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BODIPY

BODIPY (boron-dipyrromethene) dyes are a class of synthetic fluorescent organic compounds featuring a rigid, planar 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene core, consisting of two pyrrole rings linked by a central boron atom coordinated with two fluoride ions and a methine bridge.^[1] First synthesized in 1968 by Alfred Treibs and Franz-Heinrich Kreuzer through the condensation of pyrroles with aldehydes followed by complexation with boron trifluoride, these dyes have become prominent due to their exceptional photophysical properties.^[1]^[2] BODIPY dyes are renowned for their high molar extinction coefficients (typically 50,000–100,000 M⁻¹ cm⁻¹), near-unity fluorescence quantum yields, narrow absorption and emission bands, and robust photochemical and thermal stability, which surpass many traditional fluorophores like fluorescein or rhodamine.^[3] Their absorption and emission wavelengths are tunable across the visible to near-infrared (NIR) spectrum (approximately 450–800 nm) through structural modifications at the α-, β-, or meso-positions of the core, enabling precise control over electronic and steric properties.^[3]^[2] This versatility arises from the ease of post-synthetic functionalization, including halogenation, alkylation, and conjugation with biomolecules or polymers, often via direct C–H activation or nucleophilic substitutions.^[1] The broad utility of BODIPY dyes spans multiple disciplines, including bioimaging for live-cell labeling and viscosity sensing, photodynamic therapy as triplet photosensitizers for singlet oxygen generation, and optoelectronics in organic light-emitting diodes (OLEDs) and dye-sensitized solar cells.^[3]^[1] In sensing applications, derivatives have been developed for detecting analytes like H₂S or pH changes, while NIR-emitting variants facilitate deep-tissue imaging and photocatalysis.^[1] Ongoing research continues to expand their scope, with innovations in water-soluble and chiral BODIPYs enhancing biocompatibility and stereoselective applications.^[3]

Overview and History

Definition and Significance

BODIPY dyes, short for boron-dipyrromethene, represent a versatile class of synthetic fluorescent compounds characterized by a rigid, planar core structure consisting of two pyrrole rings linked by a bridging methene unit and coordinated to a boron atom difluoride moiety.^[4] The parent BODIPY compound has the molecular formula C₉H₇BN₂F₂ and exhibits high solubility in common organic solvents such as methanol and dichloromethane, facilitating its use in various chemical and biological contexts.^[4] This core scaffold allows for extensive derivatization at multiple positions, enabling tuning of spectral properties while maintaining desirable photophysical traits. The parent BODIPY was first isolated as a pure compound in 2009 through targeted synthesis efforts, marking a milestone in understanding the intrinsic properties of this dye class. BODIPY dyes are prized for their exceptional photophysical attributes, including fluorescence quantum yields approaching 1 (e.g., up to 0.98 in aqueous media for the parent compound), which surpass or rival those of traditional dyes like fluorescein.^[4] Furthermore, they demonstrate superior photostability under prolonged irradiation compared to fluorescein derivatives, reducing bleaching in imaging applications. These advantages extend to biological utility, where BODIPY exhibits low toxicity, high biocompatibility, and minimal interference from environmental factors such as pH or solvent polarity, making it a preferred alternative to older fluorophores for cellular and in vivo studies.

Historical Development

The boron dipyrromethene (BODIPY) class of fluorescent dyes was first synthesized in 1968 by Alfred Treibs and Franz-Heinrich Kreuzer^[5] through an unexpected reaction involving the condensation of 2,4-dimethylpyrrole with acetic anhydride in the presence of phosphorus oxychloride, followed by complexation with boron trifluoride (BF₃) to form difluoroborates of dipyrromethenes. These initial derivatives, featuring methyl and acetyl substituents, exhibited promising photophysical properties but received limited attention at the time, remaining largely obscure in the chemical literature for decades.^[6] Interest in BODIPY dyes revived in the early 2000s, driven by advancements in synthetic methodologies that enabled access to a broader range of substituted analogs with tunable emission wavelengths and enhanced stability. A pivotal 2007 review by Cyril Loudet and Kevin Burgess in Chemical Reviews synthesized the known syntheses and spectroscopic properties of BODIPY derivatives, emphasizing their potential as versatile fluorophores for biological imaging and sensing due to high quantum yields and photostability. This publication marked a turning point, spurring further research and commercialization efforts, with companies like Molecular Probes (acquired by Invitrogen, now Thermo Fisher Scientific) introducing BODIPY-based dyes—under the registered trademark BODIPY—for fluorescence microscopy and flow cytometry in the early 1990s.^[6]^[7] A significant milestone came in 2009 with the first reported synthesis of the unsubstituted parent BODIPY (4,4-difluoro-4-bora-3a,4a-diaza-s-indacene) by Ismael J. Arroyo, Rongrong Hu, Gabriel Merino, Ben Zhong Tang, and Eduardo Peña-Cabrera, achieved via desulfurization of an 8-thiomethyl precursor using triethylsilane and a palladium catalyst, yielding the core structure in near-quantitative efficiency.^[8] Concurrently, Kha Tram, Hongbin Yan, and colleagues independently isolated the parent compound through oxidation of dipyrromethane with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) followed by BF₃ complexation, confirming its exceptional fluorescence quantum yield of 97% and providing the first X-ray crystal structure.^[9] These achievements facilitated the design of minimalist BODIPY scaffolds for fundamental studies. By the 2010s, improved synthetic protocols, including one-pot condensations and post-functionalization strategies, had transformed BODIPY from niche compounds into widely available commercial dyes, with over 5,000 derivatives reported by 2014. A comprehensive 2014 review by Hua Lu, John Mack, Yongchao Yang, and Zhen Shen in Chemical Society Reviews highlighted the evolution of structural modifications for red/NIR-emitting variants, underscoring their expanding role in advanced applications while crediting early synthetic innovations for enabling this growth.

Chemical Identity

Nomenclature

BODIPY dyes are systematically named as derivatives of 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene, a nomenclature reflecting the fused ring system comprising two pyrrole units linked by a methine bridge and coordinated to a difluoroboron moiety. This IUPAC designation emphasizes the boron-centered heterocycle's structural analogy to s-indacene, with the "bora" prefix indicating the boron atom's incorporation and the "diaza" specifying the two nitrogen atoms from the pyrroles. A more detailed von Baeyer-inspired IUPAC name for the parent compound is 5,5-difluoro-5H-4λ⁵-dipyrrolo[1,2-c:2′,1′-f][1,3,2]diazaborinin-4-ylium-5-uide, highlighting the zwitterionic character with the boron as a λ⁵ center and the positive charge on the meso carbon.^[10] The acronym BODIPY originates from "BOron DIPYrromethene," denoting the core dipyrromethene ligand chelated by boron difluoride, a term coined following the initial synthesis of these compounds in 1968. In literature, the class is also frequently referred to as boron-dipyrromethene difluorides, underscoring the BF₂ coordination essential to their stability and photophysical properties. For derivatives, naming follows the parent indacene scaffold with substituents indicated by position numbers: the pyrrole rings bear positions 1,2,3,5,6,7 (with β-positions at 2 and 6, α-positions at 1,3,5,7), the meso methine bridge is position 8. For instance, 2,6-dichloro-BODIPY designates chlorine substitutions at the β-positions on each pyrrole, while meso-substituted variants like 8-phenyl-BODIPY append groups at the central carbon. This standardized numbering facilitates precise description of functionalization patterns across the thousands of reported BODIPY analogs.

Molecular Structure

The BODIPY core features a planar dipyrromethene ligand, consisting of two pyrrole rings connected by a meso carbon bridge, that chelates a central boron atom through its two nitrogen atoms. The boron is further coordinated to two fluoride ligands in a tetrahedral geometry, forming a central six-membered heterocycle (B-N-C-C-N). This chelation rigidifies the structure and enables extensive conjugation across the dipyrromethene framework.^[9] Formally, the core is zwitterionic, with a negative charge on the boron atom and a delocalized positive charge primarily on the nitrogen atoms of the dipyrromethene ligand. This charge distribution supports a conjugated π-system spanning 14 atoms, which exhibits aromatic character with 14 π electrons, contributing to the molecule's stability and planarity. The delocalization occurs over the fused ring system, including the two pyrrole units, the meso bridge, and the boron-chelated ring.^[11] X-ray crystallography of the unsubstituted BODIPY, first reported in 2009, confirms the high planarity of the core, with non-hydrogen atoms deviating by less than 0.05 Å from the mean plane, underscoring its inherent rigidity. Bond lengths in the chelate ring are characteristic: B–N distances average approximately 1.56 Å, indicative of partial double-bond character due to resonance, while B–F bonds measure about 1.39 Å. The structure is nearly symmetrical along the meso axis, except for the equivalent fluoride atoms, which adopt a trans-like orientation relative to the ligand plane.^[9]^[12]

Synthesis

Classical Synthesis

The classical synthesis of BODIPY dyes follows a two-step process that begins with the acid-catalyzed condensation of pyrrole and an aldehyde to form a dipyrromethene intermediate, followed by coordination of this ligand with boron trifluoride diethyl etherate (BF₃·OEt₂) in the presence of a base. In the first step, excess pyrrole (typically 25–40 equivalents) reacts with the aldehyde under mild acidic conditions, such as trifluoroacetic acid (TFA) or hydrochloric acid (HCl) catalysis, in solvents like dichloromethane or water at room temperature for 2–24 hours. This condensation, a variant of the acid-mediated pyrrole-aldehyde coupling akin to early steps in porphyrin synthesis, yields a dipyrromethene after oxidation with agents like 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) or p-chloranil to remove excess hydrogens and prevent over-polymerization. The dipyrromethene intermediate is notably unstable and prone to decomposition, necessitating careful handling and immediate progression to the second step to avoid significant losses. The second step involves treating the dipyrromethene with BF₃·OEt₂ and a base such as triethylamine (Et₃N) or 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in an inert atmosphere, typically in dichloromethane, to facilitate boron chelation and form the rigid BODIPY core. The reaction can be represented as:

\text{Dipyrromethene} + \text{BF}_3 \cdot \text{OEt}_2 \rightarrow \text{BODIPY} + 2 \text{Et}_2\text{O}

This coordination step locks the dipyrromethene into a planar, conjugated structure with enhanced stability and fluorescence properties. Overall yields for the two-step process range from 50% to 80%, depending on substituents and conditions, though challenges such as pyrrole polymerization, formation of oligopyrromethene side products, and purification difficulties from colored byproducts often reduce efficiency. This method was first reported in 1968 by Treibs and Kreuzer, who serendipitously obtained early BODIPY derivatives during attempts to synthesize pyrrole complexes with BF₃, using 2,4-dimethylpyrrole and acetic anhydride under Lewis acid conditions.^[13] Their one-pot variant laid the groundwork, but the general two-step approach was refined in subsequent decades to accommodate diverse aldehydes and pyrroles.^[13] Optimizations in the 2000s, particularly for the unsubstituted BODIPY core, addressed long-standing difficulties in handling α-unsubstituted dipyrromethenes by employing milder oxidants like DDQ and streamlined purification, enabling isolation of the parent compound in yields up to 70% for the first time in 2009. These improvements, including reduced pyrrole excess and controlled oxidation, have made the classical route the most widely adopted for preparing symmetrically substituted BODIPYs.

Alternative Methods

Alternative synthetic strategies for BODIPY have emerged to address limitations of the classical two-step method, such as multi-step processes and reliance on fluoride sources, by emphasizing streamlined, environmentally friendly approaches that enhance efficiency, yield, and versatility. One-pot syntheses, for instance, integrate the condensation of pyrroles with aldehydes or acyl chlorides and subsequent boron complexation in a single vessel, often accelerated by microwave irradiation to achieve reaction times as short as minutes while using minimal solvent volumes. This microwave-assisted protocol, developed in 2022, operates at low temperatures (around 100°C) and delivers good yields (up to 70%) for diverse BODIPY derivatives, including those with aryl substituents, making it scalable and suitable for library synthesis.^[14] Solvent-free mechanochemical methods represent another efficient alternative, employing grinding techniques like ball milling or pestle-and-mortar to facilitate the reaction without organic solvents, thereby reducing environmental impact and waste. These approaches complete BODIPY formation in under 5 minutes at room temperature, yielding up to 90% for symmetric derivatives from dipyrromethanes and boron sources, and are particularly advantageous for sensitive substrates prone to side reactions in solution. Multicomponent reactions (MCRs) further simplify the process by enabling protecting-group-free assembly of the dipyrromethene core directly from pyrroles, aldehydes, and boron reagents in one step, improving atomic economy and avoiding purification challenges associated with intermediate isolation.^[15] To access non-fluoride BODIPY analogs, alternative boron sources like boron trichloride (BCl₃) or trialkyl borates (B(OR)₃) are employed during the complexation step, yielding chloro- or alkoxy-substituted variants that facilitate subsequent functionalizations. For chloro-BODIPYs, BCl₃ reacts with dipyrromethenes in the presence of a base to form BCl₂ complexes in high yields (over 80%), which exhibit enhanced reactivity toward nucleophilic substitutions compared to BF₂ analogs, enabling easy installation of B-OR or B-NR₂ groups without disrupting the chromophore. Similarly, B(OR)₃, such as trimethyl borate, complexes directly with dipyrromethenes under mild conditions to produce dimethoxy-BODIPYs, though yields are moderate (around 40%), these compounds offer improved solubility and stability for further derivatization at boron. These methods, detailed in a 2024 review, prioritize boron variants with minimal impact on photophysical properties while broadening synthetic accessibility.^[16] Recent advances from 2022 to 2025 have focused on sustainable, green syntheses to mitigate toxicity from traditional reagents like BF₃·OEt₂, incorporating multicomponent and flow-based strategies for broader applicability. Continuous flow reactors address industrial scalability by enabling precise control over reaction parameters, such as residence time and temperature, to produce BODIPY photosensitizers at rates up to grams per hour with reduced solvent use and high reproducibility, overcoming batch limitations like inconsistent yields during scale-up. These innovations, including enzyme-free catalytic cascades in flow, align with green chemistry principles by minimizing waste and energy consumption, as highlighted in comprehensive 2025 analyses of BODIPY methodologies.^[15]^[17]

Photophysical Properties

Absorption and Emission Spectra

BODIPY dyes exhibit intense absorption in the visible region, typically spanning 420–520 nm, with a characteristic sharp peak arising from the S₀ → S₁ π-π* transition within the dipyrromethene core.^[18] This transition is responsible for their high molar extinction coefficients, often exceeding 70,000 M⁻¹ cm⁻¹, enabling efficient light harvesting.^[18] The corresponding fluorescence emission occurs in the 480–580 nm range, producing bright green to yellow light with narrow bandwidths of approximately 50 nm.^[18] For the parent BODIPY compound, measured in dichloromethane, the absorption maximum is observed at 503 nm, while the emission maximum is at 512 nm, resulting in a small Stokes shift of about 9 nm. This minimal shift reflects the rigid, planar structure of the chromophore, which experiences little geometric relaxation in the excited state.^[18] Such properties contribute to the dyes' utility in applications requiring high spectral resolution, as the overlap between absorption and emission is limited.^[18] Spectral tuning of BODIPY dyes is readily achieved through strategic substitution on the pyrrole rings or meso position, allowing shifts in absorption and emission wavelengths to cover broader regions of the spectrum. Electron-donating groups, such as alkyl or amino substituents at the β-positions (2 and 6), generally cause bathochromic shifts by raising the HOMO energy, while electron-withdrawing groups like cyano or nitro at the α-positions (1 and 7) lower the LUMO energy, further red-shifting the bands.^[18] For instance, incorporation of extended conjugated systems, such as styryl groups, can push absorption maxima beyond 600 nm and emission into the near-infrared (NIR) region around 650 nm, facilitating applications in biological imaging where deeper tissue penetration is needed.^[18] These modifications maintain the small Stokes shifts of 10–20 nm characteristic of the BODIPY family.

Quantum Yield and Stability

The quantum yield (Φ) of the parent BODIPY compound is high, for example 0.79 in air-saturated toluene, reflecting its efficient radiative decay from the singlet excited state.^[4]^[19] This efficiency arises from the rigid, planar structure that minimizes non-radiative pathways like vibrational relaxation. However, for many BODIPY derivatives, particularly hydrophobic ones, the quantum yield can drop significantly in aqueous environments due to aggregation-induced quenching, where π-π stacking forms non-fluorescent dimers or higher-order aggregates.^[19]^[20] Typical fluorescence lifetimes for BODIPY dyes range from 6 to 10 ns in non-polar media, measured using time-correlated single-photon counting (TCSPC), a standard technique that resolves the decay kinetics with high temporal resolution.^[4]^[21] These lifetimes indicate a stable excited state, with minimal solvent-dependent variation for the parent compound (e.g., 6.02 ns in toluene to 7.36 ns in water), though oxygen quenching can shorten them in aerated solutions.^[4] BODIPY dyes exhibit high photostability compared to fluorescein, resisting photobleaching under prolonged irradiation due to their robust boron-fluoride coordination and low triplet-state population.^[7] This makes them ideal for extended imaging applications, where fluorescein derivatives often degrade faster via oxidative mechanisms. Thermally, BODIPY-based materials remain stable up to approximately 200°C, as evidenced by thermogravimetric analysis showing no significant decomposition below this threshold.^[22] Key factors influencing quantum yield include solvent polarity and pH, with increased polarity promoting twisted intramolecular charge transfer that enhances non-radiative decay and reduces emission efficiency. For pH-sensitive variants, acidic conditions can protonate the core, altering the electronic structure and lowering Φ by up to an order of magnitude in some cases. Recent 2024 studies on solvatochromic BODIPY derivatives highlight this effect, demonstrating diminished emission in polar media due to enhanced charge separation in the excited state.^[23]^[24]

Derivatives and Functionalization

Core Substitutions

Core substitutions in BODIPY dyes primarily occur at the carbon atoms of the dipyrromethene ligand, specifically positions 1, 2, 3, 5, 6, and 7 on the pyrrole rings and position 8 at the meso bridge. These modifications enable fine-tuning of the dye's electronic and steric properties without altering the central boron atom. Among these, the β-positions (2 and 6) are particularly reactive toward electrophilic substitution, often introducing halogens such as bromine or iodine to facilitate subsequent cross-coupling reactions. The α-positions (3 and 5) and the 1 and 7 positions adjacent to the nitrogens are also common sites for derivatization, influencing conjugation and molecular geometry. The meso position (8) typically bears aryl or alkyl groups from the synthesis precursor, but can be further modified via specialized couplings.^[25] Substitutions can be introduced either during the initial core assembly using appropriately functionalized precursors or through post-synthetic functionalization of the preformed BODIPY scaffold. In precursor-based methods, substituted pyrroles or aldehydes are condensed under acid catalysis (e.g., TFA or HCl) to directly incorporate groups at the pyrrole positions (1–3, 5–7) or meso site, yielding 7–70%.^[25] Post-functionalization often begins with electrophilic halogenation at the 2 and 6 positions using NCS, NBS, or I2, producing 2,6-dihalo-BODIPYs in high yields, which serve as versatile intermediates for Pd-catalyzed Suzuki-Miyaura or Stille couplings to install aryl, alkenyl, or alkyl substituents. For meso modifications, nucleophilic displacement on 8-methylthio-BODIPYs via Liebeskind-Srogl coupling achieves 60–93% yields for aryl exchanges.^[25] These approaches allow regioselective control, though steric factors at crowded sites like 1 and 7 may require milder conditions to avoid side reactions. The placement and nature of substituents significantly impact the BODIPY core's planarity and electronic structure. Bulky groups at the 1 and 7 positions introduce steric hindrance, twisting the pyrrole rings out of plane and restricting rotation of the meso substituent, which can enhance fluorescence quantum yields by reducing non-radiative decay (e.g., from 0.3 to >0.8 in ortho-substituted meso-phenyl variants). Electron-withdrawing groups such as nitro or cyano at the 3 and 5 positions disrupt π-conjugation, leading to blue-shifted absorption and hypsochromic emission, while also increasing redox potentials for improved stability in oxidative environments. In contrast, halogens at 2 and 6 cause modest red-shifts due to inductive effects but enable extended conjugation via coupling, tuning photophysical properties for specific needs. These electronic perturbations at 3 and 5 primarily affect the HOMO-LUMO gap without major planarity changes, unlike steric effects at 1 and 7.^[26] Representative examples highlight the utility of core substitutions for derivatization. The 2,6-dibromo- or diiodo-BODIPYs, synthesized via direct halogenation, are staples for iterative cross-couplings, enabling π-extension with styryl or aryl units to red-shift emission beyond 600 nm while maintaining high quantum yields (>0.5). Recent advances include multi-substituted probes, such as 8-meso-pyridyl-BODIPYs with electron-withdrawing methylester groups at 2 and 6, which enhance solubility. In 2025, chalcogen-based functionalizations at core positions have emerged for tuning photophysical properties in sensing and imaging applications.^[27]^[28]

Boron Modifications

The BF₂ moiety in BODIPY dyes serves as a key site for post-synthetic modifications through nucleophilic substitution of the fluoride ligands, enabling the introduction of alternative substituents that enhance reactivity without altering the core chromophore. Treatment of BF₂-BODIPY with BCl₃ facilitates the replacement of both fluorides with chlorides, yielding 4,4-dichloro derivatives that exhibit heightened susceptibility to further nucleophilic attacks due to the weaker B–Cl bonds.^[16] Bromide substitution follows analogous halogen exchange pathways, often via BBr₃ intermediates, producing BBr₂ complexes with similar reactivity profiles but increased lability in polar media.^[29] Alkoxy groups (OR) are introduced via reaction with alkoxides such as sodium methoxide, forming B(OR)₂ species like dimethoxy-BODIPY, which shift the redox potentials by approximately 0.1 V per methoxy unit and improve solubility in polar solvents.^[16] These boron alterations provide versatile reactive handles for advanced functionalization. Boronic ester variants, exemplified by B(OR)₂ where R includes alkyl or aryl chains, act as precursors to boronic acids upon hydrolysis, enabling bioconjugation through dynamic covalent interactions with vicinal diols on carbohydrates or proteins.^[16] Azide functionalization of BODIPY supports copper-catalyzed azide-alkyne cycloaddition (CuAAC) for efficient click chemistry labeling in biological systems, though such derivatives require careful handling to maintain fluorophore integrity.^[30] A primary trade-off in these modifications involves stability versus reactivity: the BF₂ core offers superior chemical and photostability, preserving high fluorescence quantum yields (often >0.5) essential for imaging applications, whereas softer ligands like B(OR)₂ are more labile, prone to hydrolysis or ligand exchange in aqueous or protic environments, which can limit long-term performance but facilitates on-demand reactivity.^[16] Halogen replacements such as Cl or Br introduce a heavy-atom effect that quenches fluorescence (quantum yields dropping to <0.1 in some cases) but accelerate subsequent substitutions for synthetic diversification. Recent advancements from 2022 to 2025 have focused on boron-substituted variants to address solubility challenges, with organometallic approaches introducing hydrophilic appendages like –CH₂CH₂OH directly onto the boron, yielding water-soluble BODIPYs suitable for live-cell imaging without compromising emission efficiency.^[16] In 2025, streamlined asymmetric synthesis of boron-stereogenic BODIPY libraries has enabled stereoselective applications in chiral recognition and catalysis.^[31] These modifications have also enabled boron-reactive probes for environmental sensing, including 2024 developments in cyanide detection where nucleophilic displacement at the boron site triggers colorimetric and fluorogenic responses with detection limits below 1 μM in aqueous media.

Applications

Biological and Imaging Uses

BODIPY dyes are extensively employed in cellular imaging owing to their tunable emission spectra, which span from visible to near-infrared wavelengths, enabling the development of organelle-specific probes with minimal autofluorescence interference. Mitochondria-targeted derivatives, such as those bearing triphenylphosphonium cations, selectively accumulate via the organelle's negative membrane potential, facilitating high-resolution visualization of mitochondrial morphology and dynamics in live cells like HeLa. Lysosome-specific probes, incorporating protonatable groups like morpholine, localize to the acidic lysosomal lumen, allowing precise tracking of lysosomal trafficking and function in various cell types. These attributes, combined with BODIPY's high photostability, support applications in super-resolution microscopy and multiplexed imaging of subcellular structures.^[32] As of 2025, advances in water-soluble and cell membrane-permeable BODIPY dyes have further improved their utility in precise subcellular targeting and live-cell imaging.^[33] As of late 2024, advances in enantiopure BODIPYs have enabled stereoselective bioimaging and sensing applications.^[34] In photodynamic therapy (PDT), BODIPY derivatives function as efficient photosensitizers by generating singlet oxygen upon photoexcitation, inducing oxidative damage to targeted cancer cells while sparing healthy tissue. For instance, aza-BODIPY (AZB-I) coencapsulated with cannabidiol in lecithin-based nanoparticles enhances singlet oxygen yield (ΦΔ = 0.048 under 660 nm irradiation), promoting apoptosis and pyroptosis in liver cancer cells with an IC50 of 4.3 nM. Multifunctional variants like FBD-M, featuring oxygen-carrying pentafluorobenzene and lysosome-targeting morpholine moieties, alleviate tumor hypoxia and boost ROS production for synergistic chemo-phototherapy against solid tumors. Recent progress includes BODIPY systems engineered to exploit glutathione in glioma cells, improving PDT efficacy by countering resistance mechanisms in hypoxic environments.^[35]^[36]^[37] BODIPY-based ratiometric sensors provide quantitative detection of reactive species and ions in biological contexts, leveraging dual-emission shifts for accurate intracellular monitoring. The mitochondria-targeted MOBDP-I probe senses peroxynitrite (ONOO⁻, a reactive nitrogen species) through oxidative cleavage of a C=C bond, yielding an 18-fold fluorescence enhancement at 510 nm with a detection limit of 9.6 nM and response time under 1 second; it has imaged oxidative stress in inflammatory models like rheumatoid arthritis in mice. For ions, an α-benzithiazolyl 3-pyrrolyl BODIPY chemodosimeter selectively detects cyanide (CN⁻) via nucleophilic addition, producing a 180 nm blue-shift in emission with a 13 nM limit of detection and 10-second response, suitable for live-cell bioimaging. pH-sensitive BODIPY sensors exploit aggregation-induced emission to ratiometrically track lysosomal acidification, as demonstrated in crystalline silica-exposed cells undergoing metabolic stress.^[38]^[39] BODIPY's biocompatibility stems from its low cytotoxicity across cell lines, with many derivatives showing IC50 values exceeding 100 µM in assays on HeLa and cancer cells, supporting prolonged in vivo imaging without significant adverse effects. Recent 2025 developments include straightforward chemical modifications to convert hydrophobic BODIPYs into water-soluble variants, enhancing their biocompatibility and applications in aqueous environments.^[40] This low toxicity profile, coupled with structural versatility, facilitates conjugation to antibodies or ligands like biotin for targeted delivery, as in AminoBODIPY systems that direct payloads to specific receptors on tumor cells, enhancing therapeutic selectivity and minimizing systemic exposure.^[41]

Materials and Energy Applications

BODIPY derivatives have emerged as effective photocatalysts in visible-light-driven reactions, particularly for hydrogen evolution and CO₂ reduction. In photocatalytic water splitting, alkyl-substituted BODIPY dyes, such as those with fluorine-induced intramolecular charge transfer, enhance hydrogen production rates when sensitized on TiO₂ in aqueous ascorbic acid solutions. For instance, a BODIPY dye with a long alkyl chain (7c) achieves a hydrogen evolution rate of 496.5 µmol g⁻¹ h⁻¹ and an apparent quantum yield of 1.4% at 650 nm, attributed to improved hydrophobicity and charge separation in the second coordination sphere.^[42] Similarly, BODIPY-thiophene covalent organic polymers integrated with TiO₂ yield hydrogen at 0.197 mmol g⁻¹ h⁻¹ under visible light, benefiting from enhanced electron transfer and hydrophilicity from hydroxyl groups.^[43] For CO₂ reduction, cross-linked carbazole-BODIPY photocatalysts on platinum electrodes selectively produce ethanol with a Faradaic efficiency of 34.79% at -1.15 V, demonstrating stable turnover over extended irradiation due to efficient charge generation under sunlight.^[44] These post-2021 advancements highlight BODIPY's tunable photophysical properties for sustainable energy conversion, often leveraging core substitutions for better light harvesting and stability.^[42] In energy storage, BODIPY dyes serve as active species in organic redox flow batteries, offering high stability and capacity through their reversible redox behavior. A seminal study characterized the BODIPY dye PM567 in an all-organic flow cell, revealing a theoretical voltage of 2.32 V and a stable discharge voltage of ~1.6 V, with Coulombic efficiency reaching 73% after initial cycling.^[45] The dye's fluorescence and multi-electron transfer capabilities enable efficient energy density, though degradation products form stable redox-active species over time, supporting long-term operation.^[45] Recent research from 2022 onward builds on this by incorporating BODIPY into non-aqueous electrolytes for scalable batteries, emphasizing its role in decoupling power and energy for grid storage.^[46] In 2025, new BODIPY dyes have been developed as photoinitiators for free radical polymerization under long-wavelength light, enabling efficient photopolymerization processes for materials synthesis.^[47] BODIPY compounds are widely used as sensors for environmental monitoring, particularly for detecting heavy metal ions due to their selective fluorescence responses. Quinoline-functionalized BODIPY derivatives detect Hg²⁺ with a limit of detection of 3.06 × 10⁻⁸ M in water samples, forming a 1:1 complex that quenches emission via chelation-enhanced fluorescence.^[48] These sensors operate through mechanisms like photoinduced electron transfer (PET) and intramolecular charge transfer (ICT), enabling real-time monitoring in tap water and low-cytotoxicity applications.^[49] For broader IIB metals (Zn²⁺, Cd²⁺, Hg²⁺), BODIPY-based probes exhibit high selectivity and sensitivity in environmental matrices, with detection limits often below 10⁻⁷ M, facilitating pollution assessment without interference from common ions.^[49] As laser dyes, BODIPYs excel due to their narrow emission bandwidths and high photostability, enabling efficient amplified spontaneous emission in the red to near-infrared range. Extended polyphenyl- and polythiophene-BODIPYs lase from 610 to 750 nm with efficiencies up to 20% and photostabilities exceeding 10 GJ/mol, suitable for telecommunications and imaging.^[50] The narrow full-width at half-maximum (typically 20-30 nm) minimizes spectral overlap, while donor-acceptor substitutions tune output for solid-state or liquid lasers.^[50] Emerging applications include BODIPY-ZnO nanocomposites for antibacterial materials and roles in organic electronics. BODIPY-modified ZnO nanoparticles (BIN-ZnO) enhance visible-light antibacterial activity against E. coli and S. aureus by generating reactive oxygen species and accelerating Zn²⁺ release, achieving complete bacterial inactivation in 2 hours under LED illumination.^[51] In organic electronics, BODIPY-based nonfullerene acceptors in solar cells achieve power conversion efficiencies of 13.94% through NIR absorption and optimized charge transport.^[52] For OLEDs, structurally optimized green-emitting BODIPY derivatives deliver external quantum efficiencies of 20% with narrow emissions (FWHM 25 nm) and operational lifetimes over 200 hours, leveraging steric and electronic tuning for hyperfluorescence.^[53]

References

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Apr 28, 2020 · BODIPY (boron-dipyrromethene) is a fluorescent dye with structural versatility, used in many scientific and technological fields.
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[PDF] Boron Dipyrromethenes: Synthesis and Computational Analysis
Apr 1, 2019 · Boron dipyrromethene (BODIPY, 4,4ʹ-difluoro-4-bora-3a,4a-diaza-s-indacene) compounds are an exciting class of fluorescent molecules1–16. In 1968 ...<|control11|><|separator|>
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BODIPY Dyes and Their Photophysical Properties - Nature
BODIPY dyes, based on the boron dipyrromethene core, are renowned for their exceptional photophysical properties – notably high fluorescence quantum yields, ...
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[8]
4,4-Difluoro-4-bora-3a,4a-diaza-s-indacene - PubChem
4,4-Difluoro-4-bora-3a,4a-diaza-s-indacene | C9H7BF2N2 | CID 25058173 - structure, chemical names, physical and chemical properties, classification, ...Missing: color | Show results with:color
[9]
BODIPY Conjugates as Functional Compounds for Medical ...
The combination of the bowl-shaped structure and delocalized 14π-electron aromatic conjugation system governs intense fluorescence and nonlinear optical ...
[10]
Fluorinated Boron-Dipyrromethene (BODIPY) Dyes: Bright and ... - NIH
F-BODIPYs are bright, photostable fluorophores used as dual labels for surface analysis, especially for quantifying amino groups via XPS and fluorescence.
[11]
https://pmc.ncbi.nlm.nih.gov/articles/PMC8877204/
[12]
Microwave-assisted direct synthesis of BODIPY dyes and derivatives
This protocol features short reaction times, low temperatures, minimum amount of solvent, scalability, versatility, and good yields of the products. These ...
[13]
https://doi.org/10.1002/jlac.19687180119
[14]
https://pubs.rsc.org/en/content/articlelanding/2022/ob/d2ob01349e
[15]
Continuous-flow synthesis and application of polymer-supported ...
Feb 13, 2020 · The polymer-supported BODIPY resins could be irradiated for 96 h without loss of photosensitising ability. Additional material synthetic ...
[16]
https://doi.org/10.3390/molecules29215157
[17]
Modulating the Optical Properties of BODIPY Dyes by Noncovalent ...
Oct 2, 2020 · Besides the inclusion of Ag+ ions, the large absorption change of fullerene C60 and altered emission of a BODIPY dimer are obsd.
[18]
A Concise Route to Water-Soluble 2,6-Disubstituted BODIPY ...
Jun 22, 2021 · (1) In this context, the consideration of boron dipyrromethene difluoride (BODIPY) dyes, e.g., 1 (Figure 1), has amply surpassed that of the ...
[19]
Fluorescence Lifetime Imaging of Molecular Rotors in Living Cells
Feb 9, 2012 · We have developed a practical and versatile approach to map the microviscosity in cells based on FLIM of fluorescent molecular rotors.
[20]
BODIPY Dye Series—Section 1.4 | Thermo Fisher Scientific - US
2 The structure and numbering of the BODIPY fluorophore, 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene. The core structure of the BODIPY fluorophore is shown in ...Missing: compound C9H7BN2F2
[21]
Postmethylation of BODIPY-Based Covalent Organic Framework ...
(37) Thermogravimetric analysis (TGA) curves (Figure S1) showed that both samples were thermally stable up to 200 °C, suggesting their potential as photothermal ...
[22]
Fluorescent pH sensors based on BODIPY structure sensitive in ...
The BODIPY with methyl substituents 1 shows quantum yields of fluorescence one magnitude higher (Φf = 0.30–0.55) compared to 2. •. Both BODIPY dyes show pH ...
[23]
Solvatochromic and biological studies of new meso-benzodioxole ...
Nov 1, 2024 · This paper focuses on solvatochromic studies of a new synthesised BODIPY dye with piperonal and ortho-hydroxy aryl Schiff base substituents (BD-2-Schiff).
[24]
A Review on the Synthetic Methods for the BODIPY Core - MDPI
As early as 1968, Treibs and Kreuzer unexpectedly obtained the BODIPY core substituted with 2-acetyl and 2,6-diacetyl groups by reacting pyrrole with acetic ...<|control11|><|separator|>
[25]
Effects of Nitro-Substitution on the Spectroscopic and Self-Assembly ...
The absolute fluorescence quantum yields observed for all BODIPYs were always higher in toluene compared with acetonitrile, even for the non-nitrated parent ...<|separator|>
[26]
8(meso)-Pyridyl-BODIPYs: Effects of 2,6-Substitution with Electron ...
Jun 6, 2023 · The presence of the methyl groups at the 1,7-positions of these 8(meso)-pyridyl-BODIPYs prevents the rotation of the meso-pyridyl groups, ...
[27]
https://pmc.ncbi.nlm.nih.gov/articles/PMC10303842/
[28]
Investigation and Development of the BODIPY-Embedded Isotopic ...
Oct 2, 2024 · We investigated the potential of BODIPY FL azide as a click chemistry enabled chemoproteomics reagent due to the presence of boron and the ...
[29]
BODIPY Dyes: A New Frontier in Cellular Imaging and Theragnostic ...
BODIPY dyes are particularly advantageous due to their exceptional photostability, elevated quantum yield, narrow absorption profiles, straightforward ...
[30]
Cannabidiol and Aza-BODIPY Coencapsulation for Photodynamic ...
May 22, 2024 · Photodynamic therapy (PDT) and cannabidiol (CBD) have been explored for their potential in synergistic cancer treatment.
[31]
An oxygen-carrying and lysosome-targeting BODIPY derivative for ...
In this study, we designed a multifunctional BODIPY derivative, FBD-M, for synergistic chemo-phototherapy against hypoxic tumors.
[32]
Molecular Determinants for Photodynamic Therapy Resistance and ...
However, the presence of GSH in glioma cells can also be used to improve the effect of PDT. Hwang et al. engineered PS ubiquinone-BODIPY, whose reduction by ...
[33]
BODIPY-Based Ratiometric Fluorescent Probe for Sensing ...
Dec 22, 2024 · BODIPY-based fluorescent probes have been developed for the detection of ONOO− through structural modifications of the BODIPY core [26,27,28,29] ...
[34]
An α-benzithiazolyl 3-pyrrolyl BODIPY probe for ratiometric selective ...
The probe acted as an exclusive colorimetric and chemodosimetric sensor for CN − ions over other anions with high sensitivity (LOD = 13 nM) and quick response ...Missing: ROS RNS pH
[35]
BODIPY-Based Molecules for Biomedical Applications - PMC - NIH
Nov 30, 2023 · The high quantum yields of BODIPY dyes suggest that a considerable percentage of the absorbed energy is transformed into fluorescence. The ...
[36]
The acceleration of BODIPY dye-sensitized photocatalytic hydrogen production in aqueous ascorbic acid solutions using alkyl-chain formed second coordination sphere effects
### Summary of BODIPY Dyes for Photocatalytic H₂ Production
[37]
Light driven photocatalytic hydrogen generation using BODIPY ...
Aug 14, 2025 · Boron-dipyrromethene (BODIPY) - based dyes have recently garnered attention as sensitizers for photocatalytic hydrogen production.Missing: CO2 | Show results with:CO2
[38]
A New Strategy for Photo‐Electrochemical Reduction of Carbon ...
Dec 1, 2024 · This study demonstrates the efficient conversion of carbon dioxide to ethanol under sunlight using a novel cross-linked carbazole-BODIPY ...
[39]
Characterization of a BODIPY Dye as an Active Species for Redox ...
Dec 8, 2016 · An all-organic redox flow battery (RFB) employing a fluorescent boron-dipyrromethene (BODIPY) dye (PM567) was investigated.Missing: 2022-2025 | Show results with:2022-2025
[40]
Designing the next generation of symmetrical organic redox flow ...
Mar 20, 2024 · In this manuscript, we will present our contribution to this field through the design of tunable bipolar molecules within the helicene carbocation class.
[41]
Bodipy-based quinoline derivative as a highly Hg 2+
These approaches are efficient and accurate in detecting heavy metal ions. The literature has highlighted significant progress in the design and development of ...
[42]
Recent developments on BODIPY based chemosensors for the ...
This review highlights the recent progress in the design of BODIPY based chemosensors for the detection of IIB metal ions environmental as well as biological ...
[43]
Extended BODIPYs as Red–NIR Laser Radiation Sources with ... - NIH
All these laser dyes display absorption and emission bands in the red edge of the visible spectrum reaching the near-infrared with thiophene functionalization.Missing: narrow | Show results with:narrow
[44]
Study of synergetic effect between BODIPY and ZnO on visible light ...
The study shows that the synergistic effect of BIN and ZnO increases ROS yields and accelerates Zn ion release, enhancing antibacterial activity. BIN-ZnO shows ...
[45]
Emerging BODIPY‐Based NonFullerene Acceptors: Innovations for Organic Solar Cells
### Summary of BODIPY-Based Nonfullerene Acceptors for Organic Solar Cells
[46]
Structural Optimization of BODIPY Derivatives: Achieving Stable and ...
We developed a new design strategy to regulate the emission of BODIPY derivatives by modifying the electronic and steric dominance using functionalities.