Aliphatic azo compounds as programmable nitrogen donors in alkyne-mediated.
Universidad de Alcalá, Departamento de Química Orgánica y Química Inorgánica.
Keywords: Aliphatic azo compounds; Azo-alkyne cycloadditions; Heterocycle synthesis; Nitrogen donors; Nitrogen transfer; Pyrazoles; Pyrroles
Abstract
Nitrogen-containing heterocycles constitute the core of many approved drugs and
Divergent heterocycle synthesis enabled by switchable reaction of azobenzenes with alkynes.
Resumen
Azobenzenes are long-standing photochromic switches now emerging as synthetic reagents.Their reactions with alkynes enable efficient access to diverse nitrogen heterocycles.Distinct activation modes (metal, photoredox, thermal) dictate divergent reaction pathways.Mechanistic studies reveal complementary polar and radical manifolds.This reactivity opens new opportunities in drug discovery and molecular materials.
Publications > Morales-Ortega et al
Visible-light-initiated metal-free C(sp(3)) -C(sp(3)) to C(sp(3)) -N conversion in homobenzylic sulfonamides with N-iodoimides.
1. Departamento de Química Orgánica y Química Inorgánica, Instituto de Investigación Química "Andrés M. del Río" (IQAR), Universidad de Alcalá Alcalá de Henares Madrid 28805 Spain. 2. Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS) Madrid 28034 Spain.
javier.carreras@uah.es
Abstract
We report a simple protocol for the transformation of C(sp(3)) -C(sp(3)) to C(sp(3)) -N in homobenzylic sulfonamides in combination with N-iodoimides to form gem-diamino derivatives. The reaction exhibits a wide functional group tolerance and allows the incorporation of bioactive-derived fragments. The mechanistic insights provided by control experiments and DFT calculations suggest that an imine intermediate is formed after C-C bond cleavage.
Publications > Sánchez-Pavón et al
Highly efficient unbridged D-A+(D) chromophores based on the quinolizinium cation for nonlinear optical (NLO) applications.
Palabras clave: Quinolizinium cation; D-A(D) unbridged chromophores; Nonlinear optical application; First hyperpolarizability
Resumen
Novel charged D-A+ chromophores based on quinolizinium cations as acceptor unit have been prepared by treating haloquinolizinium salts with N-heteroarylstannanes under Stille reaction conditions. This approach provides an easy access to potential one-dimensional D-A+ and two-dimensional D-A+-D chromophores in which the acceptor moiety (A+) is the simple azonia cation and the donors are different π-rich N-heterocycles. The first hyperpolarizabilities (β) were measured by hyper-Rayleigh scattering experiments and the experimental data confirmed that the inherent polarization between donor and acceptor fragments modulates the NLO properties. The electronic structures and properties (including both the linear and nonlinear optical properties) of the quinolizinium chromophores were examined by theoretical (DFT, HF and MP2) calculations. A promising strategy for the rational design of D-A building blocks to create new organic-based NLO materials is proposed.
Two-photon activated precision molecular photosensitizer targeting mitochondria.
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.
A new family of fluorescent pyridazinobenzimidazolium cations with DNA binding properties.
1. Departamento de Química Orgánica y Química Inorgánica, Universidad de Alcalá, 28871, Alcalá de Henares, Madrid, Spain. 2. Departamento de Química Analítica, Química Física e Ingeniería Química, 28805, Alcalá de Henares, Madrid, Spain. 3. Departamento de Biología de Sistemas, Instituto de Investigación Química “Andrés M. Del Río” (IQAR), Universidad de Alcalá, IRYCIS, 28805, Alcalá de Henares, Madrid, Spain. 4. Departamento de Química Orgánica y Química Inorgánica, 28805, Alcalá de Henares, Madrid, Spain.
Abstract
A series of novel azonia aromatic heterocycles formed by a pyridazinobenzimidazolium system has been synthesized. Spectrofluorimetric and circular dichroism measurements, as well as theoretical simulations for these materials, have shown their interesting fluorescence properties and DNA-binding ability. Stoichiometries and binding constants were obtained by fluorescence and the induced circular dichroism spectra analysis. Moreover, the potential of these compounds for cell staining has been investigated in living HeLa cells by confocal microscopy imaging.
Synthesis and Photophysical Behavior of a Highly Fluorescent Family of Unsymmetrical Organoboron Complexes Containing 5-(Pyridin-2-ylmethylene)imidazolidine-2,4-dione Moieties.
1. Departamento de Quimica Organica y Quimica Inorganica, Instituto de Investigacion Quimica "Andres M. del Rio" (IQAR) , Universidad de Alcala, IRYCIS , 28805 Alcala de Henares , Spain. 2. Departamento de Quimica, Centro de Investigacion en Sintesis Quimica (CISQ) , Universidad de La Rioja , Madre de Dios 53 , 26006 Logrono , Spain.
Abstract
A new and highly fluorescent family of unsymmetrical organoboron complexes containing 5-(pyridin-2-ylmethylene)imidazolidine-2,4-dione moieties has been synthesized in three steps. These compounds show strong absorptions covering a wide range of the UV-vis spectrum and are strongly emissive (varphif of up to 0.92 in CH3CN). Moreover, two fluorophores that include an alkyne or an azide group at the end of the alkyl chain and with potential utility in bioorthogonal chemistry have been developed. One of these, in which the glycol substituent provides an enhanced water solubility without compromising the fluorescence (varphif = 0.85 in water), may be of particular importance.
Dibenzopyridoimidazocinnolinium cations: a new family of light-up fluorescent DNA probes.
1. Departamento de Quimica Organica y Quimica Inorganica, Instituto de Investigacion Quimica "Andres M. del Rio" (IQAR) , Universidad de Alcala , 28805 Alcala de Henares , Spain. 2. Departamento de Química Analítica, Química Física e Ingeniería Química, Universidad de Alcalá, Spain. 3. Departamento de Biología de Sistemas, Universidad de Alcalá, Spain.
Abstract
Steady-state and time-resolved fluorescence, circular dichroism and molecular modelling techniques have been applied to a new family of weakly fluorescent dibenzopyridoimidazocinnolinium derivatives whose fluorescence intensity increases significantly (larger than × 3.5) upon DNA addition. The synthesis of these azonia cations, which bind to DNA by intercalation, was carried out using a Westphal condensation and a Suzuki cross coupling reaction as key steps. A live-cell staining analysis by confocal microscopy imaging was also performed and showed the capacity of these new compounds for active uptake and accumulation by living cells, with complex patterns of intracellular distribution observed.
Azonia aromatic heterocycles as a new acceptor unit in D-π-A%@2B vs D-A%@2B nonlinear optical chromophores.
1. Departamento de Química Orgánica y Química Inorgánica, Universidad de Alcalá, 28871, Alcalá de Henares, Madrid, Spain. 2. Department of Physics, Skidmore College, Saratoga Springs, NY, United States. 3. Department of Chemistry, University of Leuven, Celestijnenlaan 200 D, 3001, Leuven, Belgium. 4. Departamento de Química Analítica, Química Física e Ingeniería Química, Universidad de Alcalá, 28871, Alcalá de Henares, Madrid, Spain.
Abstract
A comparison of D-π-A%@2B and D-A%@2B cationic chromophores based on the quinolizinium system as new acceptor units is reported along with the results of studies into their linear and non-linear optical properties and electrochemical data. Experimental and theoretical data show that quinolizinium-based chromophores may provide a new generation of second-order non-linear materials with enhanced performance. The first hyperpolarizabilities were measured by Hyper-Rayleigh scattering experiments and the experimental data are supported by a theoretical analysis. In some chromophores the absence of a bridge (D-A%@2B) between the donor and acceptor fragments enhances the NLO properties and the single crystal structure of such a material has been determined by X-ray diffraction.
Imidazopyridinium cations: A new family of azonia aromatic heterocycles with applications as DNA intercalators.
1. Departamento de Química Inorgánica y Química Orgánica, Química Física e Ingeniería Química, Universidad de Alcalá, 28871, Alcalá de Henares, Madrid, Spain. 2. Departamento de Biología de Sistemas, Química Física e Ingeniería Química, Universidad de Alcalá, 28871, Alcalá de Henares, Madrid, Spain. 3. Departamento de Química Analítica, Química Física e Ingeniería Química, Universidad de Alcalá, 28871, Alcalá de Henares, Madrid, Spain.
Abstract
Two novel imidazopyridinium cations formed by a hexacyclic azonia aromatic system have been synthesized. Spectrofluorimetric titrations, circular dichroism measurements, theoretical simulations and fluorescence-based thermal denaturation experiments on these materials have shown the interesting fluorescence properties and DNA-binding ability by intercalation, with a marked preference for AT-rich sequences. Compound 2 presents the highest fluorescence quantum yield (0.32 in 5% DMSO/water and 0.46 in MeOH) and affinity for DNA (binding constant of ∼4.5 × 105 M−1). Moreover, the potential of these compounds for cell staining has been investigated in living HeLa cells by confocal microscopy imaging. This analysis showed the remarkable capacity of both compounds for uptake and accumulation by living cells.