Presence Of Substituents Research Articles

RuCl2(η6-p-cymene)(P*)] and [RuCl2(κ-P*-η6-arene)] Complexes Containing P-Stereogenic Phosphines. Activity in Transfer Hydrogenation and Interactions with DNA

The preparation of a series of half-sandwich ruthenium complexes, [RuCl2(η6-p-cymene)(P*)] (P* = S-PMeRR′) and [RuCl2(κ-P*-η6-arene)], containing P-stereogenic phosphines is reported. The borane-protected P-stereogenic phosphines have been obtained by addition of the (H3B)PMe2R (R = t-Bu (1), Cy (2), Fc (3))/sec-BuLi/(−)-sparteine adduct to benzyl halides, carbonyl functions, and epoxides with yields between 40 and 90% and ee values in the 70–99% range. Those containing an aryl secondary function have been used in the preparation of [RuCl2(η6-p-cymene)(P*)] complexes. Borane deprotection has been performed using HBF4, except for (H3B)PRMe(CH2SiMe2Ph) phosphines, where DABCO was used to avoid partial cleavage of the CH2–Si bond. In the case of (H3B)P(t-Bu)Me(CH2C(OH)Ph2) (1l) the dehydrated phosphine was obtained. The tethered complexes were obtained by p-cymene substitution in chlorobenzene at 120 °C, except for ferrocenyl-containing complexes, which decomposed upon heating. The presence of substituents i...

Thieno[2,3-d]Pyrimidin-4-Ones. Part 3.* Electrophilic Ipso-Substitution Reactions of Methyl and Methoxycarbonyl Groups

Interactions of 5,6-dimethyl- (1), 3,5,6-trimethylthieno[2,3-d]pyrimidin-4(3H)-ones ( 2) and 2,3-dimethyl- (5-7), 2-methyl-3-methoxycarbonylthieno[2,3-d]dihydropyrrolo-, tetrahydropyrido-, tetrahydroazepino[1,2-a]pyrimidin-4-ones ( 14-16 ) with nitrating mixture were investigated. For the first time it is shown, that in dependence on the presence of substituent in position 2 and 3 of pyrimidine and thiophene rings reaction goes in various directions; by electrophilic ipso-substitution of methyl groups at C-5 by nitro group, or its oxidation up to carboxyl groups with formation corresponding 5-carboxy derivatives. It is revealed, that at absence of the substituent in position 3 (compound 1) the electrophilic ipso-substitution of methyl group by nitro group with formation of 5-nitro derivative took

Functionalized 3-pyrrolyl boron-dipyrromethenes

A series of mono-functionalized 3-pyrrolyl boron-dipyrromethenes containing functional groups such as bromo, formyl, cyano, nitro and trimethylsilylacetylene groups at the α-position of the uncoordinated pyrrole group were synthesized. Further to show the use of functionalized 3-pyrrolyl BODIPY, we treated α-bromo BODIPY with four different boronic acids such as phenyl, biphenyl, phenylacetyl and thienyl boronic acids under mild Pd(0) coupling conditions to afford α-aryl substituted 3-pyrrolyl BODIPYs. α-Dipyrromethanyl substituted 3-pyrrolyl BODIPY was synthesized by treating α-formyl 3-pyrrolyl BODIPY with pyrrole in the presence of TFA in CHCl3. The 3-pyrrolyl BODIPY appended with BODIPY (BODIPY dyad) at the α-position of uncoordinated pyrrole was synthesized by oxidizing 3-dipyrromethanyl BODIPY with DDQ followed by complexation with BF3·Et2O. All compounds were characterized by HRMS mass, NMR, absorption, electrochemical and fluorescence techniques. The spectral studies indicated that the presence of substituent at the α-position of uncoordinated pyrrole of 3-pyrrolyl BODIPY alter the electronic properties of the BODIPY core. The photophysical studies on BODIPY dyad indicated a possibility of energy transfer from the appended BODIPY unit to the 3-pyrrolyl BODIPY unit in BODIPY dyad.

Structure-activity relationships of bergenin derivatives effect on α-glucosidase inhibition

The α-glucosidase inhibitory activities of bergenin derivatives were evaluated. Bergenin derivatives were synthesized from bergenin which is a characteristic compound of B. ligulata. A new bergenin derivative, 11-O-(3′,4′-dimethoxybenzoyl)-bergenin showed the highest potent inhibitory activity among those of bergenin derivatives. The presence of substituents at 3′,4′-position in bergenin derivatives altered the α-glucosidase inhibitory activity. 11-O-(3′,4′-dimethoxybenzoyl)-bergenin was noncompetitive inhibitor for α-glucosidase. The present study reveals that bergenin derivatives could be classified as a new group of α-glucosidase inhibitors.

Electronics and Optics of Graphene Nanoflakes: Edge Functionalization and Structural Distortions

The effects of edge covalent functionalization on the structural, electronic and optical properties of elongated armchair graphene nanoflakes (AGNFs) are analyzed in detail for a wide range of terminations, within the ramework of Hartree-Fock-based semi-empirical methods. The chemical features of the functional groups, their distribution and the resulting system symmetry are identified as the key factors that determine the modification of structural and optoelectronic features. While the electronic gap is always reduced in presence of substituents, functionalization-induced distortions contribute to the observed lowering by about 35-55%. This effect is paired with a red shift of the first optical peak, corresponding to about 75% of the total optical gap reduction. Further, the functionalization pattern and the specific features of the edge-substituent bond are found to influence the strength and the character of the low energy excitations. All these effects are discussed for flakes of different width, representing the three families of AGNFs.

Photochemical isomerization of aryl hydrazones of 1,2,4-oxadiazole derivatives into the corresponding triazoles

The photochemical version of the Boulton-Katritzky reaction has been studied, examining the behaviour of the arylhydrazones of 3-benzoyl-5-X-1,2,4-oxadiazoles. The effect of several modifications of the substrates structure (the E and/or Z structures of arylhydrazones, the possible presence of substituents in the arylhydrazono moiety, and the nature of substituents at C-5 of the 1,2,4-oxadiazole ring) on the course of the photochemical rearrangement has been examined.

Viable and straightforward approach to the preparation of water soluble pyrazol-5-one derivatives through glycoconjugation

The synthesis of water soluble pyrazol-5-one azo-dyes has been achieved. 6′-Aminolactosetriacetonide 9 was selected as the key building block to glyconjugate the pyrazole ring at its 3 position via a carboxamide or via a benzeneamide moiety in position 1 of the heterocycle. Diethyl-3-oxopentandionate 2 led eventually to a bicyclic compound, hampering the glyconjugation coupling process. The values of the molar extinction coefficients (ɛ) confirmed the tendency of pyrazolone azo dyes to exist in their tautomeric hydrazo form (especially in polar solvents); whereas the presence of substituents on the phenylazo group influenced the visible absorption maxima negligibly.

Differences in the Activation Processes of Phosphine-Containing and Grubbs–Hoveyda-Type Alkene Metathesis Catalysts

A detailed exploration of the three proposed mechanisms (associative, dissociative, and interchange) for the activation of Grubbs–Hoveyda-type precatalysts is performed, using DFT (B3LYP) calculations. The effects induced by the nature of the reacting alkene, the bulk of the chelating alkoxy group, and the presence of substituents in the Hoveyda ligand are taken into account. Results show that, while the associative mechanism has always high energy barriers, neither the dissociative nor the interchange mechanism can be ruled out for the first step of the activation process. In fact, the preference for one or the other mechanism seems to be influenced, to a large extent, by the nature of the chelating alkoxy group in such a way that small OR groups tend to favor the interchange pathway. Moreover, for all considered Grubbs–Hoveyda-type precatalysts, the highest transition structure corresponds to the Hoveyda ligand decoordination at the end of the cross-metathesis process. It is worth noting that this is observed regardless of the initial alkene coordination pathway (dissociative or interchange), precursor nature, and substrate and, thus, the rate-determining transition structure in all considered cases is the final alkene decoordination process. In contrast, the highest transition structure for the activation process of the phosphine-containing complexes is the initial phosphine dissociation, for which the reacting alkene is not yet involved. Overall, although the interchange mechanism may also have a role, the present calculations show that the different sign of the experimentally measured activation entropies is more likely associated with a change in the nature of the rate-determining transition structure rather than in a change of the nature of the elementary steps.

Alstiphyllanines I–O, ajmaline type alkaloids from Alstonia macrophylla showing vasorelaxant activity

Seven new ajmaline type alkaloids, alstiphyllanines I–O (1–7) were isolated from the leaves of Alstonia macrophylla together with six related alkaloids (8–13). Structures and stereochemistry of 1–7 were fully elucidated and characterized by 2D NMR analysis. A series of alstiphyllanines I–O (1–7) as well as the known ajmaline type alkaloids (8–13) showed that they relaxed phenylephrine (PE)-induced contractions against rat aortic ring. Among them, vincamedine (10) showed potent vasorelaxant activity, which may be mediated through inhibition of Ca2+ influx through voltage-dependent Ca2+ channels (VDCs) and/or receptor-operated Ca2+ channels (ROCs) as well as partially mediated the NO release from endothelial cells. The presence of substituents at both N-1 and C-17 may be important to show vasorelaxation activity.

ChemInform Abstract: Ruthenium‐Catalyzed Coupling of Oxabenzonorbornadienes with Alkynes Bearing a Propargylic Oxygen Atom: Access to Stereodefined Benzonorcaradienes.

AbstractThe diastereoselectivity of the unprecedented coupling reaction depends on the presence of substituents on the bridgehead positions of the substrates.

The electronic structure of the lutein triplet state in plant light-harvesting complex II

Carotenoid molecules are essential for the life of photosynthetic organisms in that they protect the cell from the photo-oxidative damage induced by light-stress conditions. One of the photo-protective mechanisms involves triplet-triplet energy transfer from the chlorophyll molecules to the carotenoids: a process that is strongly dependent on the electronic properties of the triplet states involved. Here, we obtain a clear description of the triplet state of lutein in LHCII from higher plants for the first time by density functional theory (DFT) calculations. DFT predictions have been validated by comparison with hyperfine couplings obtained with pulsed-ENDOR spectroscopy. Knowledge of the spin density distribution, the frontier orbitals and orbital excitations forms a basis for discussing the requirements for an efficient triplet-triplet energy transfer. The results obtained for the lutein in LHCII are compared with those of the highly-substituted carotenoid peridinin in PCP from Amphidinium carterae [Di Valentin et al., Biochim. Biophys. Acta, 2008, 1777, 295-307]. The presence of substituents in the peridinin molecule does not alter significantly the triplet state electronic structure compared to lutein. Despite the unusual spectroscopic behaviour of the peridinin excited singlet state, lutein and peridinin have similar triplet state properties. In both molecules the unpaired spins are delocalized uniformly over the whole π-conjugated system in an alternating even-odd pattern.

Towards organic film passivation of germanium wafers using diazonium salts: Mechanism and ambient stability

Germanium is well-known for its good electronic properties, but also for the poor passivation quality of its natural or thermally-grown oxide layer. The robust passivation of Ge surfaces is thus a crucial step on the way to its integration in electronics at nanoscale. Before passivation, the natural oxide layer must be removed from the surface. Different methods were investigated and compared. The surfaces were analysed by X-ray photoelectron spectroscopy and by atomic force microscopy to determine the impact of the etching on the roughness. Oxide-free Cl-terminated surfaces were chosen and functionalized with various arenediazonium salts. The grafting is a fast reaction (less than 30 min) and proceeds in soft conditions (room temperature in acetonitrile solutions). The functionalization was found to proceed even at low temperature (−18 °C). The modified surfaces were mainly studied by XPS and AFM. The morphology of the organic layer was influenced by the temperature and duration of the grafting as well as by the presence of substituents on the aromatic ring. We demonstrated that smooth oxide-free Ge surfaces could be prepared by a cyclic oxidation- rinsing- etching procedure and could be functionalized with various arenediazonium salts. The stability of the organic layer was compared to the stability of a self-assembled monolayer of alkanethiolates. The absolute coverage was also determined. This constitutes a first step towards Ge crystal passivation by organic thin films.

Hydrogen Bonding as a Modulator of Aromaticity and Electronic Structure of Selectedortho-Hydroxybenzaldehyde Derivatives

Properties of hydrogen bonds can induce changes in geometric or electronic structure parameters in the vicinity of the bridge. Here, we focused primarily on the influence of intramolecular H-bonding on the molecular properties in selected ortho-hydroxybenzaldehydes, with additional restricted insight into substituent effects. Static models were obtained in the framework of density functional theory at B3LYP/6-311+G(d,p) level. The electronic structure parameters evolution was analyzed on the basis of Atoms In Molecules (AIM) and Natural Bond Orbitals methods. The aromaticity changes related to the variable proton position and presence of substituents were studied using Harmonic Oscillator Model of Aromaticity (HOMA), Nucleus-Independent Chemical Shift (NICS) and AIM-based parameter of Matta and Hernández-Trujillo. Finally, Car-Parrinello molecular dynamics was applied to study variability of the hydrogen bridge dynamics. The interplay between effects of the substitution and variable position of the bridged proton was discussed. It was found that the hydrogen bond energies are ca. 9-10 kcal/mol, and the bridged proton exhibits some degree of penetration into the acceptor region. The covalent character of the studied hydrogen bond was most observable when the bridged proton reached the middle position between the donor and acceptor regions. The aromaticity indexes showed that the aromaticity of the central phenyl ring is strongly dependent on the bridged proton position. Correlations between these parameters were found and discussed. In the applied time-scale, the analysis of time evolution of geometric parameters showed that the resonance strengthening does not play a crucial role in the studied compounds.

Differential toxicity of Disperse Red 1 and Disperse Red 13 in the Ames test, HepG2 cytotoxicity assay, and Daphnia acute toxicity test

Azo dyes are of environmental concern due to their degradation products, widespread use, and low-removal rate during conventional treatment. Their toxic properties are related to the nature and position of the substituents with respect to the aromatic rings and amino nitrogen atom. The dyes Disperse Red 1 and Disperse Red 13 were tested for Salmonella mutagenicity, cell viability by annexin V, and propidium iodide in HepG2 and by aquatic toxicity assays using daphnids. Both dyes tested positive in the Salmonella assay, and the suggestion was made that these compounds induce mainly frame-shift mutations and that the enzymes nitroreductase and O-acetyltransferase play an important role in the observed effect. In addition, it was shown that the presence of the chlorine substituent in Disperse Red 13 decreased the mutagenicity about 14 times when compared with Disperse Red 1, which shows the same structure as Disperse Red 13, but without the chlorine substituent. The presence of this substituent did not cause cytotoxicity in HepG2 cells, but toxicity to the water flea Daphnia similis increased in the presence of the chlorine substituent. These data suggest that the insertion of a chlorine substituent could be an alternative in the design of dyes with low-mutagenic potency, although the ecotoxicity should be carefully evaluated.

Ruthenium‐Catalyzed Coupling of Oxabenzonorbornadienes with Alkynes Bearing a Propargylic Oxygen Atom: Access to Stereodefined Benzonorcaradienes

Stereodefined: The title reaction provides an atom-economic route to benzonorcaradienes. The diastereoselectivity of the coupling relies upon the structure of the alkene; unsubstituted bicyclic alkenes afforded exclusively exo-benzonorcaradienes (see scheme) whereas the bicyclic alkenes with substituents at the bridgehead positions resulted in endo-benzonorcaradienes.

Thiodiacetate–Manganese Chemistry with N ligands: Unique Control of the Supramolecular Arrangement over the Metal Coordination Mode

Compounds based on the Mn-tda unit (tda=S(CH(2)COO)(2)(-2) ) and N co-ligands have been analyzed in terms of structural, spectroscopic, magnetic properties and DFT calculations. The precursors [Mn(tda)(H(2)O)](n) (1) and [Mn(tda)(H(2)O)(3)]·H(2)O (2) have been characterized by powder and X-ray diffraction, respectively. Their derivatives with bipyridyl-type ligands have formulas [Mn(tda)(bipy)](n) (3), [{Mn(N-N)}(2)(μ-H(2)O)(μ-tda)(2)](n) (N-N=4,4'-Me(2)bipy (4), 5,5'-Me(2)bipy, (5)) and [Mn(tda){(MeO)(2)bipy}·2H(2)O](n) (6). Depending on the presence/position of substituents at bipy, the supramolecular arrangement can affect the metal coordination type. While all the complexes consist of 1D coordination polymers, only 3 has a copper-acetate core with local trigonal prismatic metal coordination. The presence of substituents in 4-6, together with water co-ligands, reduces the supramolecular interactions and typical octahedral Mn(II) ions are observed. The unicity of 3 is also supported by magnetic studies and by DFT calculations, which confirm that the unusual Mn coordination is a consequence of extended noncovalent interactions (π-π stacking) between bipy ligands. Moreover, 3 is an example of broken paradigm for supramolecular chemistry. In fact, the desired stereochemical properties are achieved by using rigid metal building blocks, whereas in 3 the accumulation of weak noncovalent interactions controls the metal geometry. Other N co-ligands have also been reacted with 1 to give the compounds [Mn(tda)(phen)](2)·6H(2)O (7) (phen=1,10-phenanthroline), [Mn(tda)(terpy)](n) (8) (terpy=2,2':6,2''-terpyridine), [Mn(tda)(pyterpy)](n) (9) (pyterpy=4'-(4-pyridyl)-2,2':6,2''-terpyridine), [Mn(tda)(tpt)(H(2)O)]·2H(2)O (10) and [Mn(tda)(tpt)(H(2)O)](2)·2H(2)O (11) (tpt=2,4,6-tris(2-pyridyl)-1,3,5-triazine). Their identified mono-, bi- or polynuclear structures clearly indicate that hydrogen bonding is variously competitive with π-π stacking.

Demonstration of the presence of acetylation and arabinose branching as structural features of locust bean gum galactomannans

Galactomannans from locust bean gum (LBG) are polysaccharides containing single Galp residues as side chains in a β-(1→4)-Manp backbone. Nevertheless, sugars other than mannose and galactose are always detected, namely, arabinose and glucose, although in small amounts. In order to demonstrate that LBG galactomannans contain other structural features than those usually reported in literature, the galactomannans from LBG obtained from two different commercial sources were submitted to a selective degradation by Aspergillus niger endo-β-d-mannanase and the oligosaccharides (OS) obtained were fractioned by size exclusion chromatography using a Biogel-P2 (100–1800Da). A. niger endo-β-d-mannanase is able to hydrolyse the β-(1→4)-linked mannan backbone when the mannose residues are not hindered by the presence of substituents. This enables collection of fragments of the substituted mannan polysaccharide in the different chromatographic fractions that can be analysed by Electrospray Tandem Mass Spectrometry (ESI-MSn). Both samples showed the presence of hexose OS (Hex3–6), acetylated hexoses (AcHex3–6), hexoses substituted with a pentose unit (PentHex3–6), and OS composed by acetylated hexoses substituted with a pentose unit (PentAcHex3–6). These structures were confirmed by GC–qMS of reduced and permethylated oligosaccharides. Sugar and glycosidic-linkage analysis allowed to assign the pentose unit to a terminally-linked arabinofuranose residue at the O-6 of a (1→4)-Manp residue. The presence of arabinose substituted OS and acetylated mannoses have never been reported to occur in LBG.

Mechanistic Insights into Ring‐Closing Enyne Metathesis with the Second‐Generation Grubbs–Hoveyda Catalyst: A DFT Study

The full catalytic process (precatalyst activation, propagating cycle and active-species interconversion) of the ring-closing enyne metathesis (RCEYM) reaction of 1-allyloxy-2-propyne with the Grubbs-Hoveyda complex as catalyst was studied by B3LYP density functional theory. Both the ene-then-yne and yne-then-ene pathways are considered and, for the productive catalytic cycle, the feasibility of the endo-yne-then-ene route is also explored. Calculations predict that the ene-then-yne and yne-then-ene pathways proceed through equivalent steps, the only major difference being the order in which they take place. In this way, all alkene metathesis processes studied here involve four steps: olefin coordination, cycloaddition, cycloreversion and olefin decoordination. Among them, the two more energetically demanding ones are the olefin coordination and decoordination steps. The reaction of the alkyne fragment consists of two steps: alkyne coordination and alkyne skeletal reorganization, the latter of which has the highest Gibbs energy barrier. Comparison between the ene-then-yne and yne-then-ene pathways shows that there is no clear energetic preference for either of the two processes, and thus both should be operative when unsubstituted enynes are involved. In addition, although the endo orientation is computed to be slightly disfavored, it is not ruled out for 1-allyloxy-2-propyne, and thus calculations seem to indicate that the exo versus endo selectivity is strongly influenced by the presence of substituents in the reagent.

Experimental and theoretical investigation of substituent effects in a two-pathway reaction of tetrahydro-1,5-benzodiazepine-2-thiones with 4-substituted 2-bromoacetophenones

Abstract The interaction of 5-acetyl(or formyl)-3-R 1 -(CH 3 , H)-4-R 2 (CH 3 , Ph, H)-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine-2-thiones with 2-bromo-4 0 -X(CH 3 , OCH 3 ,Br, H)-acetophenones leads to a mixture of products: 5,6-dihydro-4H-[1,3]thiazolo[3,2-a][1,5]benzodiazepinium saltsand S-[2-oxo-2-(4-X-phenyl)ethyl] 3-(1H-benzimidazol-1-yl)propane(or butane-)thioate hydrobromides. The courseof the concurrent reactions depends on the presence ofsubstituents of the starting thiones and on the nature of the4-substituent of the bromoacetophenones. SemiempiricalAustin method 1 (AM1) and density functional theory(DFT) B3LYP computational studies for the interpretationof two concurrent reaction pathways are presented.Keywords 5-Acyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine-2-thiones Cyclizations Density functional theory Structure–activityrelationships Semiempirical calculationsIntroductionIn recent years, great effort has been applied in the ben-zodiazepine area to develop new members of this family.Among the new compounds are those containing differentheterocyclic rings annulated to the basic 1,5-benzodiaze-pine system [1].In previous papers [2–4] we reported a cyclofunctional-ization strategy of the 1,5-benzodiazepine system, whichexploited the reactivity of the C=S bond of the heptatomicnucleus by interaction with a-halogen carbonyl compounds.Tricyclic thiazolo[1,5]benzodiazepines were obtainedfrom 1,3,4,5-tetrahydro-1,5-benzodiazepine-2-thiones bytreatment with bromoacetaldehyde diethylacetal [2],chloroacetone [3], and 2-bromo(or 2,4

ChemInform Abstract: Base‐Free NIS Promoted Electrophilic Cyclization of Alkynes: An Efficient Synthesis of Iodo Substituted Pyrano[4,3‐b]quinolines.

Abstract A simple and mild procedure for the synthesis of iodo substituted 1H-pyrano[4,3-b]quinolines has been achieved using NIS reagent in the absence of base from 2-alkynylquinoline-3-carboxaldehydes via intramolecular electrophilic cyclization onto alkynes in good to excellent yields in a short duration of time. The reactions proceeded smoothly in a normal solvent in aerobic atmosphere at room temperature. The presence of substituent at either quinoline or alkyne moieties did not show effect on reaction rate of cyclization. The palladium-catalyzed transformations of iodo group to C–C bond are also discussed.