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[M+CuCl+H]2+ ions were generated using electrospray ionization (ESI); where M is a molecule of 3,5-bis(2,2'-bipyridin-4-ylethynyl)benzoic acid or its methyl ester (1 and 2, respectively). The ions were subjected to CID-MS/MS analysis. It was found that their gas phase decomposition lead to the formation of rare di-cations [M]2+, namely [1]2+ and [2]2+ ions. The formation of [1]2+ ion from [3+H+CuCl]2+ ion in the second fragmentation, where 3 is ethyl ester of 3,5-bis(2,2-bipyridin-4-ylethynyl)benzoic acid, was also observed since in the first fragmentation step the loss of ethylene molecule from [3+H+CuCl]2+ ion took place. To the best of our knowledge, it is the first time that [M]2+ ions formation from respective metal complexes has been reported. It is also unusual that formation of [M]2+ ions is not accompanied by formation of [M]+∙ ions. Furthermore, as expected, theoretical calculation and electron ionization mass spectra show that 1 and 2 are not especially prone to form [M]2+ ions. Thus formation of [M]2+ ions under CID conditions is very surprising. [ABSTRACT FROM AUTHOR]

Copper(II)-nicotine complexes with chelating perchlorate, nitrate, acetate and formate ligands have been synthesized and characterized in solid state by elemental analysis and FT-IR spectroscopy. Coordination of Cu(II) by nicotine molecule has been also studied in water solution of various pH by potentiometry and spectroscopic (VIS, EPR and NMR) methods. Furthermore, quantum-mechanical calculations helped elucidate the experimental data as they provided some information on the energetic of the possible interaction modes of Cu(II) with nicotine. The studies showed that nicotine acts as a monodentate ligand utilizing for this purpose the pyridine nitrogen atom. In the Cu(II)/Nicotine system the MHL and ML type complexes were formed in 1:1 metal:ligand ratio. [ABSTRACT FROM AUTHOR]

The conformations of isolated molecules of (2S,3S)-2,3-dideoxy-2,3-difluorotartaric acid (FTA) and its dimethyl diester (FME), diamide (FAM) and N,N,N',N'-tetramethyldiamide (FTMA) were examined. The results of high-level ab initio calculations up to MP2/6-311++G**//RHF/6-31G* showed that at the highest level of theory, 23 conformers were located for FTA, 15 for FME, nine for FAM and 11 for FTMA. It was also shown that the substitution of the OH group by a F atom leads to profound changes in conformational preferences of isolated molecules.

This study determines the effect of spent garnet as a replacement for natural sand in 3D-printed mortar at early ages. Five mixes with different spent garnet amounts were prepared (0%, 25%, 50%, 75% and 100% by volume). The ratio of binder to aggregate remained unchanged. In all mixes the water/binder ratio was assumed as a constant value of 0.375. Tests were performed to confirm the printability of the mix (a path quality test using a gantry robot with an extruder). Determinations of key buildability properties of the mix (green strength and Young's Modulus) during uniaxial compressive strength at 15 min, 30 min and 45 min after adding water were conducted. A hydraulic press and the GOM ARAMIS precision image analysis system were used to conduct the study. The results showed that an increase in spent garnet content caused a decrease in green strength and Young's Modulus (up to 69.91% and 80.37%, respectively). It was found that to maintain proper buildability, the recommended maximum replacement rate of natural sand with garnet is 50%. This research contributes new knowledge in terms of using recycled waste in the 3D printing technology of cementitious materials. [ABSTRACT FROM AUTHOR]

During milling of flexible workpieces a regenerative chatter vibration may become a critical factor that limits productivity. It is shown in this paper that a selection of cutting parameters based on a stability lobes diagram may not always be a remedy for low productivity due to increased forced vibration level. Additionally, other factors such as tool wear may limit the selection of stable spindle speeds. This paper presents an active control system that counteracts the development of chatter vibration. The proposed active control system employs Linear Quadratic Gaussian (LQG) algorithm and piezoelectric actuator to suppress vibration during cutting. The Kalman filter is used to estimate the state of the system required by LQG algorithm. The active control introduces damping into the system, thereby raising the critical depth of cut and reducing forced vibration amplitude. It enables stable cutting under a much wider range of cutting parameters than for the uncontrolled system. Cutting tests are performed to demonstrate an effectiveness of the control system. Practical issues limiting applications of the proposed technique are discussed. [ABSTRACT FROM PUBLISHER]

The use of the MM2QM tool in a combined docking + molecular dynamics (MD) + molecular mechanics (MM) + quantum mechanical (QM) binding affinity prediction study is presented, and the tool itself is discussed. The system of interest is Mycobacterium tuberculosis (MTB) pantothenate synthetase in complexes with three highly similar sulfonamide inhibitors, for which crystal structures are available. Starting from the structure of MTB pantothenate synthetase in the 'open' conformation and following the combined docking + MD + MM + QM procedure, we were able to capture the closing of the enzyme binding pocket and to reproduce the position of the ligands with an average root mean square deviation of 1.6 Å. Protein-ligand interaction energies were reproduced with an average error lower than 10%. The discussion on the MD part and a protein flexibility importance is carried out. The presented approach may be useful especially for finding analog inhibitors or improving drug candidates. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Drug design with machine learning support can speed up new drug discoveries. While current databases of known compounds are smaller in magnitude (approximately 10 8 ), the number of small drug-like molecules is estimated to be between 10 23 and 10 60 . The use of molecular docking algorithms can help in new drug development by sieving out the worst drug-receptor complexes. New chemical spaces can be efficiently searched with the application of artificial intelligence. From that, new structures can be proposed. The research proposed aims to create new chemical structures supported by a deep neural network that will possess an affinity to the selected protein domains. Transferring chemical structures into SELFIES codes helped us pass chemical information to a neural network. On the basis of vectorized SELFIES, new chemical structures can be created. With the use of the created neural network, novel compounds that are chemically sensible can be generated. Newly created chemical structures are sieved by the quantitative estimation of the drug-likeness descriptor, Lipinski's rule of 5, and the synthetic Bayesian accessibility classifier score. The affinity to selected protein domains was verified with the use of the AutoDock tool. As per the results, we obtained the structures that possess an affinity to the selected protein domains, namely PDB IDs 7NPC, 7NP5, and 7KXD. [ABSTRACT FROM AUTHOR]

Abstract: We investigated the photo-induced cis/trans isomerization of double bonds in fluorinated derivatives of 1,3-dimethyl-5-propenyl uracils. When 1,3-dimethyl-5-(E-1,2,3,3,3-pentafluoropropenyl)uracil was irradiated by light λ >300nm, we obtained the photostationary state involving equilibration with 1,3-dimethyl-5-(Z-1,2,3,3,3-pentafluoropropenyl)uracil where the more sterically congested isomer Z was the major product (E:Z =1:1.5). Irradiation of Z isomer as the starting material also led to the identical photostationary state. In the case of 1,3-dimethyl-5-(1,3,3,3-tetrafluoropropenyl)uracil the more sterically congested isomer E was even more abundant (Z:E =1:7.5). The results of DFT calculations suggest that photo-induced cis/trans isomerization of these compounds can run through the formation of allylmethylene biradical species, which are the transition states produced during photoexcitation. Preference of the formation of more sterically hindered isomers in photostationary state one can rationalize on the basis of the difference in oscillator strength and the role of equilibration between conformers s-cis/s-trans. [Copyright &y& Elsevier]

Abstract: Research in the last ten years has demonstrated that light energy can be used to power artificial nanomotors by exploiting photochemical processes in appropriately designed systems. The photochemical properties of fluorinated derivatives of 1,3-dimethyl-5-propenyl uracils were studied assuming that the electrocyclization of the diene would be a dominant reaction. The primarily formed intermediate, a cyclobutene derivative was expected to undergo further electrocyclic conrotatory ring-opening leading to corresponding E or Z isomer. Keeping in mind the Woodward–Hoffmann and torquoselectivity rules, this photoisomerization is the stereospecific reaction, where the isomerization of each of isomers processes through a different trans–cis cyclobutene-intermediates. This is a cycle of a sequent reactions capable to provide the selective 360° clockwork rotation, which can be used as a model to design a light-fueled nanomotor. [Copyright &y& Elsevier]

The protein effects on the initial step of O2 binding to the diiron active site in the Methane Monooxygenase (MMO) were studied at the ONIOM(QM:MM) level with and without electronic embedding. The significant part of the hydroxylase component of MMO, every aminoacid residue at least one atom of which is within 11 Å radius from either of the iron-centers of the active site, was included into the calculations. The computed ‘real’ system contained almost 1200 atoms and we treated it at, ONIOM low level, Amber molecular mechanics force field. Position of every atom of each amino acid residue within 7-Å radius from either of the iron atoms as well as all hydrogen atoms was optimized. The ‘model’ system, treated at the B3LYP/lan12dz level (ONIOM high level) encompassed 44 atoms including: (i) two iron atoms, (ii) functional groups forming first coordination sphere, such as two water molecules, two imodazoles, two bridging (between the Fe atoms) and two terminal carboxylates, as well as (iii) the dioxygen molecule. The comparison of the obtained results in vacuo and in protein, both with and without electronic embedding, clearly indicates that the protein profoundly affects initial binding of dioxygen molecule to the diiron center of the MMOHred. It was shown that at the early stages methane monooxygenase protein environment plays a crucial role as it effectively facilitates the activation of the dioxygen molecule. Furthermore, the obtained results demonstrated the usefulness of the ONIOM approach in studying such large systems including a dozen of hundreds atoms. [ABSTRACT FROM AUTHOR]

We present a methodology for the synthesis of inorganic-organic Janus-type molecules based on mono-T8 and difunctionalized double-decker silsesquioxanes (DDSQs) via hydrosilylation reactions, achieving exceptionally high yields and selectivities. The synthesized compounds were extensively characterized using various spectroscopic techniques, and their sizes and spatial arrangements were predicted through molecular modelling and density functional theory (DFT) calculations. Quantum chemical calculations were employed to examine the interactions among four molecules of the synthesized compounds. These computational results allowed us to determine the propensity for molecular aggregation, identify the functional groups involved in these interactions, and understand the changes in interatomic distances during aggregation. Understanding the aggregation behaviour of silsesquioxane molecules is crucial for tailoring their properties for specific applications, such as nanocomposites, surface coatings, drug delivery systems, and catalysts. Through a combination of experimental and computational approaches, this study provides valuable insights into the design and optimization of silsesquioxane-based Janus-type molecules for enhanced performance across various fields. [ABSTRACT FROM AUTHOR]

In the field of anticancer therapy study it is of great interest to find effective G‐quadruplex ligands which may be of potential use in medical treatment or cancer prevention. Since among the compounds of natural origin, flavonoids have attracted notable attention because of their unique properties and promising therapeutic applications, an interesting question was to identify the flavonoid structural features that could provide effective binding properties toward G‐quadruplex. By using electrospray ionization mass spectrometry, followed by the survival yield method, it has been shown that the flavonoid molecules which contain an available C4=O carbonyl group form more stable adducts with G‐tetrads than the other ones. Molecular docking has shown that C4=O carbonyl group can be a source of hydrogen bonds and/or π‐stacking interactions. Therefore, the flavonoid molecules which contain an available C4=O carbonyl group can be regarded as good binders of G‐quadruplexes. [ABSTRACT FROM AUTHOR]

In this study, we used ultraviolet-visible (UV-Vis), fluorescence, and circular dichroism (CD) techniques, as well as molecular modeling, to probe the interactions between carbazole derivatives and the G-quadruplex structure formed in the promoter region of gene Bcl-2. This gene is a rational target for anticancer therapy due to its high expression in a variety of tumors as well as resistance to chemotherapy-induced apoptosis. We employed a sequence with a specific dual G-to-T mutation that may form a mixed-type hybrid G-quadruplex structure in the Bcl-2 P1 promoter region. The three tested carbazole compounds differing in substitution on the nitrogen atom of carbazole interact with the Bcl-2 G-quadruplex by the same binding mode with the very comparable binding affinities in the order of 105 M−1. During absorption and fluorescence measurements, large changes in the ligand spectra were observed at higher G4 concentrations. The spectrophotometric titration results showed a two-step complex formation between the ligands and the G-quadruplex in the form of initial hypochromicity followed by hyperchromicity with a bathochromic shift. The strong fluorescence enhancement of ligands was observed after binding to the DNA. All of the used analytical techniques, as well as molecular modeling, suggested the π–π interaction between carbazole ligands and a guanine tetrad of the Bcl-2 G-quadruplex. Molecular modeling has shown differences in the interaction between each of the ligands and the tested G-quadruplex, which potentially had an impact on the binding strength. [ABSTRACT FROM AUTHOR]

Herein, we present the application of fluorinated carbohydrate-derived building blocks for α-hydroxy β-fluoro/β-trifluoromethyl and unsaturated phosphonates synthesis. Pudovik and Horner–Wadsworth–Emmons reactions were applied to achieve this goal. The proposed pathway of the key reactions is supported by the experimental results, as well as quantum chemical calculations. The structure of the products was established by spectroscopic (1D, 2D NMR) and spectrometric (MS) techniques. Based on our data received, we claim that the progress of the Pudovik and HWE reactions is significantly influenced by the acidic protons present in the molecules as assessed by pKa values of the reagent. [ABSTRACT FROM AUTHOR]

The application of DFT computational method (B3LYP/6-311++G(d,p)) to mono- and poly(CF3)substituted naphthalene derivatives helps to study changes in the electronic properties of these compounds under the influence of 11 substituents (-Br, -CF3, -CH3, -CHO, -Cl, -CN, -F, -NH2, -NMe2, -NO2, and -OH) to confront substituent effects in naphthalene with an analogous situation in benzene. This paper shows the dependencies of theoretically calculated SESE (Substituent Effect Stabilization Energy) values on empirically determined, well-defined Hammett-type constants (σp, σm, R, and F). Described poly(CF3)substituted derivatives of naphthalene are, so far, the most sensitive molecular probes for the substituent effects in the aromatic system. The presence of the trifluoromethyl groups of such an expressive nature significantly increases the sensitivity of the SESE to changes caused by another substitution. Further, the more -CF3 groups are attached to the naphthalene ring, the more sensitive the probe is. Certain groups of probes show additivity of sensitivity: the obtained sensitivity relates to the sum of the sensitivities of the mono(CF3)substituted probes. [ABSTRACT FROM AUTHOR]

This article discusses the problem of vibrations during machining. The manufacturing process of generator turbine blades is highly complex. Machining using Computerized Numerical Control (CNC) requires low cutting parameters in order to avoid vibration problems. However, even under these conditions, the surface quality and accuracy of the manufactured objects suffer from high levels of vibrations. Hence, the aim of this research is to counteract this phenomenon. Basic issues related to vibration problems will also be also discussed and a short review of currently available solutions for both active and passive vibration monitoring during machining will be presented. The authors developed a method which does not require any additional equipment other than modified CNC code. The proposed method can be applied to any CNC machine, and is especially suitable for lathes. The method seeks to eradicate the phenomenon of vibrations by providing enhanced control through Input Shaping Control (ISC). For this purpose, the authors present a method for modeling the machining process and design an ISC filter; the model is then implemented in the Matlab and Simulink environment. The last part of the article presents the results, together with a discussion, and includes a brief summary. [ABSTRACT FROM AUTHOR]

A series of facial fac-[Ir(5-R-bzq)3] and meridional mer-[Ir(5-R-bzq)3] Ir(III) complexes bearing benzo[h]quinoline-based ligands have been studied with the help of density functional theory (DFT) methods. A detailed electronic structure comparison of the two isomers has been addressed to point out the differences in their stability and photophysical properties. An influence of substituent impact on optical and electronic properties of Ir(III) homoleptic complexes was also explored by introducing into the cyclometalated ligands substituents characterized with different electronic properties, e.g., R = H, F, OPh, NMe2, C6F5, and p-C6H4-NPh2. The results herein show that fac and mer isomers exhibit remarkable differences in stability and photophysical properties. The introduction of different functional groups into bzq ligands, despite very similar geometrical structures, significantly affected HOMO and LUMO energy levels and energy gaps of the examined Ir(III) complexes. [ABSTRACT FROM AUTHOR]

In the contemporary era, the exploration of machine learning (ML) has gained widespread attention and is being leveraged to augment traditional methodologies in quantitative structure–activity relationship (QSAR) investigations. The principal objective of this research was to assess the anticancer potential of colchicine-based compounds across five distinct cell lines. This research endeavor ultimately sought to construct ML models proficient in forecasting anticancer activity as quantified by the I C 50 value, while concurrently generating innovative colchicine-derived compounds. The resistance index (RI) is computed to evaluate the drug resistance exhibited by LoVo/DX cells relative to LoVo cancer cell lines. Meanwhile, the selectivity index (SI) is computed to determine the potential of a compound to demonstrate superior efficacy against tumor cells compared to its toxicity against normal cells, such as BALB/3T3. We introduce a novel ML system adept at recommending novel chemical structures predicated on known anticancer activity. Our investigation entailed the assessment of inhibitory capabilities across five cell lines, employing predictive models utilizing various algorithms, including random forest, decision tree, support vector machines, k-nearest neighbors, and multiple linear regression. The most proficient model, as determined by quality metrics, was employed to predict the anticancer activity of novel colchicine-based compounds. This methodological approach yielded the establishment of a library encompassing new colchicine-based compounds, each assigned an I C 50 value. Additionally, this study resulted in the development of a validated predictive model, capable of reasonably estimating I C 50 values based on molecular structure input. [ABSTRACT FROM AUTHOR]

Background: Predicting the popularity of and harm caused by psychoactive agents is a serious problem that would be difficult to do by a single simple method. However, because of the growing number of drugs it is very important to provide a simple and fast tool for predicting some characteristics of these substances. We were inspired by the Google Flu Trends study on the activity of the influenza virus, which showed that influenza virus activity worldwide can be monitored based on queries entered into the Google search engine.Objective: Our aim was to propose a fast method for ranking the most popular and most harmful drugs based on easily available data gathered from the Internet.Methods: We used the Google search engine to acquire data for the ranking lists. Subsequently, using the resulting list and the frequency of hits for the respective psychoactive drugs combined with the word "harm" or "harmful", we estimated quickly how much harm is associated with each drug.Results: We ranked the most popular and harmful psychoactive drugs. As we conducted the research over a period of several months, we noted that the relative popularity indexes tended to change depending on when we obtained them. This suggests that the data may be useful in monitoring changes over time in the use of each of these psychoactive agents.Conclusions: Our data correlate well with the results from a multicriteria decision analysis of drug harms in the United Kingdom. We showed that Google search data can be a valuable source of information to assess the popularity of and harm caused by psychoactive agents and may help in monitoring drug use trends. [ABSTRACT FROM AUTHOR]

Artificial intelligence (AI) is widely explored nowadays, and it gives opportunities to enhance classical approaches in QSAR studies. The aim of this study was to investigate the cytoprotective activity parameter under oxidative stress conditions for indole-based structures, with the ultimate goal of developing AI models capable of predicting cytoprotective activity and generating novel indole-based compounds. We propose a new AI system capable of suggesting new chemical structures based on some known cytoprotective activity. Cytoprotective activity prediction models, employing algorithms such as random forest, decision tree, support vector machines, K-nearest neighbors, and multiple linear regression, were built, and the best (based on quality measurements) was used to make predictions. Finally, the experimental evaluation of the computational results was undertaken in vitro. The proposed methodology resulted in the creation of a library of new indole-based compounds with assigned cytoprotective activity. The other outcome of this study was the development of a validated predictive model capable of estimating cytoprotective activity to a certain extent using molecular structure as input, supported by experimental confirmation. [ABSTRACT FROM AUTHOR]

The reactions of vinyl arenes with hydrodisiloxanes in the presence of sodium triethylborohydride were studied using experimental and computational methods. The expected hydrosilylation products were not detected because triethylborohydrides did not exhibit the catalytic activity observed in previous studies; instead, the product of formal silylation with dimethylsilane was identified, and triethylborohydride was consumed in stoichiometric amounts. In this article, the mechanism of the reaction is described in detail, with due consideration given to the conformational freedom of important intermediates and the two-dimensional curvature of the potential energy hypersurface cross sections. A simple way to reestablish the catalytic character of the transformation was identified and explained with reference to its mechanism. The reaction presented here is an example of the application of a simple transition-metal-free catalyst in the synthesis of silylation products, with flammable gaseous reagents replaced by a more convenient silane surrogate. [ABSTRACT FROM AUTHOR]