BODIPY Dimers Research Articles

Liposomal Formulations of Novel BODIPY Dimers as Promising Photosensitizers for Antibacterial and Anticancer Treatment

Synthesis, photochemical properties, liposomal encapsulation, and in vitro photodynamic activity studies of novel BODIPY dimer connected at meso-meso positions and its brominated and iodinated analogs were described. UV-Vis measurements indicated that the dimeric structure of obtained BODIPYs did not significantly influence the positions of the absorption maxima. Emission properties and singlet oxygen generation studies revealed a strong heavy atom effect of brominated and iodinated BODIPY dimers, manifested by fluorescence intensity reduction and increased singlet oxygen generation ability compared to analog without halogen atoms. For the in vitro photodynamic activity studies, dimers were incorporated into two different types of liposomes: positively charged DOTAP:POPC and negatively charged POPG:POPC. The photoinactivation studies revealed high activity of brominated and iodinated dimers incorporated into DOTAP:POPC liposomes on both Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli. Anticancer studies on human breast adenocarcinoma MDA-MB-231 and human ovarian carcinoma A2780 cells revealed that DOTAP:POPC liposomes containing brominated and iodinated dimers were active even at low nanomolar concentrations. In addition, they were more active against MDA-MB-231 cells than A2780 cells, which is particularly important since the MDA-MB-231 cell line represents triple-negative breast cancer, which has limited therapeutic options.

γ-γ Directly linked BODIPY dimer: Synthesis and optical properties

The presence of several reactive sites (i.e., α, β, γ, meso) in the BODIPY core endows directly linked BODIPY dimers with diverse structures and properties, however, γ-γ BODIPY dimer has not been explored. We assumed that BODIPY with only γ-position could conduct oxidative coupling to form γ-γ BODIPY dimer, thus BODIPY 2 embracing cyclohexyl groups at the periphery to occupy α and β-position was designed, one of cyclohexyl groups can be oxidized to β-oxo and aromatic ring. The aromatic-fused BODIPY contributed to the construction of the γ-γ BODIPY dimer. Interestingly, the γ-γ BODIPY dimer displayed red fluorescence at 684 nm and large Stokes shift up to 146 nm in solution, which is one of the largest Stokes shift in BODIPY derivatives. The singlet oxygen test and electron paramagnetic resonance (EPR) experiments confirmed that this dimer can be used as a photosensitizer.

The controllable of BODIPY dimers without installing blocking groups as both fluorescence and singlet oxygen generators

AbstractWe compared a range of BODIPY dimer derivatives without installing blocking groups by optimizing geometry structures and analyzing energies, frontier molecular orbitals, Chole&Cele map, electron density difference, spin‐orbit coupling (SOC) matrix and decay rate constants from excited states. The dihedral angles of the β‐β‐linked BODIPY dimer and the α‐α‐linked BODIPY dimer tend to flatten in the T1 state, which is detrimental to the occurrence of the intersystem crossing (ISC). Conversely, the dihedral angle of the meso‐β‐linked BODIPY dimer, the meso‐meso‐linked BODIPY dimer and α‐γ‐linked BODIPY dimer is within the range of 125°–143° in the T1 state, facilitating ISC and the generation of singlet oxygen. Notably, the transition from S1 to S0 involving lowest unoccupied molecular orbital to highest occupied molecular orbital with long‐wavelength emission and moderate oscillator strength underpins the remarkable long emission peaks observed experimentally for α‐γ‐linked BODIPY dimer. Moreover, the apparent SOC matrix enhances the ISC process, resulting in a respectable efficiency in generating singlet oxygen for this dimer. In meso‐β‐linked BODIPY, meso‐meso‐linked BODIPY, and α‐γ‐linked BODIPY, the S1→T1 process is characterized by a significant charge transfer, specifically transitioning from the 1CT state to the 3LE state, indicative of a spin‐orbit charge transfer ISC (SOCT‐ISC) mechanism. The ability to regulate the photosensitivity of BODIPY dimers by adjusting the dihedral angle between the two units in the T1 state unveils new avenues for designing high‐performance photosensitizers for both therapeutic and imaging applications.

β-β-alkynyl-bridged BODIPY dimers: Synthesis, one- and two-photon photophysical properties

Six β-β-linked BODIPY dimers with different EDG-EDG and EDG-EWG were synthesized by changing the nature of the EDG and EWG at the meso position. The fluorescence lifetimes and quantum yield of z4 and z5 with the same substituent groups at the two meso positions are much higher than those of the BODIPY dimers with two different substituents. Compound z4 exhibits the highest fluorescence quantum yield (11.24 %) and fluorescence lifetime (1.32 ns). Both compounds z4 and z5 show important two-photon induced fluorescence in the 800–1000 nm region with a clear quadratic dependency of the emission intensity vs the laser excitation power.

Nucleophilic Aromatic Substitution (SNAr) as an Approach to Challenging Nitrogen-Bridged BODIPY Oligomers.

A series of nitrogen-bridged BODIPY oligomers were synthesized via nucleophilic aromatic substitution (SNAr) as a convenient approach. Further transformations achieved novel α,α-aryl BODIPY dimers as well as a BODIPY hexamer efficiently. These BODIPY oligomers showed good photophysical properties, such as apparent absorption and emission both in visible and near-infrared regions. Interestingly, the high air and photothermal stability, strong NIR absorption, and high photothermal conversion rates of hexamer B6 suggest potential applications in photothermal therapy.

A Rational Way to Control the Triplet State Wave Function Confinement of Organic Chromophores: Effect of the Connection Sites and Spin Density Distribution-Guided Molecular Structure Design Principles in Bodipy Dimers.

To study the intersystem crossing (ISC) and the spatial confinement of the triplet excited states of organic chromophores, we prepared a series of Bodipy dimers. We found that the connection position of the two units has a significant effect on the absorption and fluorescence. Singlet oxygen quantum yields of 3.8-12.4% were observed for the dimers, which are independent of solvent polarity. Nanosecond transient absorption spectra indicate the population of long-lived triplet excited states with lifetimes (τT) of 45-454 μs. Pulsed laser-excited time-resolved electron paramagnetic resonance (TREPR) spectra show that the T1 triplet states are essentially delocalized, which is different from the case for the previously reported Bodipy dimers. The TREPR spectra of the triplet states imply that the delocalization over the whole dimer essentially depends on the electron density of the carbon atoms at the connection sites. This property may become a universal rule for controlling the T1 state confinement in multichromophore organic molecules.

NIR-absorbing and emitting α,α-nitrogen-bridged BODIPY dimers with strong excitonic coupling.

Three new distinct NIR α,α-NH-bridged BODIPY dimers were prepared by a direct nucleophilic substitution reaction. The synergistic effects of the nitrogen bridges and strong excitonic coupling between each BODIPY unit play major roles in enhancing the delocalization of an electron spin over the entire BODIPY dimers. The in situ formed aminyl radical dimer showed an absorption maximum at 1040 nm.

Small molecular donor materials based on β-β-bridged BODIPY dimers with a triphenylamine or carbazole unit for efficient organic solar cells.

Herein, we have designed and synthesized two novel BODIPY dimer-based small molecules, denoted as ZMH-1 and ZMH-2, covalently linked and functionalized with triphenylamine (TPA) (ZMH-1) and carbazole (CZ) (ZMH-2) units as the electron donor at the 3- and 5-positions of the BODIPY core, respectively. Their optical and electrochemical properties were investigated. We have fabricated all small molecule bulk heterojunction organic solar cells using these BODIPY-based small molecules as electron donors along with fullerene derivative (PC71BM) and medium bandgap non-fullerene acceptor IDT-TC as electron acceptors. The optimized OSCs based on ZMH-1:PC71BM, ZMH-2:PC71BM, ZMH-1:IDT-IC, and ZMH-2:IDT-IC attain overall PCEs of 8.91%, 6.61%, 11.28%, and 5.48%, respectively. Moreover, when a small amount of PC71BM as guest acceptor is added to the binary host ZMH-1:IDT-TC and ZMH-2:IDT-TC, the ternary OSCs based on ZMH-1 and ZMH-2 reach PCEs of 13.70% and 12.71%, respectively.

Front Cover: Geometry‐Independent Ultrafast Energy Transfer in Bioinspired Arrays Containing Electronically Coupled BODIPY Dimers as Energy Donors (Chem. Eur. J. 58/2023)

Front Cover: Geometry‐Independent Ultrafast Energy Transfer in Bioinspired Arrays Containing Electronically Coupled BODIPY Dimers as Energy Donors (Chem. Eur. J. 58/2023)

Geometry-Independent Ultrafast Energy Transfer in Bioinspired Arrays Containing Electronically Coupled BODIPY Dimers as Energy Donors.

In photosynthetic light-harvesting complexes, strong interaction between chromophores enables efficient absorption of solar radiation and has been suggested to enable ultrafast energy funneling to the reaction center. To examine whether similar effects can be realized in synthetic systems, and to determine the mechanisms of energy transfer, we synthesized and characterized a series of bioinspired arrays containing strongly-coupled BODIPY dimers as energy donors and chlorin derivatives as energy acceptors. The BODIPY dimers feature broad absorption in the range of 500-600 nm, complementing the chlorin absorption to provide absorption across the entire visible spectrum. Ultrafast (~10 ps) energy transfer was observed from photoexcited BODIPY dyads to chlorin subunits. Surprisingly, the energy-transfer rate is nearly independent of the position where the BODIPY dimer is attached to the chlorin and of the type of connecting linker. In addition, the energy-transfer rate from BODIPY dimers to chlorin is slower than the corresponding rate in arrays containing BODIPY monomers. The lower rate, corresponding to less efficient through-bond transfer, is most likely due to weaker electronic coupling between the ground state of the chlorin acceptor and the delocalized electronic state of the BODIPY dimer, compared to the localized state of a BODIPY monomer.

Stimulated Resonance Raman and Excited-State Dynamics in an Excitonically Coupled Bodipy Dimer: A Test for TD-DFT and the Polarizable Continuum Model.

Bodipy is one of the most versatile and studied functional dyes due to its myriad applications and tunable spectral properties. One of the strategies to adjust their properties is the formation of Bodipy dimers and oligomers whose properties differ significantly from the corresponding monomer. Recently, we have developed a novel strategy for synthesizing α,α-ethylene-bridged Bodipy dimers; however, their excited-state dynamics was heretofore unknown. This work presents the ultrafast excited-state dynamics of a novel α,α-ethylene-bridge Bodipy dimer and its monomeric parent. The dimer's steady-state absorption and fluorescence suggest a Coulombic interaction between the monomeric units' transition dipole moments (TDMs), forming what is often termed a "J-dimer". The excited-state properties of the dimer were studied using molecular excitonic theory and time-dependent density functional theory (TD-DFT). We chose the M06 exchange-correlation functional (XCF) based on its ability to reproduce the experimental oscillator strength and resonance Raman spectra. Ultrafast laser spectroscopy reveals symmetry-breaking charge separation (SB-CS) in the dimer in polar solvents and the subsequent population of the charge-separated ion-pair state. The charge separation rate falls into the normal regime, while the charge recombination is in the inverted regime. Conversely, in nonpolar solvents, the charge separation is thermodynamically not feasible. In contrast, the monomer's excited-state dynamics shows no dependence on the solvent polarity. Furthermore, we found no evidence of significant structural rearrangement upon photoexcitation, regardless of the deactivation pathway. After an extensive analysis of the electronic transitions, we concluded that the solvent fluctuations in the local environment around the dimer create an asymmetry that drives and stabilizes the charge separation. This work sheds light on the charge-transfer process in this new set of molecular systems and how excited-state dynamics can be modeled by combining the experiment and theory.

Formylation as a Chemical Tool to Modulate the Performance of Photosensitizers Based on Boron Dipyrromethene Dimers.

Heavy-atom-free photosensitizers are envisioned as the next generation of photoactive molecules for photo-theragnosis. In this approach, and after suitable irradiation, a single molecular scaffold is able to visualize and kill tumour cells by fluorescence signalling and photodynamic therapy (PDT), respectively, with minimal side effects. In this regard, BODIPY-based orthogonal dimers have irrupted as suitable candidates for this aim. Herein, we analyse the photophysical properties of a set of formyl-functionalized BODIPY dimers to ascertain their suitability as fluorescent photosensitizers. The conducted computationally aided spectroscopic study determined that the fluorescence/singlet oxygen generation dual performance of these valuable BODIPY dimers not only depends on the BODIPY-BODIPY linkage and the steric hindrance around it, but also can be modulated by proper formyl functionalization at specific chromophoric positions. Thus, we propose regioselective formylation as an effective tool to modulate such a delicate photonic balance in BODIPY-based dimeric photosensitizers. The taming of the excited-state dynamics, in particular intramolecular charge transfer as the key underlying process mediating fluorescence deactivation vs. intersystem crossing increasing, could serve to increase fluorescence for brighter bioimaging, enhance the generation of singlet oxygen for killing activity, or balance both for photo-theragnosis.

Bodipy Dimer for Enhancing Triplet-Triplet Annihilation Upconversion Performance.

Triplet-triplet annihilation upconversion (TTA-UC) has considerable potential for emerging applications in bioimaging, optogenetics, photoredox catalysis, solar energy harvesting, etc. Fluoroboron dipyrrole (Bodipy) dyes are an essential type of annihilator in TTA-UC. However, conventional Bodipy dyes generally have large molar extinction coefficients and small Stokes shifts (<20 nm), subjecting them to severe internal filtration effects at high concentrations, and resulting in low upconversion quantum efficiency of TTA-UC systems using Bodipy dyes as annihilators. In this study, a Bodipy dimer (B-2) with large Stokes shifts was synthesized using the strategy of dimerization of an already reported Bodipy annihilator (B-1). Photophysical characterization and theoretical chemical analysis showed that both B-1 and B-2 can couple with the red light-activated photosensitizer PdTPBP to fulfill TTA-UC; however, the higher fluorescence quantum yield of B-2 resulted in a higher upconversion efficiency (ηUC) for PdTPBP/B-2 (10.7%) than for PdTPBP/B-1 (4.0%). This study proposes a new strategy to expand Bodipy Stokes shifts and improve TTA-UC performance, which can facilitate the application of TTA-UC in photonics and biophotonics.

Regioselective Synthesis of Directly Connected BODIPY Dimers through Oxidative Coupling of α-Amino-Substituted BODIPYs.

A family of directly β,β-linked BODIPY dimers with amino groups at α-positions were regioselectively prepared by the oxidative coupling reaction of α-amino-substituted BODIPYs. The structure of one representative dimer was elucidated by X-ray diffraction analysis, showing its twisted orientation of two BODIPY units with a dihedral angle of 49°. Comparing with the corresponding monomers, these dimers showed red-shifted absorptions and emissions along with efficient intersystem crossing, giving ΦΔ of 43% for dimer 4b in toluene, indicating potential use as heavy-atom-free photosensitizers.

A new BODIPY dimer containing carbazole group as a small molecule donor for ternary organic solar cells with the PCE up to 14.97%

The investigation of donor based on small molecules as the active component of bulk-heterojunction organic solar cells (BHJ-OSCs) continues to attract great attention due to their advantages over polymer solar cells. Herein, we report the synthesis and solar cell fabrication of small molecule donors based on BODIPY dimer. The BODIPY dimer features thiophene and carbazole groups as donor units attached to the α and β-positions of the BODIPY core and dicyanodistyryl group as bridging group, and which is named as DI-BDP-CZ and showing complementary absorption with PC71BM and Y6. The electrochemical research results indicate that the frontier energy levels of DI-BDP-CZ (HOMO = −5.55 eV and LUMO = −3.83 eV) is well matched with energy levels of both PC71BM and Y6. The photovoltaic performance of DI-BDP-CZ used as electron-donors along with PC71BM or Y6 as acceptor was evaluated in bulk heterojunction organic solar cells. The OSCs based on optimized DI-BDP-CZ: PC71BM and DI-BDP-CZ: Y6 attained overall PCE of 7.63% and 12.58%, respectively. After the optimization of the active layer, the ternary organic solar cells based on DI-BDP-CZ: PC71BM:Y6 can achieve overall power conversion efficiency (PCE) as high as 14.97%, which is higher than the corresponding binary organic solar cells. The higher PCE of the ternary OSC is ascribed to the efficient exciton dissociation, balanced charge transport, better crystallinity and appropriate phase separation.

4,4′-Dicyano- versus 4,4′-Difluoro-BODIPYs in Chemoselective Postfunctionalization Reactions: Synthetic Advantages and Applications

The presence of F or CN substituents at boron in BODIPYs causes a dramatic effect on their reactivity, which allows their chemoselective postfunctionalization. Thus, whereas 1,3,5,7-tetramethyl B(CN)2-BODIPYs displayed enhanced reactivity in Knoevenagel condensations with aldehydes, the corresponding BF2-BODIPYs can experience selective aromatic electrophilic substitution (SEAr) reactions in the presence of the former. These (selective) reactions have been employed in the preparation of BODIPY dimers and tetramers, with balanced fluorescence and singlet oxygen formation, and all-BODIPY trimers and heptamers, with potential application as light-harvesting systems.

1,4-Bisvinylbenzene-Bridged BODIPY Dimers for Fluorescence Imaging in the Second Near-Infrared Window.

Herein, we report a class of 1,4-bisvinylbenzene-bridged BODIPY dimers with fluorescence emission in the second near-infrared window (NIR-II, 1000-1700 nm). These dyes show excellent NIR-II fluorescence properties and can be easily functionalized to achieve good water-solubility or tumor-targeting ability. In vivo imaging results demonstrate that these dyes have high resolution and deep-penetration NIR-II imaging ability, which enable them to be used as promising NIR-II imaging agents.

Conformation-dependent photophysical properties of butadiyne-linked π-extended BODIPY dimers

A hitherto unknown butadiyne-linked BODIPY dimer (4) has been synthesized under the conventional Glaser coupling reaction conditions using the ethynyl-substituted pyrrolyl-BODIPY (2) prepared by gold-catalyzed C-H alkynylation. Due to the [Formula: see text]-extended structure of the BODIPY chromophore in 4, a characteristic broad absorption band in the near-infrared (NIR) region has emerged. Upon photoexcitation, the environment-dependent fluorescence spectral features were observed. The fluorescent response varied with solvents, viscosity, and temperature, which was found to originate from the conformational changes between the coplanar and twisted conformers in the otherwise rigid butadiyne-bridged dimer 4. Therefore, the BODIPY dimer 4 would be a potential NIR fluorescence material for use in the probes responding to the distinct viscous environment in biological tissues.

Observation of the triplet energy transfer in orthogonal photoexcited iodinated-BODIPY dimers.

Intramolecular charge and energy transfer processes initiated by light absorption can change the photosensitization properties of molecular conjugates. Transient optical and electron paramagnetic resonance (TREPR) spectroscopies are well suited for the study of these processes. In the TREPR spectra of the triplet state of an iodinated BODIPY dimer, we have observed the effect of the averaging of the zero-field (ZFS) parameter E, which becomes more efficient with increasing temperature. This property is associated with triplet energy transfer from one chromophore in the dimer to another, implying the presence of a dynamic equilibrium between the two chromophores of the dimer. From the comparison of the ZFS parameters of the monomer and the dimer, the rates of the reversible hopping are derived within the framework of a two-site model. The obtained data indicate that the triplet states are separated by an energy barrier of ca. 70 K (ca. 0.006 eV) and that below this temperature energy transfer occurs via tunneling.

Tuning CPL by helical pitch modulation in helically flexible small organic multichromophores

Modulating the helical pitch by simply playing with steric effects in a series of helically flexible BODIPY dimers allows easy tuning of the luminescence dissymmetry factors associated with their circularly polarized emissions.