Publicaciones > Carmona et al

Dyes and Pigments. 2014 Apr 1; :106-117. doi: 10.1016/j.dyepig.2013.12.003

Cucurbit[n]urils as a potential fine-tuned instrument for modifying photophysical properties of D–π–A+–π–D “push–pull” chromophores.

Thais Carmona¹, Tatiana Cañeque², Raul Custodio², Ana M. Cuadro², Juan J Vaquero², Francisco Mendicuti¹

1. Departamento de Química Analítica, Química Física e Ingeniería Química, Universidad de Alcalá, 28871 Alcalá de Henares, Madrid, Spain.  2. Departamento de Química Orgánica y Química Inorgánica, Universidad de Alcalá, 28871 Alcalá de Henares, Madrid, Spain.

Abstract

Photophysical properties of supramolecular complexes between cucurbit[7]uril (CB[7]) and one- (1D, linear) and two-dimensional (2D, V-shaped) D–π–A+–π–D pyridinium (A+) based “push–pull” chromophores, were investigated by UV–Vis and fluorescence techniques, as well as Molecular Mechanics and Molecular Dynamics simulations. Both chromophores formed stable complexes with CB[7] of different stoichiometries. Complexation was accompanied by significant changes in the photophysical properties of the guests: (i) bathochromic shifts for the π–π* charge transfer absorption band, which is more evident for the 1D than for the V-shaped one, (ii) significant enhancement of the fluorescence intensity, (iii) displacement to the blue of the emission and (iv) change in their fluorescence lifetimes, which is more patent for the V-shaped one. 1D chromophore/CB[7] complex formation was both enthalpically and entropically favored, whereas inclusion of the V-shaped one, accompanied by a little positive enthalpy change, was entropically governed. Variation of fluorescence lifetime and fluorescence anisotropy upon complexation exhibited quite different behaviors. MM and MD calculations were performed to simulate the complexation processes in the presence of water, determine their preferred structures and establish the host:guest interactions responsible for the complexes formation which were preferentially electrostatics.

Publicaciones > Cañeque et al

Dyes and Pigments. 2014 Feb 1; :116-121. doi: 10.1016/j.dyepig.2013.09.031

Novel charged NLO chromophores based on quinolizinium acceptor units.

Tatiana Cañeque¹, Ana M. Cuadro¹, Julio Alvarez-Builla¹, Julio Alvarez-Builla², Javier Pérez-Moreno³, Koen Clays³, Obis Castaño⁴, José L. Andrés⁵, Juan J Vaquero¹

1. Departamento de Química Orgánica y Química Inorgánica, Universidad de Alcalá, 28871 Alcalá de Henares, Madrid, Spain.  2. Departamento de Química Orgánica y Química Inorgánica, Universidad de Alcalá, 28871, Alcalá de Henares, Madrid, Spain.  3. Department of Chemistry, University of Leuven, Celestijnenlaan 200 D, B-3001, Belgium.  4. Departamento de Química Analítica, Química Física e Ingeniería Química, Universidad de Alcalá, 28871 Alcalá de Henares, Madrid, Spain.  5. IES Matarraña, 44580 Valderrobres, Teruel, Spain.

Abstract

An azonia cation has been explored for the first time as an acceptor unit in charged π-donor π-acceptor chromophores. Initial experimental and theoretical data show that quinolizinium, the simplest heteroaromatic azonia cation, behaved as a good acceptor unit and conferred promising nonlinear optical properties to simple push–pull cationic chromophores.

Publicaciones > Coppola et al

Org Lett. 2013 Jul 5;15(13):3388-91. doi: 10.1021/ol401433x. PubMed 23795915

Remote aryl cyanation via isocyanide-cyanide rearrangement on tosylmethyl isocyanide derivatives.

Anna Coppola, Patricia Sanchez-Alonso, David Sucunza, Carolina Burgos, Ramon Alajarin, Julio Alvarez-Builla, Marta E G Mosquera, Juan J Vaquero

Departamento de Quimica Organica y Quimica Inorganica, Universidad de Alcala, 28871 - Alcala de Henares, Madrid, Spain.

Abstract

The reaction of alkyl tosylmethyl isocyanides and 2-bromobenzyl bromides in the presence of t-BuLi gives rise to a cascade reaction to give unexpected 2-substituted 2,3-dihydro-1H-indenimines which, upon treatment with t-BuOK, rearrange to 2-vinylbenzonitriles in high overall yields. This simple procedure represents a new approach to the synthesis of aromatic nitriles via isocyanide-cyanide interconversion.

Publicaciones > Ramirez et al

Org. Biomol. Chem. 2013; 11(41):7145 -7154. doi: 10.1039/c3ob41159a

Synthesis of charged bis-heteroaryl donor-acceptor (D-A+) NLO-phores coupling (π-deficient-π-excessive) heteroaromatic rings.

M.A. Ramirez^{1, 2, 3, 4}, R. Custodio, A.M. Cuadro, J. Alvarez-Builla, K. Clays, I. Asselberghs, F. Mendicuti, O. Castaño, J.L. Andrés, J.J. Vaquero

1. Departamento de Química Orgánica y Química Inorgánica, Universidad de Alcalá, 28871-Alcalá de Henares, Madrid, Spain.  2. Department of Chemistry, University of Leuven, Celestijnenlaan 200 D, 3001 Leuven, Belgium.  3. Departamento de Quimica Analitica, Quimica Fisica e Ingenieria Quimica, Universidad de Alcalá, 28871 Alcalá de Henares, Madrid, Spain.  4. IES Matarraña, 44580 Valderrobres, Teruel, Spain.

Resumen

Charged chromophores based on heteroaromatic cations were prepared by reaction of alkylazinium salts with N-heteroarylstannanes under Stille conditions. This approach provides easy access to potential single donor D-A+ chromophores in which the acceptor moiety A+ is the pyridinium cation and the donors are different π-excessive N-heterocycles. The β hyperpolarizabilities were measured in hyper-Rayleigh scattering experiments and the experimental data are supported by a theoretical analysis that combines a variety of computational procedures, including density functional theory and correlated Hartree-Fock-based methods. In some chromophores, the absence of a bridge between donor and acceptor fragments increases the NLO properties. © 2013 The Royal Society of Chemistry.

Publicaciones > G.-Deligeorgiev et al

Current Materials Science. 2013; 6(2):81 -119. doi: 10.2174/1874464811306020001

Fluorescent Dyes for Bio-Applications in the Patent LiteratureFluorescent Dyes for Bio-Applications in the Patent Literature

Todor G. Deligeorgiev, Aleksey A. Vasilev, Stefka S. Kaloyanova and Juan-Jose Vaquero

Palabras clave: Biosensors; covalently binding dyes; DNA binders; fluorescent dyes; intercalation; non-covalently binding dyes; protein fluorescent probes.

Resumen

For life science research the fluorescent probes are essential tools and their use is continually increasing due to their low cost and higher sensitivity comparing other methods, and the capability for quantitative determination of bioanalytes. In this article the recent patents related to fluorescent probes for detection of nucleic acids, protein detection, bio-imaging, covalent labeling of amino groups, thiol groups, fluorescent dyes for detection of cations in bio-objects and chemiluminescent dyes are reviewed. The dyes applied in new and promptly developing research fields as fluorescence image-guided surgery, fluorescence bio-sensors, fluorescnent nanoparticles are also described. The future trends in the fluorescence bio-labeling are also addressed.

Publicaciones > Sánchez et al

Bioorg. Med. Chem. 2013; 21(8):2370 -2378. doi: 10.1016/j.bmc.2013.01.067

Synthesis and evaluation of quinazoline derivatives as phosphodiesterase 7 inhibitors.

A.I. Sánchez¹, V. Martínez-Barrasa², C. Burgos³, J.J. Vaquero⁴, J. Alvarez-Builla, E. Terricabras, V. Segarra

1. Departamento de Quimica Orgánica, Universidad de Alcala, 28871 Alcalá de Henares, Madrid, Spain.  2. Almirall-Prodesfarma, Laureà Miró 408-410, 08980 Sant Felíu de Llobregat, Barcelona, Spain.  3. Centro Nacional de Referencia Sobre Contaminantes Orgánicos Persistentes (CNRCOP), Parque Científico Tecnológico, Universidad de Alcalá, C/Punto Net, 4, 28871 Alcalá de Henares, Madrid, Spain.  4. Pharma Mar S.A., Avda. De los Reyes, 1 Pol. Ind. La Mina-Norte, 28770 Colmenar Viejo, Madrid, Spain.

Resumen

The latest scientific findings concerning PDE7 and PDE4 inhibition suggest that selective small-molecule inhibitors of both enzymes could provide a novel approach to treat a variety of immunological diseases. In this context, we describe a new series of quinazoline derivatives from quinazolin-4-thiones which include a substituted biphenyl fragment. Some of these compounds show inhibitory potencies at sub-micromolar levels against the catalytic domain of PDE7. © 2013 Elsevier Ltd. All rights reserved.

Publicaciones > Moron et al

Chem. Commun. 2012 Jul 23;48:9171–9173. doi: 10.1039/c2cc34539k.

A cascade reaction of azolopyrimidines. Synthesis of unusual indole and azaindole derivatives.

María Morón¹, Carolina Burgos¹, Julio Alvarez-Builla¹, Antonio Salgado², Marta E. G. Mosquera^3, a, Juan J Vaquero^1, a

1. Departamento de Química Orgánica, Universidad de Alcalá, 28871-Alcalá de Henares, Madrid, Spain.  2. Department of Medicinal Chemistry, Centro Nacional de Investigaciones Oncológicas (CNIO), Melchor Fernández Almagro 3, E-28029-Madrid, Spain.  3. Departamento de Química Inorgánica Universidad de Alcalá, 28871-Alcalá de Henares, Madrid, Spain.

a. juanjose.vaquero@uah.es

Abstract

The reaction of bromo substituted pyrido[3',2':4,5]pyrrolo-[1,2-c]pyrimidine and pyrimido[1,6-a]indole methyl carboxylates with primary amines is described. The expected amide formation occurs but it is followed by an unexpected cascade process involving attack of the amine to the pyrimidine ring, opening of the pyrimidine ring, loss of the bromine substituent and competitive cyclizations to afford unusual imidazolidene substituted indoles and azaindoles.

Publicaciones > Ramírez et al

Org. Biomol. Chem. 2012; 10(8):1659 -1669. doi: 10.1039/c2ob06427h

Donor-(π-bridge)-azinium as D-π-A + one-dimensional and D-π-A +-π-D multidimensional V-shaped chromophores.

M.A. Ramírez^1, 2, 3, A.M. Cuadro, J. Alvarez-Builla, O. Castaño, J.L. Andrés, F. Mendicuti, K. Clays, I. Asselberghs, J.J. Vaquero

1. Departamento de Química Orgánica, Universidad de Alcalá, 28871, Alcalá de Henares Madrid, Spain.  2. Departamento de Química Física, Universidad de Alcalá, 28871, Alcalá de Henares Madrid, Spain.  3. Department of Chemistry, University of Leuven, Celestijnenlaan 200, D 3001, Leuven, Belgium.

Resumen

Heteroaromatic cations reacted with N-heteroarylacetylenes under Sonogashira conditions to allow easy access to potential single donor D-π-A + and V-shaped D-π-A +-π-D chromophores, where the acceptor moiety A is the π-deficient pyridinium cation and the donor moiety is represented by different π-excessive N-heterocycles. The β hyperpolarizabilities were measured using hyper-Rayleigh scattering experiments and the experimental data are supported by a theoretical analysis that combines a variety of computational procedures, including Density Functional Theory (DFT) and correlated Hartree-Fock-based methods (RCIS(D)). © 2012 The Royal Society of Chemistry.

Publicaciones > Belayev et al

Translational Stroke Research 2012; 3(1):154 -163. doi: 10.1007/s12975-011-0116-y

Superior Neuroprotective Efficacy of LAU-0901, a Novel Platelet-Activating Factor Antagonist, in Experimental Stroke.

Ludmila Belayev, Tiffany N. Eady, Larissa Khoutorova, Kristal D. Atkins, Andre Obenaus, Marta Cordoba, Juan J. Vaquero, Julio Alvarez-Builla, Nicolas G. Bazan

Resumen

Platelet-activating factor (PAF) accumulates during cerebral ischemia, and inhibition of this process plays a critical role in neuronal survival. Recently, we demonstrated that LAU-0901, a novel PAF receptor antagonist, is neuroprotective in experimental stroke. We used magnetic resonance imaging in conjunction with behavior and immunohistopathology to expand our understanding of this novel therapeutic approach. Sprague–Dawley rats received 2 h middle cerebral artery occlusion (MCAo) and were treated with LAU-0901 (60 mg/kg) or vehicle 2 h from MCAo onset. Behavioral function, T2-weighted imaging (T2WI), and apparent diffusion coefficients were performed on days 1, 3, and 7 after MCAo. Infarct volume and number of GFAP, ED-1, and NeuN-positive cells were conducted on day 7. Behavioral deficit was significantly improved by LAU-0901 treatment compared to vehicle on days 1, 3, and 7. Total lesion volumes computed from T2WI were significantly reduced by LAU-0901 on days 1, 3, and 7 (by 83%, 90%, and 96%, respectively), which was consistent with decreased edema formation. Histopathology revealed that LAU-0901 treatment resulted in significant reduction of cortical and subcortical infarct volumes, attenuated microglial infiltration, and promoted astrocytic and neuronal survival. These findings suggest LAU-0901 is a promising neuroprotectant and provide the basis for future therapeutics in patients suffering ischemic stroke.

Publicaciones > Suárez et al

Molecules. 2012; 17(8). doi: 10.3390/molecules17088735

Synthesis of 9,9′-[1,2-Ethanediylbis(oxymethylene)]bis-2-amino-1,9-dihydro-6H-purin-6-one, an Impurity of Acyclovir.

Rosa M. Suárez, Maria Paz Matía, José Luis Novella, Andres Molina, Antonio Cosme, Juan José Vaquero, Julio Alvarez-Builla

Palabras clave: nucleosides; acyclovir; drug impurities; phase transfer catalysis

Resumen

The synthesis of 9,9'-[1,2-ethanediylbis(oxymethylene)]bis-2-amino-1,9-dihydro-6H-purin-6-one, a minor impurity of acyclovir, is described. Starting with commercial N-(9-acetyl-6-oxo-1H-purin-2-yl)acetamide, the process uses an acid catalysed phase transfer catalysis (PTC) process to produce the selective alkylation at the 9 position of the guanine ring.