A Comparative Study of Molecular Structure,pKa, Lipophilicity,Solubility, Absorption and Polar Surface Area of Some Antiplatelet Drugs

Theoretical chemistry methods have been used to study the molecular properties of antiplatelet agents (ticlopidine, clopidogrel, prasugrel, elinogrel, ticagrelor and cangrelor) and several thiol-containing active metabolites. The geometries and energies of most stable conformers of these drugs have been computed at the Becke3LYP/6-311++G(d,p) level of density functional theory. Computed dissociation constants show that the active metabolites of prodrugs (ticlopidine, clopidogrel and prasugrel) and drugs elinogrel and cangrelor are completely ionized at pH 7.4. Both ticagrelor and its active metabolite are present at pH = 7.4 in neutral undissociated form. The thienopyridine prodrugs ticlopidine, clopidogrel and prasugrel are lipophilic and insoluble in water. Their lipophilicity is very high (about 2.5–3.5 logP values). The polar surface area, with regard to the structurally-heterogeneous character of these antiplatelet drugs, is from very large interval of values of 3–255 Ų. Thienopyridine prodrugs, like ticlopidine, clopidogrel and prasugrel, with the lowest polar surface area (PSA) values, exhibit the largest absorption. A high value of polar surface area (PSA) of cangrelor (255 Ų) results in substantial worsening of the absorption in comparison with thienopyridine drugs.     

Small‐angle X‐ray scattering analysis of nanophase titanium dioxide,poly[N‐(4‐sulfophenyl)aniline], and their composite

Small‐angle X‐ray scattering and spectroscopic (infrared and ultraviolet–visible) techniques were used to investigate the interactions between titanium dioxide (TiO₂) and the semiconductor polymer poly[N‐(4‐sulfophenyl)aniline] (PSA) in a poly[N‐(4‐sulfophenyl)aniline]/TiO₂ composite (TPSA). The radius of gyration of the cross section, the radius and length of the rodlike particle, the persistence length, the surface fractal dimension, and the PSA layer thickness on TiO₂ in aqueous solutions and in powder form were calculated. The results indicated that the aggregation of TiO₂ particles on drying was reduced by the formation of the composite with the semiconductor polymer. Only the particle length of the TPSA particle (which had a rodlike shape) increased on drying, probably because of increasing void sizes and the formation of aggregation. The persistence length of the TPSA particles decreased with respect to its individual components. The PSA layer thickness on TiO₂ was about 3.6 nm and decreased (to 2.6 nm) on dehydration because of the expulsions of water molecules from the TiO₂/PSA composite. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 88: 3183–3187, 2003     

Development of specific "drug-like property" rules for carboxylate-containing oral drug candidates

The carboxylate moiety is an important pharmacophore in the medicinal chemist's arsenal and is sometimes an irreplaceable functionality in drug–target interactions. Thus, practical guidance on its use in the most optimized manner would be a welcome addition to rational drug design. Key physicochemical and ADMET‐PK properties from a dataset of drugs containing a carboxylate (COOH) moiety were assembled and compared with those of a broader, general drug dataset. Our main objective was to identify features specific to COOH‐containing oral drugs that could be converted into simple rules delineating the boundaries within which prospective COOH‐containing chemical series and COOH‐containing drug candidates would be reasonably expected to possess properties suitable for oral administration. These specific “drug‐like” property rules include molecular weight, the number of rotatable bonds, the number of hydrogen bond donors and acceptors, predictions of lipophilic character (calculated log P and log D values), topological polar surface area (TPSA), and the pK_a value of the carboxylate moiety. Similar to the various sets of criteria that have emerged over the past decade and which have significantly reshaped the way medicinal chemists think about preferred drug chemical space, we propose these specific COOH “drug‐like” property rules as a guide for the design of superior COOH‐containing drug candidates and as a tool to better manage the liabilities generally associated with the presence of a COOH moiety.     

Calculation of the Free Surface Energy of Coals from the Donets Basin and Graphites

The methodologies of the determination of the free surface energy of solids were analyzed. It was shown that the currently available models for the calculation of free surface energy are based on the measurements of the angles of contact, and they contain an internal contradiction that consists in the fact that the surface energy is divided into two or three components: a polar component, hydrogen bonds, and a dispersion component. The free surface energy was calculated for the metamorphic series of coals from the Donets Basin (long-flame, gas, coke, and lean coals and anthracites) and graphites. Considerable differences in the values of free surface energy for different coalmine beds of anthracites were not revealed. Technical-grade and spectral graphites are insignificantly different from anthracites in terms of free surface energy, but a polar component of free surface energy has lower values of 0.0054–0.0117 J/m².     

On the interpretation of contact angle hysteresis

The determination of solid surface free energy is still an open problem. The method proposed by van Oss and coworkers gives scattered values for apolar Lifshitz-van der Waals and polar (Lewis acid-base) electron-donor and electron-acceptor components for the investigated solid. The values of the components depend on the kind of three probe liquids used for their determination. In this paper a new alternative approach employing contact angle hysteresis is offered. It is based on three measurable parameters: advancing and receding contact angles (hysteresis of the contact angle) and the liquid surface tension. The equation obtained allows calculation of total surface free energy for the investigated solid. The equation is tested using some literature values, as well as advancing and receding contact angles measured for six probe liquids on microscope glass slides and poly(methyl methacrylate) PMMA, plates. It was found that for the tested solids thus calculated total surface free energy depended, to some extent, on the liquid used. Also, the surface free energy components of these solids determined by van Oss and coworkers' method and then the total surface free energy calculated from them varied depending on for which liquid-set the advancing contact angles were used for the calculations. However, the average values of the surface free energy, both for glass and PMMA, determined from these two approaches were in an excellent agreement. Therefore, it was concluded that using other condensed phase (liquid), thus determined value of solid surface free energy is an apparent one, because it seemingly depends not only on the kind but also on the strength of interactions operating across the solid/liquid interface, which are different for different liquids.     

Synthesis,Molecular Docking Analysis and Biological Evaluations of Saccharide-Modified Thiadiazole Sulfonamide Derivatives

A series of saccharide-modified thiadiazole sulfonamide derivatives has been designed and synthesized by the “tail approach” and evaluated for inhibitory activity against carbonic anhydrases II, IX, and XII. Most of the compounds showed high topological polar surface area (TPSA) values and excellent enzyme inhibitory activity. The impacts of some compounds on the viability of HT-29, MDA-MB-231, and MG-63 human cancer cell lines were examined under both normoxic and hypoxic conditions, and they showed certain inhibitory effects on cell viability. Moreover, it was found that the series of compounds had the ability to raise the pH of the tumor cell microenvironment. All the results proved that saccharide-modified thiadiazole sulfonamides have important research prospects for the development of CA IX inhibitors.     

丙烯酸酯PSA环形初粘力影响因素研究

以反应型乳化剂(DNS-86)/阴离子型乳化剂(2A1)为复合乳化剂、甲基丙烯酸(MAA)与甲基丙烯酸羟乙酯(HEMA)为极性单体和正十二硫醇为链转移剂时,采用单体预乳化法和半连续乳液聚合法制备丙烯酸酯PSA(压敏胶)乳液。考察了PSA胶带的基材、干胶厚度、烘干条件、复合乳化剂、极性单体和链转移剂等对环形初粘力的影响。结果表明:当基材为白色BOPP(双向拉伸聚丙烯)薄膜、干胶厚度为50μm、烘干时间为3 min、烘干温度为110~115℃、w(正十二硫醇)=0.09%、同时引入MAA和HEMA极性单体、w(复合乳化剂)=1.5%和m(2A1)∶m(DNS-86)=2∶1时,相应丙烯酸酯PSA乳液的环形初粘力相对最大(14.73 N/25 mm)。     

The Use of AFM and Surface Energy Measurements to Investigate Drug-Canister Material Interactions in a Model Pressurized Metered Dose Inhaler Formulation

The aim of the project was to investigate the interactions between micronized salbutamol sulphate, budesonide, and formoterol fumarate dihydrate and different canister surfaces materials (Aluminium, anodized aluminium, perfluoroalkoxy, fluorinated ethylene propylene—polyether sulphone, and polytetrafluoroethylene) used in pressurized metered dose inhalers (pMDIs).

The surface component approach for polar and apolar interfacial interactions was used to predict the adhesion behavior of micronized drugs with the inner surfaces of pMDI canisters. This was achieved using a combination of in situ colloid probe atomic force microscopy (AFM) measurements and theoretical treatment of the surface free energy measurements, via a contact angle–based technique of the interacting surfaces.

All three drugs exhibited similar dispersive surface energy free values. A greater variation was, however, found in the polar component of the surface free energy measurements. These results were also reflected in the dispersive and polar components of the canister materials. Moreover, the linear relationship between the work of adhesion and AFM measured adhesion was shown to be correlated on the polar contributions of the surface free energies of the interacting materials. AFM measurements indicated that salbutamol sulphate was found to have the strongest adhesive forces with respect to the canister surface materials while budesonide and formoterol fumarate dihydrate appeared to have similar adhesive characteristics. The present study suggests that investigations into the design and characterization of pMDI formulations would benefit from considerations of the polar contribution of the surface free energy and relative work of adhesion of the drug and various components of a pMDI system.     

Molecular Physicochemical Properties of Selected Pesticides as Predictive Factors for Oxidative Stress and Apoptosis-Dependent Cell Death in Caco-2 and HepG2 Cells

In this work, three pesticides of different physicochemical properties: glyphosate (GLY, herbicide), imidacloprid (IMD, insecticide), and imazalil (IMZ, fungicide), were selected to assess their cytotoxicity against Caco-2 and HepG2 cells. Cell viability was assessed by the Alamar Blue assay, after 24 and 48 h exposure to different concentrations, and IC₅₀ values were calculated. The mechanisms underlying toxicity, namely cellular reactive oxygen species (ROS), glutathione (GSH) content, lipid peroxidation, loss of mitochondrial membrane potential (MMP), and apoptosis/necrosis induction were assessed by flow cytometry. Cytotoxic profiles were further correlated with the molecular physicochemical parameters of pesticides, namely: water solubility, partition coefficient in an n-octanol/water (Log P_ow) system, topological polar surface area (TPSA), the number of hydrogen-bonds (donor/acceptor), and rotatable bonds. In vitro outputs resulted in the following toxicity level: IMZ (Caco-2: IC₅₀ = 253.5 ± 3.37 μM, and HepG2: IC₅₀ = 94 ± 12 μM) > IMD (Caco-2: IC₅₀ > 1 mM and HepG2: IC₅₀ = 624 ± 24 μM) > GLY (IC₅₀ >>1 mM, both cell lines), after 24 h treatment, being toxicity time-dependent (lower IC₅₀ values at 48 h). Toxicity is explained by oxidative stress, as IMZ induced a higher intracellular ROS increase and lipid peroxidation, followed by IMD, while GLY did not change these markers. However, the three pesticides induced loss of MMP in HepG2 cells while in Caco-2 cells only IMZ produced significant MMP loss. Increased ROS and loss of MMP promoted apoptosis in Caco-2 cells subjected to IMZ, and in HepG2 cells exposed to IMD and IMZ, as assessed by Annexin-V/PI. The toxicity profile of pesticides is directly correlated with their Log P_ow, as affinity for the lipophilic environment favours interaction with cell membranes governs, and is inversely correlated with their TPSA; however, membrane permeation is favoured by lower TPSA. IMZ presents the best molecular properties for membrane interaction and cell permeation, i.e., higher Log P_ow, lower TPSA and lower hydrogen-bond (H-bond) donor/acceptor correlating with its higher toxicity. In conclusion, molecular physicochemical factors such as Log P_ow, TPSA, and H-bond are likely to be directly correlated with pesticide-induced toxicity, thus they are key factors to potentially predict the toxicity of other compounds.     

Chemical oxidation of high-density polyethylene: Surface energy,functionality, and adhesion to liquid epoxy

The application of polyolefins has increased significantly over the past few decades. However, their chemical inertness and low surface energy limits their application in many industries where high adhesion to polar materials is required, such as for composites and protective coatings. Herein, six different acids are used to create polar functional groups on High-Density Polyethylene's (HDPE) surface and to increase its adhesion to liquid epoxy (LE). Contact angle measurements, Fourier Transform Infrared Spectroscopy (FTIR), X-ray Photoelectron Spectroscopy (XPS), and pull-off strength measurements are used to analyze the surface energy and functionality of HDPE and to measure its adhesion to LE. The results show that each acid increases both the polar and disperse surface energies of HDPE to a different extent, but that this is not necessarily a function of acid strength. Chlorosulfonic acid and chromic acid increase the oxygen to carbon ratio by a factor of 8 and increase HDPE's adhesion to LE by more than 400%. Furthermore, a comparison between predicted work of adhesion values from the OWRK model and experimental results shows that the latter are significantly higher than what is predicted, especially with increasing surface polarity.     

色谱斜率法测过量自由焓之模型参数的研究

研究了色谱测定(σγ/σx)_(x=0)的两种公式——修正的Kikic-Renon公式及Valentin-Guiochon公式,实测了29个二元系的γ_1~∞,分别按两种公式测定(σγ/σx)_(x=0),求取两参数过量自由焓模型参数,进而预测全浓度范围汽液平衡,得到了较为满意的结果.对Valentin-Guiochon公式合理简化,提出了一个较为简便的(σγ/σx)_(x=0) 公式.利用Gmehling等汇编的56个含醇及含水二元系γ_1~∞数据,直接计算该公式的(σγ/σx)_(x=0)之值,进而推算过量自由焓模型参数,并预测汽液平衡.又用气液色谱测定了各种含有极性与非极性组分、挥发与难挥发组分的不同类型43个二元系的γ_1~∞值,按上述方法预测全浓度范围汽液平衡,与文献中已发表的汽液平衡数据比较,结果都符合良好.最后,讨论了三种斜率公式各自的适用范围和两参数过量自由焓模型转化为单参数模型的一般方法.     

Calculation of the Energy of Explosives with a Partial Reaction Model. Comparison with Cylinder Test Data

The energy delivered by explosives is described by means of the useful expansion work along the isentrope of the detonation products. A thermodynamic code (W‐DETCOM) is used, in which a partial reaction model has been implemented. In this model, the reacted fraction of the explosive in the detonation state is used as a fitting factor so that the calculated detonation velocity meets the experimental value. Calculations based on such a model have been carried out for a number of commercial explosives of ANFO and emulsion types. The BKW (Becker‐Kistiakowsky‐Wilson) equation of state is used for the detonation gases with the Sandia parameter set (BKWS). The energy delivered in the expansion (useful work) is calculated, and the values obtained are compared with the Gurney energies from cylinder test data at various expansion ratios. The expansion work values obtained are much more realistic than those from an ideal detonation calculation and, in most cases, the values predicted by the calculation are in good agreement with the experimental ones.     

Characterization of an acrylic polymer under hygrothermal aging as an optically clear adhesive for touch screen panels

Optically clear adhesives (OCAs) are key components of touch screen panels (TSPs). It is important that OCAs do not affect the transparent electrodes in TSPs because OCAs are contacted to the transparent electrodes. Therefore, N-vinyl caprolactam (NVC) was incorporated in the composition of an acrylic pressure sensitive adhesive (PSA) with excluding an acidic component to maintain the cohesion for OCA preparation. With increasing amounts of NVC, the tack and peel strength of UV-cured PSA increased, but high amounts of NVC led to decreased peel strength. The UV-cured PSA films were placed in a high temperature and humidity chamber for 8 weeks to investigate the durability and corrosion property under hygrothermal conditions. In this study, the corrosion test method using copper foil was suggested as a simple and economical method and was used to evaluate the effect of NVC on the corrosion property of PSA. This method helped identify suitable OCAs that do not have corrosive property. PSA films containing more than 20 wt% of NVC promoted the corrosion of copper foil under hygrothermal aging conditions. The caprolactam ring was opened by moisture, and the PSA structure morphed into a polar structure during the aging process. This change caused a glass transition shift, an increase in the storage modulus at the rubbery plateau, and an increase in peel strength. The surface free energy of the PSA films also increased due to the increase in the polar property. However, high amounts of NVC caused a decrease in the peel strength after 8 weeks of aging because of increased molecular interactions.     

Stockmayer force constants for the viscosity of polar gases

Relationships have been developed for the calculation of the viscosity of a polar gas at atmospheric pressure from macroscopic parameters available for the substance. The molecular force constants for the Stockmayer potential determined by Monchick and Mason from viscosity data were related to the critical constants of the substance and the parameters ω and × defined through the vapor pressure. For 10 polar gases, an average deviation of approximately 3.0% was obtained between experimental viscosities and values calculated with the relationships of this study. The relationships were also utilized to calculate diffusion coefficients for a number of polar binary mixtures.     

How does the surface free energy influence the tack of acrylic pressure-sensitive adhesives (PSAs)?

This article describes a comparative study of the tack properties of a model acrylic pressure-sensitive adhesive (PSA) crosslinked using aluminum acetylacetonate on several substrates, including stainless steel, glass, polyethylene, polypropylene, polytetrafluoroethylene, polycarbonate, and poly(methyl methacrylate). The tack measurements were conducted using a technique commonly used to measure the tack of an adhesive tape in the PSA industries. The surface free energy (SFE) values of the materials were evaluated using the Owens–Wendt and van Oss–Chaudhury–Good methods. The experiments showed a clear relationship between the SFE of the substrate and the tack of the model acrylic PSA. In general, larger differences between the SFE values of the substrate and adhesive (Δ_SFE) were correlated with greater tack values. The tack of the model acrylic PSA was found to be optimal over the Δ_SFE range of 7.0–13.1 mJ/m². The trend in the tack as a function of the SFE difference was attributed to the quantity of energy dissipated at the jointed points during the separation stage in the loop tack test.     

用密度泛函理论研究非极性混合流体表面性质

应用密度泛函理论研究了二元非极性混合流体的表面性质.分子作为球形链处理,不同分子内的两链节相互作用以硬核Yukawa势能表示.为了避免计算中势能作用数值积分截断导致的误差,采用了合理的长程校正方法.根据微扰理论建立了流体的状态方程以计算汽液相平衡.从纯流体汽液相平衡数据回归得分子的链节作用参数ε/k、d和m_s,这些参数预测纯流体表面张力时可获得较好结果.继而引入混合参数k_ij表示不同分子链节作用情况,计算了6种非极性混合流体的汽液相平衡、表面张力、表面密度剖面.结果表明,本方法应用于二元非极性流体混合物时汽液表面张力计算值与实验值符合良好,同时显示某些二元混合流体表面区可能出现组分的相对富集现象.     

Self‐aggregated nanoparticles of N‐dodecyl,N′‐glycidyl(chitosan) as pH‐responsive drug delivery systems for quercetin

In this study, pH‐responsive amphiphilic chitosan (CS) nanoparticles were used to encapsulate quercetin (QCT) for sustained release in cancer therapy. The novel CS derivatives were obtained by synthesis with 2,3‐epoxy‐1‐propanol, also known as glycidol, followed by acylation with dodecyl aldehyde. Characterization was performed by spectroscopic, viscosimetric, and size‐determination methods. Critical aggregation concentration, morphology, entrapment efficiency, drug release profile, cytotoxicity, and hemocompatibility studies were also carried out. The average size distribution of the self‐assembling nanoparticles measured by dynamic light scattering ranged from 140 to 300 nm. In vitro QCT release and Korsmeyer–Peppas model indicated that pH had a major role in drug release. Cytotoxicity assessments indicated that the nanoparticles were non‐cytotoxic. 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay further revealed that QCT‐loaded nanoparticles could inhibit MCF‐7 cell growth. In vitro erythrocyte‐induced hemolysis indicated the good hemocompatibility of the nanoparticles. These results suggest that the synthesized copolymers might be potential carriers for hydrophobic drugs in cancer therapy. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 45678.     

Predicting the surface tension of biodiesel fuels from their fatty acid composition

The emergence of biodiesel fuels as diesel fuel substitutes has led to several studies on their properties. Surface tension, which plays a role in atomization, has lacked attention compared to other properties. This paper presents a method to predict the surface tension of biodiesel fuels based on the fatty acid composition. Several binary, ternary, and quaternary mixtures of fatty acid ethyl ester gas chromatographic (GC) standards were prepared, and we found that a mass-average equation predicted the surface tension of these mixtures within ±3.5% of their measured values. Six complex mixtures of fatty acid methyl ester GC standards that simulated typical oils used as biodiesel fuels were also prepared. For these complex mixtures the predicted surface tensions of the mixtures, calculated from a mass-average equation, were 2–6% higher than the measured values. A mass-average equation was developed in which we used a weighted surface tension for the individual components, and we found that this method predicted the surface tension of the simulated oils within ±4.5% of their measured values. Five natural vegetable oils were used to produce biodiesel fuels by the transesterification process. The predicted surface tensions of these fuels were all within ±3.5% of their measured values. The surface tensions of 15 biodiesel types were then predicted, based on their fatty acid composition as published in the literature. These results show that the differences in surface tension between biodiesel types are not the main cause of the reported differences in engine tests.