From Structure–Activity to Structure–Selectivity Relationships: Quantitative Assessment,Selectivity Cliffs,and Key Compounds

The exploration of structure–activity relationships (SARs) in chemical lead optimization is mostly focused on activity against single targets. Because many active compounds have the potential to act against multiple targets, achieving a sufficient degree of target selectivity often becomes a major issue during optimization. Herein we report a data analysis approach to explore compound selectivity in a systematic and quantitative manner. Sets of compounds that are active against multiple targets provide a basis for exploring structure–selectivity relationships (SSRs). Compound similarity and selectivity data are analyzed with the aid of network‐like similarity graphs (NSGs), which organize molecular networks on the basis of similarity relationships and SAR index (SARI) values. For this purpose, the SARI framework has been adapted to quantify SSRs. Using sets of compounds with differential activity against four cathepsin thiol proteases, we show that SSRs can be quantitatively described and categorized. Furthermore, local SSR environments are identified, the analysis of which provides insight into compound selectivity determinants at the molecular level. These environments often contain “selectivity cliffs” formed by pairs or groups of similar compounds with significantly different selectivity. Moreover, key compounds are identified that determine characteristic features of single‐target SARs and dual‐target SSRs. The comparison of compounds involved in the formation of selectivity cliffs often reveals chemical modifications that render compounds target selective.     

Fuel grade ethanol by diffusion distillation: an experimental study

BACKGROUND: Fuel grade ethanol (anhydrous ethanol) is considered to be an excellent alternative clean burning fuel to gasoline. It is now used as an additive to gasoline to enhance its octane number and combustibility. Owing to its high energy values, ethanol is the most promising future biofuel. Because of azeotrope formation, anhydrous ethanol cannot be achieved by conventional distillation. Diffusion distillation is one of the several processes that can be used to separate azeotropes. Diffusion distillation takes advantage of differences in relative rates of diffusion using inert gas as selective filter. RESULTS: Effect of vaporization temperature and feed composition on diffusion distillation of an ethanol–water mixture using air as the inert gas has been studied. A new quantity S_az(N₂/N₁) has been suggested to find the optimum vaporization temperature. In the present study this was found to be about 46 °C. The pseudo‐azeotrope has been observed at 0.697 mole fraction of ethanol at a vaporization temperature of 50 °C. Separation is effected by diffusion distillation even at the azeotropic ethanol mole fraction of 0.894. The experimental results were compared with a Stefan–Maxwell equations based mathematical model and found to be in good agreement with theoretical results. CONCLUSIONS: Experimental results demonstrate that fuel grade ethanol can be produced by diffusion distillation. The new quantity S_az(N₂/N₁) is a key variable for vaporization temperature optimization. Copyright © 2011 Society of Chemical Industry     

Yeast‐mediated stereo‐selective reduction of estrone by continuous cell culture with dual stirred tanks for product yield improvement

BACKGROUND: β‐Estradiol is an important hormone for the treatment of breast cancer and osteoporosis. β‐Estradiol can be produced via Saccharomyces cerevisiae mediated reduction of estrone. However, substrate inhibition and low production yield have been observed in the batch cell culture. RESULTS: An innovative continuous cell culture with dual stirred tanks in series was designed to solve the above problems. The growth medium was fed continuously to the incubation tank where the cells were incubated aerobically; the viable cells were then supplied continuously to the reaction tank in which the yeast‐mediated anaerobic reduction of estrone was performed with continuous feed of the substrate medium and continuous withdawal of the reaction cell culture. Thus, an increase in cell productivity from about 3‐fold to 7‐fold was obtained when compared with the batch cell culture. The β‐estradiol yield was improved to 64.8% on the second reaction day, accompanied by an accumulation of 12.9 mg β‐estradiol on the third reaction day. The yield was about 10% more and the accumulated recovery of β‐estradiol was 4.3‐fold better than with the batch cell culture. The diastereomeric excess value (%de) of β‐estradiol was more than 99%. CONCLUSION: A high product yield with excellent stereo‐selectivity was achieved in a short reaction period with the developed continuous cell culture and the dual stirred tank. Copyright © 2010 Society of Chemical Industry     

The final bleaching of eucalypt kraft pulps with hydrogen peroxide: relationship with industrial ECF bleaching history and cellulose degradation

BACKGROUND: The process of chemical pulp bleaching is based for the most part in chlorine dioxide within elemental chlorine free (ECF) technologies. The use of greener alternatives such as bleaching with hydrogen peroxide (P stage) is not widely used owing to selectivity concerns related to transition metal‐catalyzed decomposition reactions. Even at the final stage where peroxide is recognized to boost brightness and improve the brightness stability of the bleached pulp, cellulose degradation often overcomes these advantages. This paper presents the results of studies intended to optimize final peroxide bleaching performance considering two standard ECF industrial bleaching sequences: the conventional DED and the ECF‐light OQ(PO)D (stages name: D—chlorine dioxide; E—alkaline extraction; O—oxygen; Q—chelation, (PO)—hydrogen peroxide pressurized with oxygen). RESULTS: The addition of sodium diethylenetriaminepentaacetate (DTPA) was the most effective option in terms of DED pulp bleachability and selectivity with hydrogen peroxide, as well as in terms of brightness reversion. As regards the OQ(PO)D pulp, a blend of DTPA and magnesium was the most beneficial in those properties. CONCLUSIONS: The choice of the best hydrogen peroxide stabilizer, among the different tested combinations of magnesium and chelants (EDTA and DTPA) studied, in terms of pulp bleachability, bleaching selectivity and brightness reversion is dependent on the impact of the previous bleaching stages on metallic nature and content. The pulp Mg/(Fe + Cu) ratio was highlighted as a process parameter controlling cellulose degradation in peroxide bleaching. Copyright © 2010 Society of Chemical Industry     

Petrochemicals from ethanol over a W-Si-based nanocomposite bidisperse solid acid catalyst

Very high ethylene selectivity values approaching 100% and very high ethanol conversion values approaching 85% were obtained in dehydration of ethanol over a new W-silicate-based nanocomposite catalyst having both meso and macropores and containing a W/Si atomic ratio of 0.85. Silicotungsticacid was successfully incorporated into the catalyst structure following a one-pot hydrothermal synthesis procedure. This catalyst is highly stable and does not loose activity in polar solvents and it has a sufficiently high surface area for catalytic applications. Calcination temperature of the catalyst was found to have a very significant effect on the catalyst structure and also on its catalytic performance in ethanol dehydration. Maximum selectivity of the second major reaction product diethylether was obtained as 0.7 at 200 °C, with the catalyst which was calcined at 400 °C. Very high ethylene and diethylether yield values obtained in this study at different reaction conditions are highly promising for the production of petrochemicals from ethanol.     

Age-related differences in emotion recognition ability: A cross-sectional study.

Experimental studies indicate that recognition of emotions, particularly negative emotions, decreases with age. However, there is no consensus at which age the decrease in emotion recognition begins, how selective this is to negative emotions, and whether this applies to both facial and vocal expression. In the current cross-sectional study, 607 participants ranging in age from 18 to 84 years (mean age = 32.6 ± 14.9 years) were asked to recognize emotions expressed either facially or vocally. In general, older participants were found to be less accurate at recognizing emotions, with the most distinctive age difference pertaining to a certain group of negative emotions. Both modalities revealed an age-related decline in the recognition of sadness and—to a lesser degree—anger, starting at about 30 years of age. Although age-related differences in the recognition of expression of emotion were not mediated by personality traits, 2 of the Big 5 traits, openness and conscientiousness, made an independent contribution to emotion-recognition performance. Implications of age-related differences in facial and vocal emotion expression and early onset of the selective decrease in emotion recognition are discussed in terms of previous findings and relevant theoretical models. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Linear hexane isomerization over the natural zeolite based catalysts depending on the zeolite phase composition

A range of Pd-containing catalysts on the basis of mordenite–clinoptilolite rocks of different starting phase compositions is synthesized. Final phase composition and acidity of rocks change as the conditions of their dealumination are changed. The efficiency of catalysts synthesized is weakly influenced by change of mordenite component contents within 50–80%, and it is not inferior to the efficiency of the catalysts on the synthetic mordenite basis. The nature of active sites as trifunction ones and isomerization mechanism are proposed.     

Ti-Si-O双功能催化吸附材料的汽油光催化-吸附耦合脱硫性能

研究新型双功能Ti-Si-O吸附催化材料在紫外光照射下对汽油的光催化-吸附耦合脱硫性能。采用溶胶-凝胶法制备了Ti-Si-O双功能催化吸附材料,并用N₂吸附法、XRD等对Ti-Si-O进行了结构表征;有机硫化物的含量和种类采用液相色谱、库仑仪、GC-MS和GC-SCD检测。实验结果表明:当钛硅摩尔比为3:7时,所制得的Ti-Si-O材料的光催化-吸附耦合脱硫性能最好,脱硫率达96%,优于单一的TiO₂和SiO₂材料;Ti_0.3Si_0.7O₂对汽油中的3种有机硫化物的光催化-吸附耦合脱硫速率大小顺序为T > MT > BT;GC-MS产物检测表明汽油中的有机硫在Ti_0.3Si_0.7O₂双功能催化吸附材料表面转化成极性较强的砜类物质,而后选择性地吸附在Ti_0.3Si_0.7O₂表面;Ti_0.3Si_0.7O₂可经过丙酮洗涤和热空气氧化法再生,5次循环使用后的脱硫性能基本维持不变;在光催化-吸附耦合工艺下,Ti_0.3Si_0.7O₂材料可将真实汽油的硫含量降低至10 mg·g^-1以下。