Synthesis and Properties of Bright Red-to-NIR BODIPY Dyes for Targeting Fluorescence Imaging and Near-Infrared Photothermal Conversion.

An efficient synthesis of 3-pyrrolylBODIPY dyes has been developed from a rational mixture of various aromatic aldehydes and pyrrole in a straightforward condensation reaction, followed by in situ successively oxidative nucleophilic substitution using a one-pot strategy. These resultant 3-pyrrolylBODIPYs without blocking substituents not only exhibit the finely tunable photophysical properties induced by the flexible meso-aryl substituents but also serve as a valuable synthetic framework for further selective functionalization. As a proof of such potential, one 3-pyrrolylBODIPY dye (581/603 nm) through the installation of the morpholine group is applicable for lysosome-targeting imaging. Furthermore, an ethene-bridged 3,3'-dipyrrolylBODIPY dimer was constructed, which displayed a near-infrared (NIR) emission extended to 1200 nm with a large fluorescence brightness (2840 M-1 cm-1). The corresponding dimer nanoparticles (NPs) afforded a high photothermal conversion efficiency (PCE) value of 72.5%, eventually resulting in favorable photocytotoxicity (IC50 = 9.4 µM) and efficient in vitro eradication of HeLa cells under 808 nm laser irradiation, highlighting their potential application for photothermal therapy in the NIR window.

Boron-Templated Synthesis of B(III)-Submonoazaporphyrins: The Hybrids of B(III)-Subporphyrins and B(III)-Subporphyrazines.

A new class of hybridized and core-contracted porphyrinoids, B(III)-submonoazaporphyrins, which may be viewed as the hybrids of B(III)-subporphyrins and B(III)-subporphyrazines, was reported. The versatile single-step synthesis was based on an efficient intramolecular nucleophilic substitution reaction on readily available α-amino-α'-bromotripyrromethenes, while boronic acids, trifluoroborate salts, or trimethoxyborate simultaneously acted as the template and provider of apical substituent. Those new hybrids, as robust and photostable compounds, were fully characterized by NMR, mass spectrometry, and X-ray crystallography. They showed intense absorption and emission in the visible region, and their electrochemical properties and computational calculation are also discussed.

Organotrifluoroborate Salts as Complexation Reagents for Synthesizing BODIPY Dyes Containing Both Fluoride and an Organo Substituent at the Boron Center.

A convenient procedure for the preparation of functionalized BODIPYs bearing both F and an organo substituent at the boron center, using one-pot reactions between in situ formed dipyrromethenes and organotrifluoroborate salts, has been reported. The complexation reaction utilizes stable and commercial accessible organotrifluoroborate potassium salts and provides a facile access to a variety of novel B-functionalized BODIPYs, which are hard to access through current synthetic methods.

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.

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

A family of directly ß,ß-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.

Aryl-Boron-Substituted BODIPYs: Direct Access via Aluminum-Chloride-Mediated Arylation from Arylstannanes and Tuning the Optoelectronic Properties.

An efficient procedure is presented for functionalization of BODIPYs at boron with arylstannanes as weak nucleophiles in the presence of aluminum chloride, providing new aryl-boron-substituted BODIPY and aza-BODIPY derivatives of singular importance. Most of these aryl-boron-substituted BODIPYs showed bright emission in the aqueous solution with significant aggregation-induced emission enhancement and high solid-state emission as a result of the restricted rotation of the meso-phenyl group and boron-substituted aryl groups as well as the formation of J-type aggregates.

Tuning of Redox Potentials and LUMO Levels of BODIPYs via Site-Selective Direct Cyanation.

Through a strong oxidant Pb(OAc)4 promoted oxidative nucleophilic hydrogen substitution, site-selective direct and stepwise cyanation of BODIPYs using tetrabutylammonium cyanide was developed to give α-cyanated BODIPY derivatives. Characterization of optical and electrochemical properties of these dyes provides substantial enhancement of the electron affinity, with a reduction potential and LUMO level as low as -0.04 V and -4.43 eV, respectively. Radical anions of these electron-deficient 3,5-dicyanated BODIPYs were characterized by absorption and EPR spectroscopy.

Visible-Light-Induced Direct Photoamination of BODIPY Dyes with Aqueous Ammonia.

By taking advantage of their strong absorption ability, visible-light-induced direct photoamination of BODIPY dyes with aqueous ammonia was developed to give structurally diverse α-amino BODIPYs. The excited state of BODIPYs possessed higher electron affinity than the ground state and thus showed largely enhanced reactivity toward weak nucleophile of ammonia. Those α-amino BODIPYs are valuable synthetic intermediates and have been successfully demonstrated in several post-transformation reactions. The work indicates that photoreaction is an excellent alternative to conventional functionalization of this popular fluorophore.

Palladium(II)-Catalyzed Dehydrogenative Strategy for Direct and Regioselective Oligomerization of BODIPY Dyes.

A family of directly ß,γ-linked BODIPY oligomers up to pentamers were regioselectively prepared via Pd(II)-catalyzed oxidative C-H cross-coupling. The structural integrity of ß,γ-linked dimers was unambiguously confirmed by X-ray crystallography. These structurally unprecedented oligomers showed red-shifted absorptions and near-infrared emissions along with efficient intersystem crossing, giving ΦΔ in the range of 12-43%, for potential use as heavy-atom-free photosensitizers.

FeCl3-promoted regioselective synthesis of BODIPY dimers through oxidative aromatic homocoupling reactions.

The direct 3,3'-dimerization of BODIPYs lacking substituent groups in the 1,2,6, and 7 positions was developed by oxidative coupling with FeCl3. This regioselective dimerization was achieved for BODIPYs substituted only in the 5-position with Cl or aryl groups. Further functionalization of the 5,5'-dichloride dimer gave the corresponding pyrrole or 4-(2-aminoethyl)morpholine disubstituted dimers 2f and 2g, respectively. While dimer 2f exhibited intense NIR absorption/emission maxima at 773/827 nm in toluene, dimer 2g showed favorable lysosome-targeting NIR fluorescence in living cells.

Strategic Construction of Ethene-Bridged BODIPY Arrays with Absorption Bands Reaching the Near-Infrared II Region.

An efficient strategy for the controllable synthesis of BODIPY arrays based on the Stille cross-coupling reaction has been developed, from which a family of well-defined ethene-bridged BODIPY arrays from dimer to hexamer was synthesized. These arrays showed strong absorptions reaching the near-infrared II (NIR II, 1000-1700 nm) region with maxima tunable from 702 nm (dimer) to 1114 nm (hexamer) and possessed efficient light-harvesting capabilities, excellent photostability, and good photothermal conversion abilities under NIR light irradiation.

Visible-Light Excitation of BODIPYs Enables Self-Promoted Radical Arylation at Their 3,5-Positions with Diazonium Salts.

A metal- and additive-free photochemical strategy for the direct arylation of boron dipyrromethene dyes (BODIPYs) at their 3,5-positions is reported. The operationally simple approach occurs under illumination by visible light in the absence of any external photoredox catalyst. The chemistry is driven by the singlet excited state (1PS*) of BODIPYs upon visible-light absorption while successively triggering the formation of aryl radicals from aryl diazonium salts. Furthermore, a new type of indole-fused BODIPY with NIR absorption has also been synthesized for the first time.