### Publications 2009

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