All posts by administrador

2021, AzaBN, Publicación

Valencia et al. J Org Chem. 2021;:. 1,10a-Dihydro-1-aza-10a-boraphenanthrene and 6a,7-Dihydro-7-aza-6a-boratetraphene: Two New Fluorescent BN-PAHs.

Publications > Valencia et al

J Org Chem. 2021 Nov 22. doi: 10.1021/acs.joc.1c01095. PubMed 34806882

1,10a-Dihydro-1-aza-10a-boraphenanthrene and 6a,7-Dihydro-7-aza-6a-boratetraphene: Two New Fluorescent BN-PAHs.

Isabel Valencia1, Patricia García-García1, David Sucunza1, Francisco Mendicuti2, Juan J Vaquero1

1. Departamento de Química Orgánica y Química Inorgánica, Instituto de Investigación Química "Andrés M. del Río" (IQAR), Universidad de Alcalá, IRYCIS, Campus Científico-Tecnológico, 28805 Alcalá de Henares, Spain.  2. Departamento de Química Analítica, Química Física e Ingeniería Química, Instituto de Investigación Química "Andrés M. del Río" (IQAR), Universidad de Alcalá, Campus Científico-Tecnológico, 28805 Alcalá de Henares, Spain.

Abstract

Previously unknown 1,10a-dihydro-1-aza-10a-boraphenanthrene and 6a,7-dihydro-7-aza-6a-boratetraphene have been efficiently synthesized. Bromination of these BN-PAHs proceeds with complete regioselectivity, resulting in the formation of different substituted derivatives via cross-coupling reactions. These compounds exhibit rather high fluorescence quantum yields (up to ϕ(F) = 0.80).

Noticias

J. Org. Chem. 11.21

1,10a-Dihydro-1-aza-10a-boraphenanthrene and 6a,7-Dihydro-7-aza-6a-boratetraphene: Two New Fluorescent BN-PAHs

Isabel Valencia, Patricia García-García, David Sucunza*, Francisco Mendicuti, Juan J. Vaquero*

J. Org. Chem. 2021, 86, 23, 16259–16267
DOI: 10.1021/acs.joc.1c01095

Previously unknown 1,10a-dihydro-1-aza-10a-boraphenanthrene and 6a,7-dihydro-7-aza-6a-boratetraphene have been efficiently synthesized. Bromination of these BN-PAHs proceeds with complete regioselectivity, resulting in the formation of different substituted derivatives via cross-coupling reactions. These compounds exhibit rather high fluorescence quantum yields (up to ϕF = 0.80).
Noticias

Eur. J. Med. Chem. 10.21

Pyridazino-pyrrolo-quinoxalinium salts as highly potent and selective leishmanicidal agents targeting trypanothione reductase

Héctor de Lucio, Javier García-Marín, Patricia Sánchez-Alonso, Juan Carlos García-Soriano, Miguel Ángel Toro, Juan J Vaquero, Federico Gago, Ramón Alajarín, Antonio Jiménez-Ruiz

Eur. J. Med. Chem. , 2021
DOI: 10.1016/j.ejmech.2021.113915

Fifteen pyridazino-pyrrolo-quinoxalinium salts were synthesized and tested for their antiprotozoal activity against Leishmania infantum amastigotes. Eleven of them turned out to be leishmanicidal, with EC(50) values in the nanomolar range, and displayed low toxicity against the human THP-1 cell line. Selectivity indices for these compounds range from 10 to more than 1000. Compounds 3b and 3f behave as potent inhibitors of the oxidoreductase activity of the essential enzyme trypanothione disulfide reductase (TryR). Interestingly, binding of 3f is not affected by high trypanothione concentrations, as revealed by the noncompetitive pattern of inhibition observed when tested in the presence of increasing concentrations of this substrate. Furthermore, when analyzed at varying NADPH concentrations, the characteristic pattern of hyperbolic uncompetitive inhibition supports the view that binding of NADPH to TryR is a prerequisite for inhibitor-protein association. Similar to other TryR uncompetitive inhibitors for NADPH, 3f is responsible for TryR-dependent reduction of cytochrome c in a reaction that is typically inhibited by superoxide dismutase.
Noticias

Commun. Chem. 10.21

Two-photon activated precision molecular photosensitizer targeting mitochondria

Inês F. A. Mariz, Sandra N. Pinto, Ana M. Santiago, José M. G. Martinho, Javier Recio, Juan J. Vaquero, Ana M. Cuadro,* Ermelinda Maçôas*

Commun Chem 2021, 4, 142
DOI: 10.1038/s42004-021-00581-4

Mitochondria metabolism is an emergent target for the development of novel anticancer agents. It is amply recognized that strategies that allow for modulation of mitochondrial function in specific cell populations need to be developed for the therapeutic potential of mitochondria-targeting agents to become a reality in the clinic. In this work, we report dipolar and quadrupolar quinolizinium and benzimidazolium cations that show mitochondria targeting ability and localized light-induced mitochondria damage in live animal cells. Some of the dyes induce a very efficient disruption of mitochondrial potential and subsequent cell death under two-photon excitation in the Near-infrared (NIR) opening up possible applications of azonia/azolium aromatic heterocycles as precision photosensitizers. The dipolar compounds could be excited in the NIR due to a high two-photon brightness while exhibiting emission in the red part of the visible spectra (600–700 nm). Interaction with the mitochondria leads to an unexpected blue-shift of the emission of the far-red emitting compounds, which we assign to emission from the locally excited state. Interaction and possibly aggregation at the mitochondria prevents access to the intramolecular charge transfer state responsible for far-red emission.
2021, BioImag, Publicación

Mariz et al. Journal. 2021;4(1):142. Two-photon activated precision molecular photosensitizer targeting mitochondria.

Publications > Mariz et al

2021; 4(1):142.

Two-photon activated precision molecular photosensitizer targeting mitochondria.

Inês F. A. Mariz, Sandra N. Pinto, Ana M. Santiago, José M. G. Martinho, Javier Recio, Juan J. Vaquero, Ana M. Cuadro, Ermelinda Maçôas

Resumen

Mitochondria metabolism is an emergent target for the development of novel anticancer agents. It is amply recognized that strategies that allow for modulation of mitochondrial function in specific cell populations need to be developed for the therapeutic potential of mitochondria-targeting agents to become a reality in the clinic. In this work, we report dipolar and quadrupolar quinolizinium and benzimidazolium cations that show mitochondria targeting ability and localized light-induced mitochondria damage in live animal cells. Some of the dyes induce a very efficient disruption of mitochondrial potential and subsequent cell death under two-photon excitation in the Near-infrared (NIR) opening up possible applications of azonia/azolium aromatic heterocycles as precision photosensitizers. The dipolar compounds could be excited in the NIR due to a high two-photon brightness while exhibiting emission in the red part of the visible spectra (600–700 nm). Interaction with the mitochondria leads to an unexpected blue-shift of the emission of the far-red emitting compounds, which we assign to emission from the locally excited state. Interaction and possibly aggregation at the mitochondria prevents access to the intramolecular charge transfer state responsible for far-red emission.

Noticias

RSEQ Symposium 2021

Participación RSEQ Symposium 2021

 

RSEQ Symposium 2021, September 27-30th:

– Oral:
· Enantioselective synthesis of 2,3-substituted cyclopropylboronates
Julia Altarejos, David Sucunza, Juan J. Vaquero, Javier Carreras

– Póster:
· Visible light-mediated enantioselective aminoarylation of alkenes: streamlined access to ?,?-diarylethylamines
Estíbaliz Merino, Cedric Hervieu, Mariia Kirillova,Yawen Hu, Cristina Nevado

· Metal-Free Temperature-controlled Regiodivergent Borylative Cyclization of enynes: a Boron-migration Promoted Skeletal Rearrangement
Ana Milián, Manuel A. Fernández-Rodriguez, Patricia García-García, Estíbaliz Merino, Juan J. Vaquero

· Functionalization of 4a,8a-Dihydro-4a-Aza-8a-Boranaphthalene via Regioselective Iridium-Catalyzed C−H Borylation
Patricia García-García, David Sucunza, Juan J. Vaquero, Isabel Valencia

2021, Publicación, Renal

García-Marín et al. ChemMedChem. 2021;16(18):2895-2906. A Computer-Driven Scaffold-Hopping Approach Generating New PTP1B Inhibitors from the Pyrrolo[1,2-a]quinoxaline Core.

Publications > García-Marín et al

ChemMedChem. 2021 Sep 16;16(18):2895-2906. doi: 10.1002/cmdc.202100338. PubMed 34137509

A Computer-Driven Scaffold-Hopping Approach Generating New PTP1B Inhibitors from the Pyrrolo[1,2-a]quinoxaline Core.

Javier García-Marín1, Mercedes Griera2, Ramón Alajarín3, Manuel Rodríguez-Puyol4, Diego Rodríguez-Puyol5, Juan J Vaquero6

1. Departamento de Química Orgánica y Química Inorgánica, Universidad de Alcalá, 28805, Alcalá de Henares, Spain.  2. Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Ctra. Colmenar Viejo, km. 9100, 28034, Madrid, Spain.  3. Instituto de Investigación Química Andrés Manuel del Río (IQAR), Universidad de Alcalá, Alcalá de Henares, Spain.  4. Departamento de Química Biológica y Estructural, Centro de Investigaciones Biológicas Margarita Salas (CIB-CSIC), Calle Ramiro de Maeztu 9, 28040, Madrid, Spain.  5. Graphenano Medical Care, S.L., C/Pablo Casals, no. 13, Yecla, Murcia, Spain.  6. Departamento de Biología de Sistemas, Universidad de Alcalá, 28805, Alcalá de Henares, Spain.

Keywords: MM-ISMSA; PTP1B, phosphatase; glucose uptake; molecular dynamics; molecular modelling; pyrrolo[1,2-a]quinoxaline; scaffold hopping

Abstract

Protein tyrosine phosphatase 1B (PTP1B) is a very promising target for the treatment of metabolic disorders such as type II diabetes mellitus. Although it was validated as a promising target for this disease more than 30 years ago, as yet there is no drug in advanced clinical trials, and its biochemical mechanism and functions are still being studied. In the present study, based on our experience generating PTP1B inhibitors, we have developed and implemented a scaffold-hopping approach to vary the pyrrole ring of the pyrrolo[1,2-a]quinoxaline core, supported by extensive computational techniques aimed to explain the molecular interaction with PTP1B. Using a combination of docking, molecular dynamics and end-point free-energy calculations, we have rationally designed a hypothesis for new PTP1B inhibitors, supporting their recognition mechanism at a molecular level. After the design phase, we were able to easily synthesize proposed candidates and their evaluation against PTP1B was found to be in good concordance with our predictions. Moreover, the best candidates exhibited glucose uptake increments in cellulo model, thus confirming their utility for PTP1B inhibition and validating this approach for inhibitors design and molecules thus obtained.

2021, Publicación

Risco et al. Journal. 2021;159:105323. Chemical recovery of waste electrical and electronic equipment by microwave-assisted pyrolysis: A review.

Publications > Risco et al

2021; 159:105323.

Chemical recovery of waste electrical and electronic equipment by microwave-assisted pyrolysis: A review.

Álvaro Risco, David Sucunza, Sergio González-Egido

Palabras clave: Electronic waste; Chemical recycling; Microwave pyrolysis; Catalytic pyrolysis; Brominated flame-retardants

Resumen

Over the past few decades, electrical and electronic equipment has become more accessible to people of different social status. Currently, however, only a small fraction of the resulting waste is treated properly, even though it has the potential to become a major source of raw materials. Waste electrical and electronic equipment (WEEE), or e-waste, is mainly composed of plastics and metals that can be recovered with a lower environmental impact and more efficiently in comparison with conventional processes, even when similar technologies are used. Pyrolysis is a thermochemical processing technique that is able to exploit the polymers in WEEE as well as concentrate the metals into a solid residue. Furthermore, this process can be adapted or combined with other technologies to minimize the content of organic halides that stem from the hazardous brominated flame-retardants (BFRs), which are common additives used in these products. Microwave-assisted pyrolysis (MAP) uses a heating mechanism that differs significantly but has advantages over conventional pyrolysis, such as a rapid volumetric heating or a higher energy efficiency. Despite the increasing interest in the application of MAP over the last years, research to date in this field remains scarce. As such, this article reviews current studies into the treatment of WEEE by MAP, thereby shedding light on the different variables that have an impact on its effectiveness and efficiency, to provide a comprehensive understanding of this technology. In addition, this review offers an overview of the characteristics of pyrolysis products and possible routes for their subsequent refining.