Prediction of Chameleonic Efficiency

Chameleonic properties, i. e., the capacity of a molecule to hide polarity in non-polar environments and expose it in water, help achieving sufficient permeability and solubility for drug molecules with high MW. We present models of experimental measures of polarity for a set of 24 FDA approved drugs (MW 405-1113) and one PROTAC (MW 1034). Conformational ensembles in aqueous and non-polar environments were generated using molecular dynamics. A linear regression model that predicts chromatographic apparent polarity (EPSA) with a mean unsigned error of 10 Ų was derived based on separate terms for donor, acceptor, and total molecular SASA. A good correlation (R²=0.92) with an experimental measure of hydrogen bond donor potential, Δlog P_oct-tol, was found for the mean hydrogen bond donor SASA of the conformational ensemble scaled with Abraham's A hydrogen bond acidity. Two quantitative measures of chameleonic behaviour, the chameleonic efficiency indices, are introduced. We envision that the methods presented herein will be useful to triage designed molecules and prioritize those with the best chance of achieving acceptable permeability and solubility.     

On the linear correlation between microhardness and mechanical properties in polar polymers and blends

The tensile elastic modulus (E), yield stress (σ_Y) and microhardness (MH) of neat and binary and ternary blends of glassy semicrystalline ethylene–vinyl alcohol copolymer (EVOH), a glassy amorphous polyamide and a semicrystalline nylon‐containing ionomer covering a broad range of properties were examined. The tests were carried out on dry and water‐equilibrated samples to produce stiffer and softer materials, respectively. From the results, more accurate linear correlations were found to describe adequately the microhardness, modulus and yield stress of these strongly self‐associated polymers through hydrogen bonding. Copyright © 2003 Society of Chemical Industry     

砂岩酸化中水化硅沉淀的影响因素分析

讨论了砂岩酸化中产生水化硅沉淀的反应机理。使高岭土与1.0%HF和多种配比的HCl HF在不同温度(20-90℃)反应不同时间(10-300分钟),用等离子吸收光谱法(ICP)测定酸液中可溶性硅的浓度(mg/L),取某时段测定值的减小量为该时段水化硅沉淀生成量,讨论了多种因素的影响,得到了如下结果和结论。反应温度越高,则高岭土与HF之间的反应越快,形成水化硅沉淀的时间越短,最终生成的沉淀量越大;在HF中加入HCl(使用土酸体系)、减小土酸中HF质量分数、加大土酸中HCl、HF质量分数比,均可使生成沉淀时间延后,使最终生成沉淀量减少。60℃时300分钟沉淀量,在1.0%HF、5.0%HCl 1.0%HF、9.0%HCl 1.0%HF中分别为482、321、201mg/L。提出了在酸化设计与施工中可以采取的6条简便易行的减少水化硅沉淀量的措施。图4表1参6。     

山区长输气管线的曲线测设

该文介绍了在山区长输气管线测量中 ,管线的折点桩之间大部分不通视且部分点上空有障碍物 ,采用GPS不能施测坐标时 ,结合山区的自然地理条件 ,采用全站仪间接施测折点水平角 ,极坐标法测设曲线以及跨越障碍物测设曲线的内容和方法 ,可在一定精度要求下应用     

Oleuropein Inhibits LDL Oxidation Induced by Cooking Oil Frying By-products and Platelet Aggregation Induced by Platelet-Activating Factor

Oleuropein, a polyphenolic glucoside, constituent of olive fruit and oil, has been previously shown to exhibit, in vitro, potent properties as a biological antioxidant. In the present paper, two new properties are demonstrated in vitro as well, concerning its vascular protection activity, against the atheromatic lesion formation and its blood antithrombotic effect. Firstly, it was found that the oxidation of low-density lipoproteins (LDL), induced by different quantities of total polar materials (TPM), was inhibited by 10 μ M (final concentration) of oleuropein, revealing approx. 50% protection. Secondly, platelet-rich human plasma aggregation, induced by either the platelet-activating factor or adenosine diphospate or arachidonic acid, was inhibited by oleuropein. The 10 μ M (final concentration) of oleuropein was proven to be the most effective among the tested concentrations against LDL oxidation, while an IC₅₀=0.41 mM was calculated for its inhibitory activity against platelet aggregation induced by 0.7 μ M platelet-activating factor.     

Analysis of polar compound classes in SRC-II liquids: Comparison of non-aqueous titrametric,i.r. spectrometric and h.p.l.c. methods

Results for various types of polar compounds in SRC-11 coal-derived liquids and other fuels were obtained by one or more of the three analytical methods: non-aqueous titration, i.r. spectroscopy and h.p.l.c. Practical aspects as well as precision, accuracy and assumptions necessary for effective application of each of the methods are discussed. H.p.l.c. is applicable to the widest variety of compound types, is the most rapid, most sensitive and shows the best promise for increased development and improvement. Application and development of these techniques is a logical step toward improving process monitoring, catalyst development, toxicological screening and general fuel analysis.     

Organochlorine and Mercury Residues in Young-of-the-Year Spottail Shiners from the Detroit River,Lake St. Clair,and Lake Erie

Young-of-the-year spottail shiners (Notropis hudsonius) were used as biomonitors to determine the spatial distribution (1982/83) and assess trend data for organochlorine and mercury residues. Significantly (p < 0.01) higher PCB residues were found in Detroit River spottail shiners than in collections from southwestern Lake St. Clair and northwestern Lake Erie. The highest PCB residues were found in the west bank collections from Michigan waters (912–2,997ng/g) compared to the mid-stream (96–290 ng/g) and east bank collections (153–316 ng/g). Chlordane residues were found to be elevated in all spottail shiner samples from urbanized areas. Octachlorostyrene and ∑ DDT residues were distributed uniformly within the study area, whereas mercury concentrations were found to be lower in spottail shiners from northwestern Lake Erie than in comparable samples from the Detroit River and southwestern Lake St. Clair. Residues for BHC, heptachlor, aldrin, and chlorinated benzenes were near their detection limits; mirex and chlorinated phenols were not detectable. Recent (1982/83) PCB residue levels in spottail shiners exceeded the IJC aquatic life objective (Great Lakes Water Quality Agreement of 1978) at all the sites sampled, except at Pike Creek in Lake St. Clair. PCB residues in spottail shiners from Pike Creek, Big Creek, and Leamington have declined significantly (p < 0.01) since the mid-seventies. Mercury and chlordane residues have decreased in spottail shiner samples from Leamington, but have remained virtually unchanged at Big Creek and Pike Creek.     

Stimulatory effects of tannins and cholic acid on tryptic hydrolysis of proteins: Ecological implications

The biochemical basis for considering tannins as digestion inhibitors has been reexamined. Both stimulatory and inhibitory effects of tannins on tryptic hydrolysis are reported. We show how stimulation may result from tannin-induced structural changes in the substrate protein, effectively denaturing it. The surfactant and bile constituent cholic acid also produced similar stimulatory effects. These results have considerable implications for normal digestive physiology as well as for the impact of tannins on argicultural and natural herbivore populations.     

Effects of Contaminants on Toxicity of the Lampricides TFM and Bayer 73 to Three Species of Fish

Waters in the Great Lakes basin contain more than 400 contaminant chemicals that potentially affect fishery resources, commerce, and human inhabitants. We determined in the laboratory the effects of selected contaminants on the toxicity of the widely used lampricides TFM (3-trifluoromethyl-4-nitrophenol) and Bayer 73 (2′,5-dichloro-4′-nitrosalicylanilide) to three species of fish—rainbow trout (Salmo gairdneri), white sucker (Catostomus commersoni), and fathead minnow (Pimephales promelas). The fish were exposed to paired mixtures of lampricides and selected contaminants in standardized, acute static toxicity tests to determine the resulting type of response—less than additive, additive, or greater than additive (synergistic). As expected, the toxicities of combinations of lampricides with organic pesticides, metal, industrial or municipal pollutants, and tannic acid were mostly additive. However, the toxicity of a combination of TFM, Delnav, and malathion was synergistic, and extremely small quantities of each chemical became lethal when mixed. The concentration that produced 50% mortality was 1.64 mg/L for TFM alone but only 0.041 mg/L for TFM with the pesticides. Toxicities of the pesticides in the combination also increased commensurately. The triple combination of chemicals produced extraordinary synergism and effectively demonstrated the hazards that may result if certain chemical combinations occur in the aquatic environment. However, synergism is not the only kind of toxic action that produces hazards to aquatic organisms. All three types of toxic action are of concern because toxic units produced by contaminant chemicals add to the toxic units of applied management chemicals. Since the toxicity of the majority of chemical combinations is simply additive, this cumulative toxic action contributes more total units to aquatic environments than the extreme actions of less than additive and synergism. The toxicity of the lampricide TFM, as well as other management chemicals, is reinforced by the presence of any contaminant that contributes additional units of toxicity. Therefore, all types of cumulative toxic action should be of concern to people and agencies involved with protecting the environment.