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A series of mono‐ to hexachlorinated BODIPY dyes have been prepared in good to excellent yields through the use of 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., Spanish Ministerio de Economia y Competitividad (MINECO), European Social Fund (ESF), Basque Government, Depto. de Química Orgánica, Fac. de Ciencias Químicas, TRUE, pub

235 p., En este trabajo se han propuesto nuevos colorantes basados principalmente en la estructura del cromóforo BODIPY, así como nuevos nanosistemas híbridos fotoactivos para su potencial implementación en el campo biomedicina, en particular para bioimagen y terapia fotodinámica del cáncer.Primero, el desarrollo de nuevos biomarcadores fluorescentes se basó en la modificación del cromóforo BODIPY para mejorar su solubiliad en medios acuosos y su selectividad hacia orgánulos específicos de la célula i.e. mitocondria. Para ellos, se añadieron grupos hidrofílicos y biomoleculas especificas, respectivamente. Posteriormente, se estudió la funcionalización del cromóforo BODIPY con el objetivo de lograr fotosensibilizadores con alta producción de oxigeno singlete por un lado mediante la introducción de átomos halogenados y además sistemas ¿-conjugados que desplazan la absorción hacia la región roja dentro de la ventana clínica, o por otro lado anclando grupos dadores de electrones que activen un estado de transferencia de carga intramolecular capaz de modular la capacidad fluorescente junto con la generación de oxígeno singlete, ideal para aplicaciones teranosticas.Además, se sintetizaron tres tipos de nanopartículas esféricas de sílice (no porosas, mesoporosas y ormosil) de entorno a 50 nm de tamaño, que junto con una nanoarcilla sintética (laponita) de unos 100 nm, se utilizaron como trasportadores de colorantes: fluoroforos (principalmente ocluidos en el core) o fotosensibilizadores (unidos covalentemente en la superficie externa). Estos nanosistemas se funcionalizaron además con polietilen glicol y ácido fólico para mejorar su estabilidad en agua y su selectividad hacia células tumorales.

The first fluorescent probes that are actively channeled into the mitochondrial matrix by a specific mitochondrial membrane transporter in living cells have been developed. The new functional probes (BCT) have a minimalist structural design based on the highly efficient and photostable BODIPY chromophore and carnitine as a biotargeting element. Both units are orthogonally bonded through the common boron atom, thus avoiding the use of complex polyatomic connectors. In contrast to known mitochondria-specific dyes, BCTs selectively label these organelles regardless of their transmembrane potential and in an enantioselective way. The obtained experimental evidence supports carnitine-acylcarnitine translocase (CACT) as the key transporter protein for BCTs, which behave therefore as acylcarnitine biomimetics. This simple structural design can be readily extended to other structurally diverse starting FBODIPYs to obtain BCTs with varied emission wavelengths along the visible and NIR spectral regions and with multifunctional capabilities. BCTs are the first fluorescent derivatives of carnitine to be used in cell microscopy and stand as promising research tools to explore the role of the carnitine shuttle system in cancer and metabolic diseases. Extension of this approach to other small-molecule mitochondrial transporters is envisaged.

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.

Functionalized fluorescent silica nanoparticles were designed and synthesized to selectively target cancer cells for bioimaging analysis. The synthesis method and characterization of functionalized fluorescent silica nanoparticles (50–60 nm), as well as internalization and subcellular localization in HeLa cells is reported here. The dye, rhodamine 101 (R101) was physically embedded during the sol–gel synthesis. The dye loading was optimized by varying the synthesis conditions (temperature and dye concentration added to the gel) and by the use of different organotriethoxysilanes as a second silica precursor. Additionally, R101, was also covalently bound to the functionalized external surface of the silica nanoparticles. The quantum yields of the dye-doped silica nanoparticles range from 0.25 to 0.50 and demonstrated an enhanced brightness of 230–260 fold respect to the free dye in solution. The shell of the nanoparticles was further decorated with PEG of 2000 Da and folic acid (FA) to ensure good stability in water and to enhance selectivity to cancer cells, respectively. In vitro assays with HeLa cells showed that fluorescent nanoparticles were internalized by cells accumulating exclusively into lysosomes. Quantitative analysis showed a significantly higher accumulation of FA functionalized fluorescent silica nanoparticles compared to nanoparticles without FA, proving that the former may represent good candidates for targeting cancer cells.

235 p., En este trabajo se han propuesto nuevos colorantes basados principalmente en la estructura del cromóforo BODIPY, así como nuevos nanosistemas híbridos fotoactivos para su potencial implementación en el campo biomedicina, en particular para bioimagen y terapia fotodinámica del cáncer.Primero, el desarrollo de nuevos biomarcadores fluorescentes se basó en la modificación del cromóforo BODIPY para mejorar su solubiliad en medios acuosos y su selectividad hacia orgánulos específicos de la célula i.e. mitocondria. Para ellos, se añadieron grupos hidrofílicos y biomoleculas especificas, respectivamente. Posteriormente, se estudió la funcionalización del cromóforo BODIPY con el objetivo de lograr fotosensibilizadores con alta producción de oxigeno singlete por un lado mediante la introducción de átomos halogenados y además sistemas ¿-conjugados que desplazan la absorción hacia la región roja dentro de la ventana clínica, o por otro lado anclando grupos dadores de electrones que activen un estado de transferencia de carga intramolecular capaz de modular la capacidad fluorescente junto con la generación de oxígeno singlete, ideal para aplicaciones teranosticas.Además, se sintetizaron tres tipos de nanopartículas esféricas de sílice (no porosas, mesoporosas y ormosil) de entorno a 50 nm de tamaño, que junto con una nanoarcilla sintética (laponita) de unos 100 nm, se utilizaron como trasportadores de colorantes: fluoroforos (principalmente ocluidos en el core) o fotosensibilizadores (unidos covalentemente en la superficie externa). Estos nanosistemas se funcionalizaron además con polietilen glicol y ácido fólico para mejorar su estabilidad en agua y su selectividad hacia células tumorales.

We took advantage of the chemoselective meso-functionalization of 2,3,5,6-tetrabromo-8-methylthioBODIPY 6 to prepare a series of 2,3,5,6-tetrabromo-8-arylBODIPY derivatives suitable for S Ar substitution reactions with phenols exclusively at positions 3 and 5. Pd(0)-catalyzed intramolecular arylation reaction ensued on the remaining brominated positions 2 and 6 to give a new family of benzofuran-fused BODIPY dyes. This method utilizes readily available starting materials and allows for the preparation of the title compounds with excellent functional group tolerance. Moreover, it was demonstrated that the methodology described herein is amenable for the incorporation of biomolecules. The photophysical and lasing properties of the benzofuran-fused BODIPY dyes were thoroughly analyzed with the aid of electrochemical measurements and quantum mechanical simulations. These dyes show bright and intriguing emission (both fluorescence and laser) toward the red edge of the visible spectrum with remarkable tolerance under strong and continuous irradiation. ©

Taking advantage of the outstanding properties of a naphthalenediimide-based entangled porous coordination polymer, a simple strategy for the achievement of white light emission is herein presented. The dynamic structural transformation of the [Zn₂(bdc)₂(dpNDI)]n metal-organic framework enhances the interactions with aryl-guests giving rise to different luminescence colors upon UV (ultraviolet) illumination. Thus, through the rational selection of those small aromatic guest molecules with different electron donor substituents at the appropriate proportion, the emission color was tuned by mixture ratio of guest molecules and even white light emission was achieved. Furthermore, domains in large crystals with a complementary response to linearly polarized light were noticed.

246 p., In this thesis, atomistic simulations have been used to study and predict the properties of molecules and materials. The information provided by the molecular dynamics simulations complements and supports the experiments, helping in the interpretations of the results and serving as a guide for the design of new materials. First, the intercalation of two organic dyes, LDS-722 and pyronin Y, with two smectite clays, Laponite and saponite, has been studied. The simulation of these dye/clay systems has enable the understanding of their photophysical behavior, the dye aggregation and its diffusivity. The mechanical properties of these hybrid materials has also been characterized. Second, the retention of radiocesium in calcium silicate hydrates (C-S-H gel) has been evaluated, considering the impact of Cs concentration, Ca/Si ratio, counterions and Al incorporation in the silicate chains to form C-A-S-H. Third, the strengthening mechanisms in C-S-H gel that incorporates organic additives, APTES and PEG, has also been explored by molecular dynamics simulations. The bulk and Young¿s moduli have been determined by applying a hydrostatic and uniaxial pressures to the simulated systems, considering the effects of the hydrostatic pressure on the silicate chains and hydrogen bond network. The results presented in this thesis contribute to a better understanding of the guest-host interactions at atomic scale in the studied systems and may help in the design of new materials.

beta-dicalcium silicate (beta-Ca2SiO4 or beta-C2S in cement chemistry notation) is one of the most important minerals in cement. An improvement of its hydration rate would be the key point for developing environmentally-friendly cements with lower energy consumption and CO2 emissions. However, there is a lack of fundamental understanding on the water/beta-C2S surface interactions. In this work, we aim to evaluate the water adsorption on three beta-C2S surfaces at the atomic scale using density functional theory (DFT) calculations. Our results indicate that thermodynamically favorable water adsorption takes place in several surface sites with a broad range of adsorption energies (-0.78 to -1.48 eV) depending on the particular mineral surface and adsorption site. To clarify the key factor governing the adsorption of the electronic properties of water at the surface were analyzed. The partial density of states (DOS), charge analysis, and electron density difference analyses suggest a dual interaction of water with a beta-C2S (100) surface including a nucleophilic interaction of the water oxygen lone pair with surface calcium atoms and an electrophilic interaction (hydrogen bond) of one water hydrogen with surface oxygen atoms. Despite the elucidation of the adsorption mechanism, no correlation was found between the electronic structure and the adsorption energies.

Taking advantage of the outstanding properties of a naphthalenediimide-based entangled porous coordination polymer, a simple strategy for the achievement of white light emission is herein presented. The dynamic structural transformation of the [Zn-2(bdc)(2)(dpNDI)](n) metal-organic framework enhances the interactions with aryl-guests giving rise to different luminescence colors upon UV (ultraviolet) illumination. Thus, through the rational selection of those small aromatic guest molecules with different electron donor substituents at the appropriate proportion, the emission color was tuned by mixture ratio of guest molecules and even white light emission was achieved. Furthermore, domains in large crystals with a complementary response to linearly polarized light were noticed.

The photodynamics of an orthogonal BODIPY dimer, particularly the formation of triplet states, has been explored by femtosecond and nanosecond transient absorption measurements. The short time scale data show the appearance of transient features of triplet character that, according to quantitative analysis of their intensities, account for more than 100% of the initially excited molecules, which reveals the occurrence of a singlet fission process in the isolated dimers. The formation rate of the triplet correlated state (TT) is found to depend on the solvent polarity, pointing to the mediation of a charge transfer character state. The dissociation of the (TT) state into pairs of individual triplets determines the triplet yield measured in the long time scales. The kinetic model derived from the results provides a comprehensive view of the photodynamics of BODIPY dimers and permits rationalization of the photophysical parameters of these systems.

A cyanine dye (PIC) was occluded into two 1D-nanopoporus Mg-containing aluminophosphates with different pore size (MgAPO-5 and MgAPO-36 with AFI and ATS zeolitic structure types, with cylindrical channels of 7.3 Å diameter and elliptical channels of 6.7 Å × 7.5 Å, respectively) by crystallization inclusion method. Different J-aggregates are photophysically characterized as a consequence of the different pore size of the MgAPO frameworks, with emission bands at 565 nm and at 610 nm in MgAPO-5 and MgAPO-36, respectively. Computational results indicate a more linear geometry of the J-aggregates inside the nanochannels of the MgAPO-36 sample than those in MgAPO-5, which is as a consequence of the more constrained environment in the former. For the same reason, the fluorescence of the PIC monomers at 550 nm is also activated within the MgAPO-36 channels. Owing to the strategic distribution of the fluorescent PIC species in MgAPO-36 crystals (monomers at one edge and J-aggregates with intriguing emission properties at the other edge) an efficient and one-directional antenna system is obtained. The unidirectional energy transfer process from monomers to J-aggregates is demonstrated by remote excitation experiments along tens of microns of distance.

The herein reported work describes the development of hierarchically-organized fluorescent nanomaterials inspired by plant antenna systems. These hybrid materials are based on nanostructured zeolitic materials (LTL zeolite) doped with laser dyes, which implies a synergism between organic and inorganic moieties. The non-interconnected channeled structure and pore dimensions (7.1 angstrom) of the inorganic host are ideal to order and align the allocated fluorophores inside, inferring also high thermal and chemical stability. These artificial antennae harvest a broad range of chromatic radiation and convert it into predominant red-edge or alternatively white-light emission, just choosing the right dye combination and concentration ratio to modulate the efficiency of the ongoing energy transfer hops. A further degree of organization can be achieved by functionalizing the channel entrances of LTL zeolite with specific tailor-made (stopcock) molecules via a covalent linkage. These molecules plug the channels to avoid the leakage of the guest molecules absorbed inside, as well as connect the inner space of the zeolite with the outside thanks to energy transfer processes, making the coupling of the material with external devices easier.

232 p., In this work different versatile photoactive hybrid materials with interesting features for optics and biomedicine are achieved and exhaustively characterized. Firstly, by means of the occlusion of different fluorescent dyes, by the crystallization inclusion method, into several 1D-channeled magnesium aluminophosphate (MgAPO) hosts (with different sized and shaped pores), optically dense fluorescent hybrid materials which show highly anisotropic response to linearly polarized light are obtained. Depending on the dye embedded within the selected MgAPO framework, interesting applications have been attained, such as one-directional artificial photonic antenna systems covering the whole UV-Visible spectral range, Second Harmonic Generators under NIR radiation, optically switchable hybrid systems and white light emitters. White light emission is also obtained from the luminescence that arises from embedding simultaneously different small aromatic molecules into a Metal Organic Framework (MOF), named [Zn2(bdc)2(dpNDI)]n, which contains a photoactive naphtalemediimide as organic pillar. The incorporation of halide-substituted aromatic molecules into this MOF also promotes phosphorescence at room temperature. Finally, the attachment of a BODIPY chromophore to a cyclometalated Ir(III) metallic centre results in the achievement of efficient photosensitizers for singlet oxygen generation upon visible excitation light. Moreover, these hybrid compounds also show fluorescence emission, thus, they are interesting for bioimaging as well, and as a consequence, extensible to their use in theragnosis.

Novel modified Biellmann BODIPYs were prepared using a C-H arylation reaction with in-situ formed aryldiazonium salts. The post-functionalization of the methylthio group of these derivatives was demonstrated in SNAr and the Liebeskind-Srogl cross-coupling reactions. The series of compounds herein designed with specific and selective functionalization featuring electron donor and acceptor groups provides valuable information about the impact of the molecular structure and stereoelectronic properties of the substituent on the photophysical signatures of BODIYs. In fact, push-pull dyes showing unexpected high fluorescence response towards the red edge of the visible spectrum can be designed, or, alternatively, chromophores ongoing the expected intramolecular charge transfer states (dark or fluorescent depending on the substituent, the attachment position and the surrounding media) can be also attained owing to the characteristic high charge separation of this king of dyes. We envisage that the reactivity of the selected scaffold as well as the guidelines derived from the computationally-aided spectroscopy study of these luminophores pave the way to the development of tailor made BODIPYs with specific and finely modulable spectroscopic and optical properties.