Towards Symmetric Thioamides: Microwave-Aided Synthesis of Terephthalic Acid Derivatives.

The multistep synthesis of novel bis-terephthalthioamides based on methyl esters of amino acids (AAs) was proposed using conventional heating and microwave-assisted approaches. In fact, the comparative case study on the thionation of new symmetrical diamides with Lawesson's reagent (LR) was performed. The microwave-accelerated small-scale methodology was successfully employed on the whole pathway from substrates (Gly, Ala, Val, Tyr, Ser) to products (symmetrical dithioamides of terephthalic acid), resulting in significantly reduced reaction time, energy requirements, and slightly increased reaction yields when compared to conventional heating. Moreover, the intermolecular similarity of novel terephthalic acid derivatives was estimated in the multidimensional space (mDS) of the structure/property-related in silico descriptors using principal component analysis (PCA) and hierarchical clustering analysis (HCA). The distance-oriented structure/property distribution was also correlated with the experimental lipophilic data.

Towards Arginase Inhibition: Hybrid SAR Protocol for Property Mapping of Chlorinated N-arylcinnamamides.

A series of seventeen 4-chlorocinnamanilides and seventeen 3,4-dichlorocinnamanilides were characterized for their antiplasmodial activity. In vitro screening on a chloroquine-sensitive strain of Plasmodium falciparum 3D7/MRA-102 highlighted that 23 compounds possessed IC50 < 30 µM. Typically, 3,4-dichlorocinnamanilides showed a broader range of activity compared to 4-chlorocinnamanilides. (2E)-N-[3,5-bis(trifluoromethyl)phenyl]-3-(3,4-dichlorophenyl)prop-2-en-amide with IC50 = 1.6 µM was the most effective agent, while the other eight most active derivatives showed IC50 in the range from 1.8 to 4.6 µM. A good correlation between the experimental logk and the estimated clogP was recorded for the whole ensemble of the lipophilicity generators. Moreover, the SAR-mediated similarity assessment of the novel (di)chlorinated N-arylcinnamamides was conducted using the collaborative (hybrid) ligand-based and structure-related protocols. In consequence, an 'averaged' selection-driven interaction pattern was produced based in namely 'pseudo-consensus' 3D pharmacophore mapping. The molecular docking approach was engaged for the most potent antiplasmodial agents in order to gain an insight into the arginase-inhibitor binding mode. The docking study revealed that (di)chlorinated aromatic (C-phenyl) rings are oriented towards the binuclear manganese cluster in the energetically favorable poses of the chloroquine and the most potent arginase inhibitors. Additionally, the water-mediated hydrogen bonds were formed via carbonyl function present in the new N-arylcinnamamides and the fluorine substituent (alone or in trifluoromethyl group) of N-phenyl ring seems to play a key role in forming the halogen bonds.

Machine Learning Approach for Application-Tailored Nanolubricants' Design.

The fascinating tribological phenomenon of carbon nanotubes (CNTs) observed at the nanoscale was confirmed in our numerous macroscale experiments. We designed and employed CNT-containing nanolubricants strictly for polymer lubrication. In this paper, we present the experiment characterising how the CNT structure determines its lubricity on various types of polymers. There is a complex correlation between the microscopic and spectral properties of CNTs and the tribological parameters of the resulting lubricants. This confirms indirectly that the nature of the tribological mechanisms driven by the variety of CNT-polymer interactions might be far more complex than ever described before. We propose plasmonic interactions as an extension for existing models describing the tribological roles of nanomaterials. In the absence of quantitative microscopic calculations of tribological parameters, phenomenological strategies must be employed. One of the most powerful emerging numerical methods is machine learning (ML). Here, we propose to use this technique, in combination with molecular and supramolecular recognition, to understand the morphology and macro-assembly processing strategies for the targeted design of superlubricants.

Biological Activities and ADMET-Related Properties of Novel Set of Cinnamanilides.

A series of nineteen novel ring-substituted N-arylcinnamanilides was synthesized and characterized. All investigated compounds were tested against Staphylococcus aureus as the reference strain, two clinical isolates of methicillin-resistant S. aureus (MRSA), and Mycobacterium tuberculosis. (2E)-N-[3-Fluoro-4-(trifluoromethyl)phenyl]-3-phenylprop-2-enamide showed even better activity (minimum inhibitory concentration (MIC) 25.9 and 12.9 µM) against MRSA isolates than the commonly used ampicillin (MIC 45.8 µM). The screening of the cell viability was performed using THP1-Blue™ NF-κB cells and, except for (2E)-N-(4-bromo-3-chlorophenyl)-3-phenylprop-2-enamide (IC50 6.5 µM), none of the discussed compounds showed any significant cytotoxic effect up to 20 µM. Moreover, all compounds were tested for their anti-inflammatory potential; several compounds attenuated the lipopolysaccharide-induced NF-κB activation and were more potent than the parental cinnamic acid. The lipophilicity values were specified experimentally as well. In addition, in silico approximation of the lipophilicity values was performed employing a set of free/commercial clogP estimators, corrected afterwards by the corresponding pKa calculated at physiological pH and subsequently cross-compared with the experimental parameters. The similarity-driven property space evaluation of structural analogs was carried out using the principal component analysis, Tanimoto metrics, and Kohonen mapping.

Real-Time Corrosion Monitoring of AISI 1010 Carbon Steel with Metal Surface Mapping in Sulfolane.

Solvents are widely used in organic synthesis. Sulfolane is a five-membered heterocyclic organosulfur sulfone (R-SO2-R', where R/R' is alkyl, alkenyl, or aryl) and an anthropogenic medium commonly used as industrial extractive solvent in the liquid-liquid and liquid-vapor extraction processes. Under standard conditions sulfolane is not aggressive towards steel, but at higher temperatures and in oxygen, water, or chlorides presence, it can be decomposed into some corrosive (by-)products with generation of SO2 and subsequent formation of corrosive H2SO3. This pilot-case study provides data from laboratory measurements performed in low conductivity sulfolane-based fluids using an industrial multi-electrochemical technique for reliable detection of corrosion processes. In particular, a comprehensive evaluation of the aqueous phase impact on general and localized corrosion of AISI 1010 carbon steel in sulfolane is presented. Assessment of corrosive damage was carried out using an open circuit potential method, potentiodynamic polarization curves, SEM/EDS and scanning Kelvin probe technique. It was found that an increase in the water content (1-3 vol.%) in sulfolane causes a decrease in the corrosion resistance of AISI 1010 carbon steel on both uniform and pitting corrosion due to higher conductance of the sulfolane-based fluids.

Novel Benzene-Based Carbamates for AChE/BChE Inhibition: Synthesis and Ligand/Structure-Oriented SAR Study.

A series of new benzene-based derivatives was designed, synthesized and comprehensively characterized. All of the tested compounds were evaluated for their in vitro ability to potentially inhibit the acetyl- and butyrylcholinesterase enzymes. The selectivity index of individual molecules to cholinesterases was also determined. Generally, the inhibitory potency was stronger against butyryl- compared to acetylcholinesterase; however, some of the compounds showed a promising inhibition of both enzymes. In fact, two compounds (23, benzyl ethyl(1-oxo-1-phenylpropan-2-yl)carbamate and 28, benzyl (1-(3-chlorophenyl)-1-oxopropan-2-yl) (methyl)carbamate) had a very high selectivity index, while the second one (28) reached the lowest inhibitory concentration IC50 value, which corresponds quite well with galanthamine. Moreover, comparative receptor-independent and receptor-dependent structure⁻activity studies were conducted to explain the observed variations in inhibiting the potential of the investigated carbamate series. The principal objective of the ligand-based study was to comparatively analyze the molecular surface to gain insight into the electronic and/or steric factors that govern the ability to inhibit enzyme activities. The spatial distribution of potentially important steric and electrostatic factors was determined using the probability-guided pharmacophore mapping procedure, which is based on the iterative variable elimination method. Additionally, planar and spatial maps of the host⁻target interactions were created for all of the active compounds and compared with the drug molecules using the docking methodology.