Ortho Position Research Articles

Structure and Conformational Properties of a Short Polyaniline Chain in a Mixture of Water and Ionic Liquid [1-Ethyl-3-methyl-imidazolium][bistriflimide] Investigated by All-Atom Molecular Dynamics Simulations.

Development of antifouling membranes for water treatment using conducting polymers and their composites is a fundamental strategy to mitigate the fouling. This manuscript presents an all-atom molecular dynamics simulations of a conducting polymer, polyaniline (PANI), immersed in an ionic liquids (ILs)-water mixtures. We have considered the ionic liquid 1-ethyl-3-methyl imidazolium bistriflimide, [EMIM]+[BIS]-. The two forms of polyaniline, emeraldine base (EB) and emeraldine salt (ES), were considered. Various intra- and intermolecular structural properties of PANI were analyzed, such as polymer chain radius of gyration Rg, radial distribution functions, and torsional angle distributions. The Rg of EB shows an increase, while the Rg of ES shows a decrease with an increase in the IL concentration. The backbone torsional angle probability distributions show a significant trans state for EB, while a combination of trans and gauche states was observed for ES. Similar supportive distributions were seen in the backbone angular distributions. Radial distribution functions between the carbon atoms at ortho and meta positions of the benzene ring on both ES and EB, as well as the amine group attached between two benzene rings, show an enhanced interaction with the ionic liquid compared to water. Anions have a dominant interaction with the polymer chain when compared to cations. The solvent accessible surface area (SASA) calculations were in accordance with the EB and ES structural properties. The SASA values are more favorable for ES than for EB. H-bond analysis shows a decrease in the number of H-bonds with water as the IL concentration increases.

Synthesis of 9,10‐Dibenzoyl‐phenanthrene Derivatives Through a Palladium‐Catalyzed Domino Approach

AbstractA palladium‐catalyzed domino approach toward synthetically challenging phenanthrene derivatives has been developed. The procedure involves a sequence of oxidative homocoupling, cyclization, and oxidation starting from deoxybenzoin derivatives halogenated in the ortho position. Good assembly efficiency and good functional group tolerance have been observed with yields from moderate to excellent. A plausible reaction mechanism has been proposed based on experimental results and literature data.

A Molecular Electron Density Theory Study of the Domino Reaction of N-Phenyl Iminoboranes with Benzaldehyde Yielding Fused Bicyclic Compounds.

The reaction of N-phenyl iminoborane with benzaldehyde yielding a fused aromatic compound, recently reported by Liu et al., has been studied within the Molecular Electron Density Theory (MEDT). Formation of the fused aromatic compound is a domino process that comprises three consecutive reactions: (i) formation of a weak molecular complex between the reagents; (ii) an intramolecular electrophilic attack of the activated carbonyl carbon of benzaldehyde on the ortho position of the N-phenyl substituent of iminoborane; and (iii) a formal 1,3-hydrogen shift yielding the final fused aromatic compound. The two last steps correspond to a Friedel-Crafts acylation reaction, the product of the second reaction being the tetrahedral intermediate of an electrophilic aromatic substitution reaction. However, the presence of the imino group adjacent to the aromatic ring strongly stabilizes the corresponding intermediate, being the reaction product when the ortho positions are occupied by t-butyl substituents. This domino reaction shows a great similitude with the Brønsted acid catalyzed Povarov reaction. Although N-phenyl iminoborane can experience a formal [2+2] cycloaddition reaction with benzaldehyde, its higher activation Gibbs free energy compared to the intramolecular electrophilic attack of the activated carbonyl carbon of benzaldehyde on the ortho position of the N-phenyl substituent, 6.6 kcal·mol-1, prevents the formation of the formal [2+2] cycloadduct. The present MEDT study provides a different vision of the molecular mechanism of these reactions based on the electron density.

Pharmacological evaluations of amide carboxylates as potential anti-Alzheimer agents: anti-radicals, enzyme inhibition, simulation and behavioral studies in animal models

Alzheimer’s disease (AD) is a neurological disorder that progresses gradually but irreversibly leading to dementia and is difficult to prevent and treat. There is a considerable time window in which the progression of the disease can be intervened. Scientific advances were required to help the researchers to identify the effective methods for the prevention and treatment of disease. This research was designed to investigate potential mediators for the remedy of AD, five new carboxylate amide zinc complexes (AAZ9–AAZ13) were synthesized and characterized by spectroscopic and physicochemical techniques. The biological evaluation was carried out based on the cholinesterase inhibitory mechanism. The preparation methodology provided the effective synthesis of targeted moieties. The in vitro pharmacological activities were evaluated involving AChE/BChE inhibition and antioxidant potential. All synthesized compounds displayed activity against both enzymes in higher or comparable to the standard drug Galantamine, a reversible inhibitor but the results displayed by compound AAZ10 indicated IC50 of 0.0013 µM (AChE) and 0.061 µM (BChE) as high values for dual AChE/BChE inhibition with potent anti-oxidant results. Structure activity relationship (SAR) indicated that the potent activity of compound AAZ10 appeared due to the presence of nitro clusters at the ortho position of an aromatic ring. The potent synthesized compound AAZ10 was also explored for the in-vivo Anti-Alzheimer activity and anti-oxidant activity. Binding approaches of all synthesized compounds were revealed through molecular docking studies concerning binding pockets of enzymes that analyzed the best posture interaction with amino acid (AA) residues providing an appreciable understanding of enzyme inhibitory mechanisms. Results indicate that synthesized zinc (II) amide carboxylates can behave as an effective remedy in the treatment of Alzheimer’s disease. Communicated by Ramaswamy H. Sarma

Various Techniques for the Synthesis of 2-Nitrophenylamino-1,4-naphthoquinone Derivatives

Nitrated products are important since they are intermediates in the synthesis of other compounds, such as explosives, perfumes, dyes and plastics, among others, and they have an easy capacity to convert into other functional groups. The synthesis of compounds with biological activity that have a nitro group in their structure is relevant to improving and/or enhancing their effect. In this work, different methodologies for the nitration of naphthoquinone derivative compounds are presented. The nitration of 3-R-2-(phenylamino)-1,4-naphthoquinone derivatives was carried out with nitric acid and sulfuric acid; milder reaction conditions were also established by diluting the acids or performing the reaction with weaker acids. Other methodologies were tested using nitrate salts for mononitrate product synthesis. We used a solvent-free reaction with oxalic acid using 3-R-2-(phenylamino)-1,4-naphthoquinones (R=H, Br or Cl), noting that the electronegativity of the chlorine group is decisive for achieving nitration with good yields. Finally, a Michael addition was performed with some nitrated anilines. To obtain denitrated compounds in the ortho and para positions, the reaction with strong acids is feasible; however, for the formation of mononitrated products, the Michael-type addition is more convenient.

Photodegradation of Flutamide and Halogen Derivatives of Nitrobenzotrifluoride: The NO Release Channel.

The photodegradation of the nonsteroidal antiandrogen drug flutamide has been long linked to the photoisomerization involving the nitro group. In this work, the dynamics of NO photoelimination upon photolysis at 266 nm of flutamide, nitrobenzotrifluoride, and its halogen derivatives were investigated. Similar to nitrobenzene and its derivatives, a bimodal translational energy distribution was observed for the NO photofragment indicating the presence of two distinct elimination channels resulting in slow and fast components. The trends in the slow/fast branching ratio show that halogen substitution at the para position increases the triplet state yield due to the internal heavy-atom effect leading to enhancement of the fast component. Furthermore, the topology of the triplet state potential energy surface showed that the minimum energy path favors the oxaziridine ring-type intermediate over the NO2 roaming mechanism in all five molecules investigated. The steric interaction between the NO2 group and the CF3 group, which are placed in the ortho position, lowers the barrier for the formation of the oxaziridine transition state compared to that of nitrobenzene.

Synthesis and Antidiabetic Evaluation of <i>N</i>’-Benzylidenebenzohydrazide Derivatives by <i>In Silico</i> Studies

Two new of N’-benzylidenebenzohydrazide (NBB) derivatives were successfully synthesized and yielded 50–58%. FTIR, ESI-MS, 1H-NMR and 13C-NMR were used to investigate the characteristic of NBB derivates. The structure and relationship of NBB derivatives into α-glucosidase and α-amylase as good targets for diabetes treatment were evaluated using in silico screening. Molecular Mechanics-Poisson Boltzmann/Generalized Born Surface Area (MM-PB/GBSA) was used to calculate the free binding energy (ΔGbind (MM-GBSA)) of NBB to α-glucosidase and α-amylase receptors showed that the results of −0.45 and −20.79 kcal/mol respectively. In the ortho position, NBB derivatives exhibited electron donating groups (EDG like -OCH3, -OH and -Cl with binding free energies of −21.94, −6.71 and 21.94, respectively, and acarbose, a native ligand energy of 32.62 kcal/mol. In addition, the binding free energy of N-2-(-OCH3, -OH and -Cl)-NBB to the α-amylase receptor showed the number of −39.33, −43.96, −42.81, respectively and −46.51 kcal/mol in comparing with a native ligand. As a result, it was found that all the NBB derivatives were able to interact with several amino acids in the α-glucosidase cavity as well as the native ones, including Ala281, Asp282, and Asp616. NBB and native ligand showed similar interaction between α-amylase with Gly110 amino acid residue.

Influence of Internal Noncovalent Bonds on Rotational Dynamics.

While a good deal of information has accumulated concerning the manner in which an intramolecular noncovalent bond can affect the relative energies of various conformers, less is known about how such bonds might affect the dynamics of interconversion between them. A series of molecules are constructed in which symmetrically equivalent conformers containing a noncovalent bond can be interconverted by a bond rotation, the energy barrier to which is computed by quantum chemical methods. The rotation of a CF3 group attached to a phenyl ring is speeded up if a Se··F chalcogen bond can be formed with a SeH or SeF group placed in an ortho position, a bond that is present in and stabilizes the rotational transition state. The analogous SnF3 group can, on the other hand, engage in a Sn··Se tetrel bond in its global minimum. The energetic cost of breakage of this bond is not fully compensated by the appearance of a Se··F chalcogen bond in the rotational transition state. Other systems were designed by placing two phenyl rings on opposite ends of an octahedrally disposed SeF4 group. A high barrier inhibits their rotation with bulky Br atoms in ortho positions, but this barrier is lowered if Br is replaced by groups that can engage in either chalcogen (SeH or SeF) or pnicogen (AsH2) bonds with the F atoms in the rotational transition state. The barrier reduction is closely related to the strength of these noncovalent bonds.

Synthesis and Characterization of Novel 4-aryl-4H-chromene Derivatives Using Borax and Evaluation of their Anticancer Effects.

4-aryl-4H-chromenes have attracted attention as potential anticancer agents. In an effort to discover effective compounds, we designed a new series of these chromenes with methoxy substitution at 2, 3, 4, 5, and 6 positions. The synthesized compounds were tested for anticancer properties against two human cancer cell lines (MCF-7 and PC3) as well as a normal cell line. The MTT assay showed that the 5g derivative, with methoxy groups at ortho and meta positions, exhibited the highest potency (IC50 = 40 µM) against the PC3 cell line. Furthermore, induction of apoptosis was explored through various methods, such as flow cytometry analysis, morphological changes, activation of caspase 3, ROS, and MMP. Our findings revealed that compound 5g induced apoptosis in the PC3 cell line, which was demonstrated by activation of caspase 3, an increase in ROS levels, and early apoptosis percentage. These results suggest that compound 5g holds promise as a potential therapeutic approach to cancer treatment.

Determination of Total Phenolic Compounds and SPF ( Sun Protection Factor)Value of Methanol Extract & Fraction Brotowali Leaves ( Tinospora crispa L.)

Flavonoid is one of the compounds that are important for the body because it has a function as an antidote to free radicals by overcoming and preventing the occurrence of oxidative stress conditions are antioxidants. Phenolic compounds are known to have antioxidant activity due to the substitution of hydroxy groups at the ortho and para positions to the – OH and –OR groups. Phenolic compounds are known to have various pharmacological activities, one of that is photoprotective which useful for protecting the skin from the dangers of UV exposure. Brotowali contains secondary metabolites such as alkaloids, phenolics, steroids, and tannins. The presence of these compounds indicates that brotowali has the ability to inhibit free radical compounds. This study aims to determine the total phenolic levels and SPF (Sun Protection Factor) in methanol extract and leaf fraction of brotowali (Tinospora crispa L.). The research methods include maceration, fractionation, phytochemical screening test, specific and non-specific parameter testing, assay by Folin-Ciocalteau method using gallic acid as a standard, and SPF (Sun Protection Factor) value. Based on the research results obtained, the ethyl acetate fraction of brotowali leaves contains phenolic compounds of 675.6522 mg GAE/gram sample with the highest SPF value at a concentration of 1000ppm of 48.79.

Synthesis and structure determination of a synthetic cannabinoid CUMYL-THPINACA metabolite with differentiation between the ortho-, meta-, and para-hydroxyl positions of the cumyl moiety.

Synthetic cannabinoids, a type of new psychoactive substances, are likely to be rapidly metabolized; thus, the detection of their metabolites, rather than the parent compound, is a common method used to prove drug consumption. Although the analysis of metabolites is generally performed by mass spectrometry, it is limited to structural estimation because of few commercially available standards. In particular, distinguishing between positional isomers is difficult. Synthetic cannabinoids with a cumyl moiety can be hydroxylated at the cumyl moiety during metabolism, but it remains unclear whether the hydroxylation occurs at the ortho, meta, or para position. This study determined the structures of a metabolite formed by mono-hydroxylation at the cumyl moiety of the synthetic cannabinoid CUMYL-THPINACA, used as a model compound. Chemical synthesis was performed to create possible metabolites with one hydroxyl group at the ortho, meta, or para positions of the cumyl moiety. Using the synthesized metabolites and liquid chromatography-quadrupole time-of-flight mass spectrometry, the metabolite detected in the microsomal reaction of CUMYL-THPINACA was identified as a compound mono-hydroxylated at the para position based on retention time and product ion spectra. Moreover, the rapid metabolism of CUMYL-THPINACA was demonstrated with an in vitro half-life of 4.9 min and the identified metabolite could be detected for a relatively long time in vitro. The synthesized metabolite may be utilized as a good reference standard for proof of CUMYL-THPINACA consumption. These findings have potential applications in the synthesis of metabolites of other synthetic cannabinoids bearing a cumyl moiety.

<i>para</i>-substituted anilines in reactions with tropyl salts and dibenzosuberenol

The features of the interaction of para-substituted anilines with tropyl salts and dibenzosuberenol have been studied. By the interaction of para-substituted anilines with tropyl salts (perchlorate or tetrafluoroborate) in an ethanol or tetrahydrofuran medium, the corresponding azomethines were obtained instead of the expected ortho-tropylated anilines. The tropilidene cycle (1,3,5-cycloheptariene cycle) underwent benzilidene narrowing due to an increase in temperature during a chemical reaction. The structurally related tropilidene - dibenzosuberene cycle can be introduced into the ortho position of para-substituted anilines to form stable ortho products. Dibenzosuberenol in an acidic environment is able to interact with ethanol to form an ether.

Benzodithiazoles‐Sulfoximines: Preparation, Properties and Reactivities as Radical Perfluoroalkylating Agents

AbstractWe describe the preparation of S‐perfluoroalkyl benzodithiazole trioxides as radical perfluoroalkylating reagents. Their syntheses were performed on a multi‐gram scale by an oxidative cyclization connecting the nitrogen of a sulfoximine and a sulfur atom previously introduced in theorthoposition of this group. The structures and properties of these new molecules were carefully examined by X‐Ray diffraction, DFT calculations and cyclic voltammetry. These data clearly highlight the enhanced reactivity of these cyclic sulfoximines compared to their open analogues. This was confirmed by photoredox catalysis experiments that revealed interesting reactivity, most especially for the introduction of di‐ and monofluoroalkyl chains.

Reaction Mechanism and Kinetics Study of Wheat Polysaccharide via Modified Reductor Technique in Bead Making Process

The reaction mechanism and kinetics investigation of the substitution of titanium in wheat flour polysaccharide (referred to here as titaniumation) in aqua medium during bead making process was carried out. The use of the Modified Reductor Technique was implored to study the reaction kinetics. The study was carried out at varying temperatures between 25 – 70oC. The study showed that the titaniumation of the wheat polysaccharide molecules increased with time and temperature. Hence, at 25oC, the degree of titaniumation (DT) of the ring increased from 0.41 % to 0.49 % and at elevated temperature of 70oC, DT increased from 0.58 to 0.94 % as time progressed from 30 to 210 mins, respectively, while keeping both amount of wheat polysaccharide and TiO2 constant, and thus achieving >1.9-fold. This also implies that the titaniumation of wheat polysaccharide using TiO2 is favourable at elevated temperature. The study was able to reveal that the reaction mechanism of the titaniumation of the polysaccharide molecules is an electrophilic substitution reaction, favouring the ortho position, while the kinetics study showed that the titaniumation reaction is of first order reaction.

Beyond the Limits of Atropochirality: Design of Highly Conformationally Restrained Biaryls with Bridgehead Phosphine Oxide.

In the last three decades, reacting sterically congested ortho-substituted arenes to form atropochiral biaryls is an appealing venture and a challenging subject that has garnered significant attention. Therefore, there is interest in developing methods to prepare these compounds. In this study, an efficient approach to produce a new class 2,2' disubstituted biaryls bridgehead phosphine oxides with an unusual topology and exceptional conformational stability is presented. Our methodology demonstrates that depending on the substitution pattern on the aryl moieties, the methanophosphocine backbone could be rigid enough to observe a double atropochirality, resulting in an under covered class of molecules. Notably, our studies revealed that replacing only one hydrogen at the ortho position by a fluorine atom led to sufficiently restricted rotation at temperatures below 80 °C, extending "far away" the limits of atropostability. Finally, our investigations, which employed variable-temperature NMR spectroscopy and DFT calculations, yielded unique insights into the isomerisation mechanism, indicating that the two biaryl motifs are fully independent in spite of their proximity.

Structure determination through powder X-ray diffraction, Hirshfeld surface analysis, and DFT studies of 2- and 4-(methylthio)benzoic acid

Abstract 2-(methylthio)benzoic acid (1) is an ortho-substituted benzoic acid derivative, whereas 4-(methylthio)benzoic acid (2) is a para-substituted benzoic acid derivative. The structural analysis of both compounds was carried out using PXRD data. 2-(methylthio)benzoic acid shows a triclinic system with the P 1 ‾ $P\overline{1}$ space group, whereas 4-(methylthio)benzoic acid shows a monoclinic system and crystallizes in the P21/a space group. The strength, as well as relative contributions of intermolecular hydrogen bonds, have been examined through Hirshfeld surfaces as well as 2D fingerprint plots. A weak intramolecular hydrogen bond was found only in the case of ortho-substituted 2-(methylthio)benzoic acid. Supramolecular frameworks for 1 are formed by the interplay of intramolecular and intermolecular interactions, whereas for 2, intermolecular contacts form supramolecular assemblies. Intermolecular O–H⋯O interactions involving carboxyl groups form the R2 2(8) graph-set motif for both compounds. Theoretical DFT calculations using the B3LYP correlation functional reveal that the energy gap of HOMO–LUMO orbitals in compound 1, with the methylthio moiety in the ortho position relative to the carboxyl group, is lower than that of compound 2, with the methylthio moiety in the para position. Vertical and adiabatic ionization energies are also calculated for both compounds.

An electrochemical route to a tetracyclic dimer through the anodic oxidation of 3-(4-fluorophenyl)-2-methyl-[1,2a] benzimidazolo-1, 3, 5-triazin-4-thione

This work reports the electrosynthesis of 7,7′-Bi(2-methyl-8-thia-1,3,3a1,4-tetraazacyclopenta[def]fluorene), as a novel coating derivative on a platinum grid through the anodic oxidation of 3-(4-fluorophenyl)-2-methyl-[1,2a]benzimidazolo-1,3,5-triazine-4-thione, in an acetonitrile solution.3-(4-fluorophenyl)-2-methyl-[1,2a]benzimidazolo-1,3,5-triazine-4-thione was crystallography characterized and electrochemically studied for the first time using the pentiodynamic, and potentiostatic approaches. Cyclic voltammetry on a platinum disk reveals a succession of three irreversible anodic waves that the first step was concerned by the potentiostatic electrolysis on a platinum grid, leading to an electrodeposited symmetrical dimer of tetracyclic units. Through the electrochemical investigations, conjointly to the quantum chemical calculations, a CC bond formation between the aromatic rings of two starting molecules was suggested, as well as CS bonds establishment through intramolecular cyclization, in the CC ortho position of the benzimidazole ring, and two fluorobenzene molecules elimination.

Nonaxisymmetrical 9,10-diarylanthracenes: Separable swivel conformers and promising optoelectronic properties

The chemical and physical functions of organic molecules are closely related to their conformations in both solutions and solid states, but the successful separation of organic conformers is usually very difficult because of the rapid internal rotation of single bonds. In the current work, we first demonstrate two stable and separable conformers with swivel cross-conjugated configuration based on 9,10-diphenylanthracene derivatives, and they are confirmed by 1H NMR spectra and single crystal analysis. The introduction of two bulky groups at the ortho positions of the two phenyls can enhance the internal rotation barrier of phenyl–anthryl single bond to fully stabilize the conformers in respective conformation even in reflux toluene. We find that they show similar solution but very different solid-state optical properties such as different emission wavelength and fluorescence efficiency. Moreover, only the syn conformer crystal can exhibit mechanochromic luminescence and mechanoluminescence.

Methoxy 13C NMR Chemical Shift as a Molecular Descriptor in the Structural Analysis of Flavonoids and Other Phenolic Compounds

The interpretation of nuclear magnetic resonance (NMR) chemical shifts plays an increasingly important role in the structure elucidation of flavonoids. Despite the fact that the 3H signal of the methoxy (OMe) group appears as a singlet in the 1H NMR spectrum, its chemical shift is not reliably indicative of the OMe-substitution in the aromatic rings, unlike its 13C NMR chemical shift, which can be useful for the determination of the molecular structure of flavonoids. For example, the chemical shift of ortho-substitutions is at 56 ± 1 ppm for flavonoids having one OMe-substituent in either the ortho or orthó position and 61.5 ± 2 ppm for those having substituents in both ortho positions. The nuclear Overhauser effect spectroscopy ( δH-OMe→ ortho-aryl-H or adjacent substituent) and heteronuclear multiple-bond correlation ( δH-OMe→ ipso-aryl-C) data have been widely employed for the structure analysis of flavonoids and to identify the site of OMe-substitution. Thus, OMe chemical shifts can act as molecular descriptors. However, we have noticed that there are several examples that are not in accordance with this generalization, and a reinvestigation of such reported data seems to be relevant for reconsideration of assigned structures, and a few examples are cited herein.

Compressed and Expanded Lattices - Barriers to Spin-State Switching in Mn3+ Complexes.

We report the structural and magnetic properties of two new Mn3+ complex cations in the spin crossover (SCO) [Mn(R-sal2323)]+ series, in lattices with seven different counterions in each case. We investigate the effect on the Mn3+ spin state of appending electron-withdrawing and electron-donating groups on the phenolate donors of the ligand. This was achieved by substitution of the ortho and para positions on the phenolate donors with nitro and methoxy substituents in both possible geometric isomeric forms. Using this design paradigm, the [MnL1]+ (a) and [MnL2]+ (b) complex cations were prepared by complexation of Mn3+ to the hexadentate Schiff base ligands with 3-nitro-5-methoxy-phenolate or 3-methoxy-5-nitro-phenolate substituents, respectively. A clear trend emerges with adoption of the spin triplet form in complexes 1a-7a, with the 3-nitro-5-methoxy-phenolate donors, and spin triplet, spin quintet and thermal SCO in complexes 1b-7b with the 3-methoxy-5-nitro-phenolate ligand isomer. The outcomes are discussed in terms of geometric and steric factors in the 14 new compounds and by a wider analysis of electronic choices of Mn3+ with related ligands by comparison of bond length and angular distortion data of previously reported analogues in the [Mn(R-sal2323)]+ family. The structural and magnetic data published to date suggest a barrier to switching may exist for high spin forms of Mn3+ in those complexes with the longest bond lengths and highest distortion parameters. A barrier to switching from low spin to high spin is less clear but may operate in the seven [Mn(3-NO2-5-OMe-sal2323)]+ complexes 1a-7a reported here which were all low spin in the solid state at room temperature.