Anthracene-Fused Oligo-BODIPYs: A New Class of π-Extended NIR-Absorbing Materials.

Large π-conjugated systems are key in the area of molecular materials. Herein, we prepare via AuI -catalyzed cyclization a series of fully π-conjugated anthracene-fused oligo-BODIPYs. Their structural and optoelectronic properties were studied by several techniques, ranging from X-ray, UV/Vis, and cyclic voltammetry to transient absorption spectroscopy. As a complement, their electronic structures were explored by means of Density Functional Theory (DFT) calculations. Depending on the size and shape of the π-conjugated skeleton, unique features-such as face-to-face supramolecular organization, NIR absorption and fluorescence as well as strong electron accepting character-were noted. All in all, the aforementioned features render them valuable for technological applications.

Exploring the Application of the Negishi Reaction of HaloBODIPYs: Generality, Regioselectivity, and Synthetic Utility in the Development of BODIPY Laser Dyes.

The generality of the palladium-catalyzed C-C coupling Negishi reaction when applied to haloBODIPYs is demonstrated on the basis of selected starting BODIPYs, including polyhalogenated and/or asymmetrical systems, and organozinc reagents. This reaction is an interesting synthetic tool in BODIPY chemistry, mainly because it allows a valuable regioselective postfunctionalization of BODIPY chromophores with different functional groups. In this way, functional patterns that are difficult to obtain by other procedures (e.g., asymmetrically functionalized BODIPYs involving halogenated positions) can now be made. The regioselectivity is achieved by controlling the reaction conditions and is based on almost-general reactivity preferences, and the nature of the involved halogens and their positions. This ability is exemplified by the preparation of a series of new BODIPY dyes with unprecedented substitution patterns allowing noticeable lasing properties.

First highly efficient and photostable E and C†derivatives of 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) as dye lasers in the liquid phase, thin films, and solid-state rods.

A new library of E- and C-4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) derivatives has been synthesized through a straightforward protocol from commercially available BODIPY complexes, and a systematic study of the photophysical properties and laser behavior related to the electronic properties of the B-substituent group (alkynyl, cyano, vinyl, aryl, and alkyl) has been carried out. The replacement of fluorine atoms by electron-withdrawing groups enhances the fluorescence response of the dye, whereas electron-donor groups diminish the fluorescence efficiency. As a consequence, these compounds exhibit enhanced laser action with respect to their parent dyes, both in liquid solution and in the solid phase, with lasing efficiencies under transversal pumping up to 73 % in liquid solution and 53 % in a solid matrix. The new dyes also showed enhanced photostability. In a solid matrix, the derivative of commercial dye PM597 that incorporated cyano groups at the boron center exhibited a very high lasing stability, with the laser emission remaining at the initial level after 100 000 pump pulses in the same position of the sample at a 10 Hz repetition rate. Distributed feedback laser emission was demonstrated with organic films that incorporated parent dye PM597 and its cyano derivative. The films were deposited onto quartz substrates engraved with appropriate periodical structures. The C derivative exhibited a laser threshold lower than that of the parent dye as well as lasing intensities up to three orders of magnitude higher.

Observing bioorthogonal macrocyclizations in the nuclear envelope of live cells using on/on fluorescence lifetime microscopy.

The reactive partnership between azides and strained alkynes is at the forefront of bioorthogonal reactions, with their in situ cellular studies often achieved through the use of off to on fluorophores with fluorescence microscopy. In this work, the first demonstration of a bioorthogonal, macrocycle-forming reaction occurring within the nuclear envelope of live cells has been accomplished, utilising on/on fluorescence lifetime imaging microscopy for real-time continuous observation of the transformation. The fluorescent, macrocyclic BF2 azadipyrromethene was accessible through a double 1,3-dipolar cycloaddition within minutes, between a precursor bis-azido substituted fluorophore and Sondheimer diyne in water or organic solvents. Photophysical properties of both the starting bis-azide BF2 azadipyrromethene and the fluorescent macrocyclic products were obtained, with near identical emission wavelengths and intensities, but different lifetimes. In a novel approach, the progress of the live-cell bioorthogonal macrocyclization was successfully tracked through a fluorescence lifetime change of 0.6 ns from starting material to products, with reaction completion achieved within 45 min. The continuous monitoring and imaging of this bioorthogonal transformation in the nuclear membrane and invaginations, of two different cancer cell lines, has been demonstrated using a combination of fluorescence intensity and lifetime imaging with phasor plot analysis. As there is a discernible difference in fluorescence lifetimes between starting material and products, this approach removes the necessity for off-to-on fluorogenic probes when preparing for bioorthogonal cell-imaging and microscopy.

Double click macrocyclization with Sondheimer diyne of aza-dipyrrins for B-Free bioorthogonal imaging.

Sequential azide/diyne cycloadditions proved highly effective for the macrocyclization of a bis-azido aza-dipyrrin. Macrocyclic aza-dipyrrin could be produced in 30 min at rt in water with changes in fluorescence intensity and lifetimes measurable upon reaction. Live cell microscopy showed that aza-dipyrrins were suitable for confocal and STED super-resolution imaging and a bioorthogonal response to macrocyclization could be detected in cellular compartments. These results will encourage a broader examination of the sensing and imaging uses of aza-dipyrrins.

Glycosylated BODIPY- Incorporated Pt(II) Metallacycles for Targeted and Synergistic Chemo-Photodynamic Therapy.

Pt(II)-BODIPY complexes combine the chemotherapeutic activity of Pt(II) with the photocytotoxicity of BODIPYs. Additional conjugation with targeting ligands can boost the uptake by cancer cells that overexpress the corresponding receptors. We describe two Pt(II) triangles, 1 and 2, built with pyridyl BODIPYs functionalized with glucose (3) or triethylene glycol methyl ether (4), respectively. Both 1 and 2 showed higher singlet oxygen quantum yields than 3 and 4, due to the enhanced singlet-to-triplet intersystem crossing. To evaluate the targeting effect of the glycosylated derivative, in vitro experiments were performed using glucose transporter 1 (GLUT1)-positive HT29 and A549 cancer cells, and noncancerous HEK293 cells as control. Both 1 and 2 showed higher cellular uptake than 3 and 4. Specifically, 1 was selective and highly cytotoxic toward HT29 and A549 cells. The synergistic chemo- and photodynamic behavior of the metallacycles was also confirmed. Notably, 1 exhibited superior efficacy toward the cisplatin-resistant R-HepG2 cells.

Annulative π-extension of BODIPYs made easy via gold(i)-catalyzed cycloisomerization.

Here we report gold(i)-catalyzed cycloisomerization as a new powerful synthetic tool for the preparation of π-extended BODIPY derivatives. The catalytic system PPhF 3AuCl/AgSbF6 enables the synthesis of [b]-[2,1]naphtho-fused-BODIPYs (2a-2c) under mild conditions, in excellent yields and short reaction times. The reaction is totally regioselective to the 6-endo-dig product and for the α-position of the BODIPY, which is both the kinetically and thermodynamically favored pathway, as supported by the free energy profile calculated by means of Density Functional Theory (DFT). Moreover, this methodology also allows the synthesis of two new families of [b]-aryl-fused-BODIPYs, namely, [3,4]phenanthro- (2e and 2f) and [1,2]naphtho-fused (2g) BODIPYs. Their molecular and electronic structures were established by NMR and UV-vis spectroscopies as well as single-crystal X-ray diffraction analysis. As can be noted from the X-ray structures, 2a, 2e and 2g present interesting structural differences at both the molecular and packing level. Interestingly, despite being isomers, the UV/vis spectra of 2a and 2g revealed significant differences in their electronic structures. The origin of this finding was studied by Time-Dependent DFT calculations. Calculated DFT Nuclear Independent Chemical Shift (NICS(0)) values also supported the different electronic structures of 2a and 2g.

A DIE responsive NIR-fluorescent cell membrane probe.

It is challenging to achieve selective off to on modulation of the emissive state of a fluorophore within a complex and heterogeneous cellular environment. Herein we show that the dis-assembly of a non-fluorescent aggregate to produce individual fluorescent molecules, termed disaggregation induced emission (DIE), can be utilised to achieve this goal with an amphiphilic BF2-azadipyrromethene (NIR-AZA) probe. Optical near-infrared properties of the NIR-AZA probe used in this study include absorption and emission maxima at 700 and 726 nm respectively when in the emissive non-aggregated state. Key to the success of the probe is the bis-sulfonic acid substitution of the NIR-AZA fluorophore, which is atypical for membrane probes as it does not contain zwitterionic lipid substituents. The aggregation/disaggregation properties of the NIR-fluorophore have been investigated in model surfactant and synthetic liposomal systems and shown to be emissive responsive to both. Real-time live cell imaging experiments in HeLa Kyoto and MC3T3 cells showed a rapid switch on of emission specific to the plasma membrane of viable and apoptotic cells attributable to a disaggregation-induced emission of the probe. Image analysis software confirmed localisation of fluorescence to the plasma membrane. Cell membrane staining was also effective for formaldehyde fixed cells, with staining possible either before or after fixation. This study adds new and important findings to recent developments of DIE responsive probes and further applications of this controllable emission-switching event are anticipated.

Endogenous exosome labelling with an amphiphilic NIR-fluorescent probe.

The recognition of the biological, diagnostic and medical importance of exosomes has given rise to an urgent need for efficient labelling of these extracellular vesicles in ways that do not alter their inherent characteristics. We report for the first time an endogenous method to NIR-fluorescent labelled exosomes using an amphiphilic probe without the need for immunolabelling or synthetic or chromatographic manipulation of exosomes. Comparative analyses of labelled and unlabelled exosomes with NTA, AFM, flow cytometry and immunoblot analysis all show a high degree of similarity. Spectroscopic analysis and fluorescence imaging confirmed the ability to visualise purified NIR-exosomes.

BF2-azadipyrromethene NIR-emissive fluorophores with research and clinical potential.

The use of near-infrared fluorescence for in vivo research and intraoperative clinical imaging is rapidly expanding, with new applications being proposed and developed. While imaging hardware and software have significantly progressed in recent times, the molecular fluorescent agents remain a limiting factor. In this report, the design, synthesis, photophysical characterization and bio-medical imaging assessment of two new NIR-fluorophores based on the BF2-azadipyrromethene fluorophore class are described. Inclusion of dimethylamino substituents on these BF2-azadipyrromethene probes results in very large bathochromic shifts with photophysical measurements showing absorption and emission maxima between 757 and 818 nm within the desired NIR spectra region. Testing of the probes shows that they are suitable for fluorescence imaging with both research and clinical instrumentation. Preclinical imaging assessment shows their suitability as fluorescent markers (tattoos) of lesions for intraoperative identification and lymphatic mapping in ex vivo human colonic tissue. These new clinical wavelength-compatible fluorophores may contribute towards the on-going expansion of medical uses for NIR-fluorescence.

An asymmetric BODIPY triad with panchromatic absorption for high-performance red-edge laser emission.

A rational design of an unprecedented asymmetric cassette triad based entirely on BODIPY chromophores allows efficient light harvesting over the UV-vis spectral region, leading to a bright and stable red-edge laser emission via efficient energy-transfer processes.

Remarkable observations on triplet-sensitized reactions. the di-pi-methane rearrangement of acyclic 1,4-dienes in the triplet excited state.

Previous studies have led to the conclusion that a large majority of acyclic 1,4-dienes do not undergo photochemical di-pi-methane (DPM) rearrangement under triplet-sensitized irradiation. The results of a detailed analysis of these processes demonstrate that a series of these compounds do indeed undergo highly efficient DPM rearrangement from their triplet excited states when suitable triplet sensitizers are used.