Caracterización fotofísica y simulación estructural de nuevos colorantes BODIPY para aplicaciones fotónicas

133 p. + anexosLa presente tesis doctoral se centra en el análisis de la influencia de la estructura molecular en laspropiedades fotofísicas de los cromóforos conocidos como BODIPYs. Se pretende, de esta forma,relacionar las propiedades espectroscópicas con el comportamiento de los colorantes como mediosactivos de láseres sintonizables principalmente, y también como sondas moleculares para monitorizar laspropiedades fisicoquímicas del medio que les rodea.El patrón de sustitución del BODIPY ha permitido modular y optimizar sus propiedadesespectroscópicas. De hecho, tanto la posición cromofórica en la que se incorpore el sustituyente como sucarácter dador/aceptor de electrones determina la respuesta fluorescente del colorante. ,Así, la modificación controlada de la estructura molecular básica del BODIPY ha permitido no sólooptimizar la eficiencia en la región verde/amarilla del espectro visible (funcionalización del puente deboro), sino también extenderla de forma modulable hacia el extremo azul (heteroátomos en mesa) oalternativamente a la región roja/NIR (extensión del sistema re deslocalizado). Como resultado se handesarrollado nuevos colorantes láser BODIPY cubriendo toda la región espectral visible y conprestaciones fotofísicas y láser mejoradas respecto a los colorantes comerciales existentes.Además, la funcionalización selectiva ha facilitado también promover la activación de nuevos procesosfotofísicos. La inducción de procesos de transferencia de carga por medio de la aminación o la nitración,permite emplear dichos fluoróforos como sondas fluorescentes de polaridad. Por otra parte, los procesosde transferencia de energía que tienen lugar en sistemas multicromofóricos basados en estructuras deBODIPYs y cumarinás unidas covalentemente, posibilita mejorar la absorción de luz y obtener labrillante emisión del BODIPY tanto bajo excitación visible como ultravioleta

Unprecedented J-Aggregated Dyes in Pure Organic Solvents

We describe the design and synthesis of the first organic dyes enabling spontaneous formation of stable J-aggregates in common organic solvents without additives. The new dyes are O-BODIPYs with a B-spiranic 4,4-diacyloxyl substitution pattern. Key to the effectiveness of the J-aggregation process is the high conformational rigidity of the Bspiranic molecular design as well as the orthogonal disposition of the B-diacyloxyl substituent and the meso-aryl group with respect to the mean plane of the borodiazaindacene. Atomistic simulations, both in vacuum and in a solvent cage, support the dynamics of the J-aggregation process as well as its dependence on the alkylation pattern of the BODIPY chromophore. A detailed analysis of the photophysical and laser properties of the new dyes provides convincing evidence for the unambiguous assignment of these J-aggregates and their dependence on the environmental conditions.We gratefully acknowledge financial support by the Spanish Ministerio de Economia y Competitividad (projects MAT2014-51937-C3-1-P, MAT2014- 51937-C3-2-P, MAT2014-51937-C3-3-P, and MAT2015-68837-REDT). I. E. thanks the Gobierno Vasco (IT339-10) for a predoctoral contract. H. M. acknowledges the Spanish Ministerio de Economia y Competitividad for a Juan de la Cierva postdoctoral contract. The authors thank SGIker of UPV/EHU for technical and human support with the X-ray diffraction measurements and computational calculations, which were carried out in the “arina” informatic cluster. We also thank Diego Plaza Lozano for preliminary synthetic studies.Peer reviewe

Ikusgai-eremu elektromagnetiko osoan zehar igorpen sintonizagarria duten BODIPY laser-koloratzaileak

The herein reported work deals with the photophysical signatures of the dyes known as BODIPY. In particular, it is focused on the molecular structure impact towards the development of active media for tunable dye lasers from the blue to the red edge of the visible region. The spectroscopic properties of BODIPYs can be finely modulated and improved just changing the substitution pattern. Thus, taking as starting point the simplest core (absorption/emission at the green/yellow visible region) and af-ter suitable chemical modifications of the backbone, its spectral bands can be deeply shifted to the blue (heteroatoms at meso position) as well as to the red-edge (extended π-system). Therefore, novel BODIPY dyes covering the whole visible spectral region have been developed with improved photophysical and laser performance with regard to the comercially available dyes.; Lan honetan, molekula-egiturak BODIPY deritzen koloratzaileen pro-pietate fotofisikoetan duen eragina aztertzen da, gehienbat alde ikusgai gorritik urdi-nera laser sintonizagarrien ingurune aktiboa garatzeko. BODIPYaren ordezkapen-pa-troiaren arabera propietate espektroskopikoak modula eta optimiza daitezke. Horrela, BODIPYaren oinarrizko kromoforoa abiapuntutzat hartuta (absortzio/igorpen eremu ikusgai berde/horian) aldaketak egin dira egitura molekularrean banda espektralak le-rrokatzeko, bai eremu urdinera (heteroatomoak meso posizioan sartuz), bai eremu go-rrira (π sistema deslokalizatua hedatuz). Ondorioz, koloratzaile komertzialekin konpa-ratuz gero, eremu espektral ikusgai osoa betetzen duten BODIPY koloratzaile berriak garatu dira, propietate fotofisiko eta laser hobetuekin

Phase-selective staining of model and cell membranes, lipid droplets and lipoproteins with fluorescent solvatochromic pyrene probes

The push-pull solvatochromic pyrene derivatives PA and PK have been applied to the study of model membrane vesicles, cells and purified human serum lipoproteins, using both confocal fluorescence microscopy and fluorescence spectroscopy. These polarity-sensitive probes provide information similar to that obtained by Laurdan or Prodan, i.e. mainly lipid order in biomembranes, but they have the essential advantage of being excitable by a standard 405 nm laser light, bypassing the use of multiphoton excitation. In addition, they are brighter and much more photostable than those dimethylamino naphthalene derivatives. Our results with model membrane spectroscopy (multilamellar vesicles) and with microscopy (giant unilamellar vesicles) showed the capacity of PA and PK to report differently on liquid-disordered, liquid-ordered and gel phase bilayers. Moreover, a ratiometric parameter, the Red/Blue Intensity Ratio (RBIR) could be used for inter-domain, inter-vesicle and even inter-technique comparison, and the appropriate microscopy-spectroscopy conversion coefficients could be estimated. In studies at the cellular level, PA probe stained almost exclusively the plasma membrane of red blood cells, revealing its high degree of lipid order. Using Chinese Hamster Ovary cells PA was shown to be an excellent probe for the detection of cytoplasmic lipid droplets, superior to Nile Red in that PA provides simultaneously a detailed information of membrane order in the whole cell, in which the lipid droplets appear with a very good contrast. Moreover, spectrofluorometric data of PA-stained serum lipoproteins indicated an essentially identical value of RBIR for lipid droplets and for high-density lipoproteins.This work was supported in part by grants from the Spanish Ministry of Science (FEDER MINECO PGC2018-099857-B-I00) and the Basque Government (grants No. IT1264-19 and IT1270-19), by the Fundación Biofísica Bizkaia and by the Basque Excellence Research Centre (BERC) program of the Basque Government.Peer reviewe

Modulation of the photophysical properties of BODIPY dyes by substitution at their meso position.

We report the photophysical properties of new BODIPY derivatives monosubstituted at the central position. The presence of different functional groups induced the appearance of new photophysical processes in BODIPY dyes, such as intramolecular charge or energy transfer. These phenomena are sensitive to solvent properties (mainly the polarity) and have a potential use as fluorescent probes. Adequate modifications in their molecular structure or in the environment polarity can modulate the emission region of these fluorophores in the visible spectral region. Specifically, different processes and photophysical behaviors can be achieved depending on the excited chromophore and/or the solvent characteristics in a bichromophoric pyrene-BODIPY system

Carboxylates versus Fluorines: Boosting the Emission Properties of Commercial BODIPYs in Liquid and Solid Media

<A new and facile strategy for the development of photonic materials is presented that fufi lls the conditions of being effi cient, stable, and tunable laser emitters over the visible region of spectrum, with the possibility of being easily processable and cost-effective. This approach uses poly(methyl methacrylate) (PMMA) as a host for new dyes with improved effi ciency and photostability synthesized. Using a simple protocol, fl uorine atoms in the commercial (4,4-difl uoro-4-bora-3a,4a-diaza-s-indacene) ( F -BODIPY) by carboxylate groups. The new O -BODIPYs exhibit enhanced optical properties and laser behavior both in the liquid and solid phases compared to their commercial analogues. Lasing effi ciencies up to 2.6 times higher than those recorded for the commercial dyes are registered with high photostabilities since the laser output remain at 80% of the initial value after 100 000 pump pulses in the same position of the sample at a repetition rate of 30 Hz; the corresponding commercial dye entirely loses its laser action after only 12 000 pump pulses. Distributed feedback laser emission is demonstrated with organic fi lms incorporating new O -BODIPYs deposited onto quartz substrates engraved with appropriated periodical structures. These dyes exhibit laser thresholds up to two times lower than those of the corresponding parent dyes with lasing intensities up to one order of magnitude higher.Spanish Ministerio de Economia y Competitividad (MINECO)Basque GovernmentDepto. de Química OrgánicaFac. de Ciencias QuímicasTRUEpu

Selective Lateral Lithiation of Methyl BODIPYs: Synthesis, Photophysics, and Electrochemistry of New <i>Meso</i> Derivatives

Selected <i>meso</i> BODIPYs (chemically reactive, difficult to obtain by established procedures, or photophysically or electrochemically attractive) have been obtained by unprecedented selective lateral lithiation of 8-methylBODIPYs. The physical study of the obtained new <i>meso</i> BODIPYs reveals interesting tunable properties related to the activation of intramolecular charge-transfer processes, endorsing the new synthetic methodology as useful for the development of smarter BODIPY dyes for technological applications

8-AminoBODIPYs: Cyanines or Hemicyanines? The Effect of the Coplanarity of the Amino Group on Their Optical Properties

The role of the amino group twisting ability in the BODIPY photophysics for nonsterically hindered and constrained molecular structures was studied. When a coplanar disposition of the amino and the BODIPY core is feasible, a hemicyanine-like delocalized π-system gives rise to novel blue and efficient BODIPY laser dyes. The key role of such rotamer is confirmed by newly synthesized derivatives where the amino and the BODIPY core are electronically decoupled by steric repulsions

Controlling Vilsmeier-Haack processes in meso-methylBODIPYs: A new way to modulate finely photophysical properties in boron dipyrromethenes

In the herein work we report the fine and selective control of competitive processes when submitting meso-methylBODIPYs to Vilsmeier-Haack reaction conditions. These competitive processes generate BODIPYs with opposed photophysical properties, from highly fluorescent dyes enabling laser emission, to non-fluorescent singlet-oxygen photosensitizers. The synthetic control is exerted on the basis of the structure of the starting BODIPY, as well as the electrophilic character (hard or soft) of the formylating reagent

A versatile fluorescent molecular probe endowed with singlet oxygen generation under white-light photosensitization

Despite fluorescent photodynamic therapy (fluorescent-PDT) dyes are promising theranostic agents, current approaches unfortunately involve crucial shortcomings (such as, narrow absorption bands, high cost, low bio-compatibility and specificity, low dual efficiency) making difficult their clinical translation. Particularly, efficient fluorescent-PDT agents triggered under white-light, with potential application in topic solar treatments, are scarce. Here, we describe the rational development of a novel fluorescent-PDT molecular biomaterial based on BODIPY building blocks able to sustain, simultaneously, synthetic accessibility, high fluorescence and phototoxicity within a broad spectral window, biocompatibility, including low dark toxicity and high cell permeability with selective accumulation in lysosomes and, what is more important, excellent efficient activity triggered under white light. These all-in-one combined properties make the new dye a valuable ground platform for the development of future smarter theranostic agents