Category Archives: 2015

2015, BioImag, Publicación

Gutierrez et al. Chemistry. 2015;21(51):18758-63. Highly Fluorescent Green Fluorescent Protein Chromophore Analogues Made by Decorating the Imidazolone Ring.

Publications > Gutierrez et al

Chem. Eur. J. 2015, 21, 18758 PubMed 26525155

Highly Fluorescent Green Fluorescent Protein Chromophore Analogues Made by Decorating the Imidazolone Ring.

Sara Gutierrez1, David Martinez-Lopez2, Maria Moron1, David Sucunza1, a, Diego Sampedro2, a, Alberto Domingo3, Antonio Salgado4, Juan J Vaquero1, a

1. Departamento de Quimica Organica y Quimica Inorganica, Universidad de Alcala, Edificio de Farmacia, 28871, Alcala de Henares, Madrid (Spain).  2. Departamento de Quimica, Centro de Investigacion en Sintesis Quimica (CISQ), Universidad de La Rioja, Madre de Dios, 53, 26006, Logrono, La Rioja (Spain).  3. Departamento de Biologia de Sistemas, Universidad de Alcala, Edificio de Medicina, 28871, Alcala de Henares, Madrid (Spain).  4. Departamento de Quimica, Universidad Yachay Tech, Hacienda San Jose s/n, San Miguel de Urcuqui, 100119 (Ecuador).

a. david.sucunza@uah.es  a. diego.sampedro@unirioja.es  a. juanjose.vaquero@uah.es

Keywords: TD-DFT calculations; cell staining; fluorescence; imidazolone derivatives; proteins

Abstract

The synthesis and photophysical behavior of an unexplored family of green fluorescent protein (GFP)-like chromophore analogues is reported. The compound (Z)-4-(4-hydroxybenzylidene)-1-propyl-2-(propylamino)-1H-imidazol-5(4 H)-one (p-HBDNI, 2 a) exhibits significantly enhanced fluorescence properties relative to the parent compound (Z)-5-(4-hydroxybenzylidene)-2,3-dimethyl-3,5-dihydro-4H-imidazol-4-one (p-HBDI, 1). p-HBDNI was considered as a model system and the photophysical properties of other novel 2-amino-3,5-dihydro-4H-imidazol-4-one derivatives were evaluated. Time-dependent DFT calculations were carried out to rationalize the results. The analogue AIDNI (2 c), in which the 4-hydroxybenzyl group of p-HBDNI was replaced by an azaindole group, showed improved photophysical properties and potential for cell staining. The uptake and intracellular distribution of 2 c in living cells was investigated by confocal microscopy imaging.

2015, Publicación

Vasilev et al. Australian Journal of Chemistry. 2015;:1399-1408. Assembly of New Merocyanine Chromophores with a 1,8-Naphthalimide Core by a New Method for the Synthesis of the Methine Function.

Publications > Vasilev et al

Aust. J. Chem. 2015, 68, 1399

Assembly of New Merocyanine Chromophores with a 1,8-Naphthalimide Core by a New Method for the Synthesis of the Methine Function.

Aleksey A. Vasilev1, Stanislav Baluschev2, Diana Cheshmedzhieva1, Sonia Ilieva1, Obis D. Castaño3, Juan J Vaquero4, Silvia E. Angelova3, Katharina Landfester2

1. Department of Pharmaceutical and Applied Organic Chemistry, Faculty of Chemistry and Pharmacy, University of Sofia, James Bourchier 1, 1164 Sofia, Bulgaria.  2. Max Planck Institute for Polymer Research, PO Box 3148 - D-55021 Mainz, Germany.  3. Departamento de Química Analítica, Química Física e Ingeniería Química, Universidad de Alcalá, 28871 Alcalá de Henares, Madrid, Spain.  4. Departamento de Química Orgánica, Universidad de Alcalá, 28871 Alcalá de Henares, Madrid, Spain.

Abstract

A new method for the synthesis of the monomethine group using nitro as a leaving group in an SN-Ar reaction is described. A series of novel merocyanine dyes has been synthesised and their photophysical properties have been elucidated. The longest wavelength absorption occurs in the range 519–619 nm and the molar absorptivities vary with the substituents and are in the range 1000–47700 L mol–1 cm–1. The dyes show high chemical and photostability. One example from the series has the ability to distinguish methanol from ethanol. The introduction of a quinoid fragment into the structure leads to a pronounced intramolecular charge transfer and hence a noticeable positive solvatochromism. The structures and electronic properties of the compounds have been studied by density functional theory (DFT) and time-dependent DFT.

2015, BioImag, Publicación

Marcelo et al. The Journal of Physical Chemistry A. 2015;:2351-2362. Nonlinear Emission of Quinolizinium Based Dyes With Application in Fluorescence Lifetime Imaging.

Publications > Marcelo et al

J. Phys. Chem. A 2015, 119, 11, 2351

Nonlinear Emission of Quinolizinium Based Dyes With Application in Fluorescence Lifetime Imaging.

Gema Marcelo1, Sandra Pinto1, Tatiana Cañeque2, Inês F. A. Mariz1, Ana M. Cuadro2, Juan J Vaquero2, José M. G. Martinho1, Ermelinda M. S. Maçôas1

1. Centro de Química-Física Molecular (CQFM) and Institute of Nanoscience and Nanotechnology (IN), Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1, 1049-001 Lisboa, Portugal.  2. Departamento de Química Orgánica y Química Inorganica, Universidad de Alcalá, 28871, Alcalá de Henares, Madrid, Spain.

Abstract

Charged molecules based on the quinolizinum cation have potential applications as labels in fluorescence imaging in biological media under nonlinear excitation. A systematic study of the linear and nonlinear photophysics of derivatives of the quinolizinum cation substituted by either dimethylaniline or methoxyphenyl electron donors is performed. The effects of donor strength, conjugation length, and symmetry in the two-photon emission efficiency are analyzed in detail. The best performing nonlinear fluorophore, with two-photon absorption cross sections of 1140 GM and an emission quantum yield of 0.22, is characterized by a symmetric D-π-A%@2B-π-D architecture based on the methoxyphenyl substituent. Application of this molecule as a fluorescent marker in optical microscopy of living cells revealed that, under favorable conditions, the fluorophore can be localized in the cytoplasmatic compartment of the cell, staining vesicular shape organelles. At higher dye concentrations and longer staining times, the fluorophore can also penetrate into the nucleus. The nonlinearly excited fluorescence lifetime imaging shows that the fluorophore lifetime is sensitive to its location in the different cell compartments. Using fluorescence lifetime microscopy, a multicolor map of the cell is drafted with a single dye.

2015, Publicación

Abengozar et al. Eur J Org Chem. 2015;6(24):4214-4223. Azonia Aromatic Cations by Ring-Closing Metathesis: Synthesis ofAzaquinolizinium Cations.

Publications > Abengozar et al

Eur J Org Chem. 2015, 6, 4214

Azonia Aromatic Cations by Ring-Closing Metathesis: Synthesis ofAzaquinolizinium Cations.

Alberto Abengozar, Beatriz Abarca, Ana M. Cuadro, David Sucunza, Julio Álvarez‐Builla, Juan J Vaquero

Departamento de Quimica Organica y Quimica Inorganica, Universidad de Alcala , 28805 Alcala de Henares , Spain.

Abstract

A new approach for the synthesis of the 1‐azaquinolizinium (pyrimido[1,2‐a]pyrimidin‐5‐ium) heterocycle and some simple derivatives is described. This strategy, based on an unprecedented ring‐closing metathesis (RCM) reaction to construct the pyrimidinium ring, was also applied to the first reported synthesis for the benzo‐1‐azaquinolizinium (pyrimido[2,1‐a]isoquinolinium) cation.

2015, Publicación

Rodríguez-Sanz et al. Eur. J. Med. Chem.. 2015;:83-92. Synthesis and biological evaluation of pyridazino%@5B1′,6′:1,2%@5Dpyrido%@5B3,4-b%@5Dindolinium and pyridazino%@5B1,6-a%@5Dbenzimidazolium salts as anti-inflammatory agents.

Publications > Rodríguez-Sanz et al

Eur. J. Med. Chem. 2015, 93, 83

Synthesis and biological evaluation of pyridazino%@5B1′,6′:1,2%@5Dpyrido%@5B3,4-b%@5Dindolinium and pyridazino%@5B1,6-a%@5Dbenzimidazolium salts as anti-inflammatory agents.

Aranzazu Rodríguez-Sanz1, Patricia Sánchez-Alonso2, Teresa Bellón1, Ramón Alajarín2, Virginia Martínez-Cabeza1, Rafael Selgas3, Juan J. Vaquero2, Julio Álvarez-Builla2

1. Instituto de Salud Hospital Universitario La Paz – IdiPAZ, Madrid, Spain.  2. Departamento de Química Orgánica y Química Inorgánica, Universidad de Alcalá, Madrid, Spain.  3. Hospital Universitario La Paz, Servicio de Nefrología, IdiPAZ, IRSIN, Madrid, Spain.

Abstract

Condensed polycyclic heteroaromatic cations bearing a bridgehead nitrogen with pyridazino%@5B1′,6′:1,2%@5Dpyrido%@5B3,4-b%@5Dindolinium and pyridazino%@5B1,6-a%@5Dbenzimidazolium structures were assayed as inhibitors of LPS-induced TNF-α production by THP-1 cells. The hit compound 1e, which had the best IC50 value (4.49 μM) and low toxicity, was further assayed on human PMBCs (IC50 3.91 μM) and monocytes (IC50 1.82 μM). This compound also inhibited TNF-α production following poly I:C stimulation of human monocytes and monocyte-derived dendritic cells; in the latter case, inhibition of IL-12 production was also observed. Compound 1e was also able to inhibit TNF-α expression at the transcriptional level and proved to be effective in vivo. Compound 1e is an interesting potential therapeutic agent in IMIDs.

2015, Publicación, TosMIC

Coppola et al. Org Lett. 2015;17(1):78-81. Isoquinoline synthesis by heterocyclization of tosylmethyl isocyanide derivatives: total synthesis of mansouramycin B.

Publications > Coppola et al

Org Lett. 2015, 17, 78 PubMed 25521281

Isoquinoline synthesis by heterocyclization of tosylmethyl isocyanide derivatives: total synthesis of mansouramycin B.

Anna Coppola, David Sucunza, Carolina Burgos, Juan J Vaquero

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

Abstract

A new method for the synthesis of isoquinolines through a catalytic acid-mediated cyclization of alpha-benzyl TosMIC derivatives has been developed. This methodology has been successfully applied to the total synthesis of mansouramycin B. This is the first total synthesis of this compound to be reported in the literature.

2015, BioImag, Publicación

Suarez et al. Org Biomol Chem. 2015;13(2):527-38. Targeting DNA with small molecules: a comparative study of a library of azonia aromatic chromophores.

Publications > Suarez et al

Org Biomol Chem. 2015, 13, 527 PubMed 25378061

Targeting DNA with small molecules: a comparative study of a library of azonia aromatic chromophores.

Rosa M Suareza, Pedro Bosch, David Sucunza, Ana M Cuadro, Alberto Domingo, Francisco Mendicuti, Juan J Vaquero

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

a. juanjose.vaquero@uah.es

Abstract

A library of azonia aromatic cations has been studied in order to gain insights into the effect of the size, shape and charge distribution on the fluorescence, DNA interactions and DNA sequence selectivity properties. Fluorescence-based thermal denaturation experiments, spectrofluorimetric titrations, circular dichroism measurements and theoretical simulations have shown that some of the studied chromophores have interesting fluorescence properties and two of them also show a consistent DNA-binding ability by intercalation, with a potential preference for AT-rich sequences.