RESUMO
The self-assembled resorcinarene capsule C6 shows remarkable photoacidity upon light irradiation, which is here exploited to catalyze olefin hydroarylation reactions in confined space. An experimental pKa* value range of -3.3--2.8 was estimated for the photo-excited hexameric capsule C6*, and consequently an increase in acidity of 8.8â log units was observed with respect to its ground state (pKa=5.5-6.0). This makes the hexameric capsule the first example of a self-assembled supramolecular photoacid. The photoacid C6* can catalyze hydroarylation reaction of olefins with aromatic substrates inside its cavity, while no reaction occurred between them in the absence of irradiation and/or capsule. DFT calculations corroborated a mechanism in which the photoacidity of C6* plays a crucial role in the protonation step of the aromatic substrate. A further proton transfer to olefin with a concomitant C-C bond formation and a final deprotonation step lead to product releasing.
RESUMO
A water-soluble prism[5]arene host can form endo-cavity complexes with hydrophilic organic substances in water by displacing frustrated water molecules from its deep cavity. Water molecules structured at both rims of the prismarene host can mediate hydrogen bonding interactions with the guest. Water-mediated hydrogen bonding interactions were invoked here to elucidate the elevated binding affinities and selectivity of the prismarene host toward hydrophilic organic guests. We show that water at the interface of a host-guest complex can act as an extension of the host structure, facilitating the accommodation of neutral guests within the binding site. This study highlights the crucial role of water in facilitating supramolecular interactions between a deep-cavity prismarene host and organic hydrophilic guests in aqueous medium.
RESUMO
Hexahexyloxycalix[6]arene 2b leads to the endo-cavity complexation of linear and branched alkylammonium guests showing a conformational adaptive behavior in CDCl3 solution. Linear n-pentylammonium guest 6a+ induces the cone conformation of 2b at the expense of the 1,2,3-alternate, which is the most abundant conformer of 2b in the absence of a guest. In a different way, branched alkylammonium guests, such as tert-butylammonium 6b+ and isopropylammonium 6c+, select the 1,2,3-alternate as the favored 2b conformation (6b+/6c+⊂2b1,2,3-alt), but other complexes in which 2b adopts different conformations, namely, 6b+/6c+⊂2bcone, 6b+/6c+⊂2bpaco, and 6b+/6c+⊂2b1,2-alt, have also been revealed. Binding constant values determined via NMR experiments indicated that the 1,2,3-alternate was the best-fitting 2b conformation for the complexation of branched alkylammonium guests, followed by cone > paco > 1,2-alt. Our NCI and NBO calculations suggest that the H-bonding interactions (+N-H···O) between the ammonium group of the guest and the oxygen atoms of calixarene 2b are the main determinants of the stability order of the four complexes. These interactions are weakened by increasing the guest steric encumbrance, thus leading to a lower binding affinity. Two stabilizing H-bonds are possible with the 1,2,3-alt- and cone-2b conformations, whereas only one H-bond is possible with the other paco- and 1,2-alt-2b stereoisomers.
RESUMO
ß-lactam antibiotics are among the most important and widely used antimicrobials worldwide and are comprised of a large family of compounds, obtained by chemical modifications of the common scaffolds. Usually these modifications include the addition of active groups, but less frequently, molecules were synthesized in which either two ß-lactam rings were joined to create a single bifunctional compound, or the azetidinone ring was joined to another antibiotic scaffold or another molecule with a different activity, in order to create a molecule bearing two different pharmacophoric functions. In this review, we report some examples of these derivatives, highlighting their biological properties and discussing how this strategy can lead to the development of innovative antibiotics that can represent either novel weapons against the rampant increase of antimicrobial resistance, or molecules with a broader spectrum of action.
Assuntos
Antibacterianos/química , Azetidinas/química , Lactamas Macrocíclicas/química , beta-Lactamas/química , Animais , Antibacterianos/farmacologia , Azetidinas/farmacologia , Bactérias/efeitos dos fármacos , Infecções Bacterianas/tratamento farmacológico , Calixarenos/química , Calixarenos/farmacologia , Descoberta de Drogas , Humanos , Lactamas Macrocíclicas/farmacologia , beta-Lactamas/farmacologiaRESUMO
The composition of dynamic covalent imine libraries (DCL) adapts to the presence of the hexameric resorcinarene capsule. In the presence of the self-assembled capsule, a kinetic and thermodynamic modulation of the imine constituents of the DCLs was observed, which was induced by an unusual predatory action of the capsule on specific imine constituents. More complex 2 × 2 DCLs also adapt to the presence of the hexameric capsule, showing a thermodynamic and kinetic modulation of the constituents induced by the predatory action of the capsule. By cross-referencing experimental data, a good selectivity (up to 66%) for one constituent can be induced in a 2 × 2 DCL.
RESUMO
The novel title macrocycles, based on methylene-bridged 1,5-naphthalene units, have been obtained by template effect in a thermodynamically controlled synthesis. In detail, the prism[5]arene 1 or the prism[6]arene 3 was selectively removed from the equilibrium mixture by using the complementary ammonium-templating agent. When only the solvent 1,2-DCE was used, the 1,4-confused derivative 2 was obtained. The prism[5]arene here described shows a deep π-electron-rich aromatic cavity that exhibits a great affinity for the quaternary ammonium guests, originating from favorable cation···π and +NC-H···π interactions. This recognition motif is the basis of the templated synthesis of the prism[n]arenes here reported.
RESUMO
Antimicrobial resistance is spreading massively in the world and is becoming one of the main health threats of the 21st century. One of the possible strategies to overcome this problem is to modify the known classes of antibiotics in a rational way, with the aim of tuning their efficacy. In this paper, we present the synthesis and the evaluation of the biological activity of a series of two ß-lactam bearing cephalosporin derivatives, in which an additional isolated azetidinone ring, bearing different substituents, is joined to the classical cephalosporanic nucleus by a chain of variable length. A computational approach has been also applied in order to predict the molecular interactions between some representative derivatives and selected penicillin-binding proteins, the natural targets of ß-lactam antibiotics. All these derivatives are active against Gram-positive bacteria, with MIC100 comparable or even better than that of the reference antibiotic ceftriaxone, and show no or very low cytotoxic activity on different cell lines. Overall, these molecules appear to be able to exert their activity in particular against microorganisms belonging to some of the species more involved in the development of multidrug resistance.
Assuntos
Antibacterianos/farmacologia , Cefalosporinas/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , beta-Lactamas/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cefalosporinas/química , Relação Dose-Resposta a Droga , Humanos , Testes de Sensibilidade Microbiana , Simulação de Dinâmica Molecular , Estrutura Molecular , Relação Estrutura-Atividade , beta-Lactamas/síntese química , beta-Lactamas/químicaRESUMO
The principle of amplified halogen bonding (XB) in a small space is exploited as a catalytic tool for the activation of an XB acceptor substrate in a nanoconfined environment. The inner cavity of the resorcinarene capsule has been equipped with an XB catalyst bearing an ammonium unit acting as a Trojan horse to drive the catalyst inside the capsule. In the presence of a specific XB catalyst, the capsule is able to catalyze a Michael reaction between N-methylpyrrole and methyl vinyl ketone. In the bulk medium in absence of the resorcinarene capsule, the XB catalyst is catalytically ineffective. Quantum-mechanical investigations highlight that the Michael reaction proceeds through the activation of the carbonyl group by synergistically enhanced halogen/hydrogen-bonding interactions and takes place in an open pentameric capsule.
RESUMO
The hexameric resorcinarene capsule reported by Atwood in 1997 is able to act as a supramolecular catalyst. Its inner cavity provides a unique environment, in which organic reactions can be efficiently catalyzed, thanks to the confinement effect of the substrates. In addition, different stereo- and regiochemical outcomes can be observed with respect to reactions in the bulk solvent. The hexameric capsule shows some catalytic features reminiscent of natural enzymes. In particular, highlights of the capsule discussed herein include 1)â its ability to recognize the substrates (substrate selectivity), 2)â the possibility of stabilizing the transition states and intermediates through secondary interactions, 3)â an inherent Brønsted acidity, and 4)â its ability to act as a hydrogen-bond catalyst. In addition, it is also shown how the catalytic activity of the hexameric capsule can be modulated in the presence of competitive alkylammonium guests, which show high affinities for its internal cavity. These aspects are discussed through a critical examination of data reported in the literature in recent years.
RESUMO
We report here the synthesis of two [8]cycloparaphenylenes ([8]CPP) derivatives, 1 and 2, bearing a monosubstituted benzene moiety. The presence of the substituent implies a planar chirality for the monosubstituted [8]CPP 1 and 2, whose configuration is here described by applying the chirality descriptors pR and pS. Experimental evidence of this planar chirality has been obtained through 1H VT NMR studies and by addition of Pirkle's reagent. This was confirmed by the X-ray crystal structure of 2, which represents an interesting example of solid-state structure of a monosubstituted [8]CPP derivative. Derivative 2 crystallizes in two monoclinic crystal forms (α and ß), which show a herringbone motif. The [8]CPP ring of the α form encapsulates two dichloromethane molecules, held through C-H···π interactions, while in the ß form, open channels are partially filled by highly disordered solvent molecules.
RESUMO
Calix[6]arenes disubstituted at the methylene bridges, which are stable in the cone or 1,2,3-alternate conformation, form pseudorotaxanes with dialkylammonium axles. The cone wheel-based pseudorotaxanes are 10-100 times more stable than those obtained with the native conformationally mobile calix[6]arene wheel, as a consequence of their higher degree of preorganization. The threading of conformationally stable 1,2,3-alternate calix[6]arenes is unprecedented in the literature. Therefore, very peculiar NMR features are here evidenced for this threading process involving the less symmetrical 1,2,3-alternate calix[6]arene conformation, which implies a peculiar rototranslation motion of the axle.
RESUMO
The synthesis of the triple-calix[6]arene derivative 6 in which three calix[6]arene macrocycles are linked to a central 1,3,5-trimethylbenzene moiety is reported. Derivative 6 is able to give multiple-threading processes in the presence of dialkylammonium axles. The formation of pseudo[2]rotaxane, pseudo[3]rotaxane, and pseudo[4]rotaxane by threading one, two, and three, respectively, calix-wheels of 6 has been studied by 1D and 2D NMR, DOSY, and ESI-FT-ICR MS/MS experiments. The use of a directional alkylbenzylammonium axle led to the stereoselective formation of endo-alkyl pseudo[n]rotaxane stereoisomers.
RESUMO
BACKGROUND: One of the main concerns of the modern medicine is the frightening spread of antimicrobial resistance caused mainly by the misuse of antibiotics. The researchers worldwide are actively involved in the search for new classes of antibiotics, and for the modification of known molecules in order to face this threatening problem. We have applied a computational approach to predict the interactions between a new cephalosporin derivative containing an additional ß-lactam ring with different substituents, and several serine ß-lactamases representative of the different classes of this family of enzymes. RESULTS: The results of the simulations, performed by using a covalent docking approach, has shown that this compound, although able to bind the selected ß-lactamases, has a different predicted binding score for the two ß-lactam rings, suggesting that one of them could be more resistant to the attack of these enzymes and stay available to perform its bactericidal activity. CONCLUSIONS: The detailed analysis of the complexes obtained by these simulations suggests possible hints to modulate the affinity of this compound towards these enzymes, in order to develop new derivatives with improved features to escape to degradation.
Assuntos
Cefalosporinas/metabolismo , Simulação de Acoplamento Molecular , beta-Lactamases/metabolismo , Domínio Catalítico , Cefalosporinas/química , Ligação Proteica , beta-Lactamases/químicaRESUMO
The anthracene-incorporated [8]cycloparaphenylene 2 has been synthesized and its optoelectronic properties studied by UV-vis spectroscopy, cyclic voltammetry, and DFT calculations. NMR and computational studies indicate that the new cycloparaphenylene derivative possesses a Cs point group symmetry. The new CPP 2 exhibits peculiar optoelectronic properties: (i) fluorescence emission is blue-shifted with respect to [8]cycloparaphenylene 1, and its quantum yield is higher; (ii) in the presence of an octaethylporphyrin Pd complex, as sensitizer, it undergoes a visible light upconversion. This is the first case in which a cycloparaphenylene derivative is involved as an emitter in low power light frequency conversion.
RESUMO
This study shows that calixarene p-bromodienone derivatives can act as precursors for the formation of oxenium cations, which can be trapped with enamine C-nucleophiles. When calixarene p-bromodienones were treated with enamines, in the presence of AgClO4, the lower rim-substituted C-O-C products were obtained by an electrophilic attack of the intermediate calixarene-oxenium cation with a contemporary cone-to-partial-cone inversion of the involved aromatic ring.
RESUMO
A novel catalytic feature of a hexameric resorcinarene capsule is highlighted. The self-assembled cage was exploited to promote the Friedel-Crafts benzylation of several arenes and heteroarenes with benzyl chloride under mild conditions. Calculations showed that there are catalytically relevant hydrogen-bonding interactions between the bridging water molecules of the capsule and benzyl chloride, which is fundamental for the activation of the C-Cl bond. The capsule controls the reaction outcome. Inside the inner cavity of the capsule, N-methylpyrrole is preferentially benzylated in the unusual ß-position while mesitylene reacts faster than 1,3-dimethoxybenzene despite the greater π-nucleophilicity of the latter compound.
RESUMO
The simple tetraminocalix[4]arene 1, which contains weak H-bond-donor NH2 groups, is reported to be a highly efficient organocatalyst for the Vinylogous Mukaiyama Aldol Reaction (VMAR) of 2-(trimethylsilyloxy)furan 5 with α-ketoesters 6 a-l under "on-water" conditions owing to the hydrophobic amplification of weak H-bond interactions. The catalytic efficiency of calixarene catalyst 1 was shown to be closely related to its recognition abilities towards the reactants 5 and 6 through a multipoint recognition model. The proposed model provided good explanations for the differences on the reaction rate acceleration and on the stereoselectivity observed with different substrates.
RESUMO
The threading of monostoppered alkylbenzylammonium axles 7+ and 8+ with the calix[6]-wheel 3 can occur by both routes of entering the macrocycle 3 in the cone conformation: passage through the upper rim and the through the lower rim. Thus, under thermodynamic conditions, with both the axles 7+ and 8+, the two possible orientations of calix[2]pseudorotaxane, namely, endo-benzyl and endo-alkyl, are formed by a stereoselectivity controlled by the endo-alkyl rule. Interestingly, by 1H NMR monitoring of the threading process between 8+ and 3, we revealed two calix[2]pseudorotaxane isomers in which the calix-wheel adopts 1,2,3-alternate and cone conformations, which represent the kinetic and thermodynamic species, respectively. Finally, the synthesis of ammonium-based oriented calix[2]rotaxane is here described.
RESUMO
[8]Cycloparaphenylene derivative 1 has been synthesized and its recognition abilities toward pyridinium guests have been investigated and compared with the [8]CPP macrocycle. The results showed a fine-tuning of the binding properties of [8]CPP 1 toward pyridinium cations due to the presence of the 1,4-DMB ring. DFT calculations indicate that the close steric fitting between the rigid cavity of 1 and the pyridinium guest is the crucial factor for the stabilization of their supramolecular complex through C-H···π and N+···π1,4DMB interactions.
RESUMO
A green and efficient 1,3-dipolar cycloaddition of nitrones with different styrenes and cinnamates using a catalytic amount of γ-cyclodextrin (γ-CD) in water has been developed to give substituted isoxazolidines. γ-CD was found to be highly efficacious in carrying out this reaction under an eco-friendly environment, affording moderate to excellent yields and, in some cases, excellent diastereomeric excess (up to >95%) at 100 °C in 8-12 h. The catalyst can be easily recuperated and recycled for several times without loss of activity. Water, an eco-friendly reaction medium, has been utilized for the first time, to the best of our knowledge, in this reaction. The credit of the presented protocol includes high yields and catalyst reusability, and precludes the use of organic solvents. The use of in silico calculations allowed us to rationalize the obtained results and to improve the stereoselectivity.