Methoxy Functionalities Research Articles

QSAR and QAAR Studies on Mixtures of 3-(Benzylidene)Indolin-2-One Isomers as Leads to Develop PET Radiotracers for Detection of Parkinson's Disease

Deposition of α–synuclein, tau and β–amyloid protein plaques in brain leads to neurodegeneration. A series of indolin derivatives, which can bind to α–synuclein and detect Parkinson's disease (PD), were used for development of QSAR and QAAR models. It is the first attempt of QSAR for any radiotracer agents used for detection of PD. The binding affinity against α–synuclein was used as dependent variable while independent variables, such as structural, topological, E-state keys, electronic, molecular shape analysis and spatial molecular descriptors were used for QSAR modeling. For QAAR modeling, the binding affinities of molecules for tau and β–amyloid along with different molecular descriptors were used as independent variables. All models were successfully developed using multiple linear regression method, and validated internally and externally, based on different standard criteria. This article describes how the derived models postulate that conformation of molecules and presence of unsaturated hydrocarbon chains, nitro, methoxy and amine functionalities play an important role in determining binding affinity.

Role of the Benzodioxole Group in the Interactions between the Natural Alkaloids Chelerythrine and Coptisine and the Human Telomeric G-Quadruplex DNA. A Multiapproach Investigation.

The binding properties toward the human telomeric G-quadruplex of the two natural alkaloids coptisine and chelerythrine were studied using spectroscopic techniques, molecular modeling, and X-ray diffraction analysis. The results were compared with reported data for the parent compounds berberine and sanguinarine. Spectroscopic studies showed modest, but different rearrangements of the DNA-ligand complexes, which can be explained considering particular stereochemical features for these alkaloids, in spite of the similarity of their skeletons. In fact, the presence of a dioxolo moiety rather than the two methoxy functions improves the efficiency of coptisine and sanguinarine in comparison to berberine and chelerythrine, and the overall stability trend is sanguinarine > chelerythrine ≈ coptisine > berberine. Accordingly, the X-ray diffraction analysis confirmed the involvement of the benzodioxolo groups in the coptisine/DNA binding by means of π···π, O···π, and CH···O interactions. Similar information is provided by modeling studies, which, additionally, evidenced reasons for the quadruplex vs double-helix selectivity shown by these alkaloids. Thus, the analyses shed light on the key role of the benzodioxolo moieties in strengthening the interaction with the G4-folded human telomeric sequence and indicated the superior G4 stabilizing properties of the benzophenanthridine scaffold with respect to the protoberberine one and conversely the better G4 vs dsDNA selectivity profile of coptisine over the other alkaloids.

Synthesis of 1,2-Bis(trifluoromethylthio)arenes via Aryne Intermediates.

A general method for synthesis of 1,2-bis-trifluoromethylthioarenes has been developed. Arynes generated from silyl aryl triflates or halides react with bis(trifluoromethyl)disulfide to afford 1,2-bis-trifluoromethylthioarenes. Aryl, alkyl, ester, halide, and methoxy functionalities are compatible with reaction conditions. Use of bis(perfluoroaryl)disulfides gave moderate yields of aryne disulfenylation or cyclization to fluorinated dibenzothiophenes.

Conversion of methoxy and hydroxyl functionalities of phenolic monomers over zeolites

This study investigates the mechanisms for the conversion of methoxy and hydroxyl functionalities in phenolic monomers over zeolites during pyrolysis, identifying bottlenecks for conversion to aromatic hydrocarbons.

Effect of Induction on the Dispersion of Semiconducting and Metallic Single-Walled Carbon Nanotubes Using Conjugated Polymers

Despite significant advances in single-walled carbon nanotube (SWNT) synthesis and purification strategies, the separation of metallic and semiconducting SWNTs on a large scale remains a barrier to the realization of many commercial applications. Selective extraction of specific SWNT types by wrapping and dispersion with conjugated polymers has been found effective for semiconducting SWNTs, but structural parameters that dictate selectivity are poorly understood. Here, we report nanotube dispersions with two structurally similar conjugated copolymers, both being poly(fluorene-co-phenylene) derivatives, having comparable degrees of polymerization but differing in the extent of electron donation from functional groups on the phenylene comonomers. It is found that copolymers decorated with electron donating methoxy functionalities lead to predominant dispersion of semiconducting SWNTs, while copolymers decorated with electron withdrawing nitro functionalities bias the dispersion toward metallic SWNTs. Differentiation of semiconducting and metallic SWNT populations was carried out by a combination of UV–vis–NIR absorption spectroscopy, Raman spectroscopy using multiple excitation wavelengths, and fluorescence spectroscopy. These results provide new insight into polymer design features that dictate preferential dispersion of specific SWNT types.

Variations in the emission of polymethylene-vaulted trans-bis(salicylaldiminato)platinum(II) complexes incorporating methoxy functionalities with linkage length and substitution position

A series of methoxy-substituted trans-bis(salicylaldiminato)platinum(II) complexes (1b, 2b, 3b, 4a–d, 5a–d and 6a–d) incorporating octa-, nona-, deca-, undeca-, dodeca- and tridecamethylene bridges has been synthesized and their unique structure-dependencies in the solution state emission are described. Methoxy-substitution on the aromatic rings was found to improve the emission quantum efficiency in the glassy state in 2-MeTHF at 77K. Chromogenic control over a range of 70nm was demonstrated, with the 3-, 4-, 5- and 6-methoxy substitutions giving yellow, green, orange and yellow-green emissions, respectively. These complexes exhibited obvious linker-dependent emission chromism under the same conditions, such that a very regular hypsochromic shift from yellow to green was observed upon increasing the linker length.

Tuning solid-state emission properties of pyrene-containing chalcone derivatives

The synthesis and optical properties of chalcone dyes containing pyrene as a donor is described both in solution and in solid-state. With such molecules, we show that, while the ground-state dipole moment is almost zero, the excited state is highly polar resulting in an intramolecular charge transfer excited state. All the chalcone molecules were shown to be emissive in the solid state but the behavior is different as a function of the substituent appended on the aryl group connected to the carbonyl function of the chalcone. We evidenced the beneficial effect of a methoxy function on the aggregation yielding an enhancement of the emission quantum yield in solid-state as compared to the solution.

Understanding the Chemical Stability of Polymers for Lithium–Air Batteries

Recent studies have shown that many aprotic electrolytes used in lithium–air batteries are not stable against superoxide and peroxide species formed upon discharge and charge. However, the stability of polymers often used as binders and as electrolytes is poorly understood. In this work, we select a number of polymers heavily used in the Li–air/Li-ion battery literature, and examine their stability, and the changes in molecular structure in the presence of commercial Li2O2. Of the polymers studied, poly(acrylonitrile) (PAN), poly(vinyl chloride) (PVC), poly(vinylidene fluoride) (PVDF), poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP), and poly(vinylpyrrolidone) (PVP) are reactive and unstable in the presence of Li2O2. The presence of the electrophilic nitrile group in PAN allows for nucleophilic attack by Li2O2 at the nitrile carbon, before further degradation of the polymer backbone. For the halogenated polymers, the presence of the electron-withdrawing halogens and adjacent α and β hydrogen atoms that become electron-deficient due to hyperconjugation makes PVC, PVDF, and PVDF-HFP undergo dehydrohalogenation reactions with Li2O2. PVP is also reactive, but with much slower kinetics. On the other hand, the polymers poly(tetrafluoroethylene) (PTFE), Nafion, and poly(methyl methacrylate) (PMMA) appear stable against nucleophilic Li2O2 attack. The lack of labile hydrogen atoms and the poor leaving nature of the fluoride group allow for the stability of PTFE and Nafion, while the methyl and methoxy functionalities in PMMA reduce the number of potential reaction pathways for Li2O2 attack in PMMA. Poly(ethylene oxide) (PEO) appears relatively stable, but may undergo some cross-linking in the presence of Li2O2. Knowledge gained from this work will be essential in selecting and developing new polymers as stable binders and solid or gel electrolytes for lithium–air batteries.

ChemInform Abstract: Chemoselective and Direct Functionalization of Methyl Benzyl Ethers and Unsymmetrical Dibenzyl Ethers by Using Iron Trichloride.

AbstractFor the first time azidation, alkynylation, and cyanation with methoxy and benzyloxy functionalities as leaving groups is presented using FeCl3 as inexpensive catalyst.

Novel methoxypropylimmidazolium β-cyclodextrin for improved enantioseparation of amino acids

A new single-isomer cationic cyclodextrin, mono-6A-[3-(3-methoxypropyl)imidazol-1-ium]-6A-β-cyclodextrin chloride, has been synthesized and successfully used for the chiral separation of dansyl amino acids in capillary electrophoresis. With methoxy functionality, the new cationic cyclodextrin exhibits significantly improved enantioselectivities. Excellent enantioseparations for amino acids are obtained in chiral selector concentration range between 2.5mM to 15mM at pH 6.0. Chiral resolution as high as 7.3 was achieved for Dns-Aca with 5mM chiral selector. Comparison study and theoretical calculation with Wren’s model attribute the enhanced enantioseparation to the stronger inclusion complexation between amino acids and cyclodextrin. The binding constants for dansyl amino acids and the cationic cyclodextrins are calculated to be 173–253M−1, while the optimum cyclodextrin concentrations were estimated to be 4.1–7.6mM.

Selective defunctionalization by TiO2 of monomeric phenolics from lignin pyrolysis into simple phenols

This study is focused on defunctionalizing monomeric phenolics from lignin into simple phenols for applications such as phenol/formaldehyde resins, epoxidized novolacs, adhesives and binders. Towards this goal, Titanium dioxide (TiO2) was used to selectively remove hydroxyl, methoxy, carbonyl and carboxyl functionalities from the monomeric phenolic compounds from lignin to produce mainly phenol, cresols and xylenols. The results showed that anatase TiO2 was more selective and active compared to rutile TiO2. Catechols were found to be the most reactive phenolics and 4-ethylguaiacol the least reactive with anatase TiO2. An overall conversion of about 87% of the phenolics was achieved at 550°C with a catalyst-to-feed ratio of 5 w/w. Over 97% conversion of phenolics is achievable at moderate temperatures (550°C or ≤ 600°C) and a moderate catalyst-to-feed ratio of 6.5:1. The reactivity of catechols on TiO2 suggests that titania is a promising catalyst in the removal of hydroxyl moiety.

Synthesis and biological evaluation of indole-based, anti-cancer agents inspired by the vascular disrupting agent 2-(3′-hydroxy-4′-methoxyphenyl)-3-(3″,4″,5″-trimethoxybenzoyl)-6-methoxyindole (OXi8006)

The discovery of a 2-aryl-3-aroyl indole-based small-molecule inhibitor of tubulin assembly (referred to as OXi8006) inspired the design, synthesis, and biological evaluation of a series of diversely functionalized analogues. In the majority of examples, the pendant 2-aryl ring contained a 3-hydroxy-4-methoxy substitution pattern, and the fused aryl ring featured a 6-methoxy group. Most of the variability was in the 3-aroyl moiety, which was modified to incorporate methoxy (33–36), nitro (25–27), halogen (28–29), trifluoromethyl (30), or trifluoromethoxy (31–32) functionalities. In two analogues (34 and 36), the methoxy substitution pattern in the fused aryl ring varied, while in another derivative (35) the phenolic moiety was translocated from the pendant 2-aryl ring to position-7 of the fused aryl ring. Each of the compounds were evaluated for their cytotoxicity (in vitro) against the SK-OV-3 (ovarian), NCI-H460 (lung), and DU-145 (prostate) human cancer cell lines and for their ability to inhibit tubulin assembly. Four of the compounds (30, 31, 35, 36) proved to be potent inhibitors of tubulin assembly (IC50 <5μM), and three of these compounds (31, 35, 36) were strongly cytotoxic against the three cancer cell lines. The most active compound (36) in this series, which incorporated a methoxy group at position-7, was comparable in terms of inhibition of tubulin assembly and cytotoxicity to the lead compound OXi8006.

Optimization of cell receptor-specific targeting through multivalent surface decoration of polymeric nanocarriers

Treatment of tuberculosis is impaired by poor drug bioavailability, systemic side effects, patient non-compliance, and pathogen resistance to existing therapies. The mannose receptor (MR) is known to be involved in the recognition and internalization of Mycobacterium tuberculosis. We present a new assembly process to produce nanocarriers with variable surface densities of mannose targeting ligands in a single step, using kinetically-controlled, block copolymer-directed assembly. Nanocarrier association with murine macrophage J774 cells expressing the MR is examined as a function of incubation time and temperature, nanocarrier size, dose, and PEG corona properties. Amphiphilic diblock copolymers are prepared with terminal hydroxyl, methoxy, or mannoside functionality and incorporated into nanocarrier formulations at specific ratios by Flash NanoPrecipitation. Association of nanocarriers protected by a hydroxyl-terminated PEG corona with J774 cells is size dependent, while nanocarriers with methoxy-terminated PEG coronas do not associate with cells, regardless of size. Specific targeting of the MR is investigated using nanocarriers having 0–75% mannoside-terminated PEG chains in the PEG corona. This is a wider range of mannose densities than has been previously studied. Maximum nanocarrier association is attained with 9% mannoside-terminated PEG chains, increasing uptake more than 3-fold compared to non-targeted nanocarriers with a 5kgmol−1 methoxy-terminated PEG corona. While a 5kgmol−1 methoxy-terminated PEG corona prevents non-specific uptake, a 1.8kgmol−1 methoxy-terminated PEG corona does not sufficiently protect the nanocarriers from nonspecific association. There is continuous uptake of MR-targeted nanocarriers at 37°C, but a saturation of association at 4°C. The majority of targeted nanocarriers associated with J774E cells are internalized at 37°C and uptake is receptor-dependent, diminishing with competitive inhibition by dextran. This characterization of nanocarrier uptake and targeting provides promise for optimizing drug delivery to macrophages for TB treatment and establishes a general route for optimizing targeted formulations of nanocarriers for specific delivery at targeted sites.

Design, Synthesis, and Pharmacological Screening of Novel Porphyrin Derivatives

A series of porphyrin derivatives 2a–f was synthesized, namely, 5,10,15,20‐mesotetrakis[p‐methoxyphenyl]‐21H,23H‐porphyrin (2a), 5,10,15,20‐mesotetrakis[2,6‐dichloro‐phenyl]‐21H,23H‐porphyrin (2b), 5,10,15,20‐mesotetrakis[4‐hydroxy‐3,5‐dimethoxyphenyl]‐21H,23H‐porphyrin (2c), 5,10,15,20‐mesotetrakis[3,4‐dimethoxyphenyl]‐21H,23H‐porphyrin (2d), 5,10,15,20‐mesotetrakis[2,4‐dichlorophenyl]‐21H,23H‐porphyrin (2e), and 5,10,15,20‐mesotetrakis[3,4,5‐trimethoxyphenyl]‐21H,23H‐porphyrin (2f), in high yields using a new method via a capping mechanism. These dyes were used as a model to study the free radical‐induced damage of biological membranes and the protective effects of these porphyrins. It was demonstrated that these dyes were effective in the inhibition of the free radical‐induced oxidative haemolysis of rat blood cells. Dyes 2d and 2f which bear methoxy functionality exhibited markedly higher antihaemolysis activity than the other analogs. Molecular modeling methods using ZINDO/INDO‐1, with a configuration interaction of 26, and TD‐DFT using the energy functional B3LYP and the basis set DGTZVP were used to study the vertical electronic excitations of porphyrins 2a–f and it was shown that the λmax calculated using TD‐DFT method was in excellent agreement with the experimental results, while the ZINDO method was inferior. Moreover, excellent correlation between the LUMO energy and cytotoxicity of dyes 2a–f was found.

Synthesis and anion recognition properties of shape-persistent binaphthyl-containing chiral macrocyclic amides

We report on the synthesis and characterization of novel shape-persistent, optically active arylamide macrocycles, which can be obtained using a one-pot methodology. Resolved, axially chiral binol scaffolds, which incorporate either methoxy or acetoxy functionalities in the 2,2' positions and carboxylic functionalities in the external 3,3' positions, were used as the source of chirality. Two of these binaphthyls are joined through amidation reactions using rigid diaryl amines of differing shapes, to give homochiral tetraamidic macrocycles. The recognition properties of these supramolecular receptors have been analyzed, and the results indicate a modulation of binding affinities towards dicarboxylate anions, with a drastic change of binding mode depending on the steric and electronic features of the functional groups in the 2,2' positions.

Methoxyaryl substituted palladium bis-NHC complexes – Synthesis and electronic effects

A series of methoxyphenyl substituted chelated bis-N-heterocyclic carbene palladium(II) complexes has been synthesized and characterized by cyclovoltammetry, spectroscopy (NMR, IR), solid state structures and investigated by quantum chemical calculations. The results confirm that a methoxy functionality in para position at the aryl substituent enhances the donor properties of the ligand compared to a methoxy group in ortho or meta position.

ChemInform Abstract: Copper‐Catalyzed/Mediated Synthetic Methodology for Ebselen and Related Isoselenazolones.

Abstract Scope of the copper catalyzed/mediated selenium-nitrogen coupling reaction has been studied for the synthesis of isoselenazolones. It is noticed that the 2-chloro, 2-bromo-, and 2-iodo-aryl amides substrates can be exploited in the selenium–nitrogen coupling reaction by employing 25–100 mol % of CuI/1,10-phenanthroline (L) and potassium carbonate as a base in DMF. Furthermore, electron rich 2-chloro-arylamides also underwent selenium–nitrogen coupling reaction to give biologically important selenium–nitrogen heterocycles. Also, copper-catalyzed selenium–nitrogen coupling reaction has been meticulously applied for the synthesis of diaryl diselenides having methoxy, amine, and amide functionality from respective aryl iodides in the presence of stoichiometric amount of succinimide as an external Se–N coupling partner.

Copper catalyzed/mediated synthetic methodology for ebselen and related isoselenazolones

Scope of the copper catalyzed/mediated selenium-nitrogen coupling reaction has been studied for the synthesis of isoselenazolones. It is noticed that the 2-chloro, 2-bromo-, and 2-iodo-aryl amides substrates can be exploited in the selenium–nitrogen coupling reaction by employing 25–100 mol % of CuI/1,10-phenanthroline (L) and potassium carbonate as a base in DMF. Furthermore, electron rich 2-chloro-arylamides also underwent selenium–nitrogen coupling reaction to give biologically important selenium–nitrogen heterocycles. Also, copper-catalyzed selenium–nitrogen coupling reaction has been meticulously applied for the synthesis of diaryl diselenides having methoxy, amine, and amide functionality from respective aryl iodides in the presence of stoichiometric amount of succinimide as an external Se–N coupling partner.

Catalytic conversion of anisole over HY and HZSM-5 zeolites in the presence of different hydrocarbon mixtures

The conversion of pure anisole (with a methoxy functionality, typical of some bio-oil components) and its mixtures with propylene, n-decane, benzene, or tetralin, has been investigated over zeolites in continuous flow and pulse reactors. The dominant reaction of pure anisole is transalkylation, which produces phenol, cresols, xylenols, and methyl anisoles as main products. However, in the presence of an effective hydrogen donor like tetralin important differences in product distribution are observed. In addition, while with pure anisole in the feed a fast deactivation is observed, the addition of tetralin to the feed results in lower amounts of carbon deposits and much higher catalyst stability. By contrast, less dramatic effects on stability and carbon formation were observed with most of the other co-fed hydrocarbons investigated.

Columnar Mesophases Based on Zinc Chlorophyll Derivatives Functionalized with Peripheral Dendron Wedges

A chlorophyll derivative with a central zinc ion, a methoxy functionality at its 3(1)-position, and functionalized with a second-generation dendron (3,4-3,4,5)12G2-CH(2)OH at its 17(2)-position was synthesized starting from natural chlorophyll a (Chl a). This compound exhibits liquid crystalline (LC) behavior and its mesomorphic properties have been characterized by differential scanning calorimetry (DSC), polarisation optical microscopy (POM), powder X-ray diffraction (XRD), and scanning probe microscopy (SPM). A combination of powder XRD, high resolution scanning tunneling microscopy (STM), and atomic force microscopy (AFM) experiments revealed the formation of nano-segregated well-ordered columnar tubular superstructures consisting of about five molecules in the column stratum. These self-assembled columns are further self-organized into a two-dimensional oblique unit cell lattice. Semiconducting behavior of this compound has been studied by pulse-radiolysis time-resolved microwave conductivity (PR-TRMC) method and charge carrier mobility values of ∼10(-2) cm(2) V(-1) s(-1) are observed. Such organized columnar superstructures constructed from semisynthetic zinc chlorins are reminiscent of the tubular organization of the bacteriochlorophyll dyes in the light-harvesting chlorosomal antennae of green sulphur bacteria.