Position Of Substituents Research Articles

Photoinduced 1,3‐Dipolar Cycloadditions of Cyclic Enones and 2,5‐Disubstituted Tetrazoles: An Unprecedented Pathway to Polysubstituted Pyrazolines and Pyrazoles

AbstractWe report herein the syntheses of original pyrazolines and pyrazoles through 1,3‐dipolar cycloaddition of cyclic enones with 2,5‐disubstituted nitrile imines achieved via photochemical activation of 2,5‐diaryl substituted tetrazoles. Monitoring of the reactions, similar to nitrile imine‐mediated tetrazole‐ene cycloadditions (NITEC), could be performed by means of UV‐vis absorption and emission measurements. The presence or absence of substituents in the alpha position of the ketone function makes it possible to direct these reactions towards the selective formation of pyrazoles or pyrazolines. The choice of the cyclic enones and 2,5‐disubstituted tetrazoles proved crucial for the fluorescence properties of the polycyclic derivatives obtained.

Synthesis of New Structural Analogues of Natural Integrastatins with a Basic Epoxybenzo[7,8]oxocine Skeleton: Combined Experimental and Computational Study

AbstractIn this work, the cyclization reactivity of various 3-acetyl-2-methylpyridines (including 3-acetyl-2-methylquinoline) containing both electron donor and acceptor substituents with salicylaldehyde into epoxybenzooxocino[4,3-b]pyridine derivatives was studied. The reactions were carried out in mild (under room temperature or reflux in 2-propanol) and harsh (in a sealed glass ampoule) conditions. It was shown that 3-acetyl-2-methylpyridines with an aryl substituent in the 4-position do not react with salicylaldehyde either under normal convection heating conditions or under more severe conditions. This effect was explained by the steric hindrance of the substituents using quantum chemical calculations. It was found that electron donor substituents in 3-acetyl-2-methylpyridines significantly facilitate cyclization in epoxybenzooxocino[4,3-b]pyridines. The presence of electron acceptor substituents (NO2 group for example) in the 5-position of pyridine prevents cyclization under normal conditions, but gives a rather high conversion to oxocinopyridines under more specific conditions. This effect is quantum-chemically explained by the decrease in the basicity of pyridine. Pyridines with two pairs of methyl groups in ortho-positions to the acetyl group are capable to form mixtures of regioisomeric epoxybenzooxocinopyridines. Further, epoxybenzooxocinopyridines with methyl and acetyl groups can form a mixture of diastereomeric bisoxocins under more specific conditions. All 17 initial pyridines were studied quantum-chemically in order to understand what features of their structure and properties affect the success of the cyclization reaction and the yield of the target product. The pyridine molecules were calculated by the DFT RB3LYP/6-311++G(d,p) method taking into account the alcohol solvent within the CPCM model using Gaussian-2016 program. It was shown that the absence of steric hindrances in the form of bulky substituents in 4-position of pyridines is the main factor affecting the success of the cyclization reaction. Also, the yield of the target product is affected by the CH-acidity of the methyl group in 2-position, which, in turn, is affected by electron-donating and electron-withdrawing substituents in the 5- and 6-positions.

Synthesis of chalcone derivatives with methoxybenzene and pyridine moieties as potential antimalarial agents

Malaria remains an endemic disease in tropical regions, urgently needed the search for effective antimalarial agents due to resistance against existing drugs. This study investigated the potential antimalarial activity of pyridine-based chalcone derivatives against P. falciparum 3D7 and FCR3 strains. The chalcones were synthesized through a one-pot method using various pyridine carbaldehyde, resulting in yields ranging from 53.74 to 86.37%, and all products were characterized using FTIR, GC-MS, and NMR spectroscopies. Among the six chalcones tested, chalcone A [1-(2-methoxyphenyl)-3-(pyridin-2-yl)prop-2-en-1-one] displayed the highest antimalarial activity with IC50 values of 0.48 and 0.31 μg/mL against P. falciparum 3D7 and FCR3 strains, respectively, and a resistance index of 0.65. Molecular docking studies highlighted the interaction of the carbonyl group of all chalcones with Asn108 amino acid residue in the PfDHFR-TS active site via hydrogen bonding, demonstrating their potential as the antimalarial agent. Notably, the positioning of methoxy and pyridine substituents significantly influenced the antimalarial activity of the chalcones.

Dual Excited State Proton Transfer Pathways in the Bifunctional Photoacid 6-Amino-2-naphtol.

This study investigates the photoacidity and excited state proton transfer (ESPT) pathways of a bifunctional molecule, 6-amino-2-naphthol (6N2OH), using absorption, steady-state fluorescence, time-resolved fluorescence, and theoretical calculations. 6N2OH attains four different prototropic forms in the excited state (cation, neutral, anion, or zwitterion) depending on pH of the solution. Interestingly, ESPT at the OH site of the molecule can be controlled by the protonation state of the amino substituent. Conversion of the electron donating NH2 group to the electron withdrawing NH3+ group brings about a reduction of more than 7 pKa units for the deprotonation of OH in the excited state. Further, the position of the NH2 substituent on the naphthalene framework is found to play an important role in dictating the ESPT pathways of aminonaphthols. Unlike most aminonaphthol derivatives that undergo ESPT only at the OH site, akin to substituted naphthols, 6N2OH undergoes ESPT at both OH and NH3+ sites, indicating its similarity to substituted naphthols and substituted naphthylamines. ESPT at the NH3+ site resulting in cation ↔ neutral equilibrium of 6N2OH in the excited state is well-corroborated by comparative studies with another reference photoacid, 6-amino-2-methoxynaphthalene (6N2M). Correlation of the acidity constants of 6N2OH with the σp parameters according to the Hammett model reveals that while 6N2OH can be treated either as naphthol or as naphthylamine in the ground state, the structure-function correlation cannot be extrapolated directly in the excited state, thus highlighting the rich and complex photophysics of bifunctional photoacids.

Synthesis and Anti-Plant Pathogenic Fungal Activity of Flavokawain-Derived Flavones and Related Flavones Against Rhizoctonia solani

Flavones are organic compounds in the flavonoid family that have a diverse range of biological functions. In this research, many flavones with various substituents were designed and synthesized from flavokawains A, B, and C, and their chalcone derivatives via an iodine-catalyzed oxidative cyclization process. All synthetic flavones were investigated for antifungal activities against Rhizoctonia solani, a plant pathogenic fungus. At 400 µg, most of the substances did not inhibit the tested species and R. solani growth was inhibited by only o-bromoflavone (40) by 74.88±0.91%. This indicated that the detrimental effect of flavones depends on the type and position of substituent, with the ortho bromo group showing the most promise. The molecular docking study on the succinate dehydrogenase (SDH) enzyme revealed that the bromophenyl moiety (ring B) is a key molecular substructure of the flavone fungicide. The findings of this study will be used to develop novel plant pathogenic fungicides.

Synthesis of 2-arylbenzo-1,3-tellurazoles by oxidative cyclization of 2,2′-ditellurobis[N-(arylmethylene)benzenamines

A method has been developed to prepare 2-arylbenzo-1,3-tellurazoles from bis(2-aminophenyl) ditelluride and aromatic aldehydes by oxidative cyclization following an easily implemented one pot procedure. Imines obtained by combining aldehyde and ditelluride were cyclized with phosphorous oxychloride without prior purification, resulting in the formation of benzo-1,3-tellurazoles carrying aryl or heteroaryl substituents in position 2 in yields up to 58 %. Evidence is presented for a radical reaction pathway. This method is set apart from other options by avoiding strongly reducing conditions and minimizing the synthetic effort required to prepare aryl substituted benzo-1,3-tellurazoles. An X-ray crystallographic characterization of 2-(2-quinolinyl)benzo-1,3-tellurazole indicated only weak TeˑˑˑN secondary bonding interactions.

Sonophotochemical and photochemical efficiency of thiazole-containing metal phthalocyanines and their gold nanoconjugates.

This study presents the synthesis of some metal {M = Zn(II), Lu(III), Si(IV)} phthalocyanines bearing chlorine and 2-(4-methylthiazol-5-yl) ethoxy groups at peripheral or axial positions. The newly synthesized metal phthalocyanines were characterized by applying FT-IR, 1H NMR, mass, and UV-Vis spectroscopic approaches. Additionally, the surface of gold nanoparticles was modified with zinc(II) and silicon(IV) phthalocyanines. The resultant nanoconjugates were characterized using TEM images. Moreover, the effect of metal ions and position of substituent, and gold nanoparticles on the photochemical and sonophotochemical properties of the studied phthalocyanines was investigated. The highest singlet oxygen quantum yield was obtained for the lutetium phthalocyanine by applying photochemical and sonophotochemical methods. However, the linkage of the zinc(II) and silicon(IV) phthalocyanines to the surface of gold nanoparticles improved significantly their singlet oxygen generation capacities.

Study of the DNA damage and cell death in human peripheral blood mononuclear and HepG2/C3A cells exposed to the synthetic 3-(3-hydroxyphenyl)-7-hydroxycoumarin

ABSTRACT Hydroxycoumarins are an important source of biologically active compounds. Previous studies have shown that the number and position of the hydroxyl substituents in the scaffold play an important role for the observed biological activity. In the present study, 3-(3-hydroxyphenyl)-7-hydroxycoumarin was synthesized, and potential cytogenotoxic effects determined in human HepG2/C3A cells displaying phase 1 and phase 2 enzymes (metabolizing cell ability) and compared to human peripheral blood mononuclear cells (PBMC) without xenobiotics metabolizing capacity. Cell viability was determined with concentrations between 0.01 and 10 µg/ml of 3-(3-hydroxyphenyl)-7-hydroxycoumarin using MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) and trypan blue tests. Genotoxicity was determined utilizing the comet assay, and the clastogenic/aneugenic potential employing the micronucleus (MN) test. The results of the in vitro cytotoxicity assays showed a significant decrease in cell viability of PBMC following exposure to 10 µg/ml concentration of the studied compound after 48 and 72 hr. Comet assay observations noted significant DNA damage in PBMC after 4 hr treatment. No marked cytogenotoxic effects were found in HepG2/C3A cells. No chromosomal mutations were observed in both cell lines. It is important to note that 3-(3-hydroxyphenyl)-7-hydroxycoumarin may exert beneficial pharmacological actions at the low micromolar range and with half-life less than 24 hr. Therefore, the results obtained encourage the continuation of studies on this new molecule for medicinal purposes, but its potential toxicity at higher concentrations and longer exposure times needs to be investigated in further studies.

Regulating Intramolecular Electron Transfer of Nickel-Based Coordinations through Ligand Engineering for Aqueous Batteries.

The integration of electronic effects into complexes for the construction of novel materials has not yet attracted significant attention in the field of energy storage. In the current study, eight one-dimensional (1D)nickel-based salicylic acid complexes (Ni-XSAs, X = pH, pMe, pMeO, mMe, pBr, pCl, pF, and pCF3 ), are prepared by ligand engineering. The coordination environments in the Ni-XSAs are explored using X-ray absorption fine structure spectroscopy. The charge transfer of the complexes is modulated according to the difference in the electron-donating ability of the substituents, in combination with frontier orbital theory. Furthermore, density functional theoryis used to investigate the effect of the substituent position on the electronic properties of the complexes. Ni-mMeSA exhibits better electrical conductivity than Ni-pMeSA. The electrochemical performance of Ni-mMeSA as an aqueous battery cathode is remarkably improved with a maximum energy density of 0.30 mWh cm-2 (125Wh kg-1 ) and a peak power density of 33.72mW cm-2 (14.03kW kg-1 ). This study provides ideas for the application of new coordination chemistry in the field of energy materials science.

Verubulin (Azixa) Analogues with Increased Saturation: Synthesis, SAR and Encapsulation in Biocompatible Nanocontainers Based on Ca2+ or Mg2+ Cross-Linked Alginate.

Tubulin-targeting agents attract undiminished attention as promising compounds for the design of anti-cancer drugs. Verubulin is a potent tubulin polymerization inhibitor, binding to colchicine-binding sites. In the present work, a series of verubulin analogues containing a cyclohexane or cycloheptane ring 1,2-annulated with pyrimidine moiety and various substituents in positions 2 and 4 of pyrimidine were obtained and their cytotoxicity towards cancer and non-cancerous cell lines was estimated. The investigated compounds revealed activity against various cancer cell lines with IC50 down to 1-4 nM. According to fluorescent microscopy data, compounds that showed cytotoxicity in the MTT test disrupt the normal cytoskeleton of the cell in a pattern similar to that for combretastatin A-4. The hit compound (N-(4-methoxyphenyl)-N,2-dimethyl-5,6,7,8-tetrahydroquinazolin-4-amine) was encapsulated in biocompatible nanocontainers based on Ca2+ or Mg2+ cross-linked alginate and it was demonstrated that its cytotoxic activity was preserved after encapsulation.

Manipulation of excited-state intramolecular proton transfer by electron-donor substitution for high performance fluoride ions sensing

Excited-state intramolecular proton transfer (ESIPT) molecules has been using as a variety of functionalityled molecular systems. To investigate the relationship between the electron-donor substitution and luminescent properties of ESIPT luminogens, four 2-(2-hydroxyphenyl) benzothiazole derivatives with donor-π-acceptor (D-π-A)-structured were synthesized. The distinct fluorescence properties of them were found to be highly dependent on the electron-donor moiety (triphenylamine and anthracenyl), its substituent position (para and meta position) and solvent polarity. The M−TPA, P-En, and M−En showed ESIPT emission in organic solvents, while the P-TPA showed intramolecular charge transfer process (ICT) emission. It is due to the synergistic effect of the aggregation-induced emission (AIE) and ESIPT, that M−TPA and M−En exhibited high solid-state quantum yields and large Stokes shifts. They were used as a probe for detecting F−, which resulted in rapid colorimetric, high sensitivity and good selectivity. The M−TPA was a turn-on fluorescent probe, which had the best detection property, and the limit of detection was as low as 11 nM. Because M−TPA displayed phenol anion emission in DMSO and F− causes the deprotonation of the M−TPA, which led to significant red shift of the absorption band and enhancement of fluorescence emission. This work provides a reliable strategy for designing high-performance fluorescent sensor via ESIPT manipulation.

Adsorption of anionic methyl orange dye by polyaniline, poly(o‐methylaniline) and poly(o‐methoxyaniline)

AbstractThis study reports the effect of substituents in the ortho position of polyaniline on the adsorption capacity to remove the anionic dye methyl orange (MO) from an aqueous solution. The aim of this study is the synthesis of polyaniline (PANI) and its derivatives, poly‐o‐methylaniline (poly‐o‐toluidine, POT) and poly‐o‐methoxyaniline (poly‐o‐anisidine, POA) for the adsorption removal of MO dye. All polymers were obtained by oxidative polymerization of the corresponding monomers and characterized by scanning electron microscopy (SEM) and infrared spectroscopy (IR). The average particle size of the polymer was about 200 nm. The effect of various parameters such as pH, temperature, adsorption time and initial concentration was analyzed. It was found that the adsorption capacity for dye removal increases from 50.68 to 222.56 mg g−1 for PANI, from 16.89 to 66.57 mg g−1 for POT, and from 97.26 to 532.54 mg g−1 for POA with an increase in the initial dye concentration from 5 up to 50 mg L−1. For all polymers, the equilibrium state of MO adsorption was reached in 50 min. The results showed that MO adsorption on PANI, POT, and POA is well described by a pseudo second order kinetic model. Isothermal studies have shown that adsorption is in good agreement with the Langmuir isotherm model, as evidenced by higher values of correlation coefficients. Based on the data of thermodynamic studies, it was concluded that MO adsorption on PANI, POT, and POA is spontaneous and endothermic.

Effects of the substituent position on the structural order, work function change, and thermopower of dichloro-substituted benzenethiolate self-assembled monolayers on Au(1 1 1)

The surface structures, electrochemical behaviors, work function changes, and thermopower of dichloro-substituted benzenethiolate self-assembled monolayers (SAMs) on gold surfaces prepared by vapor deposition were investigated using scanning tunneling microscopy (STM), cyclic voltammetry, Kelvin probe force microscopy, and thermoelectric junction measurements to understand the effects of their substituent positions. STM observations revealed that the adsorption of 2,4-dichlorobenzenethiol (2,4-DCBT) on Au(111) at 363 K for 1 h led to the formation of short-range ordered domains with a (5 × 6√7)R20° structure, while the SAMs formed at 363 K for 4 h consisted of long-range well-ordered domains with a (√3 × 5) structure. 3,4-Dichlorobenzenethiol (3,4-DCBT) SAMs showed coexistence of partial ordered domains and a disordered phase, while 3,4-DCBT SAMs showed fully disordered phases regardless of deposition time. Moreover, the Seebeck coefficient (S) increased in the order of 3,4-DCBT (4.6 ± 0.1 μV/K) < 2,4-DCBT (5.0 ± 0.4 μV/K) < 3,5-DCBT (5.2 ± 0.1 μV/K). Interestingly, the trend of S values was qualitatively consistent with that of the work function change (ΔΦ) of the SAMs. The reductive desorption behavior, work function shifts, and thermopower of aromatic thiolate SAMs were significantly modified by the structural order and direction of molecular dipoles of dichloro-substituted benzenethiols.

Photoionization of pentalene and derivatives

The vertical, valence ionization energies for pentalene (C8H6) and some of its derivatives have been calculated as free molecules in the gas phase using high-level ab initio coupled-cluster method: EOM-DLPNO-CCSD. Their valence electronic structures depend on the number, type and position of substituents. We have used the calculated vertical, valence ionization energies to simulate UV photoelectron spectra. HOMO-LUMO gaps and the influence of substituents on ionization energies and electronic structure were also studied. We discuss the antiaromaticity and bis-annulation effects in pentalenes.

Tuning 2D Perovskite Passivation: Impact of Electronic and Steric Effects on the Performance of 3D/2D Perovskite Solar Cells

AbstractSurface passivation with 2D perovskites is a powerful strategy to achieve improved stability and performance in perovskite solar cells (PSCs). Various large organic cations have been successfully implemented, led by phenylethylammonium (PEA+) and its derivatives. However, systematic studies on large sets of cations to understand the effect of substituent position on 2D perovskite passivation and device performance are lacking. Herein, a collection of halogenated PEA+ iodide salts (x‐XPEAI where x: ortho (o), meta (m), para (p), X: F, Cl, Br) are synthesized by a facile method and deposited on top of 3D perovskite. The 2D perovskite layer formation is confirmed by X‐ray diffraction (XRD) and grazing‐incidence wide‐angle X‐ray scattering analyses for all cations, regardless of the nature and position of the halogen. Density functional theory analysis reveals that lower formation energies and higher interfacial dipoles achieved by m‐substituted cations are responsible for enhanced performance compared to their o‐ and p‐ counterparts. While the m‐BrPEAI‐treated device shows a champion efficiency of 23.42%, (VOC=1.13 V, FF=81.2%), considering average efficiencies, stability, and reproducibility, the treatment with m‐ClPEAI salt yields the best overall performance. This comprehensive study provides guidelines for understanding the influence of large cation modification on performance and stability of 3D/2D PSCs.

Rapid screening and characterization of 2-(2-phenylethyl)chromones in agarwood by UHPLC-Q-Exactive Orbitrap-MS.

The purpose of this study is to develop an improved comprehensive data filtering strategy, which was implemented primarily through the Microsoft Office platform's Excel software for rapid screening of potential 2-(2-phenylethyl)chromone (PEC) monomers and their dimers (PEC dimers) obtained from agarwood. A total of 108 PEC monomers and 30 PEC dimers in agarwood were characterized. In conclusion, the results obtained in this work could provide useful information for the future utilization of agarwood. In particular, it is the first time to conduct an in-depth analysis of the MS/MS fragmentation behavior of a large number of PEC monomers and PEC dimers, including the identification of substituent positions of them. The proposed data filtering strategy could improve the comprehensive characterization efficiency of complex components in spices.

Structure-Activity Relationships and Antiplasmodial Potencies of Novel 3,4-Disubstituted 1,2,5-Oxadiazoles.

The 4-substituted 3-amino-1,2,5-oxadiazole 1 from the Malaria Box Project of the Medicines for Malaria Venture foundation shows very promising selectivity and in vitro activity against Plasmodium falciparum. Within the first series of new compounds, various 3-acylamino analogs were prepared. This paper now focuses on the investigation of the importance of the aromatic substituent in ring position 4. A number of new structure-activity relationships were elaborated, showing that antiplasmodial activity and selectivity strongly depend on the substitution pattern of the 4-phenyl moiety. In addition, physicochemical parameters relevant for drug development were calculated (logP and ligand efficiency) or determined experimentally (CYP3A4-inhibition and aqueous solubility). N-[4-(3-ethoxy-4-methoxyphenyl)-1,2,5-oxadiazol-3-yl]-3-methylbenzamide 51 showed high in vitro activity against the chloroquine-sensitive strain NF54 of P. falciparum (PfNF54 IC50 = 0.034 µM), resulting in a very promising selectivity index of 1526.

Molecular design and synthesis of methoxy-substitued spiropyrans with photomodulated NIR-fluorescence.

This study focuses on the molecular design and synthesis of salt spiropyrans with near-IR fluorescence. The structure of the obtained compounds was confirmed by NMR, IR and mass spectroscopy. In the course of studying the spectral and photoluminescent characteristics, it was possible to reveal the effect of some substituents in various positions on the properties of spiropyran dyes. Due to the structural similarity of one of the isomers to cyanine dyes, the obtained compounds are of interest as potential fluorescent probes for bioimagimg, in particular, for DNA studies. To reveal their ability of binding to DNA molecules molecular docking was carried out. Toxic effects of compounds demonstrating NIR fluorescence were studied on biofilms, as well as using bacterial lux-biosensors.

Determination and Analysis of Thermodynamic Properties of Methyl Methylanthranilate Isomers.

The enthalpies of formation in the gaseous phase of methyl 3-methylanthranilate and methyl 5-methylanthranilate were determined from experimental measurements of the corresponding standard energies of combustion, obtained from combustion calorimetry, and the standard enthalpies of vaporization and sublimation, obtained from Calvet microcalorimetry and Knudsen mass-loss effusion. A computational study, using the G3(MP2)//B3LYP composite method, has also been performed for the calculation of the gas-phase standard enthalpies of formation of those two molecules at T = 298.15 K, as well as for the remaining isomers, methyl 4-methylanthranilate and methyl 6-methylanthranilate. The results have been used to evaluate and analyze the energetic effect of the methyl substituent in different positions of the ring.

Thin Films of Chlorinated Vanadyl Phthalocyanines as Active Layers of Chemiresistive Sensors for the Detection of Ammonia.

Halogenated metal phthalocyanines are promising materials for the manufacture of active layers of chemiresistive sensors for the detection of various gases. Despite the high interest in such sensors, there are few systematic studies of the position of halogen substituents in phthalocyanine macroring on the chemiresistive response of their films to gases. In this work, we prepared and studied films of novel tetrachlorosubstituted vanadyl phthalocyanine derivatives with Cl substituents in the peripheral (VOPcCl4-p) and nonperipheral (VOPcCl4-np) positions of the phthalocyanine ring as active layers of chemiresistive sensors to reveal the effect of the position of substituents on their structure and sensor response to low concentrations of NH3. It was shown that the films of VOPcCl4-p exhibited a noticeably higher sensor response to NH3 than the VOPcCl4-np ones. The limit of detection of NH3 was 0.7 ppm. The sensing layers demonstrated a reversible sensor response at room temperature with fairly low response/recovery times. It was also demonstrated that NH3 can be detected in the presence of various interfering gases (CO2 and H2) and some volatile organic vapors, as well as in a mixture of gases with a composition close to exhaled air.