Manipulating Charge-Transfer States in BODIPYs: A Model Strategy to Rapidly Develop Photodynamic Theragnostic Agents.

On the basis of a family of BINOL (1,1'-bi-2-naphthol)-based O-BODIPY (dioxyboron dipyrromethene) dyes, it is demonstrated that chemical manipulation of the chromophoric push-pull character, by playing with the electron-donating capability of the BINOL moiety (BINOL versus 3,3'-dibromoBINOL) and with the electron-acceptor ability of the BODIPY core (alkyl substitution degree), is a workable strategy to finely balance fluorescence (singlet-state emitting action) versus the capability to photogenerate cytotoxic reactive oxygen species (triplet-state photosensitizing action). It is also shown that the promotion of a suitable charge-transfer character in the involved chromophore upon excitation enhances the probability of an intersystem crossing phenomenon, which is required to populate the triple state enabling singlet oxygen production. The reported strategy opens up new perspectives for rapid development of smarter agents for photodynamic theragnosis, including heavy-atom-free agents, from a selected organic fluorophore precursor.

Functionalized Fluorescent Silica Nanoparticles for Bioimaging of Cancer Cells.

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.

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.

Chiral Microneedles from an Achiral Bis(boron dipyrromethene): Spontaneous Mirror Symmetry Breaking Leading to a Promising Photoluminescent Organic Material.

Supramolecular self-assembly of a highly flexible and achiral meso bis(boron dipyrromethene) [bis(BODIPY)] dye straightforwardly yields fluorescent microfibers, exhibiting an intriguing anisotropic photonic behavior. This performance includes the generation of chiroptical activity owing to spontaneous mirror symmetry breaking (SMSB). Repetition of several self-assembly experiments demonstrates that the involved SMSB is not stochastic but quasi deterministic in the direction of the induced chiral asymmetry. The origin of these intriguing (chiro)photonic properties is revealed by fluorescent microspectroscopy studies of individual micrometric objects, combined with X-ray diffraction elucidation of microcrystals. Such a study demonstrates that J-like excitonic coupling between bis(BODIPY) units plays a fundamental role in their supramolecular organization, leading to axial chirality. Interestingly, the photonic behavior of the obtained fibers is ruled by inherent nonradiative pathways from the involved push-pull chromophores, and mainly by the complex excitonic interactions induced by their anisotropic supramolecular organization.

Synthetic Approach to Readily Accessible Benzofuran-Fused Borondipyrromethenes as Red-Emitting Laser Dyes.

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 SNAr 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.

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

A 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 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.

Stereochemical and Steric Control of Photophysical and Chiroptical Properties in Bichromophoric Systems.

Stereochemical and steric control of the relative spatial arrangement of the chromophoric units in multichromophoric systems offers an interesting strategy for raising unusual and appealing light-induced emission states. To explore and exploit this strategy, a series of conformationally restricted boron-dipyrromethene (BODIPY) dimers were designed by using tartaric acid as a symmetrical connector between the boron atoms of the dyes. The variety of stereoisomeric forms available for this bis(hydroxy acid) allows the relative spatial orientation of the chromophoric units in the dimer to be modified, which thus opens the door to modulation of the photophysical and chiroptical properties of the new bichromophoric systems. Chromophore alkylation introduces an additional level of control through distance-dependent steric interactions between the BODIPY units in the dimer, which also modulates their relative spatial disposition and properties.

Enhancement of NIR emission by a tight confinement of a hemicyanine dye within zeolitic MgAPO-5 nanochannels.

The encapsulation of a hemicyanine dye, LDS 730, into the 1D nanochannels of MgAPO-5 aluminophosphate by "one-pot" synthesis, based on "in situ" occlusion via a crystallization inclusion method, has led to a hybrid material with emission in the NIR region. The tight fitting between the molecular size of the guest dye and the pore dimensions of the host has enabled a rigid conformation of the LDS 730 dye within the nanochannels. Consequently, fluorescence in the NIR range of the spectra is enhanced with respect to the dye in solution. The synthesis of the hybrid material was optimized through a systematic variation of the gel composition via MW in order to obtain a pure phase.

Cs-137 immobilization in C-S-H gel nanopores.

Cementation is a widespread technique to immobilize nuclear waste due to the low leachability of cementitious materials. The capacity of calcium silicate hydrate (C-S-H), the main component of cement, to retain radionuclide Cs has been empirically studied at the macroscale, yet the specific molecular scale mechanisms that govern the retention have not been determined. In this work, we employed molecular dynamics simulations to investigate the adsorption and diffusivity of Cs into a C-S-H gel nanopore. From the simulations, it was possible to distinguish three types of Cs adsorption configurations on the C-S-H: an inner-sphere surface site where Cs is strongly bound, an outer-sphere surface site where Cs is loosely bound, and Cs free in the nanopore. For each configuration, we determined the sorption energy, and the diffusion coefficients, up to two orders of magnitude lower than in bulk water due to the effect of nanoconfinement in the worst case scenario. It has also proved that Cs cannot displace the intrinsic Ca from the C-S-H surface, and we calculated the binding strength and the residence time of the cations in the surface adsorption sites. Finally, we quantified the average number of adsorption sites per nm2 of the C-S-H surface. All these results are the first insights into Cs retention in cement at the molecular scale and will be useful to build macroscopic diffusion models and devise cement formulations to improve radionuclide Cs retention from spent nuclear fuel.

Benchmark of ReaxFF force field for subcritical and supercritical water.

Water in the subcritical and supercritical states has remarkable properties that make it an excellent solvent for oxidation of hazardous chemicals, waste separation, and green synthesis. Molecular simulations are a valuable complement to experiments in order to understand and improve the relevant sub- and super-critical reaction mechanisms. Since water molecules under these conditions can act not only as a solvent but also as a reactant, dissociative force fields are especially interesting to investigate these processes. In this work, we evaluate the capacity of the ReaxFF force field to reproduce the microstructure, hydrogen bonding, dielectric constant, diffusion, and proton transfer of sub- and super-critical water. Our results indicate that ReaxFF is able to simulate water properties in these states in very good quantitative agreement with the existing experimental data, with the exception of the static dielectric constant that is reproduced only qualitatively.

Solvent-Sensitive Emitting Urea-Bridged bis-BODIPYs: Ready Access by a One-Pot Tandem Staudinger/Aza-Wittig Ureation.

Herein we describe the synthesis, and computationally aided photophysical characterization of a new set of urea-bridged bis-BODIPY derivatives. These new dyads are efficiently obtained by a one-pot tandem Staudinger/aza-Wittig ureation protocol, from easily accessible meso-phenyl ortho-azidomethyl BODIPYs. These symmetric bis-BODIPYs outstand by a high absorption probability and excellent fluorescence and laser emission in less polar media. Nevertheless, this emission ability decreases in more polar media, which is ascribed to a light-induced charge-transfer from the urea spacer to the dipyrrin core, a process that can be modulated by appropriate changes in the substitution pattern of the BODIPY core. Furthermore, this ureation protocol can also be employed for the direct conjugation of our BODIPY-azides to amine-containing compounds, thus providing access to fluorescent non-symmetric ureas.

N-BODIPYs Come into Play: Smart Dyes for Photonic Materials.

N-BODIPYs (diaminoboron dipyrromethenes) are unveiled as a new family of BODIPY dyes with huge technological potential. Synthetic access to these systems has been gained through a judicious design focused on stabilizing the involved diaminoboron chelate. Once stabilized, the obtained N-BODIPYs retain the effective photophysical behavior exhibited by other boron-substituted BODIPYs, such as O-BODIPYs. However, key bonding features of nitrogen compared to those of oxygen (enhanced bond valence and different bond directionality) open up new possibilities for functionalizing BODIPYs, allowing an increase in the number of pendant moieties (from two in O-BODIPYs, up to four in N-BODIPYs) near the chromophore and, therefore, greater control of the photophysics. As a proof of concept, the following findings are discussed: (1) the low-cost and straightforward synthesis of a selected series of N-BODIPYs; (2) their outstanding photophysical properties compared to those of related effective dyes (excellent emission signatures, including fluorescence in the solid state; notable lasing capacities in the liquid phase and when doped into polymers; improved laser performance compared to the parent F-BODIPYs); (3) the versatility of the diaminoboron moiety in allowing the generation of multifunctionalized BODIPYs, permitting access to both symmetric and asymmetric dyes; (4) the capability of such versatility to finely modulate the dye photophysics towards different photonic applications, from lasing to chemosensing.

AcetylacetonateBODIPY-Biscyclometalated Iridium(III) Complexes: Effective Strategy towards Smarter Fluorescent Photosensitizer Agents.

Biscyclometalated IrIII complexes involving boron-dipyrromethene (BODIPY)-based ancillary ligands, where the BODIPY unit is grafted to different chelating cores (acetylacetonate for Ir-1 and Ir-2, and bipyridine for Ir-3) by the BODIPY meso position, have been synthesized and characterized. Complexes with the BODIPY moiety directly grafted to acetylacetonate (Ir-1 and Ir-2) exhibit higher absorption coefficients (ϵ≈4.46×104 m-1 cm-1 and 3.38×104 m-1  cm-1 at 517 nm and 594 nm, respectively), higher moderate fluorescence emission (φfl ≈0.08 and 0.22 at 528 nm and 652 nm, respectively) and, in particular, more efficient singlet oxygen generation upon visible-light irradiation (φΔ ≈0.86 and 0.59, respectively) than that exhibited by Ir-3 (φΔ ≈0.51, but only under UV light). Phosphorescence emission, nanosecond time-resolved transient absorption, and DFT calculations suggest that BODIPY-localized long-lived 3 IL states are populated for Ir-1 and Ir-2. In vitro photodynamic therapy (PDT) activity studied for Ir-1 and Ir-2 in HeLa cells shows that such complexes are efficiently internalized into the cells, exhibiting low dark- and high photocytoxicity, even at significantly low complex concentration, making them potentially suitable as theranostic agents.

Rational Design of Advanced Photosensitizers Based on Orthogonal BODIPY Dimers to Finely Modulate Singlet Oxygen Generation.

The synthesis, photophysical characterization, and modeling of a new library of halogen-free photosensitizers (PS) based on orthogonal boron dipyrromethene (BODIPY) dimers are reported. Herein we establish key structural factors in order to enhance singlet oxygen generation by judiciously choosing the substitution patterns according to key electronic effects and synthetic accessibility factors. The photosensitization mechanism of orthogonal BODIPY dimers is demonstrated to be strongly related to their intrinsic intramolecular charge transfer (ICT) character through the spin-orbit charge-transfer intersystem crossing (SOCT-ISC) mechanism. Thus, singlet oxygen generation can be effectively modulated through the solvent polarity and the presence of electron-donating or withdrawing groups in one of the BODIPY units. The photodynamic therapy (PDT) activity is demonstrated by in vitro experiments, showing that selected photosensitizers are efficiently internalized into HeLa cells, exhibiting low dark toxicity and high phototoxicity, even at low PS concentration (0.05-5×10-6 m).

One-Pot Synthesis of Rotationally Restricted, Conjugatable, BODIPY Derivatives from Phthalides.

O-Ethylation of phthalides with Meerwein's reagent followed by reaction of the ensuing salts with pyrrole, results in the formation of 5-alkoxy-5-phenyl dipyrromethane derivatives, which function as ready precursors of ortho-substituted 8-aryl BODIPY derivatives by reaction with borontrifluoride etherate, an overall process that can be carried out in a one-pot operation.

Adapting BODIPYs to singlet oxygen production on silica nanoparticles.

A modified Stöber method is used to synthesize spherical core-shell silica nanoparticles (NPs) with an external surface functionalized by amino groups and with an average size around 50 nm. Fluorescent dyes and photosensitizers of singlet oxygen were fixed, either separately or conjointly, respectively in the core or in the shell. Rhodamines were encapsulated in the core with relatively high fluorescence quantum yields (Φfl ≥ 0.3), allowing fluorescence tracking of the particles. Various photosensitizers of singlet oxygen (PS) were covalenty coupled to the shell, allowing singlet oxygen production. The stability of NP suspensions strongly deteriorated upon grafting the PS, affecting their apparent singlet oxygen quantum yields. Agglomeration of NPs depends both on the type and on the amount of grafted photosensitizer. New, lab-made, halogenated 4,4-difluoro-4-bora-3a,4a-diaza-s-indacenes (BODIPY) grafted to the NPs achieved higher singlet oxygen quantum yields (ΦΔ âˆ¼ 0.35-0.40) than Rose Bengal (RB) grafted NPs (ΦΔ âˆ¼ 0.10-0.27). Finally, we combined both fluorescence and PS functions in the same NP, namely a rhodamine in the silica core and a BODIPY or RB grafted in the shell, achieving the performance Φfl ∼ 0.10-0.20, ΦΔ âˆ¼ 0.16-0.25 with a single excitation wavelength. Thus, proper choice of the dyes, of their concentrations inside and on the NPs and the grafting method enables fine-tuning of singlet oxygen production and fluorescence emission.

Formation of a Nonlinear Optical Host-Guest Hybrid Material by Tight Confinement of LDS†722 into Aluminophosphate 1D Nanochannels.

In this work, hemicyanine dye LDS 722 is encapsulated into the 1D elliptical nanochannels of MgAPO-11 aluminophosphate by a crystallization inclusion method. The synthesis of the hybrid material has been optimized through a systematic variation of the crystallization conditions in order to obtain pure and large crystals (around 20 µm×30 µm) suitable for optical applications. The tight fitting between the molecular size of the guest dye and the pore dimensions of the host has favored a rigid planar conformation of the dye, restricting its inherent flexibility, which is confirmed by molecular simulations. Consequently, the encapsulation of LDS 722 into MgAPO-11 has led to an astonishing enhancement of the fluorescence with respect to the dye into MgAPO-5, with slightly larger cylindrical channels, and with respect to the dye in solution. Moreover, the perfect alignment of LDS 722 (dye with intrinsic nonlinear-optical properties) along the channels of MgAPO-11 has revealed attractive second-order nonlinear properties, such as second harmonic generation, proven through microscopy measurements in single crystals.

Bis(haloBODIPYs) with Labile Helicity: Valuable Simple Organic Molecules That Enable Circularly Polarized Luminescence.

Simple organic molecules (SOM) based on bis(haloBODIPY) are shown to enable circularly polarized luminescence (CPL), giving rise to a new structural design for technologically valuable CPL-SOMs. The established design comprises together synthetic accessibility, labile helicity, possibility of reversing the handedness of the circularly polarized emission, and reactive functional groups, making it unique and attractive as advantageous platform for the development of smart CPL-SOMs.

Near-IR BODIPY Dyes à la Carte-Programmed Orthogonal Functionalization of Rationally Designed Building Blocks.

Herein, we report the synthesis of polyfunctional BODIPY building blocks suitable to be subjected to several reaction sequences with complete chemoselectivity, thereby allowing the preparation of complex BODIPY derivatives in a versatile and programmable manner. The reactions included the Liebeskind-Srogl cross-coupling reaction (LSCC), nucleophilic aromatic substitution (SN Ar), Suzuki, Sonogashira, and Stille couplings, and a desulfitative reduction of the MeS group. This novel synthetic protocol is a powerful route to design a library of compounds with tailored photophysical properties for advanced applications. In this context, it is noteworthy that it offers a straightforward and cost-effective strategy to shift the BODIPY emission deep into the near-infrared spectral region while retaining high fluorescence quantum yields as well as highly efficient and stable laser action. These new dyes outperform the lasing behaviour of dyes considered as benchmarks over the red spectral region, overcoming the important drawbacks associated with these commercial laser dyes, namely low absorption at the standard pump wavelengths (355 and 532 nm) and/or poor photostability.

FormylBODIPYs: Privileged Building Blocks for Multicomponent Reactions. The Case of the Passerini Reaction.

Eleven formyl-containing BODIPY dyes were prepared by means of either the Liebeskind-Srogl cross-coupling reaction or the Vilsmeier reaction. These dyes were used as components in the Passerini reaction to give highly substituted BODIPY dyes. A joined spectroscopic and theoretical characterization of the synthesized compounds was conducted to unravel the impact of the structural rigidity/flexibility on the photophysical signatures. These dyes were tested as fluorescent trackers for phagocytosis. Additionally, they proved to be useful to stain different blood cells with an intense and stable signal at a very low exposure time.