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Former publications

Former publications

2011

“In silico” mechanistic studies as predictive tools in microwave-assisted organic synthesis.

A M Rodriguez, P Prieto, A de la Hoz, A Díaz-Ortiz. 

Computational calculations can be used as a predictive tool in Microwave-Assisted Organic Synthesis (MAOS). A DFT study on Intramolecular Diels-Alder reactions (IMDA) indicated that the activation energy of the reaction and the polarity of the stationary points are two fundamental parameters to determine "a priori" if a reaction can be improved by using microwave irradiation. -

Org. Biomol. Chem., 2011, 9, 2371-2377

Highly Conductive Redox Protein–Carbon Nanotube Complex for Biosensing Applications

Chiara Baldacchini, Maria Antonia Herrero Chamorro, Maurizio Prato, Salvatore Cannistraro. The integration of redox proteins with nanomaterials has attracted much interest in the past years, and metallic single-walled carbon nanotubes (SWNTs) have been introduced as efficient electrical wires to connect biomolecules to metal electrodes in advanced nano-biodevices. Besides preserving biofunctionality, the protein–nanotube connection should ensure appropriate molecular orientation, flexibility, and efficient, reproducible electrical conduction. In this respect, yeast cytochrome c redox proteins are connected to gold electrodes through lying-down functionalized metallic SWNTs. Immobilization of cytochromes to nanotubes is obtained via covalent bonding between the exposed protein thiols and maleimide-terminated functional chains attached to the carbon nanotubes. A single-molecule study performed by combining scanning probe nanoscopies ascertains that the protein topological properties are preserved upon binding and provides unprecedented current images of single proteins bound to carbon nanotubes that allow a detailed IVcharacterization. Collectively, the results point out that the use as linkers of suitably functionalized metallic SWNTs results in an electrical communication between redox proteins and gold electrodes more efficient and reproducible than for proteins directly connected with metal surfaces. - Advanced Functional Materials, 2011, 1, 153–157.

Ball Milling modification of Single-Wall Carbon Nanotubes: purification, cutting and functionalization

N. Rubio, C. Fabbro, M. A. Herrero, A. de la Hoz, M. Meneghetti, J. L. G. Fierro, M. Prato, E. Vázquez. Single-walled carbon nanotubes (SWNTs) can be successfully cut with relatively homogeneous sizes using a planetary mill. The optimized conditions produce highly dispersible SWNTs that can be efficiently functionalized in a variety of synthetic ways. As clearly shown by Raman spectroscopy, the milling/cutting procedure compares very favorably with the most common way of purifying SWNTs, namely, treatment with strong oxidizing acids. Moreover a similar milling process can be used to functionalize and cut pristine SWNTs by one-step nitrene chemistry.- Small, 2011, 7, 665-674.

Influence of Polarity on the Scalability and Reproducibility of Solvent-Free Microwave-Assisted Reactions

Ángel Diaz-Ortiz, Antonio de la Hoz, Jesus R. Alcazar,  Jose; A. Carrillo, Maria Herrero, Alberto Fontana,  Juan de M. Munoz, Pilar Prieto, Abel de Cozar. Organic reactions performed in the absence of solvent in domestic ovens without appropriate temperature control are generally considered as not reproducible, particularly when different instruments are used. For this reason, reproducibility has historically been one of the major issues associated with Microwave-Assisted Organic Synthesis (MAOS) especially when domestic ovens are involved. The lack of reproducibility limits the general applicability and the scale up of these reactions. In this work several solvent-free reactions previously carried out in domestic ovens have been translated into a single-mode microwave reactor and then scaled up in a multimode oven. The results show that most of these reactions, although not considered as reproducible, can be easily updated and applied in microwave reactors using temperature-controlled conditions. Furthermore, computational calculations can assist to explain and/or predict whether a reaction will be reproducible or not. -

Combinatorial Chemistry & High Throughput Screening, 2011, 14, 2, 109-116.

Study of the Proteolytic and Lipolytic Processes in Manchego Cheese by NMR.

M. Moreno, A. Moreno, M. V. Gómez, J. M. Poveda, L. Cabezas.

Magnetic Resonance in Food Science: An Exciting Future. 2011, 52, 54-59. RSC.

Quality Markers of Red Wines from Spanish Region of Castilla-La Mancha Using Nuclear Magnetic Resonance.

A. Moreno, L. F. Labrador, M. Moreno, M. S. Pérez, M. A. González, E. M. Sánchez-Palomo, J. M. Lemus.

Magnetic Resonance in Food Science: An Exciting Future. 2011, 52, 60-67. RSC.

Comparative Study of the Thermal and Microwave Oxidation in Olive Oil. 31p-Nmr Quantitative Determination Of 1,2 And 1,3-Diglycerides And Other Minor Compounds.

C. Lucas-Torres, M. Moreno, A. Juan, A. de la Hoz, A. Moreno.

Magnetic Resonance in Food Science: An Exciting Future. 2011, 52, 100-104. RSC.

Rapid Quantitative Determination by 13C-NMR of the Composition of Acetylglycerol Mixtures as Byproduct in Biodiesel Synthesis.

A. Casas, C. Lucas-Torres. A. Moreno, A. Pérez, M. J. Ramos, A. Simón.

Fuel, 2012, 92, 180-186

Synthesis and Characterization of Metallodendritic Palladium-Biscarbene Complexes Derived from 1,1'-Methylenebis(1,2,4-triazole).

Valentín Hornillos, Javier Guerra, Abel de Cózar, Pilar Prieto, Sonia Merino, Miguel A. Maestro, Enrique Díez-Barra and Juan Tejeda. The syntheses of first generation dendritic compounds bearing 1,1′-alkane-1,1-diylbis(4-butyl-4,5-dihydro-1H-1,2,4-triazol-5-ylidene)palladium(II) dibromide on the periphery are described. The metallabiscarbene moieties have also been studied separately from the dendrimer. These compounds display a non-symmetric boat-to-boat conformational equilibrium that has axial and equatorial arrangements. The predominance of the axial conformer in the equilibrium is supported by DFT calculations. The X-ray solid state structures of axial conformers of 3-hydroxy- and 3-mesyloxy-1,1′-propane-1,1-diylbis(4-butyl-4,5-dihydro-1H-1,2,4-triazol-5-ylidene)palladium(II) dibromide are reported. These complexes display modest catalytic activity in the Heck reaction with activated aryl bromides and the dendritic catalysts were more active than the corresponding non-dendritic mononuclear species, a finding indicative of a cooperative effect.

Dalton Trans., 2011, 40, 4095-4103

Reproducibility and Scalability of Microwave Assisted Reactions: From Domestic ovens to Continuous Flow Systems.

J. Alcázar, A. de Cózar, A. de la Hoz, A. Díaz-Ortiz, J. R. Carrillo, M. A. Herrero, J. M. Muñoz, P. Prieto.

Microwave Heating ISBN 978-953-307-325-5. InTech. 2011, 137-162.

Substitution Reactions in Green Chemistry.

A. de la Hoz, A. Díaz-Ortiz. Handbook of Green Chemistry. Oxford University Press. in press.

Application of Flow Chemistry to the Reduction of Nitriles to Aldehydes.

J. de Mata Muñoz, J. Alcázar, A. Diaz-Ortiz; A. de la Hoz.

Reduction of nitriles to aldehydes with diisobutylaluminium hydride (DIBAL-H) is an important transformation in organic chemistry. But the use of this reaction is limited for the lack of reproducibility due to the instability of the intermediates formed. In the current article we disclose the improvement of the reaction applying continuous flow technology.

Tetrahedron Lett., 2011, 52, 6058-6060

Few-layer graphenes using melamine and ball milling processing.

V.  León, M. Quintana, M. A. Herrero, J. L. G. Fierro, A. de la Hoz, M. Prato, E. Vázquez.

We report a simple, practical scalable procedure to produce few-layer graphene sheets using ball-milling. Commercially available melamine can be efficiently used to exfoliate graphite and generate concentrated water or DMF dispersions. Chem. Commun., 2011, 47, 10936-10938

Electrochemical synthesis and spectroelectrochemical characterization of triazole/thiophene conjugated polymers

F. Montilla,  F. Huerta, D. Salinas-Torres, E. Morallón, C. Cebrián, P. Prieto, Á. Díaz-Ortiz, A. de la Hoz, J.R. Carrillo, C. Romero. 

Novel electropolymerizable monomers based on triazole–thiophene units were characterized by both spectroscopic and electrochemical methods. It was found that those monomers which were enriched with additional thiophene units in their chemical structure showed red-shifted electronic transitions and lower oxidation potentials when compared with the short-chain disubstituted triazole monomer. The monomers studied were electropolymerized in organic medium giving rise to their corresponding electroactive polymers. These materials can be p-doped at potentials values which can be properly correlated with the thiophene conjugation length of the parent precursor. As a general rule, it was observed that the longer the conjugation length, the lower the HOMO level. Only the alternating bisthiophene–triazole polymer, poly-TTT, can be both p- and n-doped within the electrochemical window of the solvent employed. The doping processes are characterized by the formation of charge traps that avoid the reversible recovery of the injected charge. In addition, polaronic species formed upon electrochemical doping seem to be at the origin of the electronic transition bands observed for all the materials in the visible low-frequency to near-infrared optical range.

Electrochim. Acta. 2011, 58, 215-222.

Charge Transfer Events in Semiconducting Single-Wall Carbon Nanotubes

C. Oelsner, M. A. Herrero, C. Ehli, M. Prato, D.M. Guldi

Electron-donating ferrocene units have been attached to SWNTs, with different degrees of functionalization. By means of a complementary series of novel spectroscopic techniques (i.e., steady-state and time-resolved), we have documented that mutual interactions between semiconducting SWNT and the covalently attached electron donor (i.e., ferrocene) lead, in the event of photoexcitation, to the formation of radical ion pairs. In the accordingly formed radical ion pairs, oxidation of ferrocene and reduction of SWNT were confirmed by spectroelectrochemistry. It is, however, shown that only a few semiconducting SWNTs [i.e., (9,4), (8,6), (8,7), and (9,7)] are susceptible to photoinduced electron transfer processes. These results are of relevant importance for the development of SWNT-based photovoltaics.

J. Am. Chem. Soc. 2011, 133, 18696–18706

Functional motor recovery from brain ischemic insult by carbon nanotube-mediated siRNA silencing

K.T. Al-Jamal, L. Gherardini, G. Bardi, A. Nunes, C. Guo, C. Bussy, M.A. Herrero, A. Bianco, M. Prato, K. Kostarelos, T. Pizzorusso

Stroke is the second cause of death worldwide with ischemic stroke accounting for 80% of all stroke insults. Caspase-3 activation contributes to brain tissue loss and downstream biochemical events that lead to programmed cell death after traumatic brain injury. Alleviation of symptoms following ischemic neuronal injury can be potentially achieved by either genetic disruption or pharmacological inhibition of caspases. Here, we studied whether silencing of Caspase-3 using carbon nanotube-mediated in vivo RNA interference (RNAi) could offer a therapeutic opportunity against stroke. Effective delivery of siRNA directly to the CNS has been shown to normalize phenotypes in animal models of several neurological diseases. It is shown here that peri-lesional stereotactic administration of a Caspase-3 siRNA (siCas 3) delivered by functionalized carbon nanotubes (f-CNT) reduced neurodegeneration and promoted functional preservation before and after focal ischemic damage of the rodent motor cortex using an endothelin-1 induced stroke model. These observations illustrate the opportunity offered by carbon nanotube-mediated siRNA delivery and gene silencing of neuronal tissue applicable to a variety of different neuropathological conditions where intervention at well localized brain foci may offer therapeutic and functional benefits.

Proc. Natl. Acad. Sci. U. S. A. 2011, 108, 10952-10957

 

2010

 

Microwave-Assisted Stille Reactions as a Powerful Tool for Building Polyheteroaryl Systems Bearing a (1H)-1,2,4-Triazole Moiety

C Cebrián, Ad Cózar, P Prieto, A Díaz-Ortiz, Adl Hoz, JR Carrillo, AM Rodriguez, F Montilla.

Stille couplings and the combination of Stille/Heck cross-coupling reactions provide useful access to tricyclic systems with valuable mate rial properties from 3,5-dibromo-1,2,4-triazoles. The reactions can all be dramatically improved under microwave irradiation - Synlett (2010) pp. 55-60

Computational calculations in microwave-assisted organic synthesis (MAOS). Application to cycloaddition reactions

A De Cózar, M. C Millán, C Cebrián, P Prieto, A Díaz-Ortiz, A De La Hoz, F. P Cossío.

Computational calculations represent a very useful tool to study separately the occurrence of thermal and non-thermal effects of microwave irradiation through the determination of the thermodynamic and kinetic parameters of the reaction. In this paper, we approach the computational study of two previously reported cycloaddition reactions. All of the outcomes indicate the presence of a thermal effect alone for the microwave irradiation that produces changes in the regioselectivity or in the reaction mechanism. - Org. Biomol. Chem. (2010) vol. 8 (1000) pp. 1009

On-line monitoring of a microwave-assisted chemical reaction by nanoliter NMR-spectroscopy

M Gomez, Hein Verputten, Angel Diaz-Ortiz, Andres Moreno, Antonio de la Hoz, Aldrik Velders. The authors report the use of a nanoliter NMR spectroscopy microfluidic chip hyphenated to a continuous-flow microliter-microwave irradn. set-up, for online monitoring and rapid optimization of reaction conditions. - Chem. Commun.  (2010) vol. 46 (25) pp. 4514-4516

Microwave-assisted synthesis of pyrazolyl bistriazines

Monica Moral, Amparo Ruiz, Andres Moreno, Angel Diaz-Ortiz, Isabel Lopez-Solera, Antonio de la Hoz, Ana Sanchez-Migallon. Reaction of 6-chloro-N,N'-bispyrazolyl-[1,3,5]triazine-2,4-diamines with 4-aminobenzylamine under microwave irradn. produces bistriazines in excellent yields.  The use of a diamine bearing amino groups with different reactivities allowed the reaction to be carried out in two steps and selectively gave monotriazines, bistriazines with identical substituents and differently substituted bistriazines.  The structures of these new compds. have been studied by NMR spectroscopy, mass spectrometry and in one case by X-ray crystallogrphy.  These new bistriazines have promising applications in supramol. chem. based on hydrogen bonds and/or complexation with metals.  The presence of a rigid linker can be used for the efficient prepn. of extended supramol. polymers with interesting fluorescence properties by complexation with cyanuric and barbituric acid derivs. - Tetrahedron (2010) vol. 66 (1) pp. 121-127

Gold Dendrimer Encapsulated Nanoparticles as Labeling Agents for Multiwalled Carbon Nanotubes

M Herrero, Javier Guerra, V Myers, M Gómez, Richard Crooks, Maurizio Prato.

In this paper, we report the functionalization of the surface of multiwalled carbon nanotubes (MWNTs) with Au dendrimer encapsulated nanoparticles (DENs). The results show that, when pristine MWNTs having hydrophobic surfaces are exposed to DENs, the dendrimers aggregate on the MWNT surface. However, when the MWNTs are oxidized in acid prior to exposure to DENs, well-dispersed submonolayer coverages of Au nanoparticles are observed on the MWNT surface. This suggests that acid-induced debundling of the nanotubes is an essential prerequisite for attachment of nearly monodisperse DENs. Electron microscopy and NMR spectroscopy confirm that the structures of the DENs and dendrimers are retained after immobilization on the surface of acid-functionalized MWNTs. - ACS Nano (2010) vol. 4 (2) pp. 905-912

Versatile microwave-induced reactions for the multiple functionalization of carbon nanotubes

Noelia Rubio, M Herrero, Antonio de la Hoz, Moreno Meneghetti, Maurizio Prato, Ester Vazquez. Carbon nanotubes (CNTs) have been readily functionalized by microwave activation using two different reactions affording functional derivs. characterized by two orthogonally protected amino groups.  The doubly functionalized CNTs can serve as multipurpose, versatile synthons in materials science and biol. applications. - Org. Biomol. Chem. (2010) vol. 8 (8) pp. 1936-1942

Synthesis and Characterization of a Carbon Nanotube−Dendron Series for Efficient siRNA Delivery

M Herrero, Francesca Toma, Khuloud Al-Jamal, Kostas Kostarelos, Alberto Bianco, Tatiana Da Ros, Fouzia Bano, Loredana Casalis, Giacinto Scoles, Maurizio Prato.

Corrections - J. Am. Chem. Soc. (2010) vol. 132 (5) pp. 1731-1731

Hybrid materials based on Pd nanoparticles on carbon nanostructures for environmentally benign C-C coupling chemistry

Javier Guerra, Maria Herrero. The combination of different nanomaterials such as metallic nanoparticles and carbon nanostructures in a new hybrid material should give rise to interesting properties that combine the advantages of each of the nanocomponents. This review highlights the latest advances in the synthetic design of these hybrid materials where carbon nanostructures act as supports as well as stabilizing agents for very reactive metallic nanoparticles. The striking applications of Pd nanoparticles anchored on the surface of carbon nanostructures in C–C coupling chemistry are analyzed. Special emphasis is placed on the stability of these materials, which is linked to their recyclability. Numerous examples are given that involve the use of these catalysts in Heck, Suzuki and Sonogashira coupling reactions. - Nanoscale (2010) vol. 2 (8) pp. 1390-1400

Synthesis and Spectroscopic Properties of Porphyrin Derivatives of C60

M Prato C Soombara E Vazquez J Niziol E Gondekc I Raud F Kajzarde. Chemical synthesis of two C60 fullerene derivatives: with porphyrin (C60-H2P) and of the iodide salt of Zn porphyrin (C60-ZnP)+I- is described. Both compounds are soluble in several organic solvents, with a larger solubility observed for C60-H2P. Thin films obtained by solution drawing or by spinning techniques from C60-H2P solution in organic solvents or dissolved in a polymer matrix show a peculiar granular structure with regular submicron size particles. Their size of is a little smaller in polymer matrix. The solution UV-Vis absorption spectra exhibit typical bands which can be attributed to porphyrin and to the fullerene. A solvatochromic effect is observed in C60-H2P which shows a nonzero first hyperpolarizability β, most likely due to the charge transfer between fullerene and porphyrin. - Mol. Crys. Liq. Crys. (2010) vol. 521 pp. 253-264

Functionalization of carbon nanotubes for applications in materials science and nanomedicine

Ester Vázquez, Maurizio Prato. Carbon nanotubes (CNTs) can be functionalized using a variety of efficient protocols. Especially, esterification and amidation reactions are exploited along with 1,3-dipolar cycloadditions. The use of microwaves (MWs) to activate the reactivity of CNTs is also reported. Innovative NMR methodologies can be introduced to investigate the covalent attachment of organic moieties to CNTs. - Pure Appl. Chem. (2010) vol. 82 (4) pp. 853-861

Photoluminescence and Electro-Optic Kerr Effect in Porphyrin Derivatives of C60

J Niziol, M Prato, C Soombar, E Vazquez, E Gondek, I Rau, F Kajzar. Photoluminescence and electro-optical properties of two C60 fullerene derivatives: with porphyrin (C60) and of an iodide salt of Zn porphyrin (C60-ZnP) are reported. Both studies were done in solution. In the case of the (C60) the photoluminescence spectra depend strongly on the solvent used and emission from B band is quenched in dioxane. For the idodide salt [C60-ZnP] both emissions from B and Q bands are observed. In all studied cases the photoluminescence at 650 nm is present, however it is excited in the iodide salt only for certain excitation energies. The EO Kerr effect measurements show a very slow rotation of molecules under the applied electric field. This rotation is more complex in the case of the iodide salt. - Molecular Crystals and Liquid Crystals (2010) vol. 522 pp. 191-202

Enhanced cellular internalization and gene silencing with a series of cationic dendron-multiwalled carbon nanotube:siRNA complexes

K. T Al-Jamal, F. M Toma, A Yilmazer, H Ali-Boucetta, A Nunes, M.-A Herrero, B Tian, A Eddaoui, W. T Al-Jamal, A Bianco, M Prato, K Kostarelo.

One of the major obstacles to the clinical development of gene silencing by small interfering RNA (siRNA) is its effective cytoplasmic delivery. Carbon nanotubes have been proposed as novel nanomaterials that can offer significant advantages for the intracellular delivery of nucleic acids, such as siRNA. We recently demonstrated in a proof-of-principle study that amino-functionalized multiwalled carbon nanotubes (f-MWNT) can effectively deliver in vivo an siRNA sequence, triggering cell apoptosis that results in human lung xenograft eradication and prolonged survival. In the present study, we demonstrate how a newly synthesized series of polycationic dendron-MWNT constructs with a precisely tailored number of amino functions (dendron generations) can complex and effectively deliver double-stranded siRNA to achieve gene silencing in vitro. A systematic comparison between the f-MWNT series in terms of cellular uptake, cytotoxicity, and siRNA complexation is offered. Significant improvement in siRNA delivery with the dendron-MWNT conjugates is shown, and gene silencing was obtained in 2 human cell lines using 2 different siRNA sequences. The study reveals that through f-MWNT structure-biological function analysis novel nanotube-based siRNA transfer vectors can be designed with minimal cytotoxicity and effective delivery and gene-silencing capabilities.—Al-Jamal, K. T., Toma, F. M., Yilmazer, A., Ali-Boucetta, H., Nunes, A., Herrero, M.-A., Tian, B., Eddaoui, A., Al-Jamal, W. T., Bianco, A., Prato, M., Kostarelos, K. Enhanced cellular internalization and gene silencing with a series of cationic dendron-multiwalled carbon nanotube:siRNA complexes. - The FASEB Journal (2010) vol. 24 (11) pp. 4354-4365

Synergy between microwave irradiation and heterogeneous catalysis in an environmentally friendly self-condensation of hydroxybenzene derivatives

M Gomez, Andres Moreno, Ester Vazquez, Antonio de la Hoz, Ana Aranda, Angel Diaz-Ortiz. Self-condensation of 1,3,5-trihydroxybenzene and 3,5-dimethoxyphenol using solid acid catalysts and microwave irradn. produces polyhydroxy-substituted biphenyls I (R = OH, MeO) in moderate to good yields.  Condensation of 1,3,5-trihydroxybenzene with p-benzoquinone gives 2,2'-dihydroxybiphenyls, e.g. II, in good yields.  These reactions do not occur or afford only traces of the desired products when classical heating is used. [on SciFinder(R)] - ARKIVOC (Gainesville, FL, U. S.) (2010) (3) pp. 264-273

Straightforward Generation of Helical Chirality Driven by a Versatile Heteroscorpionate Ligand: Self-Assembly of a Metal Helicate by Using CH-π Interactions

Antonio Otero, Agustín Lara-Sánchez, Juan Fernández-Baeza, Carlos Alonso-Moreno, Juan Tejeda, José A Castro-Osma, Isabel Márquez-Segovia, Luis F Sánchez-Barba, Ana M Rodríguez, M. Victoria Gómez. The synthesis of novel architectures, through the use of versatile heteroscorpionate ligands, was developed that allows helical chirality in aluminium complexes. - Chem. Eur. J. (2010) vol. 16 (29) pp. 8615-8619.

 

2009

 

Los estudios de posgrado en química sostenible en España

Antonio de la Hoz, Educación Química, 2009, 405-411

Flavonol 3-O-Glycosides Series of Vitis vinifera Cv. Petit Verdot Red Wine Grapes

Noelia Castillo-Muñoz, Sergio Gómez-Alonso, Esteban García-Romero, M Gómez, Aldrik Velders, Isidro Hermosín-Gutiérrez. To gain knowledge of the characteristic flavonol 3-O-glycosides of red grape Vitis vinifera varieties, we isolated the flavonol fraction from V. vinifera cv. Petit Verdot grape skins by solid-phase extraction using a combination of reverse-phase and ion-exchanging materials. This procedure allowed us to separate a fraction of anthocyanin-free flavonol 3-O-glycosides that was further split into neutral and acidic subfractions, thus facilitating flavonol identification. By means of semipreparative reverse-phase high-performance liquid chromatography, we isolated several of these flavonol 3-O-glycosides for structural elucidation. The identification of different flavonol 3-O-glycosides was based on liquid chromatography−diode array detection−electrospray ionization−tandem mass spectrometry and NMR data when available. The results suggest that red grape flavonol 3-O-glycosides comprise three different complete series, according to the nature of the sugar moiety linked to the C-3 position. The 3-O-glucosides were the main derivative of the six possible flavonol aglycones (kaempferol, quercetin, isorhamnetin, myricetin, laricitrin, and syringetin), whereas the 3-O-galactoside derivatives were found as minor compounds for all of the flavonol aglycones. The 3-O-glucuronides are the third kind of red grape flavonol derivatives and normally account as minor compounds for all of the flavonol aglycones, with the exception of quercetin 3-O-glucuronide, which was as abundant as quercetin 3-O-glucoside. In addition, the presence of quercetin 3-O-(6′′-rhamnosyl)-glucoside (rutin) was also detected as a trace compound in the skins of Petit Verdot grapes. - Journal of Agricultural and Food Chemistry (2009) vol. 57 (1) pp. 209-219

NMR Characterization of Fourth-Generation PAMAM Dendrimers in the Presence and Absence of Palladium Dendrimer-Encapsulated Nanoparticles

M. Victoria Gomez, Javier Guerra, Aldrik H Velders, Richard M Crooks. High-resolution solution NMR spectroscopy has been used to characterize the structure of Pd dendrimer-encapsulated nanoparticles (DENs), consisting of approximately 55-atom nanoparticles encapsulated within fourth-generation, hydroxyl-terminated poly(amidoamine) PAMAM dendrimers (G4-OH). Detailed analysis of 1D and 2D NMR spectra of dendrimers with (G4-OH(Pd55)) and without (G4-OH) nanoparticles unambiguously demonstrate that single nanoparticles are encapsulated within individual dendrimers. This conclusion is based on the following results. First, the NMR data show that signals arising from the innermost methylenes of G4-OH(Pd55) are more highly influenced by the presence of the Pd nanoparticles than are the terminal functional groups. This means that DENs are encapsulated within dendrimers rather than being adsorbed to their surface, as would be the case for aggregates consisting of multiple dendrimers and nanoparticles. Second, extraction of DENs from within their dendrimer hosts results in an increase in the NMR intensity associated with the interior methylenes, which corroborates the previous point. Third, NMR pulse-field gradient spin−echo experiments demonstrate that G4-OH and G4-OH(Pd55) have identical hydrodynamic radii, and this finding excludes the presence of dendrimer/nanoparticle aggregates.J. Am. Chem. Soc. (2009) vol. 131 (1) pp. 341-350

Nanoparticle Size Determination by 1H NMR Spectroscopy

M Gomez, Javier Guerra, V Myers, Richard Crooks, Aldrik Velders. High-resolution solution 1H NMR spectroscopy has been used to characterize the size of Pd dendrimer-encapsulated nanoparticles (DENs). The Pd nanoparticles measured by this technique contain 55, 147, 200, or 250 atoms, and they are encapsulated within sixth-generation, hydroxyl-terminated poly(amidoamine) PAMAM dendrimers (G6-OH). Detailed analysis of the NMR data shows that signals arising from the innermost protons of G6-OH(Pdn) decrease significantly as the size of the encapsulated nanoparticles increase. A mathematical correlation between this decrease in the integral value and the theoretical number of Pd atoms in the nanoparticle is extracted. It enables the elucidation of the size of Pd DENs by 1H NMR spectroscopy. NMR pulse-field gradient spin−echo experiments demonstrate that G6-OH with and without DENs have identical hydrodynamic radii, which excludes the presence of dendrimer/nanoparticle aggregates. - J. Am. Chem. Soc. (2009)

Antitumor Activity and Prolonged Survival by Carbon-Nanotube-Mediated Therapeutic siRNA Silencing in a Human Lung Xenograft Model

Jennifer Podesta, Khuloud Al-Jamal, M Herrero, Bowen Tian, Hanene Ali-Boucetta, Vikas Hegde, Alberto Bianco, Maurizio Prato, Kostas Kostarelos. Carbon nanotubes are novel nanomaterials that are thought to offer potential benefits to a variety of biomedical and clinical applications. In this study, the treatment of a human lung carcinoma model in vivo using siRNA sequences leading to cytotoxicity and cell death is carried out using either cationic liposomes (DOTAP:cholesterol) or amino-functionalized multi-walled carbon nanotubes (${\rm MWNT - NH}_3^ +$). Validation for the most cytotoxic siRNA sequence using a panel of human carcinoma and murine cells reveals that the proprietary siTOX sequence is human specific and can lead to significant cytotoxic activities delivered both by liposome or ${\rm MWNT - NH}_3^ +$ in vitro. A comparative study using both types of vector indicates that only ${\rm MWNT - NH}_3^ +$:siRNA complexes administered intratumorally can elicit delayed tumor growth and increased survival of xenograft-bearing animals. siTOX delivery via the cationic ${\rm MWNT - NH}_3^ +$ is biologically active in vivo by triggering an apoptotic cascade, leading to extensive necrosis of the human tumor mass. This suggests that carbon-nanotube-mediated delivery of siRNA by intratumoral administration leads to successful and statistically significant suppression of tumor volume, followed by a concomitant prolongation of survival of human lung tumor-bearing animals. The direct comparison between carbon nanotubes and liposomes demonstrates the potential advantages offered by carbon nanotubes for the intracellular delivery of therapeutic agents in vivo. The present work may act as the impetus for further studies to explore the therapeutic capacity of chemically functionalized carbon nanotubes to deliver siRNA directly into the cytoplasm of target cells and achieve effective therapeutic silencing in various disease indications where local delivery is feasible or desirable. - Small (2009) vol. 5 (10) pp. 1176-1185

Carbon Nanotubes and Microwaves: Interactions, Responses, and Applications

Ester Vázquez, Maurizio Prato. The interaction of microwaves with carbon nanotubes (CNTs) is an interesting topic for a variety of potential applications. Microwaves have been used for the purification of CNTs and for their chemical functionalization, providing a technique for simple, green, and large-scale protocols. In addition, the selective destruction of metallic CNTs under microwave irradiation could potentially result in a batch of semiconducting-only nanotubes. As an innovative application, the combination of microwaves with well-aligned CNTs could produce a new illumination technology. Moreover, the microwave absorbing properties of CNTs and their different behavior from typical organic compounds may open the door to the preparation of a wide range of new materials useful in many fields. A few examples of practical applications include electromagnetic interference for protecting the environment from radiation and microwave hyperthermia for cancer treatment as well as other medical therapies requiring precise heating of biological tissues. - ACS Nano (2009) vol. 3 (12) pp. 3819-3824

Efficient functionalization of carbon nanohorns via microwave irradiation

Noelia Rubio, M Herrero, Moreno Meneghetti, Angel Diaz-Ortiz, Mauro Schiavon, Maurizio Prato, Ester Vazquez. Multifunctionalization of carbon nanohorns (CNHs) is easily achieved by microwave activation. We describe an efficient strategy to produce multifunctionalized CNHs using a combination of two different addition reactions, the 1,3-dipolar cycloaddition of azomethine ylides, in solvent-free conditions, and the addition of diazonium salts in water, both a simple and fast microwave-induced method. The new CNH derivatives are soluble in common solvents as well as in water. The doubly functionalized CNHs may be valuable new tools for many interesting applications. - J. Mater. Chem. (2009) vol. 19 (25) pp. 4407-4413

Microwave-Controlled Preparation of Alkenyl-(1H)-1,2,4-triazoles: First Heck Reaction on a (1H)-1,2,4-Triazole Moiety

Angel Diaz-Ortiz, Pilar Prieto, Cozar de, Cristina Cebrian, Andres Moreno, Antonio de la Hoz. A new synthetic approach for the prepn. of alkenyl-1,2,4-triazole derivs., e.g., I based on microwave-induced C-C cross-coupling Heck reactions is described.  To the best of our knowledge, this is the first application of the Heck reaction to a dihalogenated 1,2,4-triazole.  This approach allows the introduction of a wide range of equiv. or different alkenyl substituents in the 5- and/or 3-positions, thus extending the possibilities for the prepn. of these valuable derivs.  A similar microwave-induced synthetic procedure has also been applied to the Heck reaction of 4-vinyl-1,2,3-triazoles. - Aust. J. Chem. (2009) vol. 62 (12) pp. 1600-1606

Synthesis and Characterization of a Carbon Nanotube−Dendron Series for Efficient siRNA Delivery

M Herrero, Francesca Toma, Khuloud Al-Jamal, Kostas Kostarelos, Alberto Bianco, Tatiana Da Ros, Fouzia Bano, Loredana Casalis, Giacinto Scoles, Maurizio Prato. A new series of dendron-functionalized multiwalled carbon nanotube (MWNT) derivatives, characterized by the presence of numerous positively charged tetraalkyl ammonium salts at the periphery of the dendron, has been synthesized. The positive charges on the MWNT surface, coupled with the unique ability of carbon nanotubes (CNTs) to penetrate cell membranes, make the new derivatives potentially ideal vectors for siRNA delivery. Using a fluorescently labeled, noncoding siRNA sequence, we demonstrate that cytoplasmic delivery of the nucleic acid is remarkably increased throughout the different dendron generations. The work reported here highlights the fact that dendron-functionalized CNTs can be rationally designed as efficient carriers of siRNA that can eventually lead to gene silencing. - J. Am. Chem. Soc. (2009) vol. 131 (28) pp. 9843-9848

Microwave-assisted reactions of nitroheterocycles with dienes. Diels-Alder and tandem hetero Diels-Alder/[3,3] sigmatropic shift

Gomez Victoria, Ana Aranda, Andres Moreno, Fernando Cossio, Cozar de, Angel Diaz-Ortiz, Antonio de la Hoz, Pilar Prieto. Diels-Alder cycloaddn. of 3-nitro-1-(p-toluenesulfonyl)indole (I) with dienes under microwave irradn. in solvent-free conditions gave carbazole derivs. after elimination of the nitro group and in situ aromatization.  While 3-nitro-1-(p-toluenesulfonyl)pyrrole afforded indole derivs., 4-nitro-1-(p-toluenesulfonyl)pyrazole with cyclohexadiene did not afford the expected cycloadduct but instead gave 1-cyclohexen-2-ylpyrazole.  This process occurred by hydrolysis of the 1-(p-toluenesulfonyl) group, protonation of the diene and nucleophilic addn. of the pyrazolate ion, as elucidated by computational studies.  Reaction of nitroindole I with cyclohexadiene afforded exclusively the endo stereoisomer II in a tandem hetero Diels-Alder/[3,3] sigmatropic shift, as detd. by computational calcns. - Tetrahedron (2009) vol. 65 (27) pp. 5328-5336

 

2008

 

Multiple hydrogen bonds in the self-assembly of aminotriazine and glutarimide. Decisive role of the triazine substituents

Blanca Manzano, Felix Jalon, M Soriano, Ana Rodriguez, Antonio de la Hoz, Ana Sanchez-Migallon. The self-assembly of 6-R-2,4-diamino-1,3,5-triazines (R = Ph, p-tolyl, piperidino) and glutarimide has given rise to three new complexes.  The triazine:glutarimide ratio depends on the R group (1:1 for Ph, 5, and p-tolyl, 6, and 2:1 for piperidino, 7).  In all cases, a triple hydrogen bond between the triazine and the imide is formed but the 3D structure is clearly different depending on R group.  In complexes 5 and 6, the triazine/glutarimide pairs interact through double hydrogen bonds of the type N-H···O/O···H-N to form dimers.  In the case of 5, each dimer interacts with another four situated in a different plane and a zigzag sheet is formed.  In 6, however, the dimers are almost parallel and planar sheets are thus obtained.  In the case of 7, zigzag sheets are also formed but these consist of triazine/glutarimide units bonded to triazine mols.  Weak interactions (weak hydrogen bonds, C-H···π contacts and hydrophobic contacts) on or between sheets are obsd.  Common trends concerning the 3D structures have been found in these derivs. as well as for other previously described examples.  Restricted rotation around the C-NH2 bond is obsd. at low temp. in soln. - Cryst. Growth Des. (2008) vol. 8 (5) pp. 1585-1594

Una orientación de la Química para el Siglo XXI

Antonio de la Hoz, Ángel Díaz-Ortiz. Química Sostenible. Mapfre Seguridad 2008, 110, 32-42

Anion-Dependent Self-Assembly of Silver(I) and Diaminotriazines to Coordination Polymers: Non-Covalent Bonds and Role Interchange between Silver and Hydrogen Bonds

Blanca Manzano, Felix Jalon, M Soriano, M Carrion, M Carranza, Kurt Mereiter, Ana Rodriguez, Antonio de la Hoz, Ana Sanchez-Migallon. New coordination polymers were obtained by the self-assembly of silver salts AgX (X = BF4, PF6, CF3SO3) and 2,4-diamino-6-R-1,3,5-triazines L (R = Ph and p-tolyl) AgLX (1-6).  A complex of different stoichiometry, [Ag3L2(H2O)(acetone)2](BF4)3, 7 (R = phenyl), also was synthesized.  The three-dimensional structures of five compds. were detd. by x-ray diffraction studies.  For the AgLX complexes, when X = BF4 and R = Ph or p-tolyl, chiral chains with alternating Ag and L are formed.  The chains are cross-linked by the counteranions in a three-dimensional fashion through hydrogen bonds and weak Ag···F interactions giving rise to a structure with solvent-filled channels.  Different and more compact structures were found when the counteranion is CF3SO3 (OTf).  When R = Ph, sheets are formed which consist of [Ag2(OTf)2L2] units with double triflate bridges and which contain columns of π-π stacked arenes.  Hydrogen bonds connect the sheets.  When AgOTf was used and R is p-tolyl, a different and unusual ladderlike structure was obtained in which the rungs are double asym. bridges consisting of the triflate groups bonded to Ag in κ2O,μ2-O and κ1O,μ2-O fashion.  The ladders are parallel to each other and are mutually linked by N-H···N hydrogen bonds to give a 3-dimensional architecture.  A very similar ladderlike structure was found for 7 but with a water mol. and a BF4- group acting as bridges.  The role played by the hydrogen bonds in complex 6 to form the 3-dimensional structure is played in 7 by [Ag(acetone)2] fragments.  The noncovalent interactions play an important role in the different solid-state 3-dimensional structures.  The behavior of the new derivs. in soln. also was analyzed.  A new species was detected at low temps., and this exhibits restricted rotation of the Ph ring. - Inorg. Chem. (Washington, DC, U. S.) (2008) vol. 47 (19) pp. 8957-8971

Photophysical, electrochemical, and mesomorphic properties of a liquid-crystalline [60]fullerene-peralkylated ferrocene dyad

S. Campidelli, David Scanu, Robert Deschenaux, Dragana Milic, Ester Vazquez, Maurizio Prato, Maurizio Carano, Massimo Marcaccio, Francesco Paolucci, G Rahman, Dirk Guldi. Two fullerenea-peralkylated ferrocene derivatives were synthesized: (1) a liquid-crystalline dyad (compound 1) was obtained by introduction of nonamethyl ferrocene into a liquid-crystalline fullerene derivative and (2) a reference compound (compound 2) was synthesized by attachment of nonamethyl ferrocene to a fulleropyrrolidine. The liquid-crystalline dyad displayed an enantiotropic smectic A phase from 57 to 155 A[degree]C. Oxidation and reduction processes were investigated by cyclic voltammetry, and were in agreement with the electrochemical characteristics of the redox-active units (peralkylated ferrocene, fullerene, dendrimer). Photoinduced electron transfer from ferrocene derivative to fullerene was identified. - J. Mater. Chem. (2008) vol. 18 (13) pp. 1504-1509

Dynamic Imaging of Functionalized Multi-Walled Carbon Nanotube Systemic Circulation and Urinary Excretion

L Lacerda, A Soundararajan, R Singh, G Pastorin, K. T Al-Jamal, J Turton, P Frederik, M. A Herrero, S Li, A Bao, D Emfietzoglou, S Mather, W. T Phillips, M Prato, A Bianco, B Goins, K Kostarelos. Intravenously administered multi-walled carbon nanotubes, functionalized with DTPA and radiolabeled with Indium-111, were dynamically tracked in vivo using a microSingle Photon Emission Tomography scanner. Imaging showed that nanotubes enter the systemic blood circulation and within 5 min begin to permeate through the renal glomerular filtration system into the bladder. Adv. Mater. (2008) vol. 20 (2) pp. 225-230

Synthesis of dendrimer–carbon nanotube conjugates

A García, M Herrero, S Frein, R Deschenaux, R Muñoz, I Bustero, F Toma, M Prato. We describe the coupling between Carbon Nanotubes (CNTs) and a second-generation cyanophenyl-based dendrimer. The goal of our work is the synthesis of highly functionalized CNTs without provoking damage to the conjugated π-system. One approach is the attachment of dendrimers with a high density of functional groups to the CNTs. These groups serve as anchor points for further reactions. With this aim, we have carried out a primary modification on CNTs by the use of 1,3 dipolar cycloaddition reaction. We have employed Single Wall Carbon Nanotubes (SWNTs) as well as Multi Wall Carbon Nanotubes (MWNTs) obtaining 238 μmol and 511 μmol of pyrrolidine groups per gram, respectively. The amount of amino groups introduced in the system was measured by the Kaiser test as well as thermogravimetric analyses. As a second step, dendrimer incorporation was performed by carbodiimide chemistry. Thermogravimetric Analysis, Raman Spectroscopy and Atomic Force Microscopy characterization techniques are reported for the characterization of the final CNT–dendrimer conjugate. The results show that the dendrimer has been attached covalently to the previously generated amine groups. Morphologically, the attached dendrimer with an estimated theoretical molecular length of 6.4 nm, generates a wrapping of 8 nm thick around the CNTs walls. (© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) - phys. stat. sol. (a) (2008) vol. 205 (6) pp. 1402-1407

Advances in the Covalent Functionlization of Carbon Nanotubes M.A. Herrrero, M. Prato, Molecular Crystals and Liquid Crystals, 483, 21-32, 2008

Tissue histology and physiology following intravenous administration of different types of functionalized multiwalled carbon nanotubes

Lara Lacerda, Hanene Ali-Boucetta, Maria Herrero, Giorgia Pastorin, Alberto Bianco, Maurizio Prato, Kostas Kostarelos. The present study addresses the short-term impact (first 24 h) of intravenous administration of various types of multiwalled nanotubes (MWNTs) on the physiology of healthy mice. - Nanomedicine (2008) vol. 3 (2) pp. 149-161

Carbon-Nanotube Shape and Individualization Critical for Renal Excretion

Lara Lacerda, Maria Herrero, Kerrie Venner, Alberto Bianco, Maurizio Prato, Kostas Kostarelos. Two fullerene–peralkylated ferrocene derivatives were synthesized: (1) a liquid-crystalline dyad (compound 1) was obtained by introduction of nonamethyl ferrocene into a liquid-crystalline fullerene derivative and (2) a reference compound (compound 2) was synthesized by attachment of nonamethyl ferrocene to a fulleropyrrolidine. The liquid-crystalline dyad displayed an enantiotropic smectic A phase from 57 to 155 °C. Oxidation and reduction processes were investigated by cyclic voltammetry, and were in agreement with the electrochemical characteristics of the redox-active units (peralkylated ferrocene, fullerene, dendrimer). Photoinduced electron transfer from ferrocene derivative to fullerene was identified. - Small (2008) vol. 4 (8) pp. 1130-1132

Nonthermal Microwave Effects Revisited: On the Importance of Internal Temperature Monitoring and Agitation in Microwave Chemistry

M Herrero, Jennifer Kremsner, C Kappe. The concept of nonthermal microwave effects has received considerable attention in recent years and is the subject of intense debate in the scientific community. Nonthermal microwave effects have been postulated to result from a direct stabilizing interaction of the electric field with specific (polar) molecules in the reaction medium that is not related to a macroscopic temperature effect. In order to probe the existence of nonthermal microwave effects, four synthetic transformations (Diels−Alder cycloaddition, alkylation of triphenylphosphine and 1,2,4-triazole, direct amide bond formation) were reevaluated under both microwave dielectric heating and conventional thermal heating. In all four cases, previous studies have claimed the existence of nonthermal microwave effects in these reactions. Experimentally, significant differences in conversion and/or product distribution comparing the conventionally and microwave-heated experiments performed at the same measured reaction temperature were found. The current reevaluation of these reactions was performed in a dedicated reactor setup that allowed accurate internal reaction temperature measurements using a multiple fiber-optic probe system. Using this technology, the importance of efficient stirring and internal temperature measurement in microwave-heated reactions was made evident. Inefficient agitation leads to temperature gradients within the reaction mixture due to field inhomogeneities in the microwave cavity. Using external infrared temperature sensors in some cases results in significant inaccuracies in the temperature measurement. Applying the fiber-optic probe temperature monitoring device, a critical reevaluation of all four reactions has provided no evidence for the existence of nonthermal microwave effects. Ensuring efficient agitation of the reaction mixture via magnetic stirring, no significant differences in terms of conversion and selectivity between experiments performed under microwave or oil bath conditions at the same internally measured reaction temperatures were experienced. The observed effects were purely thermal and not related to the microwave field. - The Journal of Organic Chemistry (2008) vol. 73 (1) pp. 36-47

Microwave-Induced Multiple Functionalization of Carbon Nanotubes

Fulvio Brunetti, M Herrero, Juan Muñoz, Angel Díaz-Ortiz, Jessica Alfonsi, Moreno Meneghetti, Maurizio Prato, Ester Vázquez. We describe a new synthetic strategy to produce multifunctionalized carbon nanotubes using a combination of two different addition reactions, the 1,3-dipolar cycloaddition of azomethine ylides and the addition of diazonium salts, both via a simple and fast microwave-induced method. The presence of multifunctionality on the SWNTs has been confirmed using the most useful techniques for the characterization of carbon nanotubes. The doubly functionalized SWNTs can be considered potentially useful for many interesting applications. - Journal of the American Chemical Society (2008) vol. 130 (25) pp. 8094-8100

Parasitosis and cancer Miguel Fernández Braña, Yolanda Martín-Cantalejo, Ana S. Migallón, Marina Morán The treatments of neoplastic and parasitary diseases present some common chemical and pharmacological profiles. In this paper, a comparative study between chemical structures of each therapeutic group that have similar functions is shown. The conclusion is that every new chemical with activity in any of these areas is a suitable candidate to be tested in the other one. Anales de la Real Academia Nacional de Farmacia, 2008, 74, 29-50

Supramolecular Interactions at the Picomole Level Studied by 19F NMR Spectroscopy in a Microfluidic Chip

M. Victoria Gómez, David N Reinhoudt, Aldrik H Velders.

19F NMR spectroscopy is performed on nanoliter volumes in a microfluidic chip equipped with a planar microcoil (see picture). The high resolution and sensitivity allow the detection of small chemical shift variations, which enables investigation of the supramolecular interaction between NaPF6 and α-cyclodextrin. - Small (2008) vol. 4 (9) pp. 1293-1295

Selectivity under microwave irradiation. Benzylation of 2-pyridone: an experimental and theoretical study

Antonio de la Hoz, Maria Prieto, Michel Rajzmann, Cozar de, Angel Diaz-Ortiz, Andres Moreno, Fernando Cossio. The reaction of 2-pyridone with benzyl bromide in the absence of base and under solvent-free conditions has been studied exptl. and by computational methods.  This reaction was one of the first reported examples in which modification of selectivity under microwave irradn. was obsd.  C- and/or N-alkylations were obtained depending on the benzyl halide and the heating system.  N-Alkylation through mechanism A (SN2 mechanism) is kinetically favored while C-alkylation through an SN1-type mechanism is thermodynamically favored and is obsd. under microwave irradn.  Two SN1-type mechanisms (mechanisms B and C) have been calcd., mechanism C being a kind of SNi.  The influence of the pyridone/benzyl bromide ratio was studied.  A second mol. of pyridone stabilizes the transition state and assists the leaving of the bromide ion.  The occurrence of C-alkylation under microwave irradn. is explained by the predominance of the thermodn. control in these conditions.  Under microwave irradn. N-alkylation through an SN1-type mechanism (mechanism C) can also occur.  The dependence of the outcome of N-alkylation on the benzyl bromide ratio has been explained by a shift in the mechanism from SN2 to SN1 under microwave irradn.  Computational calcns. have shown to be a useful tool for detn. of the origin of the selectivity under microwave irradn. - Tetrahedron (2008) vol. 64 (35) pp. 8169-8176

 

2007

 

Microwave-assisted synthesis of bipyrazolyls and pyrazolyl-substituted pyrimidines

Antonio de la Hoz, Angel Diaz, Jose Elguero, Agustin Jimenez, Andres Moreno, Amparo Ruiz, Ana Sanchez-Migallon. The prepn. of 1,4'-bipyrazolyls and 4-pyrazolylpyrimidines, e.g., I and II (X = O or S), by the reaction of 2-pyrazolyl-3-dimethylamino acrylate and acrylonitrile with double nucleophilic reagents such as hydrazines, urea and guanidine was described.  Reactions were performed under microwave irradn. in 5-60 min.  This could be a useful procedure for the prepn. of valuable compds. with applications in medicinal and coordination chem. - Tetrahedron (2007) vol. 63 (3) pp. 748-753

Diels-Alder Reaction of Triazoles with DMAD Catalyzed by Silica-Bound AlCl3

A Díaz-Ortiz, A De Cózar, P Prieto, A De La Hoz, A Moreno. Synfacts (2007) vol. 2007 (02) pp. 218

Reversible Microwave-Assisted Cycloaddition of Aziridines to Carbon Nanotubes

Fulvio Brunetti, M Herrero, Juan Muñoz, Silvia Giordani, Angel Díaz-Ortiz, Salvatore Filippone, Giorgio Ruaro, Moreno Meneghetti, Maurizio Prato, Ester Vázquez. We report a new approach that uses microwaves to rapidly functionalize carbon nanotubes by using 1,3-dipolar cycloaddition of aziridines, well-known precursors to azomethine ylides, in solvent-free conditions. The efficiency of our microwave-mediated protocol is confirmed by comparison to a similar protocol in classical conditions for the azomethine ylides in DMF. Under these latter conditions, the reaction proceeds in 5 days (against 1 h under microwave irradiation), and the functionalization degree is much lower, as confirmed by thermogravimetric analysis and Raman spectroscopy. With our procedure, we easily scale-up the reaction up to 250 mg of functionalized MWNT in 1 h. We also provide an indirect proof of the covalent sidewall functionalization of the tubes. - Journal of the American Chemical Society (2007) vol. 129 (47) pp. 14580-14581

M. V. Gomez, D. N. Reinhoudt, A. H. Velders, in Proceedings of Micro Total Analysis Systems, Vol. 1(Eds.: J.-L. Viovy, P. Tabeling, S. Descroix, L. Malaquin), Paris, 2007, pp. 506

Primary product distribution from the Cl-atom initiated atmospheric degradation of furan: Environmental implications

Florentina Villanueva, Ian Barnes, Esperanza Monedero, Sagrario Salgado, Mª Gómez, Pilar Martin. Furan is an aromatic hydrocarbon present in both urban and rural atmospheres, which is emitted mainly by biomass burning and the combustion of fossil fuel. Reaction of furan and Cl atoms may be important in areas where chlorine atom concentrations are potentially high such as marine and coastal regions or continental atmospheres where industrial activity emits molecular chlorine or photo-labile Cl-containing compounds. To assess the importance of this reaction and to investigate whether any unique chlorine-containing product is formed the products of the reaction of Cl atoms with furan have been determined under atmospheric conditions. For the study two different sampling/detection methods have been used: (1) Solid-Phase MicroExtraction, with subsequent analysis by thermal desorption, and gas chromatography with mass spectrometry or flame ionization detection (SPME/GC-MS/FID), and 2-“in situ” with long path fourier transform infrared spectroscopy (FTIR). The yields of primary reaction products in the absence of NO were: 5-chloro-2(5H)-furanone (64.5±10.7)%, E-butenedial (11±3)%, 5-hydroxy-2(5H)-furanone (2.4%) and Z-butenedial (1.6±0.5)%. Other products generated by secondary reactions were 2(3H)-furanone (2.8±1.9)%, HCl (21.1±3%) and CO. Maleic anhydride was detected with a yield of about 2%, however, this yield may be a combination of both primary and secondary reactions. All errors are ±2σ. The observed products confirm that addition of Cl atoms to the double bond of furan is the dominant reaction pathway. - Atmospheric Environment (2007) vol. 41 (38) pp. 8796-8810

Solvent-Free Thermal and Microwave-Assisted [3 + 2] Cycloadditions between Stabilized Azomethine Ylides and Nitrostyrenes. An Experimental and Theoretical Study

Ana Arrieta, Dorleta Otaegui, Aizpea Zubia, Fernando Cossio, Angel Diaz-Ortiz, Antonio de la Hoz, M Herrero, Pilar Prieto, Concepcion Foces-Foces, Jose Pizarro, Maria Arriortua. The stereochem. outcomes obsd. in the thermal and microwave-assisted [3 + 2] cycloaddn. between stabilized azomethine ylides and nitrostyrenes have been analyzed using exptl. and computational approaches.  It has been obsd. that, in the absence of solvent, three stereoisomers are formed, both under classical heating conditions and under microwave irradn.  This result contrasts with that obsd. in soln. under classical thermal conditions.  The 4-nitropyrrolidines obtained in this way can be aromatized under further microwave irradn. to yield mixts. of pyrroles and 4-nitropyrroles.  It is found that ground state cycloaddns. between imines and nitrostyrenes take place by three-step mechanisms.  The first step involves enolization of the starting imine, and this is followed by a pseudopericyclic 10-electron [1.4]-hydrogen shift.  Finally, the cycloaddn. takes place by a relatively asynchronous arom. six-electron supra-supra thermal mechanism. - J. Org. Chem. (2007) vol. 72 (12) pp. 4313-4322

Microwave-assisted reactions in heterocyclic compounds with applications in medicinal and supramolecular chemistry

Antonio de la Hoz, Angel Diaz-Ortiz, Andres Moreno, Ana Sanchez-Migallon, Pilar Prieto, Jose Carrillo, Ester Vazquez, Ma Gomez, Ma Herrero. A review.  Microwave irradn. was successfully applied in org. chem.  Spectacular accelerations, higher yields under milder reaction conditions and higher product purities were all reported.  Indeed, a no. of authors described success in reactions that do not occur under conventional heating and modifications in selectivity (chemo-, regio- and stereoselectivity) were even reported.  Recent advances in microwave-assisted combinatorial chem. include high-speed solid-phase and polymer-supported org. synthesis, rapid parallel synthesis of compd. libraries, and library generation by automated sequential microwave irradn.  In addn., new instrumentation for high-throughput microwave-assisted synthesis continues to be developed at a steady pace.  The impressive speed combined with the unmatched control over reaction parameters justifies the growing interest in this application of microwave heating.  In this review the authors highlighted their recent advances in this area, with a particular emphasis on cycloaddn. reactions of heterocyclic compds. both with and without supports, applications in supramol. chem. and the reproducibility and scalability of org. reactions involving the use of microwave irradn techniques. - Comb. Chem. High Throughput Screening (2007) vol. 10 (10) pp. 877-902

Editorial

Angel Diaz-Ortiz, Antonio de la Hoz. Comb. Chem. High Throughput Screening (2007) vol. 10 (9) pp. 733-734

Meet the guest editors

Angel Diaz-Ortiz, Antonio de la Hoz. Comb. Chem. High Throughput Screening (2007) vol. 10 (10) pp. 933

Review on non-thermal effects of microwave irradiation in organic synthesis Antonio de la Hoz, Angel Diaz-Ortiz, Andres Moreno. The aim of this review is to show the occurrence of non-thermal effects in organic synthesis.  The effect of microwave irradiation is a consequence of the interaction of radiation with matter and a combination of thermal and non-thermal effects.  Thermal effects are well-described and arise from the heating rate, sometimes non accessible by conventional heating, superheating, "hot spots" and the selective absorption of radiation by polar substances.  The existence of non-thermal effects of the highly polarized radiation is still a controversial topic, and one usually masked by thermal effects.  Separation and identification of thermal and non-thermal effects is a complex matter, but essential to the study of non-thermal effects.  Some predictive models have also been described. - J Microw Power Electromagn Energy (2007) vol. 41 (1) pp. 44-64

Green and chemoselective oxidation of sulfides with sodium perborate and sodium percarbonate: nucleophilic and electrophilic character of the oxidation system

M Gomez, Ruben Caballero, Ester Vazquez, Andres Moreno, Antonio de la Hoz, Angel Diaz-Ortiz. An efficient, chemoselective and environmentally friendly procedure for the oxidn. of sulfides is described.  Reactions are carried out using sodium perborate or sodium percarbonate as the oxidant, solvent-free conditions or water as the reaction medium and microwave irradn. or conventional heating as the energy source.  A comparative study concerning the effect of the oxidant and reaction conditions on yield and chemoselectivity (sulfoxide vs. sulfone) has been carried out.  In the solid phase, the nature of the solid support or catalyst has a more marked influence than the oxidant on the electrophilic and nucleophilic character of the oxidn. - Green Chem. (2007) vol. 9 (4) pp. 331-336

Reproducibility and scalability of solvent-free microwave-assisted reactions: from domestic ovens to controllable parallel applications

Angel Diaz-Ortiz, Antonio de la Hoz, Jesus Alcazar, Jose Carrillo, Maria Herrero, Alberto Fontana, Juan de Mata. The heating of different parallel arrays in domestic ovens offers the possibility to perform multiple reactions in one irradn. expt., blending the advantages of microwave heating technol. and parallel chem.  However, they are usually performed without an appropriate temp. control; thus, reproducibility becomes a major issue limiting the application of such reactions.  This is exemplified when working at a different scales or using different instruments.  For the first time a typical solvent-free reaction described in a domestic oven has been reproduced in a monomode reactor, scaled up in a controlled multimode oven and reproduced in parallel; 24 reactions were carried out in a well plate.  Parallel reactions were performed in a Weflon multiwell plate to assure identical conditions for each individual reaction.  As many reactions under microwave irradn. have been performed in solvent-free conditions, this result opens new possibilities in reproducibility, scalability and combinatorial chem. and permits to take advantage of many synthetic procedures described in domestic ovens. - Comb. Chem. High Throughput Screening (2007) vol. 10 (3) pp. 163-169

Microwave in High Throughput Synthesis (Part 1)

Antonio de la Hoz, Angel Diaz-Ortiz, Editors. Comb. Chem. High Throughput Screening, 10(9) (2007) pp. 68 pp.

 

2006

 

Microwave assisted synthesis and crystal structures of 2-imidazolines and imidazoles

Antonio de la Hoz, Angel Diaz-Ortiz, Maria Mateo, Monica Moral, Andres Moreno, Jose Elguero, Concepcion Foces-Foces, Matias Rodriguez, Ana Sanchez-Migallon. A series of 2-imidazolines and imidazoles has been synthesized using green synthetic methodologies.  The prepn. of 2-imidazolines was performed by cyclization of nitriles with ethylenediamine.  The use of microwave irradn. in solvent-free conditions enabled 2-imidazolines, e.g., I, to be obtained in high yields within short reaction times.  Aromatization of imidazolines was performed under microwave irradn. in toluene and using Magtrieve as the oxidant to give imidazoles, e.g., II, in good yields.  The X-ray structures for five of these derivs. are also provided.  In all cases, the mols. were assembled into chains through N-H···N hydrogen bonds. - Tetrahedron (2006) vol. 62 (25) pp. 5868-5874

Recyclable supported catalysts in microwave-assisted reactions: first Diels-Alder cycloaddition of a triazole ring

Angel Diaz-Ortiz, Cozar De, Pilar Prieto, Antonio de la Hoz, Andres Moreno. The authors describe here the first example in which a 1,2,3-triazole ring acts as a diene towards DMAD in microwave-assisted solvent-free Diels-Alder cycloaddns.  The extrusion of a mol. of a nitrile affords pyrazole derivs. as the products.  The yields can be markedly increased by using a recyclable supported Lewis acid catalyst, which can be reused at least five times without a decrease in the yield. - Tetrahedron Letters (2006) vol. 47 (49) pp. 8761-8764

Selectivity under the action of microwave irradiation Antonio de la Hoz, Angel Diaz-Ortiz, Andres Moreno. A review.  - Microwaves Org. Synth. (2nd Ed.) (2006) vol. 1 pp. 219-277

Microwave irradiation as an efficient tool for the generation of N-heterocyclic ortho-quinodimethanes: synthesis of polyheterocyclic compounds by Diels-Alder reactions

Angel Diaz-Ortiz, Maria Herrero, Antonio de la Hoz, Andres Moreno, Jose Carrillo. Microwave irradn. provides a general methodol. for the generation of ortho-quinodimethanes derived from 1,2,4-triazine, pyrazole, and 1,2,3-triazole.  The cycloaddn. reactions of such compds. with electron-deficient dienophiles allow the corresponding heteropolycyclic adducts to be obtained within 15 min in 51-87% yield. - Synlett (2006) (4) pp. 579-582

A dendritic fullerene-porphyrin dyad

Stephane Campidelli, Robert Deschenaux, Angela Swartz, G Rahman, Dirk Guldi, Dragana Milic, Ester Vazquez, Maurizio Prato.

We describe the synthesis, characterization and photophysical properties of a fullerene derivative whose structure includes a Zn-porphyrin and a second generation liquid-crystalline (LC) dendrimer. The size of the fullerene and porphyrin units with respect to the size of the LC dendrimer prevents the formation of liquid-crystalline phases. However, this system gives interesting photoinduced electron transfer phenomena. Compound  has been investigated by steady state and time resolved fluorescence as well as transient absorption spectroscopy in polar and apolar solvents. We demonstrate that the fluorescence of the porphyrin unit in  is quenched compared to the Zn-tetraphenylporphyrin used as reference. Femto- and picosecond transient absorption permit to identify the formation of a radical ion pair while nanosecond experiments allowed the determination of the charge recombination lifetimes. - Photochem. Photobiol. Sci. (2006) vol. 5 (12) pp. 1137-1141

Liquid-Crystalline Bisadducts of [60]Fullerene

Stéphane Campidelli, Ester Vázquez, Dragana Milic, Julie Lenoble, Carmen Atienza Castellanos, Ginka Sarova, Dirk Guldi, Robert Deschenaux, Maurizio Prato. A second-generation cyanobiphenyl-based dendrimer was used as a liquid-crystalline promoter to synthesize mesomorphic bisadducts of [60]fullerene. Liquid-crystalline trans-2,trans-3, and equatorial bisadducts were obtained by condensation of the liquid-crystalline promoter, which carries a carboxylic acid function, with the corresponding bisaminofullerene derivatives. A monoadduct of fullerene was also prepared for comparative purposes. All the compounds gave rise to smectic A phases. An additional mesophase, which could not be identified, was observed for the trans-2 derivative. The supramolecular organization of the monoadduct derivative is governed by steric constraints. Indeed, for efficient space filling, adequacy between the cross-sectional areas of fullerene (100 Å2) and of the mesogenic groups (22−25 Å2 per mesogenic group) is required. As a consequence, the monoadduct forms a bilayered smectic A phase. The supramolecular organization of the bisadducts is essentially governed by the nature and structure of the mesogenic groups and dendritic core. Therefore, the bisadducts form monolayered smectic A phases. The title compounds are promising supramolecular materials as they combine the self-organizing behavior of liquid crystals with the properties of fullerene. The Journal of Organic Chemistry (2006) vol. 71 (20) pp. 7603-7610