Methoxy Functionalities Research Articles

Facile Access to Homo‐ and Heteroleptic, Triply Bonded Dimolybdenum Hexaalkoxides with Unsaturated Alkoxide Ligands

AbstractA series of monodentate, triply bonded Mo2(OR)6 complexes [R = MBE (1) (MBE = 2‐methylbut‐3‐ene‐2‐yl), MMP (2) (MMP = 1‐methoxy‐2‐methylpropane‐2‐yl), Terp (3) [Terp = 2‐(4‐methylcyclohex‐3‐enyl)propane‐2‐yl], which exhibit C–C double bonds or an ether function in the ligand sphere, were synthesized and characterized by multinuclear (1H, 13C and 95Mo) NMR studies. The partial alcoholysis of the latter complexes with neopentyl alcohol (neopentOH) led to the heteroleptic alkoxides Mo2(OR)n(Oneopent)6–n (4–7) {n = 2 [for R = tBu (4), MBE (5), MMP (6)], 4 [for R = Terp (7)]}. This concept was further applied to the synthesis of Mo2(O2DMH)2(OtBu)2 (8) (DMH = 2,5 dimethylhexyl) by starting from the Mo2(OtBu)6 precursor. The 1H NMR spectra for the heteroleptic complexes 4–8 show signals that are significantly shifted to a higher field for the RO ligand protons compared to those of their homoleptic analogues. This is the result of a change in the spatial position of the alkoxide ligands (RO) in the homoleptic compared to the heteroleptic complexes that leads to a different magnetic environment for the alkoxide ligands due to the magnetic anisotropy of the Mo–Mo triple bond. 95Mo NMR studies of the complexes 1–8 show that the resonance strongly depends on the substitution pattern of the alkoxide and that a shift to higher field is observed when going from the tertiary to the primary alkoxides. The molecular structures for 4–8 were determined by single‐crystal X‐ray diffraction, and all of the complexes show a staggered conformation as well as an asymmetric ligand distribution, which results in unequal Mo–O bond lengths. For the heteroleptic complexes 4–7, the RO ligands (R = tBu, MBE, MMP and Terp, respectively) exhibit the longest bond lengths, which suggests that the position of the ligand strongly depends on the steric congestion of the α‐carbon atom of the alkoxide ligand. In 6, the methoxy function enables an intramolecular O→Mo coordination as is indicated by a Mo–O distance of 2.2464(7) Å. This fact is supported by a lengthening of the Mo–Mo triple bond.

Shape selectivity in the synthesis of chiral macrocyclic amides

Shape-persistent, optically-active arylamide macrocycles have been designed and approached by using a stepwise, convergent methodology. The source of chirality, an axially-chiral Binol scaffold, incorporates methoxy functionalities in the 2,2′ positions, and carboxylic functionalities in the external 3,3′ positions. The latter can be efficiently elaborated through aromatic amidation to introduce aromatic spacers of differing shapes. The peculiar arrangement of functionalities on the Binol skeleton functions as an element of rigidification of the covalent structure through the formation of stable intramolecular hydrogen bonds. When this element is counterbalanced by the use of a flexible 3,3′-diaminobiphenyl as a spacer, yields for the macrocyclization step increase to values higher than 50%. The recognition properties of this particular macrocycle have been exploited and, while they indicate modest binding affinities towards carboxylate anions, the additional stabilization of neighbouring amide functionalities suitably placed within the covalent framework induces detectable binding of proper difunctional carboxylates.

Photoinduced electron transfer within a novel synthesized short-chain dyad

The investigations were made by using electrochemical, steady state and time resolved spectroscopic (time correlated single photon counting and laser flash photolysis) techniques on a novel synthesized dyad, 1-(4-chloro-phenyl)-3-(4-methoxy-naphthalen-1-yl)-propenone ( MNCA) where the donor 1-methoxy-naphthalene ( MNT) is connected with the acceptor p-chloroacetophenone ( PCA) by an unsaturated olefinic bond. This dyad possesses mainly extended ( E-type) conformation both in the ground and excited state. The unchanged conformational geometry of this dyad even after photoexcitation makes it different from the previously studied benzothiophene–p-chloroacetophenone dyads, though both the donors present are isosteric molecules. In the cases of the latter dyads though E-type isomeric structure dominates in the ground state, considerable amount of Z-type (folded) species are produced in the excited state. It is hinted that the proximity effect of methoxy functionality in donor moiety, may be the reason for the formation of mostly E-isomeric species in the case of the present dyad MNCA system. The observed unchanged values of charge recombination and ion-pair lifetime, estimated from the analysis of transient absorption spectra of the dyad in presence of βCD and without it, confirm the proposition about the maintenance of the extended conformation even upon photoexcitation. From the transient absorption measurements it appears that due to increase of delay times between the exciting and probe pulses, higher triplet T n of the donor being generated gets involved in PET reactions with the surrounding medium ACN. From the present findings, MNCA in aqueous medium seems to be better candidate to build light energy conversion devices than the previously studied benzothiophene dyads where artificial devices like βCD were used to make elongated geometry. This geometry would help to prevent charge recombination processes within the redox components due to minimal overlapping between them.

Biosynthesis of 3-methoxy-5-methyl naphthoic acid and its incorporation into the antitumor antibiotic azinomycin B

Azinomycin B is a potent antitumor antibiotic that features a set of unusual, densely assembled functionalities. Among them, the 3-methoxy-5-methylnaphthoic acid (NPA) moiety provides an important noncovalent association with DNA, and may, therefore, contribute to the specificity of DNA alkylation for biological activity exhibition. We have previously cloned and sequenced the azinomycin B biosynthetic gene cluster, and proposed that four enzymes: AziB, AziB1, AziB2, and AziA1, are involved in the naphthoate moiety formation and incorporation. In this study, we report in vivo and/or in vitro characterizations of the P450 hydroxylase AziB1, the O-methyltransferase AziB2, and the substrate specificity of the non-ribosomal peptide synthetase (NRPS) AziA1, providing insights into the timing of individual steps in the late-stage modification of 5-methyl-NPA synthesized by the iterative type I polyketide synthase AziB. AziB1 catalyzes a regiospecific hydroxylation at the C3 position of the free naphthoic acid 5-methyl-NPA to produce 3-hydroxy-5-methyl-NPA, and the resulting hydroxyl group is subsequently O-methylated by AziB2 to furnish the methoxy functionality. The di-domain NRPS AziA1 specifically incorporates 3-methoxy-5-methyl-NPA via an unusual A domain to initiate the backbone formation of azinomycin B. AziA1 activates several analogues of the natural starter unit, suggesting a potential for production by metabolic engineering of new azinomycin analogues differing in their NPA moieties.

Synthesis, Characterization, and Oxygenation Studies of Carboxylate‐Bridged Diiron(II) Complexes with Aromatic Substrates Tethered to Pyridine Ligands and the Formation of a Unique Trinuclear Complex

In this study, diiron(II) complexes were synthesized as small molecule mimics of the reduced active sites in the hydroxylase components of bacterial multicomponent monooxygenases (BMMs). Tethered aromatic substrates were introduced in the form of 2-phenoxypyridines, incorporating hydroxy and methoxy functionalities into windmill-type diiron(II) compounds [Fe(2)(μ-O(2)CAr(R))(2)-(O(2)CAr(R))(2)(L)(2)] (1-4), where (-)O(2)CAr(R) is a sterically encumbering carboxylate, 2,6-di(4-fluorophenyl)- or 2,6-di(p-tolyl)benzoate (R = 4-FPh or Tol, respectively). The inability of 1-4 to hydroxylate the aromatic substrates was ascertained. Upon reaction with dioxygen, compounds 2 and 3 (L = 2-(m-MeOPhO)Py, 2-(p-MeOPhO)Py, respectively) decompose by a known bimolecular pathway to form mixed-valent diiron(II,III) species at low temperature. Use of 2-(pyridin-2-yloxy)phenol as the ligand L resulted in a doubly-bridged diiron complex (4) and an unprecedented phenoxide-bridged triiron(II) complex (5) under slightly modified reaction conditions.

Synthesis, spectral analysis and in vitro microbiological evaluation of 3-(3-alkyl-2,6-diarylpiperin-4-ylidene)-2-thioxoimidazolidin-4-ones as a new class of antibacterial and antifungal agents

In the present work, a new series of bis hybrid heterocycle comprising both piperidine and thiohydantoin nuclei together namely 3-(3-alkyl-2,6-diarylpiperin-4-ylidene)-2-thioxoimidazolidin-4-ones 46– 60 was synthesized by the treatment of the respective thiosemicarbazones 31– 45 with chloroethyl acetate and anhydrous sodium acetate in refluxing ethanol for 4 h and were characterized by melting point, elemental analysis, MS, FT-IR, one-dimensional NMR ( 1H, D 2O exchanged 1H and 13C), two dimensional HOMOCOSY and NOESY spectroscopic data. In addition, the title compounds were screened for their antimicrobial activities against a spectrum of clinically isolated microbial organisms. Compounds 47– 50, 52– 55 and 57– 60 with fluoro, chloro, methoxy or methyl functions at the para position of phenyl rings attached to C-2 and C-6 carbons of piperidine moiety along with and without methyl substituent at position C-3 of the piperidine ring exerted potent biological activities against Staphylococcus aureus, β- Hemolytic streptococcus, Vibrio cholerae, Escherichia coli, Pseudomonas aeruginosa, Aspergillus flavus, Candida albicans, Candida 6 and Candida 51 at a minimum inhibitory concentration.

Early maturation processes in coal. Part 2: Reactive dynamics simulations using the ReaxFF reactive force field on Morwell Brown coal structures

This paper reports reactive dynamics (RD) simulations of a macro-model of Morwell Brown coal using the ReaxFF reactive force field. We find that these reactive MD simulations successfully reproduce thermal decomposition processes of defunctionalization, depolymerization and rearrangement of the residual structure observed in various experimental studies. For example, our simulations indicate that the decarboxylation and dehydroxylation of the lignin side chain of the Morwell model involves the formation of double bonds conjugated with the aromatic rings. The process of defunctionalization of the methoxy functions involving the formation of phenolic structures in the residue has been confirmed. We also observe that gaseous hydrocarbons are generated by cleavage of C–C bonds of the lignin side chain. The success in using ReaxFF RD to describe the molecular processes underlying the kinetics in pyrolysis of this model of coal plus the success of a similar previous study on the algaenan of Botryococcus braunii race L biopolymer model of kerogens suggests that such computation can be useful in providing molecular based kinetic models for other pyrolysis processes underlying the organic transformations in sedimentary materials.

Evidence of sidewall covalent functionalization of single-walled carbon nanotubes and its advantages for composite processing

Single-walled carbon nanotubes (SWCNTs) were functionalized in a three-step procedure. The first step is a radical reaction creating a covalent bond between the carbon nanotube surface and grafted p-methoxyphenyl functional groups. In a second step, a deprotection of the methoxy functions generates free alcohol groups and in the final step an esterification is done in order to install a double bond for further polymerization. Evidence that functionalization has actually occurred on the SWCNT sidewalls is furnished through investigations involving several complementary techniques (visual dispersion tests, transmission electron microscopy, thermal gravimetric analysis and adsorption volumetry). We show that surface properties of SWCNTs are changed throughout the chemical treatments and that the obtained level of functionalization is low. Incorporation of functionalized SWCNTs in a polymer (poly(methyl methacrylate)) matrix was done through an in situ polymerization process. Observations of the obtained composites using scanning and transmission electron microscopy illustrate that interactions between the SWCNT surface and the polymer matrix are improved.

Synthesis and characterization of oligo(oxyethylene)/carbosilane copolymers for thermoset elastomers via ADMET

AbstractAcyclic diene metathesis (ADMET) polymerization has been used to synthesize latent reactive processable elastomers constructed of carbosilane and polyether segments. Two types of latent modes have been introduced: “chain‐internal” and “chain‐end” sites through the use of labile silicon methoxy functionalities. These latent reactive groups are inert when exposed to metathesis conditions allowing formation of the linear copolymer; subsequently exposure to moisture triggers hydrolysis of the methoxy groups and formation of a chemically crosslinked thermoset. The thermoset's mechanical response can be potentially varied from plastic to elastic behavior, depending on the ratio of carbosilane and oligooxyethylene monomers employed. Different lengths of glycols and numbers of methylene groups between them in the polymer backbone have been investigated to explore structure/property relationship. Polymers composed of oligooxyethylenes with eight methylene groups in between them exhibited fully amorphous character, while the ones with up to 20 methylene groups between glycol units showed their semicrystalline nature. The concentration of “chain‐internal” and “chain‐end” crosslink sites enhances strength; modification to the run length and structure of the soft phase enhances elasticity. Resultant materials have been subjected to mechanical tests using Instron; generated stress/strain curves have shown plastic and elastic behavior. Depending on the composition obtained samples have shown moduli from 0.3 to 115 MPa, tensile strengths from 0.6 to 10 MPa and elongations from 20 to 700%. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 3992–4011, 2008

Exploring the Substrate Specificity of a Mycobacterial Polyprenol Monophosphomannose‐Dependent α‐(1→6)‐Mannosyltransferase

A series of synthetic alpha-(1-->6)-linked octyl mannopyranoside oligomers was evaluated as potential acceptors of a polyprenol monophosphomannose-dependent alpha-(1-->6)-mannosyltransferase that is involved in the biosynthesis of the mannan core of mycobacterial lipoarabinomannan. Initial evaluation demonstrated that the enzyme recognizes di-, tri- and tetramannosides (5, 6 and 7) as substrates with different activities. While the highest mannosyltransferase activities were observed when the di- and trisaccharide were used as substrates, diminished enzymatic activity was seen with the tetramannoside. As octyl alpha-D-mannopyranosyl-(1-->6)-alpha-D-mannopyranoside (5) appears to be the minimum structural element required for mannosyltransferase catalysis, a panel of methoxy and deoxy disaccharide analogues (8-21) were used to probe the substrate specificity of the enzyme further. In terms of the steric requirements at the active site, the enzyme does not recognize either C2'- and C2-methoxy analogues as substrates, a result that suggests that the alpha-(1-->2)-mannopyranosyl branches, which are present in the mannan core of LAM must be added on a larger alpha-(1-->6)-oligomannan intermediate. In contrast, the presence of a methoxy functionality at the C3', C3, C4' and C4 positions are somewhat tolerated by the enzyme, although diminished enzyme activities were observed with the C4'- and C4-methoxy analogues. Moreover, the 2'- and 4-hydroxyl groups appear not to be critical for substrate binding at the active site, as both 2'- and 4-deoxy analogues are substrates for the enzyme. In contrast, replacement of the hydroxyl groups at other positions essentially abolished enzymatic activity. Further kinetic characterization of the enzyme by using the effective acceptor substrates gave apparent K(M) values ranging from 111 to 437 microM, which are within two-fold higher or lower than that for the parent dimannoside (5). Although the K(M) values indicate that the enzyme binds those acceptors with comparable affinities, the C4'-methoxy analogue (12) turns over more slowly than the others, as indicated by the apparent V(max) values.

Synthesis and characterisation of peripherally functionalised dendritic molecules

A number of peripherally functionalised dendritic molecules were synthesised in almost quantitative yield by a synthetic method involving the reaction between amines and isocyanates. The peripheral functional groups were incorporated by preparing a number of branched subunits, based on tris(hydroxymethyl)aminomethane (TRIS), 1, possessing three nitro, methoxy, methyl or maleimide terminal functionalities. Attachment of these branched units to the core molecules 4,4′-methylenebis(phenyl isocyanate)13 and 1,3,5-benzene triisocyanate20 afforded the corresponding dendritic molecules possessing 6 or 9 peripheral functional groups. Functional group conversions on the dendritic molecules have been successfully carried out, including hydrogenation of the terminal nitro to the corresponding amine and cleavage of the methoxy ether to give the corresponding phenol.

Synthesis, Antifungal Activity, and Structure−Activity Relationships of Coruscanone A Analogues

Coruscanone A, a plant-derived cyclopentenedione derivative, showed potent in vitro antifungal activity against Candida albicans and Cryptococcus neoformans comparable to amphotericin B and fluconazole. A series of analogues have been synthesized by modification of the cyclopentenedione ring, the enolic methoxy functionality, and the side chain styryl moiety of this natural product lead. A structurally close 1,4-benzoquinone analogue was also prepared. All the compounds were examined for their in vitro activity against major opportunistic fungal pathogens including C. albicans, C. neoformans, and Aspergillus fumigatus and fluconazole-resistant C. albicans strains, with several analogues demonstrating potent antifungal activity. Structure-activity relationship studies indicate that the 2-methoxymethylenecyclopent-4-ene-1,3-dione structural moiety is the pharmacophore responsible for the antifungal activity of this class of compounds while the side chain styryl-like moiety plays an important complementary role, presumably contributing to target binding.

Phenylglycine as a novel P2 scaffold in hepatitis C virus NS3 protease inhibitors

Molecular modeling and inhibitory potencies of tetrapeptide protease inhibitors of HCV NS3 proposed phenylglycine as a new promising P2 residue. The results suggest that phenylglycine might be capable of interacting with the NS3 (protease-helicase/NTPase) in ways not possible for the common P2 proline-based inhibitors. Thus, a series of tripeptides, both linear and macrocyclic, based on p-hydroxy-phenylglycine in the P2 position were prepared and their inhibitory effect determined. When the p-hydroxy group was replaced by methoxy, isoquinolin-, or quinolinyloxy functions, inhibitors with improved potencies were obtained. The P2 phenylglycine-based inhibitors were further optimized by C-terminal extension to acyl sulfonamides and by P1–P3 cyclization, which gave products with inhibition constants in the nanomolar range (∼75 nM).

Synthesis and X‐Ray Analysis of a New [6]Helicene.

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Linear Ethylene−Vinyl Ether Copolymers: Synthesis and Thermal Characterization

Linear ethylene-co-vinyl ether copolymers were synthesized via a metathesis polymerization−hydrogenation reaction sequence producing a family of well-defined ethylene-based materials. Six high molecular weight macromolecules with desired vinyl ether incorporation levels are reported having methoxy or ethoxy pendant functionality on every 11th, 15th, and 21st carbons in the polymer backbone, and structural characterization of isolated materials via NMR and FT-IR indicates excellent control over copolymer microstructure. Thermal characterization via differential scanning calorimetry (DSC) suggests semicrystallinity for every material under dynamic scanning conditions except one highly functionalized material where subsequent annealing treatments isolated a peak melting temperature deviating from melting trends established by other materials in the study. Variations of physical and spectral properties are discussed as a function of pendant group spacing and overall level of ether incorporation.

Synthesis and X‐Ray Analysis of a New [6]Helicene

A new disubstituted hexahelicene derivative 3 bearing methoxy functions at positions 3 and 14 has been prepared in racemic form through a Heck reaction followed by photocyclodehydrogenation. Suitable crystals of rac‐3 were analyzed by X‐ray crystallography and showed similar geometry to the structure of hexahelicene itself. Deprotection of 3 using boron tribromide led to 3,14‐dihydroxyhexahelicene 4 in quantitative yield. The complexation of transition metal atoms seemed to be quite possible by these two bidentate hexahelicene derivatives.

Molecular iodine catalyzed selective acetylation of alcohols with vinyl acetate

Molecular iodine is found to catalyze the acetylation of alcohols efficiently with vinyl acetate. The reaction is mild and selective with good to high yields. Molecular iodine displays significant functional group tolerance, being compatible with methoxy, double bonds, spiroketals, ketals and phenolic hydroxyl functions.

Enthalpies of Formation and Reaction for Primary Reactions of Methyl‐ and Methylmethoxysilanes from Density Functional Theory

AbstractSummary: The enthalpies of formation and enthalpies of reaction at 298 K for a set of Si:C:O:H species derived from methylsilanes and methylmethoxysilanes were computed using the B3LYP density functional theory. Total energies were calculated at the B3LYP/6‐311+G(3df,2p)//B3LYP/6‐311+G(d) level. Zero point energies and thermal corrections were calculated using B3LYP/6‐311+G(d)//B3LYP/6‐311+G(d) vibrational energies scaled by a factor of 0.96. The average absolute deviation of enthalpies of formation and reaction were 3.89 and 1.86 kcal/mol, respectively. Bond strengths and reactions with O atom and H atom are examined in the context of understanding the initial reactions in chemical vapor deposition. The SiH bond was calculated to be 8.4 kcal/mol stronger than the SiC bond in methylsilanes and to increase by 0.6 kcal/mol with increased methylation; however, the thermochemistry of methylsilane reactions with O atom favors scission of the SiH bond to produce hydroxyl and methylsilyl radicals. Thermodynamic control over the reaction pathways of methylmethoxysilanes is possible only when considering the reaction with H atom for which methylmethoxysilanol formation is favored. This illuminates a conceivable strategy to control the SiOSi bonding network while retaining methyl functionality in a CVD thin film by controlling the ratio of methoxy functionality and free hydrogen in the reactor. Density functional theory is a useful tool in understanding and subsequently controlling the initial chemistry in the CVD process.Representation of the reaction of methyltrimethoxysilane with hydrogen atoms to produce the favored products, dimethylmethoxysilanol and methyl radicals.magnified imageRepresentation of the reaction of methyltrimethoxysilane with hydrogen atoms to produce the favored products, dimethylmethoxysilanol and methyl radicals.

Chain‐End and Chain‐Internal Crosslinking in “Latent Reactive” Silicon Elastomers

AbstractSummary: Latent reactivity has been employed to create processable elastomers constructed of carbosilane and either carbosiloxane or polyether segments. Two types of latent modes have been introduced: “chain‐internal” and “chain‐end” sites through the use of labile silicon methoxy and trifunctional olefinic functionalities. These latent reactive sites remain inert during formation of the linear copolymer; subsequent exposure to moisture triggers hydrolysis of the methoxy group and formation of a chemically crosslinked thermoset. These “chain‐end” sites limit the formation of dangling chains improving the overall mechanical properties of the material. The thermoset's mechanical response can be potentially varied from plastic to elastic behavior, depending on the ratio of hard and soft monomers employed. The concentration of “chain‐internal” and “chain‐end” crosslink sites enhances strength; modification to the run length and structure of the soft phase enhances elasticity, generating samples having moduli of 6 MPa, tensile strengths of 0.6 MPa and elongations of 400%.“Latent reactive” silicon elastomer.magnified image“Latent reactive” silicon elastomer.

Synthetic disaccharide analogs as potential substrates and inhibitors of a mycobacterial polyprenol monophosphomannose-dependent α-(1→6)-mannosyltransferase

Analogs of the α- d-Man p-(1→6)-α- d-Man p-O(CH 2) 7CH 3 disaccharide 4, a known substrate for a polyprenol monophosphomannose-dependent α-(1→6)-mannosyltransferase involved in mycobacterial LAM biosynthesis, have been synthesized and screened as potential substrates and inhibitors of the enzyme. In the disaccharides synthesized, the hydroxyl groups at C-2 and C-6 on the reducing end residue have been replaced by combinations of amino, fluoro, and methoxy functionalities 9– 14. In addition, a disaccharide in which the nonreducing mannopyranose residue was replaced with a 3,6-anhydromannopyranose residue 34 was synthesized from a byproduct formed during one of the reactions leading to 14. When tested against the enzyme, none were active as substrates, as would be expected as all lack the C-6′ hydroxyl group to which an additional sugar residue would be transferred. Evaluation of these compounds as inhibitors of the enzyme revealed that only three, 11, 12, and 13, all of which contain one or more amino groups, inhibited the enzyme. The most potent inhibitor was the diamino-disaccharide, 11.