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By combining scanning transmission electron microscopy, CO chemisorption, and energy dispersive X-ray spectroscopy with CO and NO oxidation light-off measurements we investigated deactivation phenomena of Pt/Al2O3, Pd/Al2O3, and Pt-Pd/Al2O3 model diesel oxidation catalysts during stepwise hydrothermal aging. Aging induces significant particle sintering that results in a decline of the catalytic activity for all catalyst formulations. While the initial aging step caused the most pronounced deactivation and sintering due to Ostwald ripening, the deactivation rates decline during further aging and the catalyst stabilizes at a low level of activity. Most importantly, we observed pronounced morphological changes for the bimetallic catalyst sample: hydrothermal aging at 750 °C causes a stepwise transformation of the Pt-Pd alloy via core-shell structures into inhomogeneous agglomerates of palladium and platinum. Our study shines a light on the aging behavior of noble metal catalysts under industrially relevant conditions and particularly underscores the highly complex transformation of bimetallic Pt-Pd diesel oxidation catalysts during hydrothermal treatment. [ABSTRACT FROM AUTHOR]

Abstract: Silica-supported nanogold catalysts suspended in 30% hydrogen peroxide using ultrasound are highly active and selective for cyclohexene and d-glucose oxidation at room temperature. In these conditions a polar reactant, D-glucose, can be efficiently and directly converted with 100% yield using this system, while a conversion of apolar cyclohexene is limited by the addition of a surfactant improving cosolubility in the system and/or catalyst/support wettability. To our best knowledge this is the first time that hydrogen peroxide has been used efficiently in association with a gold catalyst for the selective oxidation of cyclohexene in a biphasic system. [Copyright &y& Elsevier]

Plants are masterpieces of evolution that is based on carbon chemistry. In particular, plant leaves are biosynthetic factories able to convert CO 2 into carbohydrates and oxygen. It is worth noting that mimicking the efficiency of a natural plant and natural leaf is still a challenge for contemporary chemistry. We can even better realize this when we notice that a plant and an industrial factory are equivalent in meaning. On the other hand, green technologies are under development in a quest for the artificial leaf. If we could modify the synthetic pathways in leaves, we could also design green chemistry schemes in natural leaves to produce useful chemicals or to digest wastes or toxins. Specifically, can we intensify the potential for capturing atmospheric CO 2 in leaves? Auxins are plant hormones that control the growth and development of plants. Herein, we determined whether we could efficiently transport xenobiotic auxin into leaves and if so, whether this supply could enhance the metabolism and CO 2 capturing ability. By exploring a series of dioxolanes as potential enhancers of auxin transport, we discovered for the first time that a small molecular compound, 2,2-dimethyl-1,3-dioxolane (DMD), enhances the xenobiotic auxin transport to leaves, which boosts the metabolism that is measured by H 2 O 2 production as well as CO 2 capturing ability in leaves., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: On the one hand, ligand efficiency (LE) and the binding efficiency index (BEI), which are binding properties (B) averaged versus the heavy atom count (HAC: LE) or molecular weight (MW: BEI), have recently been declared a novel universal tool for drug design. On the other hand, questions have been raised about the mathematical validity of the LE approach., Results: In fact, neither the critics nor the advocates are precise enough to provide a generally understandable and accepted chemistry of the LE metrics. In particular, this refers to the puzzle of the LE trends for small and large molecules. In this paper, we explain the chemistry and mathematics of the LE type of data. Because LE is a weight metrics related to binding per gram, its hyperbolic decrease with an increasing number of heavy atoms can be easily understood by its 1/MW dependency. Accordingly, we analyzed how this influences the LE trends for ligand-target binding, economic big data or molecular descriptor data. In particular, we compared the trends for the thermodynamic ∆G data of a series of ligands that interact with 14 different target classes, which were extracted from the BindingDB database with the market prices of a commercial compound library of ca. 2.5 mln synthetic building blocks., Conclusions: An interpretation of LE and BEI that clearly explains the observed trends for these parameters are presented here for the first time. Accordingly, we show that the main misunderstanding of the chemical meaning of the BEI and LE parameters is their interpretation as molecular descriptors that are connected with a single molecule, while binding is a statistical effect in which a population of ligands limits the formation of ligand-receptor complexes. Therefore, LE (BEI) should not be interpreted as a molecular (physicochemical) descriptor that is connected with a single molecule but as a property (binding per gram). Accordingly, the puzzle of the surprising behavior of LE is explained by the 1/MW dependency. This effect clearly explains the hyperbolic LE trend not as a real increase in binding potency but as a physical limitation due to the different population of ligands with different MWs in a 1 g sample available for the formation of ligand-receptor complexes. Graphical abstract .

Target-oriented drug discovery is the main research paradigm of contemporary drug discovery. In target-oriented approaches, we attempt to maximize in vitro drug potency by finding the optimal fit to the target. This can result in a higher molecular complexity, in particular, the higher molecular weight (MW) of the drugs. However, a comparison of the successful developments of pharmaceuticals with the general trends that can be observed in medicinal chemistry resulted in the conclusion that the so-called molecular obesity is an important reason for the attrition rate of drugs. When analyzing the list of top 100 drug bestsellers versus all of the FDA approvals, we discovered that on average lower-complexity (MW, ADMET score) drugs are winners of the top 100 list in terms of numbers but that, especially, up to some optimal MW value, a higher molecular complexity can pay off with higher incomes. This indicates that slim drugs are doing better but that fat drugs are bigger fishes to catch.

We analyzed a list of the top 100 bestselling drugs as a struggling market for new FDA approvals. Using the time from drug approval by the FDA as a measure of drug age, our analysis showed that the top 100 bestselling drugs are getting older. This reflects the stalled launch of new drugs into the market during recent years., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Series of new ring-substituted styrylquinolines and two oxorhenium complexes were prepared and characterized. The compounds were analyzed using RP-HPLC to determine lipophilicity. Primary in vitro screening of the synthesized compounds was performed against fungal and bacterial strains. Some compounds were active against bacteria at micromolar level and against fungi at submicromolar level. Compounds 5,7-dichloro-2-[2-(2-ethoxyphenyl)vinyl]quinolin-8-ol expressed excellent antifungal activity comparable with or higher than the standard fluconazole as well as antibacterial activity against Staphylococcus strains comparable with or higher than the standards bacitracin, penicillin and ciprofloxacin. The structure-activity relationships are discussed., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

While searching for new HIV integrase inhibitors we discovered that some ethyl malonate amides (EMA) are active against this enzyme. Surprisingly, the main function can only very rarely be found among the reported drug candidates. We synthesised a series of compounds in order to establish and analyse the structure-activity relationship. The similarity to the important classes of HIV integrase inhibitors as well as the synthetic availability of the different targets including this pharmacophore makes EMA compounds an interesting object of investigations., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

A detailed knowledge of hydrogen bond geometry and its directional preferences is vital for in silico investigations of the ligand-receptor short-range non-covalent interactions. The spatial arrangement of the carbonyl and hydroxyl groups seems to determine the capability of β-ketoenol derivatives to recognize the surrounding environment by forming inter- and intra-molecular hydrogen bonds (IHB). In the current study we examined the application of the MoStBioDat platform for a massive database screening of the IHB motifs in β-ketoenol subunits (O=C-C=C-OH). Then, the virtual 3D structural data derived from ZINC and PubChem repository were compared to the experimentally determined CSD data. Differences specific for each database were discovered, which indicated inaccuracies in the simulated data.

Crystal structures of three small molecular scaffolds based on quinoline, 2-methylquinoline-5,8-dione, 5-hydroxy-quinaldine-6-carboxylic acid and 8-hydroxy-quinaldine-7-carboxylic acid, were characterised. 5-Hydroxy-quinaldine-6-carboxylic acid was co-crystallized with cobalt(II) chloride to form a model of divalent metal cation-ligand interactions for potential HIV integrase inhibitors. Molecular docking into active site of HIV IN was also performed on 1WKN PDB file. Selected ligand-protein interactions have been found specific for active compounds. Studied structures can be used as scaffolds in fragment-based design of new potent drugs., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Isothiocyanates (ITC) are well-known chemopreventive agents extracted from vegetables. This activity results from the activation of human oxidoreductase. In this letter, the uncompetitive activatory mechanism of ITC was investigated using docking and molecular dynamics simulations. This indicates that NAD(P)H:quinone oxidoreductase can efficiently improve enzyme-substrate recognition within the catalytic site if the ITC activator supports the interaction in the uncompetitive binding site.

A group of styrylazanaphthalenes and azanaphthalenediones were synthesized and tested for their anti-proliferative activity. Most of the compounds were obtained with the use of microwave-assisted synthesis. The lipophilicity of the compounds was measured by RP-HPLC and their anti-proliferative activity was assayed against the human SK-N-MC neuroepithelioma and HCT116 human colon carcinoma cell lines. Active compounds were also tested in clonogenity and comet assays. Several quinazolinone and styrylquinazoline analogues were found to have markedly greater anti-proliferative activity than desferoxamine and cis-platin., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Comparative molecular surface analysis (CoMSA) with robust IVE-PLS variable elimination if tested for the benchmark CBG steroid series provides highly predictive RI 3D QSAR models, but failed however to model the activity of sulforaphane (SP) activators of quinone reductase. The application of the SP poses obtained from multipose molecular docking to model the RD IVE-PLS CoMSA resulted in a predictive form. This model indicated lipophilic potential as the activity determinant. The individual molecular surface areas of the highest contribution to the SP activity was identified and visualized by CoMSA contour plots.

Two series of amides based on quinoline scaffold were designed and synthesized in search of photosynthesis inhibitors. The compounds were tested for their photosynthesis-inhibiting activity against Spinacia oleracea L. and Chlorella vulgaris Beij. The compounds lipophilicity was determined by the RP-HPLC method. Several compounds showed biological activity similar or even higher than that of the standard (DCMU). The structure-activity relationships are discussed.

In the current paper we present a receptor-independent 4D-QSAR method based on self-organizing mapping (SOM-4D-QSAR) and in particular focus on its pharmacophore mapping ability. We use a novel stochastic procedure to verify the predictive ability of the method for a large population of 4D-QSAR models generated. This systematic study was conducted on a series of benzoic acids, azo dyes, and steroids that bind aromatase. We show that the 4D-QSAR method coupled with IVE-PLS provides a very stable and predictive modeling technique. The method enables us to identify the molecular motifs contributing the most to the fiber-dye affinity and the aromatase enzyme binding activity of the steroid. However, the method appeared much less effective for the benzoic acid series, in which the efficacy was limited by electronic effects strictly correlated to a single conformer.

The lack of the wide spectrum of biological data is an important obstacle preventing the efficient molecular design. Quinoline derivatives are known to exhibit a variety of biological effects. In the current publication, we tested a series of novel quinoline analogues for their photosynthesis-inhibiting activity (the inhibition of photosynthetic electron transport in spinach chloroplasts (Spinacia oleracea L.) and the reduction of chlorophyll content in Chlorella vulgaris Beij.). Moreover, antiproliferative activity was measured using SK-N-MC neuroepithelioma cell line. We described the structure-activity relationships (SAR) between the chemical structure and biological effects of the synthesized compounds. We also measured the lipophilicity of the novel compounds by means of the RP-HPLC and illustrate the relationships between the RP-HPLC retention parameter logK (the logarithm of capacity factor K) and logP data calculated by available programs.

The series of quinoline derivatives were prepared. The synthetic approach, analytical, and spectroscopic data of all synthesized compounds are presented. All the prepared derivatives were analyzed using the reversed-phase high performance liquid chromatography (RP-HPLC) method for the lipophilicity measurement. In the present study, the correlation between RP-HPLC retention parameter log K (the logarithm of capacity factor K) and various calculated log P data is shown. The relationships between the lipophilicity and the chemical structure of the studied compounds are discussed as well. The prepared compounds were tested for their in vitro antifungal activity. 2-[(3-Hydroxyphenylimino)methyl]quinolin-8-ol (8), 2-[(4-hydroxyphenylimino)methyl]quinolin-8-ol (9) and 2-[(2,5-dichloro-4-nitrophenylamino)methoxymethyl]quinolin-8-ol (10) showed in vitro antifungal activity comparable to or higher than that of the standard fluconazole. Structure-activity relationships among the chemical structure, the physical properties, and the biological activities of the evaluated compounds are discussed in the article.

We used the 4D-QSAR method coupled with the PLS analysis and uninformative variable elimination or its variants for the investigations of the antiviral activity of HEPT, a series of conformationally flexible molecules that bind HIV-1 reverse transcriptase. An analysis of several Hopfinger's and SOM-4D-QSAR models indicated that both methods yield comparable results. Generally, charge descriptors provide better modeling efficiency. We have shown that the method properly indicates the mode of interaction revealed by X-ray studies. It also allows us to calculate highly predictive QSAR models.

Despite recent investigations aimed at modeling 3D QSAR for dye molecules a controversy still exists: can a pharamacophore hypothesis be used for such purposes. In the present publication we reported on the application of the CoMSA method for modeling 3D QSAR of azo and anthraquinone dyes. We obtained very predictive models, which significantly outperform those reported in the previous CoMFA studies, especially for the azo dyes. Our results proved the previous conclusion that steric requirements are far less pronounced for the cellulose cavities than for the classical drug receptor. Moreover, our results indicate that all molecular surface segments are important for dye-fiber interactions, which also makes an important difference in relation to the classical drug pharmacophore. On the other hand, high predictivity of the CoMSA models indicates that a pharmacophore concept is suitable for the description of the dye-fiber interactions. However, this pharmacophore must substantially differ from the drug pharmacophore used for the illustration of the drug-receptor interactions. From a theoretical point of view dye-cellulose interactions can be an interesting case in which shape decides the activity rules not by the steric repulsion but as a cofactor determining the electrostatic potential distribution.

The application of the SOM network in drug design and molecular diversity is discussed. In particular, examples of the applications of the Comparative Molecular Surface Analysis (CoMSA) are reviewed. Molecular surface is a fuzzy category, inspired by the macroscopic world, which has no unique equivalent in the molecular scale. However, it is somewhere near the area where the molecular recognition processes are taking place. Consequently, the methods that analyze this region promise better efficiency than procedures that are based on uniform grids. An important advantage of the CoMSA method is the possibility for the generation of fuzzy molecular representations together with its ability to discover such aspects of molecular similarity that can be easily overlooked by a chemist. The ability for data compression is a further advantage. It has also been shown that the fast processing of the comparative Kohonen mapping enables one to implement this method in the field of molecular diversity.