复,在临床中具有良好的应用价值。     

Properties of novel gel particles with projections and preparations of composite particles with gold nanoparticles

Mono-dispersed gel particles with projections were prepared by dispersion polymerization with ethyleneglycol dimethacrylate and a polyethyleneglycol (PEG) block macro azo initiator in H₂O/ethanol solutions. The effects of molecular weight of PEG blocks and polymerization conditions on the morphology and some properties were examined for the gel particles. The diameters and the extent of coagulation were different with the polymerization conditions. Relatively large specific areas and large swelling ratio with H₂O were obtained, and these values were related with the polymerization conditions. By mixing the gel particles with gold nanoparticles in solutions, composite particles were formed, which were composed of gold nanoparticles adsorbed on the gel particles. Interaction between gold nanoparticles and reactive azo groups remained in the gel particles concerned for the formation of the composite particles.     

LC/MS/MS for identification of in vivo and in vitro metabolites of jatrorrhizine

The in vivo and in vitro metabolism of jatrorrhizine has been investigated using a specific and sensitive LC/MS/MS method. In vivo samples including rat feces, urine and plasma collected separately after dosing healthy rats with jatrorrhizine (34 mg/kg) orally, along with in vitro samples prepared by incubating jatrorrhizine with rat intestinal flora and liver microsome, respectively, were purified using a C(18) solid-phase extraction cartridge. The purified samples were then separated with a reversed-phase C(18) column with methanol-formic acid aqueous solution (70:30, v/v, pH3.5) as mobile phase and detected by on-line MS/MS. The structural elucidation of the metabolites was performed by comparing their molecular weights and product ions with those of the parent drug. As a result, seven new metabolites were found in rat urine, 13 metabolites were detected in rat feces, 11 metabolites were detected in rat plasma, 17 metabolites were identified in intestinal flora incubation solution and nine metabolites were detected in liver microsome incubation solution. The main biotransformation reactions of jatrorrhizine were the hydroxylation reaction, the methylation reaction, the demethylation reaction and the dehydrogenation reaction of parent drug and its relative metabolites. All the results were reported for the first time, except for some of the metabolites in rat urine.