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The [Ru(CO)ClH(PCy 3 ) 2 ] catalyzed reaction of terminal germyl-substituted alkynes with vinylboronates gives borylgermyl-substituted buta-1,3-dienes as products with high stereo- and regioselectivity. The process that proceeds via direct activation of the C sp -H bond in the germylalkyne, is a very effective and easy tool for the synthesis of unique borylgermylated alkynes. Eight new compounds were synthesized and fully characterized spectrally. We also determined the mechanism of the process on the basis of stoichiometric reactions, kinetic measurements and DFT calculations. [ABSTRACT FROM AUTHOR]

The co-dimerization reaction of vinylboronates with terminal alkynes, which was discovered in our group, is an efficient method for the synthesis of boryl- and borylsilylsubstituted buta-1,3-dienes. This study is a continuation of our previous and present results concerning the mechanism of this new catalytic reaction in boron chemistry. DFT calculations, as well as kinetic measurements carried out at several different temperatures in the range of 70–100 °C, provided rational grounds for the mechanism proposed previously on basis of stoichiometric reactions monitored by 1 H NMR. The activation energy and the rate determining step were also estimated. [ABSTRACT FROM AUTHOR]

Gas-phase decompositions of magnesium complexes with adenosine-5′-triphosphate (ATP) and adenosine-5′-diphosphate (ADP) were studied by using electrospray ionization-collision-induced dissociation-tandem mass spectrometry, in the negative ion mode. The loss of internal ribose residue was observed and was found to occur directly from the [ADP-3H+Mg]− ion. The occurrence of this process indicates the presence of a strong phosphate-Mg-adenine interaction. The performed quantum mechanics calculations confirmed the occurrence of this interaction in the [ADP-3H+Mg]− ion, namely the presence of Mg–N7 bond and hydrogen bond between the phosphate oxygen atom and amino group. Although the finding concerns the gas phase, it indicates that phosphate-Mg-adenine interaction may be also of importance for biological processes. The loss of an internal ribose residue was also observed for calcium and zinc complexes with ATP/ADP as well as for magnesium complexes with guanosine-5′-triphosphate (GTP) or guanosine-5′-diphosphate (GDP). Therefore, it is reasonable to conclude that the presence of the phosphate-metal-nucleobase interaction is a feature of gas phase [NDP-3H+metal]− ion (NDP, nucleoside-5′-diphosphate) and may also be important for biological processes. [ABSTRACT FROM AUTHOR]

For thousands years Ephedrae herba has been used in traditional Chinese herbal medicine. Its main bioactive constituents are ephedrine and pseudoephedrine. Nowadays, these alkaloids have found application in various clinical treatments, as sports-enhancing drugs and for the illicit production of amphetamine-like drugs. Ephedrine and pseudoephedrine are diastereomers, and because of their high polarity and similar pK a values, their chromatographic separation may be a challenge. In this study a possible application of direct infusion mass spectrometry and direct infusion tandem mass spectrometry has been proposed for differentiation of ephedrine and pseudoephedrine as well as the relative determination of the contents of these compounds in a mixture. At low collision energy condition, the ratio of relative abundances of ions [M+H–H 2 O]+ and [M+H]+ permit distinction of the analyzed diastereomers, and enable evaluation of their relative content in a mixture with no need of chromatographic separation. The performed quantum chemical calculation have shown that protonated pseudoephedrine contains stronger hydrogen bond than protonated ephedrine, which can justify the observed higher relative abundance of ion [M+H–H 2 O]+ in the mass spectrum of pseudoephedrine, in comparison to that of ephedrine. [Display omitted] • MS methods has been proposed for differentiation of ephedrine and pseudoephedrine. • Abundances of ions [M+H–H 2 O]+ and [M+H]+ permit distinction of the compounds. • Evaluation of their relative content in a mixture is possible. • There is no need of chromatographic separation. • Formation of ions [M+H–H 2 O]+ has been studied by quantum chemical calculations. [ABSTRACT FROM AUTHOR]

The following ions [UO2(NO3)3]−, [UO2(ClO4)3]−, [UO2(CH3COO)3]− were generated from respective salts (UO2(NO3)2, UO2(ClO4)3, UO2(CH3COO)2) by laser desorption/ionization (LDI). Collision induced dissociation of the ions has led, among others, to the formation of UO4 − ion (m/z 302). The undertaken quantum mechanical calculations showed this ion is most likely to possess square planar geometry as suggested by MP2 results or strongly deformed geometry in between tetrahedral and square planar as indicated by DFT results. Interestingly, geometrical parameters and analysis of electron density suggest it is an UVI compound, in which oxygen atoms bear unpaired electron and negative charge. [Copyright &y& Elsevier]

• Two structures of pitavastatin primary photoproduct are assumed to be possible. • The photoproduct can be formed by photochemical electrocyclization or diradical species. • Both pitavastatin and its primary photoproduct can generate singlet oxygen. • Pitavastatin exhibits fluorescent properties. • Triplet excited state is not involved in the primary photoproduct formation. Pitavastatin (PTV) - an important cholesterol-lowering drug, is one of the most potent inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, the key enzyme in cholesterol biosynthesis. PTV is sensitive to light, and upon exposure to radiation from the UVA and UVC regions undergoes partial decomposition forming photoproducts. In this study both experimental and theoretical methods were used to get insight into photophysical and photochemical properties of PTV with respect to its primary photochemistry. The PTV photodegradation quantum yield value was determined to be Ф = 0.011 (±0.002). PTV was found to undergo an intersystem crossing, however 3PTV* was formed with a low efficiency due partially to fluorescent properties exhibited by the statin. The lifetime of the excited singlet 1PTV* was calculated to be about 130 (±20) ps. 3PTV* was shown to be not involved in the formation of PTV primary photoproduct. Both PTV and its primary photoproduct were found to be able to generate singlet oxygen. Two different structures of PTV primary photoproduct were assumed to be possible on the basis of experimental measurements and quantum chemical modelling. The study provides mechanistic explanations of the both structures formation. The obtained results address to the lack of data existing till now in the scientific literature with regard to PTV phototransformations, are of great importance for safety of patients who require therapy with the statin, and should be taken into account in studies of the drug's side effects. [ABSTRACT FROM AUTHOR]

In the conditions of electrospray ionization, a diclofenac‐gold complex, namely the ion [DIC−H+AuCl3]− (DIC stands for diclofenac), was generated. According to the calculations, the most stable is the O−Au bond‐containing structure. By subjecting the anion [DIC−H+AuCl3]− to the collision‐induced dissociation, the loss of [DIC]. radical occurred and the open shell anion [AuCl3]− was formed with the unprecedentedly high efficiency. The observed gas‐phase behavior of the Au(III)‐diclofenac complex was analogical to that of the diclofenac complexes with metals (Fe(III) and Cu(II)), which are easily reduced in the gas phase, although the process Au(III)→Au(II) is rather unusual. [ABSTRACT FROM AUTHOR]

Novel perfluorophenyl phosphonate analogues of phenylglycine and homophenylalanine were prepared in good to excellent yields, and subjected to solid state characterization by single-crystal X-ray diffraction analysis, and to investigations with the use of DFT methods. The α-aminophosphonates have a big potential for biological activity, and through S N Ar reactions may give an entrance to further structurally variable analogues of both amino acids. [ABSTRACT FROM AUTHOR]

Colchicine is a tropolone alkaloid from Colchicinum autumnale. It shows antifibrotic, antimitotic, and anti-inflammatory activities, and is used to treat gout and Mediterranean fever. In this work, complexes of colchicine with zinc(II) nitrate were synthesized and investigated using DFT, H and C NMR, FT IR, and ESI MS. The counterpoise-corrected and uncorrected interaction energies of these complexes were calculated. We also calculated their H, C NMR, and IR spectra and compared them with the corresponding experimentally obtained data. According to the ESI MS mass spectra, colchicine forms stable complexes with zinc(II) nitrate that have various stoichiometries: 2:1, 1:1:1, and 2:1:1 with respect to colchichine, Zn(II), and nitrate ion. All of the complexes were investigated using the quantum theory of atoms in molecules (QTAIM). The calculated and the measured spectra showed differences before and after the complexation process. Calculated electron densities and bond critical points indicated the presence of bonds between the ligands and the central cation in the investigated complexes that satisfied the quantum theory of atoms in molecules. [ABSTRACT FROM AUTHOR]

Two series of novel 4-chlorophenyl N -alkyl phosphoramidates of 3′- O -( t -butoxycarbonyl)-5-fluoro-2′-deoxyuridine (3′-BOC-FdU) ( 9a – 9j ) and 5-fluoro-2′-deoxyuridine (FdU) ( 10a – 10j ) were synthesized by means of phosphorylation of 3′-BOC-FdU ( 4 ) with 4-chlorophenyl phosphoroditriazolide ( 7 ), followed by a reaction with the appropriate amine. Phosphoramidates 9a – 9j were converted to the corresponding 10a – 10j by removal of the 3′- t -butoxycarbonyl protecting group (BOC) under acidic conditions. The synthesized phosphoramidates 9a – 9j and 10a – 10j were evaluated for their cytotoxic activity in five human cancer cell lines: cervical (HeLa), nasopharyngeal (KB), breast (MCF-7), liver (HepG2), osteosarcoma (143B) and normal human dermal fibroblast cell line (HDF) using the sulforhodamine B (SRB) assay. Two phosphoramidates 9b and 9j with the N -ethyl and N -(methoxy-( S )-alaninyl) substituents, respectively, displayed remarkable activity in all the investigated cancer cells, and the activity was considerably higher than that of the parent nucleoside 4 and FdU. Among phosphoramidates 10a – 10j compound 10c with the N -(2,2,2-trifluoroethyl) substituent showed the highest activity. Phosphoramidate 10c was more active than the FdU in all the cancer cell lines tested. [ABSTRACT FROM AUTHOR]

Reactions of zinc(II) chloride with ( S )-(−)-nicotine (Nic), cotinine, thionicotine and selenonicotine in 1:1 molar ratio yielded new metal complexes, which were characterized by elemental analysis, infrared, 13 C and 1 H NMR spectral methods. Single crystal X-ray diffraction studies of ZnCl 2 complexes with thionicotine and selenonicotine revealed that the two complexes form isostructural crystals build of 1D coordination polymers (CP) and that coordination to metal centers alters the conformation of the parent organic ligand from syn to anti . Quantum chemical calculations indicate that in the isolated state the anti conformation of the uncoordinated chalcogen nicotine lactams is slightly more preferred energetically and it does not undergo substantial changes upon coordination to the metal center. The preference for the syn conformation in crystals of thio- and selenolactams of nicotine might be ascribed to their involvement in columnar stacking interactions, which do not operate in the isolated state and are also absent in crystals of their adducts with ZnCl 2 . This study has provided useful information regarding functionalization of ( S )-(−)-nicotine molecule as a mixed-donor-atom ligand to enforce formation of 1D coordination polymers. [ABSTRACT FROM AUTHOR]

Well-defined iron(0) complexes with multivinylsilicon ligands of the formula [Fe(CO) 3 L] and {[Fe(CO) 3 ] 2 L′}, where L = dienes, trienes or vinylfunctional silicones and L′ = tetraenes, are new very active and effective catalysts for hydrosilylation and/or dehydrogenative silylation of styrene with trisubstituted silanes and hydrosiloxanes. All catalytic data and selected kinetic measurements as well as the information on stoichiometric reactions of the new precursor catalysts with model substrates (followed by NMR and GC–MS techniques), supported by the relative energies of transition states and intermediates obtained by DFT calculations, permitted proposing a rational mechanism for the catalysis in alkene hydrosilylation, proceeding according to the Chalk-Harrod and/or modified Chalk-Harrod mechanisms. [ABSTRACT FROM AUTHOR]

A new 2,6-di(anthracen-9-yl)pyridine ligand L reacts with various silver(I) salts to give three new complexes: mononuclear [Ag L (NO 3 )] and [Ag L ( i -PrOH) 2 ](BF 4 ), and dinuclear [Ag L (μ-H 2 O)Ag L ](BF 4 ) 2 ·3CH 2 Cl 2 . The complexes have been characterized by spectroscopic techniques and elemental analysis. The solid state structures of the complexes have been determined by X-ray diffractometry. Methylene blue (MB) degradation was studied by UV–Vis spectrophotometry. The new complexes of silver(I) are active photocatalysts of MB degradation under sunlight irradiation. [ABSTRACT FROM AUTHOR]

Anabasine copper(II) and zinc(II) complexes have been studied using experimental methods and quantum-chemical studies. Preferred coordination centers and possible structures of the complexes have been determined. It has been revealed, that the main coordination center for anabasine complexes with both Cu(II) and Zn(II) ions is the piperidine nitrogen atom, while in zinc complexes also the nitrogen atom from the pyridine residue of anabasine is engaged to some small degree. In both systems investigated preferable formation of hydroxo-complexes was observed. [ABSTRACT FROM AUTHOR]

• interactions between the molecule of a plasticizer and organic peroxide have significant directional character of a hydrogen bonding. • plasticizer molecules not only dilute an organic peroxide but also provide additional stabilization, whose energy is ca -15 kcal/mol. • organic peroxide molecule has two hydrogen bond donors so the favorable plasticizer should possesses two hydrogen bond acceptors. • alternatives to phthalate plasticizers are likely to be found amongst di- or poly- esters. In this paper we would present our studies how organic peroxides are being stabilized by plasticizers used in manufacturing of organic peroxides as polymerization initiators etc. As an exemplary system, interactions between 2,2-dihydroperoxybutane and dimethyl phthalate (system already approved for commercial use) has been studied. The quantum chemical study protocol was to investigate for the first time the interactions between a plasticizer and the peroxide – indicating that the interaction energy of about -15 kcal/mol favors the formation of a supramolecular system. [Display omitted] [ABSTRACT FROM AUTHOR]

• The modification with the PET did not inhibit the rheological propertied of the fresh mix, allowing for proper printing. • Incorporation of PET results in decreased compressive and flexural strengths regardless of the specimens (printed and casted, up to 48.9% and 51.9%, respectively). • The freeze–thaw cycles and high temperature exposure caused a significant deterioration of the mechanical properties of printed mixture. • 3D printed mortar with PET granules as the replacement of natural aggregate (10 vol-% to 50 vol-%). • The inclusion of PET can lead to decrease buildability of printed structure. 3D concrete printing technology of cementitious materials is challenging in many aspects. Despite the workability and mechanical properties of a mix and hardened concrete or mortar, the researchers need to face problems with environmental impact and durability of printed elements. Furthermore, today thousands of tons of waste are produced and natural aggregates which are most used resources by volume in the construction sector are on the verge of exhaustion. To date, limited knowledge about utilized of artificial aggregate (including Polyethylene terephthalate (PET) in 3D printed mortar is available. The main objective of this study is to develop 3D printed mortar with PET granules as the replacement of natural aggregate (10 vol-% to 50 vol-%). The paper contributes to knowledge of properties of 3D printed composites with plastic aggregate. Four printable mixes were made: one reference mix and three mixes in which natural aggregate was replaced by PET granulate in quantities amounting to 10%, 30% and 50% (by volume), respectively. The replacement ratios were chosen on the base of literature review for ordinary cementitious mortars. Several strength tests were carried out for standard and printed specimens. In addition, a freeze–thaw resistance test and high temperature performance test were conducted to evaluate to validate the properties of artificial aggregate. The results show that PET granulate is useful in 3D printing owing to their buildability and extrudability properties. Furthermore, printed mixes with high amount of PET (30% and 50%) granulate shows high decreases in strength (up to 75%). Unfortunately, after the freeze–thaw resistance test specimens with a high amount of PET granulate (30% and 50%) indicated high strength reduction (up to 80%). Exposure to a temperature exceeding the melting point of PET results in significant reduction of compressive strength for printed specimens (up to 68.8 % for 50 % PET addition). In addition, mixes with up to 10% PET can be used for most structural elements even under varying thermal conditions (even under extreme cold temperature). [ABSTRACT FROM AUTHOR]

Abstract: A series of novel N-alkyl 5′-chloromethylphosphonates of 3′-azido-3′-deoxythymidine (6–15) was synthesized by means of phosphonylation of 3′-azido-3′-deoxythymidine (4) with P-chloromethylphosphonic ditriazolide (3) followed by a reaction with the appropriate amine. The synthesized phosphonamidates 6–15 were evaluated for their cytotoxic activity in two human cancer cell lines: oral (KB) and breast (MCF-7) using the sulforhodamine B (SRB) assay. The highest activity in KB human cancer cells was displayed by phosphonamidate 8 (IC50 =5.8μg/mL), however, this compound was less potent than the parent AZT (IC50 =3.1μg/mL). Phosphonamidate 10 showed only moderate activity (IC50 =12.1μg/mL) whereas the other phosphonamidates proved inactive. Similarly, the highest activity in MCF-7 human cancer cells was displayed by phosphonamidate 8 (IC50 =3.7μg/mL) but it proved somewhat less active than AZT (IC50 =2.6μg/mL). Some activity was also displayed by phosphonamidate 10 (IC50 =12.8μg/mL) but the other phosphonamidates were found inactive. Hydrolysis studies indicate that the synthesized phosphonamidates are likely to act as prodrugs of the parent nucleoside (AZT). Transport measurements showed that the most active phosphonamidates (8 and 10) were able to permeate across the intestinal epithelium in vitro. The apparent permeability coefficients determined in Caco-2 cell monolayers indicated that these compounds could be moderately absorbed in humans. [Copyright &y& Elsevier]

Abstract: Triorganophosphites containing substituents with different electronic and steric properties have been synthesized and tested as inhibitors of Karstedt''s catalyst (complex Pt(0) with divinyltetramethyldisiloxane) in cross-linking of silicones via hydrosilylation. Relatively bulky or electron-withdrawing substituents in phosphite appeared to be the most efficient inhibitors of hydrosilylation showing sufficiently long pot-life at room temperature and short curing time at high temperature. New molecular complexes of Pt(DVTMDS)–selected phosphites have been synthesized and characterized. The new complexes proved to be effective catalysts of the curing process. The free phosphites as well as the phosphite–Pt complexes have been found resistant to oxidation and hydrolysis. [Copyright &y& Elsevier]

Few studies have focused on determining the Young's modulus of 3D printed structures. This study presents the results of experimental investigations of Young's modulus of a 3D printed mortar. Specimens were prepared in four different ways to investigate possible application of different methods for 3D printed structures. Study determines the influence of the number of layers on mechanical properties of printed samples. Results have shown a strong statistical correlation between the number of layers and value of Young's modulus. The compressive strength and Young's modulus reduction compared to standard cylindrical sample were up to 43.1% and 19.8%, respectively. Results of the study shed light on the differences between the current standard specimen used for determination of Young's modulus and the specimen prepared by 3D printing. The community should discuss the problem of standardization of test methods in view of visible differences between different types of specimens. [ABSTRACT FROM AUTHOR]

We present a methodology for the synthesis of inorganic-organic Janus-type molecules based on mono-T 8 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., (© 2024. The Author(s).)

This paper explores the new potential strategy of using fine recycled aggregates (fRA) derived from waste 3D printed concrete (3DPC) as a substitute for cement in additive manufacturing. This study hypothesizes that fRA can optimize mixture design, reduce cement content, and contribute to sustainable construction practices. Experimental programs were conducted to evaluate the fresh and hardened properties, printability window, and buildability of 3DPC mixes containing fRA. Mixes with replacement rates of cement with fRA by 10 vol%, 20 vol%, 30 vol%, 40 vol%, and 50 vol% were produced. A comprehensive experimental protocol consisting of rheological studies (static and dynamic yield stress), dynamic elastic modulus determination (first 24 h of hydration), flexural and compressive strengths (2 d and 28 d), and an open porosity test was performed. The obtained results were verified by printing tests. In addition, an economic and environmental life cycle assessment (LCA) of the mixes was performed. The results indicate that up to 50 vol% cement replacement with fRA is feasible, albeit with some technical drawbacks. While fRA incorporation enhances sustainability by reducing CO 2 emissions and material costs, it adversely affects the printability window, green strength, setting time, and mechanical properties, particularly in the initial curing stages. Therefore, with higher replacement rates (above 20 vol%), potential optimization efforts are needed to mitigate drawbacks such as reduced green strength and buildability. Notably, replacement rates of up to 20 vol% can be successfully used without compromising the overall material properties or altering the mixture design. The LCA analysis shows that reducing the cement content and increasing the fRA addition results in a significant reduction in mix cost (up to 24%) and a substantial decrease in equivalent CO 2 emissions (up to 48%). In conclusion, this study underscores the potential of fRA as a sustainable alternative to cement in 3D printed concrete., Competing Interests: Author Maxime Liard was employed by the company Sika Technology AG. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Rationale: Cytosine and its conjugates are prone to form protonated, triply-bonded dimers. Therefore, the nucleic-acid cytosine-rich sequence forms the four-stranded noncanonical secondary structure known as the intercalated motif (i-motif). This process has resulted in studies on cytosine protonated dimers. This communication focuses on the protonated dimers of cytosine and its nucleoside using the survival yield (SY) method and quantum mechanics calculations., Methods: To obtain the precursor ion fragmentation curve, the plot of SY against E comδ , the product ion spectra of the protonated dimers were obtained using a Waters/Micromass Q-TOF Premier mass spectrometer. Quantum mechanics calculations were performed using GAUSSIAN 16, and full geometry optimizations and energy calculations were performed within the density functional theory framework at B3LYP/6-31G(d,p)., Results: The precursor ion fragmentation curve allowed the rating of the gas-phase stabilities of the analyzed protonated dimers. Substitution of sugar moiety at N1 cytosine atom decreased the gas-phase stabilities of the protonated dimers. The deoxycytidine dimer was found to be more stable than the cytidine dimer and cytidine-deoxycytidine dimer. Quantum chemical calculations indicated that cytosine aminohydroxy tautomer may be involved in the formation of protonated cytosine-cytosine nucleoside dimers but not in the formation of cytosine dimers., Conclusions: The results obtained for nucleoside dimers indicated that the SY method may reflect the i-motif stabilities observed under physiological conditions. Therefore, the analysis of other protonated dimers of variously substituted cytosine-cytosine nucleoside using the SY method may be important to study the effect of cytosine substitution on the i-motif stabilities. Cytosine tautomer containing C2-OH … N(2H)-C4 moiety may be involved in the formation of protonated cytosine-cytosine nucleoside dimers., (© 2023 John Wiley & Sons Ltd.)

In this study, we subjected 5,5-diethoxy-4-oxopent-2-enal (DOPE), a model amino acids cross-linking reagent, to reactions with N-acetylcysteine (Ac-Cys) and N α -acetyllysine (Ac-Lys), and identified three pyrrole cross-links. The compounds were isolated and their structures were rigorously determined by spectrometric and spectroscopic methods, including 2D NMR experiments. The use of 2D NMR spectroscopy was crucial to determine the position of the substituents in the pyrrole rings. The products were identified as 2,4-, 2,3-, and 2,5-substituted pyrroles. The data obtained from their structural characterisation can help similar studies on amino acids modifications induced by analogous bifunctional carbonyl compounds. Our results show that the study of pathways in which model electrophiles modify amino acids may be helpful for similar studies dealing with identification of structural changes in cysteine- and lysine-containing proteins associated with oxidative stress., (© 2023. The Author(s).)

Drug design with machine learning support can speed up new drug discoveries. While current databases of known compounds are smaller in magnitude (approximately 108), the number of small drug-like molecules is estimated to be between 1023 and 1060. 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.

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 pK a values of the reagent.

A number of imines, including 12 new compounds, previously not reported in the literature, derived from variously fluorinated benzaldehydes and different anilines or chiral benzylamines were synthesized by a solvent-free mechanochemical method, which was based on the manual grinding of equimolar amounts of the substrates at the room temperature. In a very short reaction time of only 15 min, the method produced the expected products with good-to-excellent yields. The yields were comparable or significantly higher than those reported in the literature for the imines synthesized by other methods. Importantly, the conditions used for the reactions with aniline derivatives also resulted in the high yields of imines obtained from chiral benzylamines, and can be extended to the synthesis with other similar amines. Structures of all imines were confirmed by NMR spectroscopy: 1 H, 13 C and 19 F. For four compounds, X-ray structures were also obtained. The synthetic approach presented in this paper contributes to the prevention of environmental pollution and can be easily extended for larger-scale syntheses. The mechanochemical solvent-free method provides a convenient strategy particularly useful for the preparation of fluorinated imines being versatile intermediates or starting material in the synthesis of drugs and other fine chemicals.

The application of DFT computational method (B3LYP/6-311++G(d,p)) to mono- and poly(CF 3 )substituted naphthalene derivatives helps to study changes in the electronic properties of these compounds under the influence of 11 substituents (-Br, -CF 3 , -CH 3 , -CHO, -Cl, -CN, -F, -NH 2 , -NMe 2 , -NO 2 , 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 ( σ p , σ m , R , and F ). Described poly(CF 3 )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 -CF 3 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(CF 3 )substituted probes.

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.

Coronaviruses are dangerous human and animal pathogens. The newly identified coronavirus SARS-CoV-2 is the causative agent of COVID-19 outbreak, which is a real threat to human health and life. The world has been struggling with this epidemic for about a year, yet there are still no targeted drugs and effective treatments are very limited. Due to the long process of developing new drugs, reposition of existing ones is one of the best ways to deal with an epidemic of emergency infectious diseases. Among the existing drugs, there are candidates potentially able to inhibit the SARS-CoV-2 replication, and thus inhibit the infection of the virus. Some therapeutics target several proteins, and many diseases share molecular paths. In such cases, the use of existing pharmaceuticals for more than one purpose can reduce the time needed to design new drugs. The aim of this review was to analyze the key targets of viral infection and potential drugs acting on them, as well as to discuss various strategies and therapeutic approaches, including the possible use of natural products. We highlighted the approach based on increasing the involvement of human deaminases, particularly APOBEC deaminases in editing of SARS-CoV-2 RNA. This can reduce the cytosine content in the viral genome, leading to the loss of its integrity. We also indicated the nucleic acid technologies as potential approaches for COVID-19 treatment. Among numerous promising natural products, we pointed out curcumin and cannabidiol as good candidates for being anti-SARS-CoV-2 agents., Competing Interests: The authors declare that there are no conflicts of interest., (© 2021 Xi'an Jiaotong University. Production and hosting by Elsevier B.V.)

Foundation piles that are made by concrete 3D printers constitute a new alternative way of founding buildings constructed using incremental technology. We are currently observing very rapid development of incremental technology for the construction industry. The systems that are used for 3D printing with the application of construction materials make it possible to form permanent formwork for strip foundations, construct load-bearing walls and partition walls, and prefabricate elements, such as stairs, lintels, and ceilings. 3D printing systems do not offer soil reinforcement by making piles. The paper presents the possibility of making concrete foundation piles in laboratory conditions using a concrete 3D printer. The paper shows the tools and procedure for pile pumping. An experiment for measuring pile bearing capacity is described and an example of a pile deployment model under a foundation is described. The results of the tests and analytical calculations have shown that the displacement piles demonstrate less settlement when compared to the analysed shallow foundation. The authors indicate that it is possible to replace the shallow foundation with a series of piles combined with a printed wall without locally widening it. This type of foundation can be used for the foundation of low-rise buildings, such as detached houses. Estimated calculations have shown that the possibility of making foundation piles by a 3D printer will reduce the cost of making foundations by shortening the time of execution of works and reducing the consumption of construction materials.

Alkali metal chloroaurates(III) were analysed by laser desorption ionization mass spectrometry. Among a number of generated gas-phase ionic clusters, the unusual ions [MAu 2 Cl 5 ] - (were M stands for Na, K, Rb, Cs) were detected. The spectra of metastable ions and quantum mechanics calculations show the presence of unprecedented Au(I)-Au(II) interactions in the clusters.

Several novel phosphono-perfluorophenylalanine derivatives, as mimetics of phenylalanine, were synthesized by subjecting diethyl (2-(perfluorophenyl)-1-(phenylamino)ethyl)-phosphonate to S N Ar reactions with different types of nucleophiles such as thiols, amines and phenols. The structure of the products was confirmed using spectroscopic and spectrometric techniques. For two compounds X-ray single crystal diffraction analysis and DFT investigations were performed providing information in regard to the preferable conformation, hydrogen bonds and other interactions. The antiproliferative potency of some of the new phosphono-perfluorophenylalanine derivatives obtained as well as representatives of previously synthesized perfluorophenyl phosphonate analogues of phenylalanine was studied on selected glioma cell lines. Preliminary evaluation of the compounds drug likeness was examined with respect to Lipinski's and Veber's rules, and showed that they meet the criteria perfectly. MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2 H -tetrazolium bromide) assay results demonstrated that the compounds exhibit moderate activity against the glioblastoma multiforme cell lines (T98G and U-118 MG). Moreover most of the studied S N Ar reaction products displayed significantly higher inhibitory activity against both cancer cell lines than the parent diethyl (2-(perfluorophenyl)-1-(phenylamino)ethyl)phosphonate., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The analysis of biochemical processes is one of the main challenges for modern computational chemistry. Probably the biggest issue facing scientists in this case is the number of factors that have to be taken into account, as even those factors that do not seem to be meaningful may eventually be crucial. Such a belief led to the investigation on the substituent effects during squalene cyclization process. We focused on the formation of lanosterol ring A through squalene epoxide and an analogue process observed in bacteria, leading to the hopene formation without an intermediate oxide. Interestingly, our results indicate that, opposite of chemical intuition, a more substituted chain is more likely to adopt a conformation suitable for the cyclization process. Presumably the rational for this behavior is the presence of intermolecular CH ... π interactions between the hydrogen atoms from methyl groups and the squalene π bonds in the open-chain structure. The effect seems to have a firm impact on the hopene formation process. Calculations were performed using two different methods: MP2 and M06-2X, combined with the cc-pVDZ basis set.

Pain of lumbosacral segment of the vertebral column and the pelvis concerns about 45% of all pregnant women. The change of the body posture during pregnancy is the result of gravity centre relocation, which affects the musculosceletal system. Development of the joint, ligament and myofascial dysfunctions, as well as the pain in the lumbosacral segment and the pelvis, are the most common reasons of spine pain. The aim of this review is to present the current state of knowledge about lumbar spine pain in pregnant women with special focus on the pain connected with muscular, joint and ligament disorders. Pregnancy is a serious burden for the female osteo-skeletal system. Lumbar pain with different location and intensification is the negative consequence of the position changes during pregnancy. Pharmacotherapy could be useful only in cases of intensive low back pain, with possible application of small spectrum of drugs that are safe during pregnancy. Physical therapy including manual therapy exercises, massage and techniques of local anesthesia are alternative methods in case of low back pain in pregnant women.

In this study quantum chemical calculations based on the density functional theory (DFT) have been carried out to examine the effects of methoxy substituent attached to a silicon atom on the reaction of silylative coupling of olefins. It has been shown, that substituted substrate undergoes the reaction according to the recently proposed insertion-rotation-elimination mechanism. During the rotation around C-C single bond additional stabilization by oxygen-ruthenium interaction was observed. Similarly to the (trimethylsilyl)ethene the rate determining step of the reaction is the insertion of the alkene into Ru-Si single bond. The substitution of SiMe(3) by Si(OMe)(3) decreases the energy span of the reaction by almost 3 kcal mol(-1) that is from 21 kcal mol(-1) to 18 kcal mol(-1). The decrease of the energy barrier of the reaction seems to be the result of the increase of point charge differences between the Ru and Si atoms which increases electrostatic attraction between these atoms. Moreover, for Si(OMe)(3) the rate-determining transition state is closer to the alkene interacting with the Ru centre side of the reaction.

The increase of multidrug-resistant strains of bacteria to known classes of antibiotics present a severe challenge for modern medicine. The most promising strategy to combat pathogenic bacteria is to discover new drug targets. In this regard, aminoacyl-tRNA synthetases are particularly well suited to develop novel drugs that show no cross-resistance to other classical antibiotics. To date various chemical structures that inhibit AA-RS have been identified. In this report we present an interesting approach towards generating of Leu-RS inhibitors by virtual click chemistry. That is we identified key fragments for ligand binding within catalytic pocket of Leu-RS, generated the collection of similar fragments with the use of Ligand.Info, identified the fragments that are most strongly bound in different areas within the catalytic pocket, and finally with the use of virtual click chemistry we generated a set of molecules which are most likely to act as highly potent bacterial Leu-RS inhibitors.

Owing to the recent development of virtual high-throughput screening (vHTS) and a vast number of compounds subjected to vHTS analyses, it has been essential to automate the processing of computational data required for the analysis and visualization of research results. Using the search for tyrosine-tRNA ligase inhibitors as an example, we present a computer application, an interface between eHiTS software for virtual high-throughput screening and VMD graphic software used to visualize calculation results.

Fluvastatin is a member of the HMG-CoA reductase inhibitor family of drugs, commonly referred to as statins. It is generally known that, under physiological conditions, statins are susceptible to pH-dependent interconversion between their active (hydroxy acid) and inactive (lactone) forms. The mechanism of this interconversion, under both acidic and basic conditions, was investigated theoretically using the density functional theory (DFT) method. Regardless of the conditions, the lactone form was always higher in energy by 6-19 kcal mol(-1). However, under basic conditions, the activation barrier for the hydrolysis was significantly lower (9 kcal mol(-1)) than for the reverse reaction (28 kcal mol(-1)), making the lactone form unstable. The activation barriers under acidic conditions were of comparable height in both directions (22 and 28 kcal mol(-1)), making the occurrence of both forms equally probable. Due to the high activation barrier (>40 kcal mol(-1)), a one-step, direct interconversion between the two forms turned out to be unfavourable. Moreover, the potential energy surface of fluvastatin was briefly inspected, revealing relatively small energetic differences (<5 kcal mol(-1)) between the key conformers.