Photosensitizer-Mesoporous Silica Nanoparticles Combination for Enhanced Photodynamic Therapy

Mesoporous silica nanoparticles (MSNs) are widely known for their versatile applications. One of the most extended is as drug delivery systems for the treatment of cancer and other diseases. This review compiles the most representative examples in the last years of functionalized MSNs as photosensitizer carriers for photodynamic therapy (PDT) against cancer. Several commercially available photosensitizers (PSs) demonstrated poor solubility in an aqueous medium and insufficient selectivity for cancer tissues. The tumor specificity of PSs is a key factor for enhancing the PDT effect and at the same time reducing side effects. The use of nanoparticles and particularly MSNs, in which PS is covalently anchored or physically embedded, can overcome these limitations. For that, PS-MSNs can be externally decorated with compounds of interest in order to act as an active target for certain cancer cells, demonstrating enhanced phototoxicity in vitro and in vivo. The objective of this review is to collect and compare different nanosystems based on PS-MSNs pointing out their advantages in PDT against diverse types of cancers.We gratefully acknowledge financial support from MCIN/AEI/10.13039/501100011033 (project PID2020-114347RB-C32), and Gobierno Vasco-Eusko Jaurlaritza (project IT1639-22). R.P.-M. thanks UPV/EHU, MIU and NGEU for their postdoctoral contract (MARSA21/71)

Ready Access to Molecular Rotors Based on Boron Dipyrromethene Dyes-Coumarin Dyads Featuring Broadband Absorption

Herein we report on a straightforward access method for boron dipyrromethene dyes (BODIPYs)-coumarin hybrids linked through their respective 8- and 6- positions, with wide functionalization of the coumarin fragment, using salicylaldehyde as a versatile building block. The computationally-assisted photophysical study unveils broadband absorption upon proper functionalization of the coumarin, as well as the key role of the conformational freedom of the coumarin appended at the meso position of the BODIPY. Such free motion almost suppresses the fluorescence signal, but enables us to apply these dyads as molecular rotors to monitor the surrounding microviscosity.This research was funded by Spanish Ministerio de Economia y Competitividad (project MAT2017-83856-C3-3-P), Gobierno Vasco (project IT912-16), CONACyT (grants 253623, 123732) and Dirección de Apoyo a la Investigación (DAIP-UG CIIC318/2019)

Proceedings of the 13th annual conference of INEBRIA

CITATION: Watson, R., et al. 2016. Proceedings of the 13th annual conference of INEBRIA. Addiction Science & Clinical Practice, 11:13, doi:10.1186/s13722-016-0062-9.The original publication is available at https://ascpjournal.biomedcentral.comENGLISH SUMMARY : Meeting abstracts.https://ascpjournal.biomedcentral.com/articles/10.1186/s13722-016-0062-9Publisher's versio

(1 R,2 S)-ephedrine: A new self-assembling chiral template for the synthesis of aluminophosphate frameworks

(1R,2S)-(-)-Ephedrine is used as a new structure-directing agent for the synthesis of nanoporous aluminophosphates. This molecule is selected based on the self-aggregating behavior through π-π type interactions between the aromatic rings and the presence of H-bond-forming groups. Additionally, this molecule possesses two chiral centers, which could enhance a potential transfer of chirality to the inorganic framework. Synthesis results showed that (1R,2S)-(-)-ephedrine is very efficient in directing the crystallization of the AFI-type structure in the presence of several catalytically active dopants. A combination of fluorescence spectroscopy and molecular mechanics simulations shows that ephedrine displays a great trend to self-assemble in water solution, establishing not only π-π type interactions between the aromatic rings but also intermolecular H-bonds between NH2 and OH moieties which compete with the formation of H-bonds with water. These molecules are invariably incorporated as aggregates within the AFI structure, regardless of the dopant introduced, showing a very strong trend to self-assemble within nanoporous frameworks as well. The stability of this supramolecular arrangement within the framework is due to a molecular recognition phenomenon based on the establishment of two H-bonds between the H atoms of the amino group and the O atoms of the hydroxyl group of the consecutive dimer, leading to an infinite supramolecular π-π H-bonded chainlike arrangement within the AFI channels.The research leading to these results has received funding from the Spanish Ministry of Science and Innovation MICINN (projects MAT2009-13569 and MAT2012-31127) and the European Research Council, under the Marie Curie Career Integration Grant program (FP7-PEOPLE-2011-CIG), Grant Agreement PCIG09-GA-2011-291877. L.G.-H. acknowledges the Spanish Ministry of Education and Science for a Juan de la Cierva contract.Peer Reviewe

(1R,2S)-ephedrine: a new self-assembling chiral template for the synthesis of aluminophosphaye frameworks

Trabajo presentado en la 5th Czech-Italian-Spanish conference on Molecular Sieves and Catalysis, celebrada en Segovia (España) del 16 al 19 de junio de 2013.In an attempt to prepare very-large pore microporous aluminophosphates, a new concept in structure-direction is developed [1,2], which consists in the use of self-assembling organic molecules that form supramolecular aggregates in aqueous solution. In this case, (1R,2S)-(-)-ephedrine (Fig. 1, top-right) is used as a new structure-directing agent for the synthesis of aluminophosphates. This molecule is rationally selected based on the self-aggregating behavior through π-π type interactions between the aromatic rings and high conformational flexibility, leading to very large structure-directing entities that will potentially form highly-porous aluminophosphates. Additionally, this molecule possesses two chiral centers, which could potentially transfer the chirality to the inorganic framework in an attempt to introduce enantioselectivity in the resulting materials. Microporous aluminophosphates were synthesized by hydrothermal methods. Gel molar compositions and synthesis conditions were systematically varied. Synthesis results showed that (1R, 2S)-(-)-ephedrine displays a great tendency to direct the crystallization of the AFI-type structure. Several catalytically active metals, such us magnesium, silicon, cobalt, zinc or manganese, have been incorporated within the framework of the AFI network. Interestingly, under certain conditions, an unknown crystalline highly-porous microporous aluminophosphate is formed. A fluorescence spectroscopy study was performed in order to analyse the supramolecular chemistry during the occlusion of ephedrine within the AFI structure (Fig. 1). Remarkably, and in contrast with previous results with benzylpyrrolidine and (S)-1- benzyl-2-pyrrolidinemethanol, we observed that ephedrine is always incorporated as aggregates within the AFI structure, regardless of the dopant incorporated, showing a very strong trend to selfassemble within microporous frameworks. Hence, (1R, 2S)-(-)-ephedrine represents a promising self-assembling structuredirecting agent for the potential crystallization of new highly-porous aluminophosphates.Peer Reviewe

Methylthio BODIPY as a standard triplet photosensitizer for singlet oxygen production: a photophysical study

International audienceA complete photophysical study on the iodinated-BODIPY, 3,5-dimethyl-2,6-diiodo-8-thiomethyl-pyrromethene (MeSBDP), demonstrated that it is an excellent triplet photosensitizer for singlet oxygen production in a broad range of apolar and polar solvents. Besides its absorption and fluorescence emission spectra, the dynamics of its excited states including its intersystem crossing rate was characterized by femtosecond transient experiments. The photophysical study of its triplet state by nanosecond transient absorption spectroscopy and phosphorescence emission concluded to a diffusion-controlled quenching of 3MeSBDP by O2 and to a fraction of triplet state quenching by O2 Image ID:c9cp03454d-t1.gif close to unity. The high (>0.87) and solvent-insensitive singlet oxygen quantum yield ϕΔ measured by singlet oxygen phosphorescence emission, together with the noticeable photostability of MeSBSP, as well as the absence of quenching of singlet oxygen by MeSBDP itself, allows claiming it as an alternative standard photosensitizer for singlet oxygen production, under excitation either in the UV or in the visible range

Un-assemblable layered aluminophosphates from self-assembling structure-directing agents: Effect of fluorine

A new strategy for the synthesis of three new un-assemblable metastable AlPO-based layered framework materials is reported. By using organic molecules with aromatic rings that tend to self-assemble in water solution by establishing π–π type interactions, three new AlPO layered frameworks have been produced with benzylpyrrolidine and its meta- and para-fluorinated derivatives. These new layered materials occlude an extremely large amount of organic material. Interestingly, UV–Visible fluorescence results show that the molecules occluded within the frameworks form supramolecular aggregates, and consequently the crystallization of these structures is strongly dependent on the self-assembly ability of the organic molecules in water. As a consequence, the ortho-fluorinated derivative, which shows the lowest trend to aggregate in water, is not able to produce a stable self-assembled AlPO framework. The self-assembly of the organic molecules within the frameworks driven by relatively weak π–π type interactions between the aromatic rings combined with a poor H–bond interaction of the heterocyclic tertiary N with terminal PO groups enable a simple un-assembly (delamination) process of the structures by treating the samples in water.The research leading to these results has recevided funding from the Spanish Ministry of Science and Innovation MICINN (projects MAT2009-13569 and MAT2012-31127) and the European Research Council, under the Marie Curie Career Integration Grant program (FP7-PEOPLE-2011-CIG), Grant Agreement PCIG09-GA-2011-291877. LGH acknowledges the Spanish Ministry of Education and Science for a Juan de la Cierva contract.Peer Reviewe

Straightforward synthetic protocol for the introduction of stabilized c nucleophiles in the BODIPY core for advanced sensing and photonic applications

©2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. A straightforward synthetic protocol to directly incorporate stabilized 1,3-dicarbonyl C nucleophiles to the meso position of BODIPY (4,4-difluoro-4-bora-3a,4a-diaza-sindacene) is reported. Soft nucleophiles generated by deprotonation of 1,3-dicarbonyl derivatives smoothly displace the 8-methylthio group from 8-(methylthio)BODIPY analogues in the presence of CuI thiophenecarboxylate in stoichiometric amounts at room temperature. Seven highly fluorescent new derivatives are prepared with varying yields (20-92%) in short reaction times (5-30 min). The excellent photophysical properties of the new dyes allow focusing on applications never analyzed before for BODIPYs substituted with stabilized C nucleophiles such as pH sensors and lasers in liquid and solid state, highlighting the relevance of the synthetic protocol described in the present work. The attainment of these dyes, with strong UV absorption and highly efficient and stable laser emission in the green spectral region, concerns to one of the greatest challenges in the ongoing development of advanced photonic materials with relevant applications. In fact, organic dyes with emission in the green are the only ones that allow, by frequency-doubling processes, the generation of tunable ultraviolet (250-350 nm) radiation, with ultra-short pulses.Peer Reviewe

Chlorinated BODIPYs: Surprisingly efficient and highly photostable laser dyes

A series of mono- to hexachlorinated BODIPY dyes have been prepared in good to excellent yields through the use of N-chlorosuccinimide as an inexpensive halogenating reagent. This library of chlorinated dyes allowed analysis in detail, from the experimental and theoretical points of view, of the dependency of the photophysical and optical properties of the dyes on the number and positions of the chlorine substituents on their BODIPY cores. Quantum mechanical calculations predict the regioselectivity of the halogenation reaction and explain why some positions are less prone to chlorination. The new chlorinated BODIPYs exhibit enhanced laser action with respect to their non-halogenated analogues, both in liquid solution and in the solid phase. In addition, chlorination is a facile and essentially costless protocol for overcoming important shortcomings exhibited by commercially available BODIPYs, which should favor their practical applications in optical and sensing fields. © 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.Peer Reviewe

Convenient access to carbohydrate - BODIPY hybrids by two complementary methods involving one-pot assembly of >clickable> BODIPY dyes

Two complementary one-pot, three component synthetic strategies based on copper(I)-catalyzed azide - alkyne cycloadditions (CuAAC) have been developed, which allow the efficient assembly of glycosyl-derived alkynes or azides with highly fluorescent boron-dipyrromethene (BODIPY) cores containing azido or alkyne moieties, respectively. The resulting carbohydrate - BODIPY derivatives display excellent photophysical and laser properties that relate to the spacer (amino group or aromatic ring) employed in each of the synthetic protocols.Peer Reviewe