固定pH滴定法测定弱酸性药物盐酸左旋咪唑

报导一种水溶液中测定弱酸弱碱性药物的固定ｐＨ滴定法。它以弱酸弱碱在水溶液中各种存在形式的分布系数与ｐＨ值的关系为理论依据，不要求滴定反应定量完成，是利用滴定到一定ｐＨ值时滴定剂消耗体积与弱酸碱物质的量之间的正比关系进行定量分析。离解常数小至１０－１２的极弱酸碱也适用。应用该法测定弱酸性药物盐酸左旋咪唑，结果与药典法一致，回收率在９９．６～１００．３％。试液浓度低至５×１０－４ｍｏｌ／Ｌ，也可用该法准确测定。操作简便、快速。制剂中的赋形剂及有色物无干扰。     

一种新型的极弱酸碱分析方法——固定pH滴定法

固定pH滴定法是一种新型的酸碱滴定方法。它的理论基础是弱酸弱碱在水溶液中各种存在形式的分布系数与溶液pH的关系。滴定时不需要确定等当点,也不需要标定滴定剂浓度,可用单标准比较法、标准曲线法或线性回归法对试样定量分析。用本法测定苯酚和甘氨酸,回收率在99.4～101%)。     

运用pH滴定法测定弱酸的电离常数

运用pH传感器和滴数传感器,采取pH滴定法测定了乙酸的电离常数和草酸的二级电离常数,分析了实验误差以及不宜选用此法测定中强酸的电离常数的原因.     

示波电位滴定法测定含硫药物

示波电位滴定法是近几年发展起来的一种最简单的电滴定法,它不需要示波极谱的切口,省去示波极谱的外接线路,只需将两支指示电极直接连于示波器的输入端即可,使设备更简单,操作更方便,便于掌握和推广.示波电位滴定法可用于酸碱、氧化还原、络合及沉淀滴定中,终点指示灵敏、直观,且不受溶液的颜色和浑浊现象的干扰.在沉淀滴定中,目前应用较多的是测定含C~-、Br~-的试样.对含硫试样的分析应用很少.曾有人研究SO_4~(2-)的测定,但由于存在生成硫     

固定pH跨度法滴定弱酸（碱）混合体系

１引言为了克服固定ｐＨ法在酸、碱干扰组分存在时，无法扣除空白的问题，我们提出了固定ｐＨ跨度法。当溶液的温度、离子强度及滴定剂浓度不变，滴定极弱酸（碱）至ｐＨ为Ａ时，消耗滴定剂体积ＶＡ与极弱酸（碱）的含量。之间存在如下关系：当滴至ｐＨ为Ｂ时（设此时反应还未完全），（２）－（１）得：αＡ、αＢ只与极弱酸（碱）的性质和ｐＨ值有关。故对于某一极弱酸（碱），当ｐＨ跨度一定时，△α为一常数，可通过滴定纯品测得。由于只取不完全质子化（失质子化）反应时由某一固定ｐＨ跨度而无须先加入强酸（碱）使待测组分完全质子化…     

固定pH法测定两组分极弱酸（碱）混合体系

将固定pH滴定法结合求解一元线性回归方程组应用于极弱酸(碱)混合体系中各组分含量的同时测定。测定了六次甲基四胺-硫酸钠和六次甲基四胺-乙酸钠混合体系中各组分的含量,回收率为96.7％～103.2％。     

多元线性回归pH配位滴定法同时测定钙和镁

将多元线性回归分析应用于pH配位滴定,提出△lgK_(MY)较小金属离子混合溶液中各组分同时测定的方法,讨论了方法的原理、回归方程和最佳条件.对钙、镁合成样品及实际水样中钙、镁含量进行测定,结果满意.     

多元弱酸及两性物质逐级稳定常数的pH法测定和计算机优化算法

本文由ｐＨ滴定法原理导出多元弱酸及两性物质逐级稳定常数ｋ＿ｉ的计算公式。编辑了由Ｍｏｎｔｅ－Ｃａｒｌｏ法确定初值，Ｈｏｏｋｅ－Ｊｅａｖｅｓ法精解的计算程序。由此算法测定了方酸及其衍生物的各级稳定常数。结果表明，该法实验简便，数值运算效率高，结果可靠     

Thermodynamics of the dissociation of 2-aminopyridinium ion in synthetic seawater and a standard for pH in marine systems

Buffer solutions composed of 2-aminopyridinium chloride and 2-aminopyridine in synthetic seawater are useful as a supplement to buffers of Tris (pH 8.2) and Bis (pH 8.8) in standardizing measurements of hydrogen ion concentration (pm _H or pH(SWS)) in oceanography. The dissociation constant of 2-amino-pyridinium ion over the range of salinities (S) from 30 to 40 has now been determined from the emf of cells without liquid junction at eight temperatures (T) from 278.15 to 313.15 K. The results fit the equation pK=2498.31/T–15.3274+2.4050 lnT+S(0.012928–2.9417×10^–5T) with a standard deviation of 0.0023. Thermodynamic constants for the dissociation process and standard reference values of pm _H and pH(SWS) were derived from the data. The pm _H of the buffer consisting of 2-aminopyridinium chloride and 2-aminopyridine (each 0.04 molal) in synthetic seawater of salinity 35 varies from 7.356 at 278.15 K to 6.601 at 313.15 K.     

CE determination of the thermodynamic pKa values and limiting ionic mobilities of 14 low molecular mass UV absorbing ampholytes for accurate characterization of the pH gradient in carrier ampholytes-based IEF and its numeric simulation

Fourteen low molecular mass UV absorbing ampholytes containing 1 or 2 weakly acidic and 1 or 2 weakly basic functional groups that best satisfy Rilbe's requirement for being good carrier ampholytes (ΔpK_a = pKa_monoanion ‒ pKa_monocation < 2) were selected from a large group of commercially readily available ampholytes in a computational study using two software packages (ChemSketch and SPARC). Their electrophoretic mobilities were measured in 10 mM ionic strength BGEs covering the 2 < pH < 12 range. Using our Debye-Hückel and Onsager-Fuoss laws-based new software, AnglerFish (freeware, https://echmet.natur.cuni.cz/software/download ), the effective mobilities were recalculated to zero ionic strength from which the thermodynamic pK_a values and limiting ionic mobilities of the ampholytes were directly calculated by Henderson-Hasselbalch equation-type nonlinear regression. The tabulated thermodynamic pK_a values and limiting ionic mobilities of these ampholytes (pI markers) facilitate both the overall and the narrow-segment characterization of the pH gradients obtained in IEF in order to mitigate the errors of analyte ampholyte pI assignments caused by the usual (but rarely proven) assumption of pH gradient linearity. These thermodynamic pK_a and limiting mobility values also enable the reality-based numeric simulation of the IEF process using, for example, Simul (freeware, https://echmet.natur.cuni.cz/software/download ).     

Acid dissociation constants of uridine-5′-diphosphate compounds determined by phosphorus nuclear magnetic resonance spectroscopy and internal pH referencing

The acid dissociation constant (pK_a) of small, biological molecules is an important physical property used for investigating enzyme mechanisms and inhibitor design. For phosphorus-containing molecules, the ³¹P nuclear magnetic resonance (NMR) chemical shift is sensitive to the local chemical environment, particularly to changes in the electronic state of the molecule. Taking advantage of this property, we present a ³¹P NMR approach that uses inorganic phosphate buffer as an internal pH reference to determine the pK_a values of the imide and second diphosphate of uridine-5′-diphosphate compounds, including the first reported values for UDP-GlcNAc and UDP-S-GlcNAc. New methods for using inorganic phosphate buffer as an internal pH reference, involving mathematical correction factors and careful control of the chemical shift reference sample, are illustrated. A comparison of the newly determined imide and diphosphate pK_a values of UDP, UDP-GlcNAc, and UDP-S-GlcNAc with other nucleotide phosphate and thio-analogs reveals the significance of the monosaccharide and sulfur position on the pK_a values.     

Thermodynamic and spectroscopic study of the interaction of Cu(II), Ni(II), Zn(II) and Ca(II) ions with 2-amino-N-(2-oxo-2-(2-(pyridin-2-yl)ethyl amino)ethyl)acetamide,a pseudo-mimic of human serum albumin

The protonation equilibria of 2-amino-N-(2-oxo-2-(2-(pyridin-2-yl)ethyl amino)ethyl)acetamide ([H₂(556)–N]) and the complexation of this ligand with Cu(II) Ca(II), Zn(II) and Ni(II) have been studied by glass electrode potentiometry and UV–visible spectrophotometry. From pH ∼2.00–11.00, five models for Cu(II) with the following complexes; MLH, ML, MLH₋₁, MLH₋₂ and MLH₋₃ were generated and observed to describe the experimental data equally well as far as the statistical criteria were concerned. The MLH₋₂ complex predominates at physiological pH in all five models, while the MLH₋₁ complex species exists only at low concentration in two models. The coordination in the MLH₋₂ complex suggested the involvement of one amino, two deprotonated peptides and one pyridyl nitrogen atoms. Molecular mechanics (MM) calculations confirmed the MLH₋₂ complex as the most stable species. Speciation calculations, using a blood plasma model, predicted that the Cu(II)–[H₂(556)–N] complex is able to mobilize Cu(II). Octanol/water partition of CuLH₋₂ showed that 30% of the complex went into the octanol phase, hence promoting percutaneous absorption of copper. The complex is a poor mimic of native copper–zinc superoxide dismutase.     

Synthesis,pharmacological evaluation,and molecular modeling studies of novel isatin hybrids as potential anticancer agents

A novel series of isatin hybrids 5a-g was designed, synthesized, and characterized spectroscopically. The synthesized compounds were evaluated for their cytotoxic activity against the human breast cancer cell line (MCF-7) by in vitro MTT assay. Amongst the tested compounds, 5e compound bearing benzyl moiety at N₄ piperazine was found to be the most active with the promising IC₅₀ (12.47 µM). Moreover, the active compounds 5e and 5g were subjected to antitumor evaluation (in vivo) against Dalton’s ascitic lymphoma (DAL) cell line and the results suggested that the best active compound 5e can normalize the blood picture in comparison to the standard drug. An in silico molecular docking study using the crystal structure of Hsp90 protein described the role of significant protein–ligand interactions and revealed more insights into the binding mode. The drug-likeliness of the compounds was predicted based on Lipinski's rule of five and pharmacokinetic ADME parameters. Hence, the synthesized isatin hybrids could be novel starting point anticancer lead compounds demonstrating drug-like properties which can be explored further for anticancer drug discovery.     

Antimycobacterial and anticancer activity of newly designed cinnamic acid hydrazides with favorable toxicity profile

A series of twelve novel hybrids of cinnamic acid and thiocarbohydrazones were designed, synthesized in high yield using a simple coupling strategy via acid chlorides, and evaluated for their impact against Mycobacterium tuberculosis (Mtb) and cancer cells survival. Among them, compound 3 demonstrated strong anti-Mtb activity by reducing bacilli survival for>90 % in all three treated Mtb isolates, whereas isoniazid and rifampicin did not. Moreover, compound 3 didn’t affect vitality of HepG-2 cells, implying on advantageous hepatotoxicity profile compared to current therapeutic options for tuberculosis. Compounds 2a and 3b displayed as strong inducers of apoptosis in A549 cells, both activating intrinsic caspase pathway and cell cycle arrest at the G0/G1 phase. Subsequent analyses disclosed differences in their activities, where 3b has ability to induce production of mitochondrial superoxide anions, while 2a significantly inhibited cellular mobility. More importantly, 3b considerably affected viability of HepG-2 and HaCaT cells, whereas 2a had moderate impact only on the later. Molecular modeling studies indicated high permeability and good absorption through the human intestine, and moderate aqueous solubility with poor blood–brain barrier permeability. In summary, our results reveal that novel compounds 3 and 2a represent promising agents for tuberculosis and cancer treatment, respectively, indicating that further investigation needs to be performed to clarify the mechanisms of their anti-Mtb and anticancer activity.