Subscribe to RSS
DOI: 10.1055/a-2045-2369
Recent Advances in Highly Fluorescent Hydrazine-Inserted Pyrrole-Based Diboron-Anchoring Fluorophores: Synthesis and Properties
The work was financially supported by the National Natural Science Foundation of China (Grants Nos. 22271002, 21971004 and 21402001), and Anhui Provincial Natural Science Foundation (Grant No. 2008085QB67).
Abstract
Hydrazine-inserted pyrrole-based diboron fluorophores that display strong fluorescence in either the solution or solid state are widely used in biomedicine and optoelectronic materials science. A growing demand calls for multiple strategies for generating novel fluorophores to solve problems of small Stokes shifts and poor solid-state fluorescence. By changing their frameworks, several series of novel diboron compounds have recently been developed as increasingly valuable classes of fluorophores owing to their tunable structures and outstanding spectroscopic properties, such as high fluorescence quantum yields, large Stokes shifts, high photostability, and low LUMO energy levels due to the presence of electron-deficient BF2 groups. This review mainly highlights key synthetic strategies for the fluorophores BOPHY, BOPPY, and BOAPY developed by our group, together with the superior properties of these compounds. Significant photophysical data for these fluorophores in solution and solid states are included within the scope of this review. The facile functionalization of these fluorophores permits practical structural modifications to generate novel versatile dyes with excellent chemical and photophysical properties. We believe that these fluorophores hold promise to make important contributions in a wide range of applications.
1 Introduction
2 BOPHY Fluorophore
2.1 Discovery of BOPHY and its Fundamental Properties
2.2 Synthesis and Properties of Modified BOPHY Derivatives
3 BOPPY and BOPYPY Fluorophores
3.1 Discovery of BOPPY and BOPYPY, and Their Fundamental Properties
3.2 Synthesis and Properties of Benzo-Fused BOPPYs from Isoindoles
3.3 Nucleophilic Substitution and Cross-Coupling Reactions of Halogenated BOPPYs
3.4 Knoevenagel Reaction
4 BOAPY and BOPAHY Fluorophores
5 Conclusion
#
Biographical Sketches
Associate Professor Changjiang Yu received his bachelor’s (2009) and master’s (2012) degrees from Anhui Normal University, P. R. of China. He then joined Anhui Normal University as a member of its laboratory staff. He gained his Ph.D. in 2016 under the supervision of Professor Lijuan Jiao at Anhui Normal University. He then served as a postdoctoral fellow (2018–2020) under the supervision of Professor Wai-Yeung Wong at Hong Kong Polytechnic University. He has been an associate professor at the College of Chemistry and Materials Science since 2022. His research focuses on the synthesis, properties, and applications of novel organic boron fluorescent dyes and isoindole-based oligopyrroles.
Professor Lijuan Jiao received her bachelor’s degree (2000) from Shandong University, P. R. of China, and her master's degree (2003) from the University of Science and Technology of China (USTC). She obtained her Ph.D. from Louisiana State University in 2007, and joined Anhui Normal University in 2008, later becoming a full professor (2010) at the College of Chemistry and Materials Science. Her research focuses on the development of novel BODIPY- and porphyrin-related dyes, understanding their photophysical properties, and studying their optoelectrical and biological applications. She received an SPP/JPP Young Investigator Award for her researches on BODIPY and oligopyrrole chemistry in 2016.
Professor Erhong Hao joined Anhui Normal University after gaining his Ph.D. from Louisiana State University in 2007. He gained his master’s degree from USTC and his bachelor’s degree from Shandong University. He has been a full professor at the College of Chemistry and Materials Science since 2009. In his researches, he aims to develop new fluorescent dyes and their applications as smart molecular probes, advanced imaging reagents, and photosensitizers.
Introduction
Highly fluorescent fluorophores have been the focus of ongoing investigations in relation to their fundamental science and their wide range of applications in biomedicine and optoelectronic materials science, ranging from bioimaging, sensing, and photodynamic therapy to optoelectronics.[1] [2] [3] [4] [5] Continuous efforts to fulfill the demands of diverse applications have resulted in the development of many new fluorescent organic chromophores. The ideal organic fluorophore should possess a low molecular weight, be readily synthesized, and be easily functionalized for tunable absorption/emission spectra; it should also display a large Stokes shift and desirable chemical and physical features, such as bright emission in combination with a large molar absorption coefficient (ε) and a high fluorescence quantum yield (φ).[6] Despite the countless useful and well-established organic fluorescent fluorophores that have been developed, none meets all the above demands. Therefore, the search for an ideal fluorophore continues apace, and developing novel and valuable fluorescent organic molecules remains one of the main challenges in fluorescence-related studies.
Organic solid-state emissive materials have also attracted much attention in recent years owing to their outstanding optoelectronic properties, resulting in successful commercialization for organic electronics.[7] However, achieving highly solid-emissive organic small-molecule fluorophore is not an easy task owing to molecular aggregation, which can easily cause emission quenching. Several efficient strategies have been developed to produce efficient solid-state fluorescence by suppressing this undesired molecular aggregation.[8] Among those, exploring a new single-molecular platform is a fascinating method for developing color-tunable solid-emissive materials.
Recently, organoboron fluorescent platforms have been explored as interesting and versatile heterocyclic dyes, because chelation with boron atoms can efficiently reduce the rotational freedom of nonfluorescent ligands, enhancing their rigidity and turning them into highly fluorescent fluorophores with markedly increased chemical stability and photostability.[9] [10] [11] [12] [13] In particular, tetracoordinate boron-chelating molecules with N–N, N–O, or O–O bidentate ligands that form five- or six-membered rings have become a hot topic of research, owing to their rich and unique properties.[12,13] Usually known by the trademark BODIPY, 5,5-difluoro-5H-dipyrrolo[1,2-c:2′,1′-f][1,3,2]diazaborinin-4-um-5-uide (Figure [1]), is a highly successful fluorophore that has been extensively studied owing to its easy synthesis, simple modification, and tunable photophysical properties.[8] [10] [11] Nevertheless, despite their intense fluorescence in solution, most available BODIPY derivatives display weak fluorescence in the solid state due to self-absorption effects closely associated with their small Stokes shift; the geometrical parameters of their crystal packing patterns are also decisive, as these usually display H-type slip angles, resulting in dark nonradiative excited states.[12] [13] [14] These factors seriously limit the range of applications of these fluorophores in optoelectronics.
The success of this well-known fluorophore has inspired investigations into similar skeletal analogues containing pyrrole or heteroarene derivatives. For example, several novel chromophores containing more than one BF2 unit have been developed (Figure [1a]); these include a 1,8-naphthyridine bisBF2 complex,[15] pyrrolopyrrole aza-BODIPY (PPAB),[16] BOIMPYs with N–B–N bridges,[17] and an NIR-absorbing BF2-bridged azafulvene dimer core with a N–B–O bridge.[18]
More recently, hydrazine-inserted pyrrole-based BOPHY (Figure [1b]),[19] [20] the asymmetric bisBF2-anchoring pyrrole and N-heteroarene fluorophores BOPPY[21] and BOPYPY,[22] and the difluoroboronate-anchored pyrrolyl-acylhydrazones BOAPY[23] and BOAPHY[24] have been developed as increasingly valuable families of fluorophores, owing to their tunable structures, promising spectroscopic properties, high photostability, and low LUMO energy levels due to their electron-deficient bisBF2 groups.[19] [20] [21] [22] [23] [24] [25] [26] [27] [28] [29] [30] [31] [32] [33] [34] [35] However, the absorption and emission wavelengths of frameworks such as BOPHY are shorter than that of the parent BODIPY (526 nm in chloroform). Furthermore, to solve the problems of small Stokes shifts and poor solid-state fluorescence increasingly, as required for various applications, multiple synthetic strategies are required for generating novel BOPHY dyes and other hydrazine-inserted pyrrole-based bisboron dyes. Therefore, strategies for the modification and functionalization of these types of hydrazine-inserted pyrrole-based bisboron fluorophores are in high demand. Furthermore, to overcome the problem of small Stokes shifts and weak solid-state fluorescence, various analogues of BOPHY, such as BOPPY and BOAPY, have also been developed. The potential applications of these hydrazine-inserted pyrrole-based bisBF2 fluorophores were soon established and their derivatives were soon used in a wide array of promising fields, ranging from bioimaging[30] [31] through cascade energy[32] to solar cells,[33] among others.
In this account, we summarize the key strategies for the syntheses of the hydrazine-inserted pyrrole-based bisboron fluorophores BOPPY, BOPYPY, BOPAHY, and BOAPY and their superior photophysical properties in solution and solid states. The significant spectroscopic data of these fluorophores are also presented. Compared with the three previous reviews on BOPHY fluorophore,[25] [26] [27] this review primarily highlights researchers on hydrazine-inserted pyrrole-based fluorophores with a focus on the synthetic strategies for premodifications and postmodifications at the α- or/and β-position of the BOPHY fluorophore.
# 2
BOPHY Fluorophore
2.1Discovery of BOPHY and its Fundamental Properties
In 2014, Ziegler, Nemykin and co-workers,[19] and our group[20] successively and independently reported the first highly fluorescent pyrrole-based bisBF2 fluorophore, BOPHY (Figure [1b]), obtained by inserting hydrazine into a BODIPY core. This novel fluorophore has a symmetric structure with a hydrazine-inserted dipyrrole Schiff ligand anchored by two electron-deficient BF2 moieties, and possesses an inversion center (C2h symmetry). There are four rigidly planar rings: two newly formed six-membered rings at the center, each bearing a BF2 unit, and two pyrrole rings at the periphery, with the fluorine atoms deviating from the plane of the chromophore. The numbering system for this chromophore, as defined by Ziessel and co-workers,[32] (Figure [1b]) is different from that of the BODIPY core. The general synthetic pathway to the BOPHY fluorophore is shown in Scheme [1a]; it can be successfully prepared by reacting a pyrrole-2-carboxaldehyde derivative with hydrazine in the presence of a Lewis acid catalyst, with subsequent complexation with boron trifluoride diethyl etherate in the presence of an organic base such as triethylamine (TEA) or N,N-diisopropylethylamine (DIPEA). For example, BOPHY dyes 1–5 were generated in isolated yields of 21-47% by conventional classical methods (Scheme [1b]).[19] [35]
These extremely versatile BOPHY pigments usually absorb light intensely in the UV–visible spectral range, and are often highly fluorescent. For example, BOPHY 1 exhibits two distinct absorption bands at 423 and 442 nm in dichloromethane (DCM) (Figure [2]) with a high molar extinction coefficient of 3.98 × 104 M–1·cm–1.[19] The emission with a band maxima at 468 nm of this chromophore is quite intense in solution, with fluorescence quantum yields close to 100% (Table [1]) in DCM for BOPHYs 1 and 2. A gradual red-shift of the absorption and emission was observed on the installation of alkyl groups on the pyrrolic position of the chromophore. For example, BOPHY derivative 2 in DCM gave a strong absorption at 453 nm and emissions at 478, and 497 nm, which were red-shifted to 455, 480, and 504 nm, respectively, in the case of 4 with substitutions at the pyrrolic position of the chromophore. The BOPHY 5 in CHCl3 intensely absorbs and emits with maxima at 508 and 524 nm, respectively, and shows a high fluorescence quantum yield of 0.96 and a narrow full width at half maximum of 78 nm.[35] These photophysical properties of BOPHY 5 with four phenyl groups are comparable with those of BOPHYs 1–4.
a Data correspond to the strongest peaks of absorption or emission.
b Calculated by using H2TPP (φ = 0.11 in DMF) as a standard for 1, fluorescein (φ = 0.90 in 0.1 M NaOH solution) as a standard for 2–4, rhodamine B (φ = 0.49 in EtOH) as a standard for 5–8, and cresyl violet perchlorate (φ = 0.54 in MeOH) as a standard for 9–11.
c Shoulder peak.
The Stokes shifts of these BOPHYs are in excess of 40 nm and the compounds display relatively high solid-state fluorescence quantum yields of up to 0.28; these values are larger than the corresponding values for BODIPYs, which suffer from small Stokes shifts of 7–15 nm and extremely low solid fluorescence quantum yields;[20] for example, the parent BOPHY (1) displays a strong fluorescence with maxima at 537 nm (φ = 0.15) as a film and 543 nm (φ = 0.12) as a solid powder. In the solid powder state, BOPHYs 2 and 3 with alkyl substituents display strong fluorescence with maxima at 550 nm (φ = 0.28) and 605 nm (φ = 0.19), respectively. The intense solid-state fluorescence of 1–3 is readily explained in terms of their well-ordered packing structures. No π−π interactions are observed in the crystal packing structures of 1 and 2. Slipped dimers are formed in the crystal-packing structure of 3, with typical J-aggregates.
Cyclic voltametric analysis of BOPHY 1 shows one irreversible reduction wave with E pc = –1.14 V, and one irreversible oxidation wave with E pa = 1.40 V. A HOMO energy level of –5.80 eV and a LUMO energy level of –3.57 eV were estimated for the parent BOPHY. In comparison with the parent BODIPY, the insertion of hydrazine and the bisBF2 group helped to decrease the LUMO energy level of the BOPHY fluorophore, making it more stable than BODIPY.
In addition, the BOPHYs are reported to have greater photostabilities in solution than 1,3,5,7-tetramethyl-BODIPY, which itself is more stable in aqueous solution than fluorescein in 0.1 M NaOH, while maintaining higher φ values. The combination of excellent properties, such as ultrahigh brightness (due to the large φ and ε values) and emissions spanning the entire visible range, as well as their high photostability, render BOPHYs ideally suitable for potential applications in various biological and medicinal fields.
# 2.2
Synthesis and Properties of Modified BOPHY Derivatives
Various functionalization reactions at the α, β, and boron positions on BOPHY have been investigated to access deep-red or NIR BOPHYs. For example, aromatic-ring-fused modification of the parent BOPHY to extend the π-conjugation system can be used as an efficient way to achieve bathochromic shifts, as successfully demonstrated in structures A–C (Figure [3]).[28] [29] [30] [31] On the other hand, linear extension to generate a push–pull structure by electrophilic substitution (such as halogenation[32] , [35] [36] [37] [38] or hydroformylation),[39] nucleophilic substitution and metal-catalyzed cross coupling reactions,[30] [32] , [35] [36] [37] [38] , [40] [41] [42] or Knoevenagel condensation reactions[20] , [32] [33] [34] is an alternative efficient strategy to red-shift the absorption and emission of BOPHYs to the visible and NIR region, as exemplified by D and E (Figure [3]). Therefore, structural modification by the incorporation of various substituents on the pyrrole units permits fine tuning of the spectroscopic properties of BOPHY fluorophores.
Premodification Approach to Ring-Fused BOPHYs
BOPHY derivatives as promising deep-red and NIR fluorescing pigments are highly desirable as they have various properties that make them suitable for promising applications in both biological and materials science. Several strategies have been adopted to modify the structure of the BOPHY core to induce significant bathochromic shifts into the red/NIR region. Among those, the most efficient approach for expanding the π-conjugation of the BOPHY core is through fusion of aromatic rings.[20] , [25] [26] [27] [28] [29] [30] [31] [32] [33] [34] The a- and b-fused BOPHYs are usually defined in terms of aromatic ring fusion in the a or b bond direction (for example, A and B; Figure [3]). Available a/b bond aromatic-ring-fused and conformationally restricted BOPHY chromophores have been obtained by a premodification approach (de novo synthesis) of modifiable 2-formylpyrrole building blocks to realize deep-red or NIR emissions. The concrete strategies include (i) benzannulation at the a bond of the BODIPY skeleton by replacement of pyrrole with isoindole, as reported by the groups of Jiao and Hao[28] and Vicente;[30] (ii) annulation at the b bond of the BOPHY skeleton by replacement with heterocyclic-fused pyrrole rings such as indolebenzothieno[3,2-b]pyrrole or benzofuro[3,2-b]pyrrole units;[20] [28] [29] or (iii) formation of conformation-restricted boron-fused N2O-type BOPHYs through intramolecular B–O ring formation, as reported by Jiao and Hao and their co-workers.[31]
2.2.1.1Benzo-Fused BOPHYs from Indoles and Isoindoles
In 2014, Jiao and Hao and their co-workers synthesized the first aromatic-ring-fused BOPHY 6 in 21% yield (Scheme [2a]) from the azine stage by starting from an indole derivative, 3-methyl-1H-indole-2-carbaldehyde.[20]
The absorption maxima of the a-phenyl-fused BOPHY 6 in DCM are red-shifted to 498 and 522 nm and its emission is shifted to 580 nm (Table [1]). Unlike 1-4, a relatively low and solvent-dependent fluorescence (φ = 0.06 in DCM and 0.45 in hexane) was observed, similar to those of previously reported indole-derived dyes.
In 2016, Jiao and co-workers[28] reported an efficient synthesis of a new class of a-benzo-fused BOPHYs 7a–c (Scheme [2b]) with a 6,5,6,6,5,6-hexacyclic ring system in overall isolated yields of 34–38%, starting from the corresponding benzo-fused precursors, the hydrazine–Schiff base-linked bisisoindoles 7d–f. Similar to their absorptions, these dyes also displayed red-shifted fluorescence emissions in DCM, with the main-band maxima in the range from 602 nm to 614 nm (Figure [4]). In DCM, the a-benzo-fused BODIPY 7a exhibited a low fluorescence quantum yield of 0.34, with an emission maximum at 608 nm (Figure [4], Table [1]) in the red region.
More recently, Vicente and co-workers[30] reported the synthesis of dodecafluorinated BOPHY 8 in an overall 53% yield from 4,5,6,7-tetrafluoroisoindole-1-carbaldehyde (prepared in three steps from tetrafluorophthalonitrile) through successive condensation with hydrazine and boron trifluoride etherate in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in refluxing toluene (Scheme [2c]). The introduction of multiple fluorine atoms onto the benzo units of the BOPHY fluorophore has several advantages; the multiple fluorine atoms not only help to solve the solubility problems of the planar moiety, but also enhance the stability of the fluorophore and provide reactive sites. The method developed by Vicente’s group avoids lengthy syntheses for constructing a-benzo-fused BOPHY derivatives and provides possibilities for preparing compounds bearing α-aryl substituents with electron-donating groups. Furthermore, the fluorinated BOPHY derivatives might find important applications in 19F NMR and NIR bioimaging.[30]
# 2.2.1.2
Heterocyclic-Fused BOPHYs from Premodified Heterocyclic Blocks
In addition to their benzo-fused BOPHYs, the Jiao group also reported an efficient synthesis of a class of b-thiophene-fused BOPHYs 9a and 9b (Scheme [3a]) with a 5,5,6,6,5,5-hexacyclic ring system in overall yields of 34–38% from the corresponding thiophene-fused pyrrole derivatives.[28] In DCM, the b-thiophene-fused BOPHYs showed strong emissions [λem = 631 nm (φ = 0.60) and λem = 648 nm (φ = 0.50), respectively] (Figure [4]) in the deep-red region; these bands were red-shifted compared with those of a-benzo-fused 7a (Table [1] and Scheme [2]). Compared with the parent BOPHY 1,[20] the emission peak of the b-thiophene-fused BOPHY 9b in DCM showed a 180 nm bathochromic shift and a decreased fluorescent quantum yield of 0.50 (Table [1]). Significant red-shifts were observed in the absorption (up to 600 nm in solution) and emission (up to 648 nm in solution and 717 nm in the solid state; Table [1] and Figure [4]). These aromatic-ring-fused BOPHY dyes also showed high chemical stability and photostability compared with the parent BOPHY.
In the same year, Liu, Han, and co-workers[29] reported the synthesis of three b-furan-fused BOPHYs from premodified furo[3,2-b]pyrroles, together with their properties (Scheme [3b]). The b-furan-fused BOPHYs 10a–c were obtained by using a Hemetsberger–Knittel reaction of the furan-fused pyrrole with hydrazine and a subsequent boron chelation in a one-pot procedure. Because slightly different substituents were used, a direct comparison of the furan-fused BOPHYs 10a–c with the thiophene-fused analogues 9a and 9b is difficult; however, it appears that the furan-fused ring provides a larger bathochromic shift. Compounds 10a–c in DCM absorb with absorption-band maxima at 606, 622, and 624 nm, respectively (Table [1]); these are slightly red-shifted in comparison with the a-benzo-fused 7a–c or the b-thiophene-fused 9a and 9b. The emission bands for 10a–c are also bathochromically shifted, with peaks at 646, 661, and 667 nm (Table [1]), respectively. These compounds also show high photostabilities and chemical stabilities in solution. Their fluorescence quantum yields in DCM are in the range 0.34–0.40. DFT calculations indicate that the HOMO and LUMO levels of dyes 10a–c with the furan-ring-fusion at the b-bond give similar electronic distributions. Moreover, the electron-donating groups at the α-position of the BOPHY lead to decreased modest fluorescence quantum yields, possibly as a result of intramolecular charge transfer (ICT).
Aromatic ring fusions induce significantly increased HOMO energy levels, giving an effective expansion of π-conjugation over these unique BOPHY systems. The fusion of aromatic rings onto the BOPHY core is therefore an efficient strategy for expanding π-conjugation, resulting in the delocalization of both HOMOs and LUMOs on the fused rings, and an efficiently narrowed HOMO–LUMO gap. However, the LUMO of a bond-fused BOPHYs appears to be less susceptible to delocalization. More importantly, compared with a bond-fused BOPHYs, the presence of a fused ring at the b bond of the parent BOPHY might be a more effective way to decrease the LUMO level, which is key to the molecular design of stable NIR dyes.
# 2.2.1.3
Conformation-Restricted Boron-Fused BOPHYs
As a highly bright fluorophore, BOPHY was immediately applied as a novel platform for further modification. However, the resulting BOPHYs often had low solubility and aggregated in solution owing to π–π stackings of the four-ring fused cores. In 2021, Jiao and Hao developed a new family of N2O-type expanded BOPHY dyes named BOBHY (Scheme [4a]). BOBHY dyes 11a–d were obtained in overall yields of 28–40% through one-pot condensation of a formylisoindole, hydrazine, and a boronic acid (Scheme [4b]).[31] In comparison with the BOPHYs, BOBPY dyes displayed good solubility in various solvents because the axial groups provided steric hindrance, preventing any possible π–π stacking and aggregation.
Owing to the extended rigidity of their structures, these BOBPY dyes display relatively broad absorption bands with maxima in the range of 634–662 nm. These are bathochromically shifted by 180 nm with respect to the parent BOPHY.[20] Similarly, these dyes also display intense NIR emissions at about 680 nm, with modest fluorescence quantum yields ranging from 0.23 to 0.43. Cyclic voltammetry analyses and DFT calculations revealed an effective extension of π-conjugation over the BOPHY as a result of the boron-restricted conformation. In addition to their intense solution and NIR solid-state fluorescence emissions, these BOBHY dyes also showed high photostability. The axial groups permit facile installation of various functionalities by adjusting the substitutions on the boronic acid, permitting further tuning of the photophysical properties of the dyes. Developed as a mitochondrial-specific NIR fluorescent probe, BOBPY 11e with a pyridinium ion was easily prepared from BOBPY 11d and methyl iodide (Scheme [4c]). Their unique molecular structures and their pleasing photophysical properties signpost various applications of this group of fluorophores as bioimaging probes.
#
# 2.2.2
Postmodification Approach to BOPHYs
As a highly attractive and promising building block, the BOPHY fluorophore can be used for constructing linear molecules with an extended π-conjugation running along their framework. Linear π-extension by Knoevenagel condensation, substitution, or cross-coupling reactions to generate a push–pull BOPHY structure is a promising efficient way to red-shift absorption and emission peaks to the deep-red or NIR region. The postmodification approach, which is usually applied to BOPHY derivatives with a reactive functionality, is crucial for broadening the range of BOPHY derivatives, especially for substitution patterns or modifications that are hard to construct by de novo synthesis.
2.2.2.1Halogenation of BOPHYs
In 2017, Dehaen and co-workers presented a high-yielding synthesis of the α,α-dichlorinated BOPHY 12 (Scheme [5a]) in 51% yield from 5-chloropyrrole-2-carbaldehyde as the starting material through an intermediate dichlorinated hydrazine-linked bispyrrole ligand (HPB) with subsequent boron chelation.[40] The halo groups permit 12 to play a crucial role as a starting material.
In addition, treatment of dodecafluoro-BOPHY 8 with ten equivalents of bromine resulted in the formation of the α,α-dibrominated BOPHY 13 in 72% yield (Scheme [5b]), providing an efficient modification method as an alternative to α-chlorination.[30] As shown in Schemes 5c and 5d, halogenation usually occurs at the 4- and 4′(β)-positions. For example, the tetraphenyl-containing BOPHY 14 was prepared in 64% yield by bromination of the 3,3′,5,5′-tetraphenylated BOPHY 5 with Br2 (Scheme [5c]).[35] The monobrominated derivative 15 and dibrominated derivative 16 were prepared from the 3,3′,5,5′-tetramethylated BOPHY 2, by treatment with one or two equivalents, respectively, of NBS (Scheme [5d]).[36] Similarly, the monoiodinated 17 was obtained in 40% yield by treatment with one equivalent of NIS.[32] [36] Unlike the dibrominated product 16, diiodinated 18 was prepared in 85% yield by using iodic acid and molecular iodine.[36] Likewise, diiodination of 2 with ICl was favored at room temperature, yielding 18 in 84% yield[38] (Schemes 5d).
Inspired by Jiao and co-workers’ regioselective bromination of BODIPYs,[8] Hao, Yu, and co-workers developed regioselective syntheses of six brominated BOPHYs containing one to six bromine atoms at various pyrrolic positions (Scheme [5e]).[41] With different amounts of liquid bromine, the mono-, di-, tri-, tetra-, penta-, and hexabrominated derivatives 19a–f (Scheme [5e]) were regioselectively synthesized in modest to high yields of 54–91% by direct bromination of the parent BOPHY.[41] Because 4-bromopyrrole-2-carbaldehyde is readily obtainable by regioselective bromination of pyrrole-2-carbaldehyde, the β,β-dibrominated compound 19b was alternatively synthesized by condensing 4-bromopyrrole-2-carbaldehyde with hydrazine, followed by BF2 complexation in the presence of triethylamine (Scheme [5f]).[41] Because of the large amount of bromine needed for the preparation of pentabrominated 19e and hexabrominated 19f, Hao, Yu, and co-workers investigated the bromination of a HBP that was stable and suitable for bromination (Scheme [5g]), which differed from the reactant used for the synthesis of BODIPY.[41] In addition, the regioselective brominations of the HBP were not the same as those of BOPHY or pyrrole-2-carbaldehyde. The penta- and hexabrominated HBPs were obtained regioselectively in yields of 87 and 92%, respectively, by using just 10 and 20 equivalents of bromine.[41] Among the three strategies for bromination, the bromination of the HBP is believed to achieve the highest reactivity. The mono-β-brominated product 19a and the β,β-dibrominated product 19b showed decreased fluorescence quantum yields of 0.53 and 0.20, respectively. This might have been due to a heavy-atom effect; however, further multiple bromination increased the fluorescence quantum yield to 0.69 for the hexabrominated product 19f.[41]
# 2.2.2.2
Nucleophilic Substitution at the α-Position of Halogenated BOPHYs
The halogenated BOPHYs described in Section 2.2.2.1 can serve as significant starting materials for the installation of a wide range of versatile functionalities. As shown in Scheme [6], α,α-dichloro BOPHY 12, α,α-dibromo BOPHYs 13 and 19g, and polybromo BOPHYs 19d and 19f reacted in high yields with S-, N-, O-, and C- nucleophiles.[30] [40] [41] Monopiperidine-substituted 20 (Scheme [6a]) was generated in 81% yield from 12 and a stoichiometric amount of piperidine at room temperature overnight.[40] Owing to an efficient ICT process, 20 is barely fluorescent, with a fluorescence quantum yield of just 3% in toluene, and less than 0.01% in methanol. With excess nucleophilic piperidine in refluxing acetonitrile overnight, disubstituted 21a (Scheme [6a]) was obtained in 83% yield; this product showed solvent-dependent fluorescence quantum yields of, for example, 57% in toluene and only 9% in methanol. A similar sulfur nucleophile proved to be successful, generating 21b in 88% yield with a fluorescence quantum yield of unity in toluene.[40] In comparison with the parent BOPHY 1, the emission maximum of 21b is red-shifted by 61 nm. Similarly, by using nucleophilic phenolate, the diphenoxy-substituted derivative 21c was obtained and showed fluorescence quantum yields of 97% in toluene and 65% in methanol.
In 2022, Vicente and co-workers[30] carried out a series of SNAr reactions on their independently developed perfluoro-a-benzo-fused fluorophore. The reactions of α,α-dibromododecafluorobenzo-fused 13 with O-, N-, S-, and C-centered nucleophiles showed high efficiency and a priority toward bromine substitution, generating the corresponding perfluorinated BOPHY derivatives 22a–c (Scheme [6b]). The researchers further investigated the interesting and varied reactivities of the resulting BOPHYs in the presence of various nucleophiles.
The reactivities of polybrominated BOPHYs in nucleophilic substitution reactions were also studied by Hao and Yu.[41] α,α-Dibrominated BOPHY 19g and six equivalents of butylamine in DCE at 70 °C gave mainly the monosubstituted product 23 in 86% yield (Scheme [6c]). Even extending the reaction time, increasing the amount of butylamine, and raising the reaction temperature failed to give the disubstituted product. A similar phenomenon was observed with 24. Unlike dibrominated 19g, tetrabromo BOPHY 19d with various amounts of butylamine gave monosubstituted 25 and disubstituted 26 in yields of 83 and 85%, respectively (Scheme [6d]), showing that the tetrabrominated compound 19d has a higher reactivity than that of the dibromo analogue 19g. In addition, by starting from tetrabromo BOPHY 19d, 27 was obtained in 78% yield in a one-pot process involving an initial reaction with 4-tert-butylaniline and a subsequent reaction with diethylamine (Scheme [6d]). In this case, the high nucleophilicity of diethylamine permits the second SNAr reaction. Similarly, hexabrominated 19f reacted with three equivalents of butylamine to give monosubstituted 28 in 93% yield. However, with a large excess of butylamine, the reaction produced 29 as the sole main product in 94% yield. The reaction between monosubstituted 28 and excess butylamine also gave 29 rather than the corresponding disubstituted BOPHY.[41] A less-reactive nucleophile, 4-tert-butylaniline, was also used in a reaction with 19f in an attempt to obtain a disubstituted BOPHY. However, only the monosubstituted 30 was isolated in 73% yield (Scheme [6e]), whereas the reaction of 19g with 4-tert-butylaniline mainly gave monosubstituted 24 in 41% yield (Scheme [6c]). In refluxing toluene, 19f reacted with pyrrole to give the mono-pyrrole-substituted product 31 (Scheme [6e]). This result shows that disubstituted BOPHYs could not be produced under the reaction conditions, which might have resulted in decomposition.
# 2.2.2.3
Cross-Coupling at the α- and β-Positions with Halogenated BOPHYs
The halogenated BOPHY derivatives α,α-dichloroBOPHY 12 and α,α-dibromoBOPHY 19g proved to be reactive in Stille, Sonogashira, and Suzuki coupling reactions.[40] [41] For example, the usual Stille coupling conditions were used to generate the α-thienyl-substituted compound 32 from 12 or 19g in yields of 67 and 86%, respectively (Schemes 7a and 7b). To check the feasibility of the Sonogashira coupling reaction, Dehaen and co-workers[40] synthesized 33 containing n-butyl groups to increase its solubility in organic solvents, resulting in a yield of 39%. In 2018, Hao and Yu[41] first realized a Suzuki coupling on an α,α-dibrominated BOPHY dye, generating 4-(dimethylamino)phenyl-substituted 34 in 83% yield (Scheme [7b]). However, an attempted Heck reaction failed to give the expected product, presumably owing to decomposition under the reaction conditions. Actually, more metal-catalyzed cross-couplings deserve to be tried on this fluorophore.
In 2015, Ziessel and co-workers reported Sonogashira reactions of β,β-diiodinated BOPHY 18 to give 35a in 96% yield and 35b in 41% yield (Scheme [7c]).[32] This conjugation extension results in red-shifted absorption bands with maxima at 493 nm for 35a and 495 nm for 35b. Product 35a emits intensely at 527 nm with a fluorescence quantum yield of 63%; however, 35b displays a quantum yield of only 2% with a maximum at 531 nm, indicating that an ICT process occurs in this product.
Son and co-workers[36] described the synthesis of BOPHYs 35c–e and 36a–c with a variety of terminal alkynes in yields of 50–79% (Scheme [7c]), starting from the iodinated BOPHYs 17 and 18. The introduction of various substituents through Sonogashira couplings led to bathochromic shifts in absorption and emission.[36] For example, 35d showed a 36 nm red-shift in emission while maintaining a fluorescence quantum yield of 0.72. The alkynylated 33, with a similar substituent at the α-position, showed a red-shift of about 100 nm in emission, indicating that the bathochromic shift produced by modification of the α-position is more measurable. The introduction of electron-donating substituents resulted in a decreased emission from the products in comparison with the parent BOPHY; for example, BOPHYs 35e and 36c exhibit relatively low fluorescence quantum yields of 46% (536 nm) and 35% (523 nm), respectively.
# 2.2.2.4
Knoevenagel Reaction at the α-Position of BOPHYs
BOPHY platforms are susceptible to postmodifications. For example, in Knoevenagel-type condensation, 2 and 3 showed comparable reactivities to those of BODIPY dyes, which could help in installing various functionalities or tether groups onto the fluorophore. In 2014, Jiao and Hao introduced an electron-donating NMe2 substituent onto the p-phenyl group at the α-position of the BOPHY chromophore through a Knoevenagel condensation (Scheme [8a]), causing significant red-shifts in the absorption and emission maxima (Table [2]).[20] For example, 37a showed 90 and 80 nm bathochromic shifts in the absorption and emission band, respectively, in comparison with 2. A similar red-shift was observed for 37b in comparison with 3. The efficient red-shifts were supported by a combined TD-DFT-SOS-CIS(D) study by Guennic and co-workers.[43] The red-shifted absorption/emission wavelength maxima of these two dyes, as well as their large Stokes shifts, make them promising candidates for applications in biomedicine. Unlike their starting materials 2 and 3, both the styryl BOPHYs showed a strongly solvent-dependent fluorescence: when the solvent polarity was increased, they exhibited large bathochromic shifts and fluorescence quenching. For example, 37a emits at 581 nm with a quantum yield of 0.45 in hexane; in acetonitrile, this was bathochromically shifted to 721 nm, with a substantially decreased fluorescence quantum yield of 0.01. This phenomenon revealed the presence of an ICT process for 37a and 37b. In addition, 37a and 37b are sensitive to different pH conditions. Addition of TFA to their DCM solutions led to an absorption blue-shift from 672 nm to 485 and 512 nm for 37a, and from 667 nm to 540 nm for 37b, owing to the protonation of the NMe2 group. Upon protonation of 37a, functionalized with the tertiary amine, the fluorescence intensity was dramatically enhanced by 1200-fold[44] with a fluorescence quantum yield of 0.98, making 37a a sensitive turn-on-type pH probe.
a Data correspond to the strongest peaks of absorption or emission.
b The fluorescence quantum yields for 37a and 37b were calculated by using Cresyl violet perchlorate (φ = 0.54 in MeOH) as a standard.
c Absolute fluorescence quantum yield in the solid state.
In 2016, Zhao and co-workers[38] developed BOPHYs 37c–f, with two iodine atoms attached, to study the formation of triplet excited states (Scheme [8a]). Due to the heavy-atom effect of iodine and the efficient ICT of electron-donating styryl moieties, the emissions of styryl-diiodo BOPHYs 37c–f are weak, and their singlet-oxygen-generation quantum yields range from 0.35 to 0.49. The triplet state energy level of diiodo BOPHY 18 with a singlet-oxygen-generation quantum yield of 0.58 was found to be higher than those of 37c–f or conventional BODIPY chromophores.[38] These results show that the BOPHY chromophore provides a promising class of organic triplet photosensitizers.
In 2017, Zang and co-workers[45] prepared a BOPHY-based Cd2+ sensor 37g bearing an electron-rich N,N-bis(pyridin-2-ylmethyl)benzenamine group by a Knoevenagel condensation (Scheme [8a]). This compound displayed a red-shifted absorption and emission due to ICT transition, with maxima at 550 and 675 nm, respectively. Binding of Cd2+ ion suppressed the ICT transition, but turned on the π−π transition of the fluorophore, thereby permitting ratiometric fluorescence sensing. In 2018, Yu and co-workers[46] synthesized a turn-on Cu2+-based fluorescence probe 37h in 40% yield (Scheme [8a]). This D-π-A-type BOPHY is barely fluorescent in acetonitrile, because the fluorescence is quenched by effective ICT from the phenothiazine moiety to the BOPHY core. The redox couple Cu2+/Cu+ selectively oxidizes the thioether to a sulfoxide in acetonitrile, thereby inhibiting ICT and turning on the emission, with a fluorescence quantum yield of 0.94.
To study the interaction between an organometallic substituent and a BOPHY fluorophore, Ziegler, Nemykin, and co-workers[34] synthesized the vinylferrocene-substituted BOPHY 37i (Scheme [8a]), which showed a broad absorption band with a maximum at 700 nm; time-dependent DFT suggests that this might result from a core-centered π–π* transition on BOPHY, as well as a metal-to-ligand charge-transfer process. The fluorescence of this compound is fully quenched, similar to that of the related BODIPY derivatives.
In 2015, Ziessel and co-workers[32] explored double Knoevenagel reactions at high temperatures (>140 °C) on the BOPHY fluorophore, and they synthesized the bis(N,N-dimethylanilinostyryl)-substituted 38 and the bis[poly(ethylene glycol)styryl]-substituted 39 and 40, with the latter also being functionalized by two iodo groups (Scheme [8b]). The extension of conjugation leads to an absorption above 625 nm, in addition to solving the problems of solubility and spectral red-shifts. These developed BOPHYs are highly fluorescent, and the efficient intramolecular cascade energy transfer from the perylene motif to the BOPHY system is almost quantitative, providing large virtual Stoke shifts (>5100 cm–1).[32] To investigate the promising applications of the BOPHY chromophore in bulk heterojunction solar cells, the same group[33] then synthesized the bis(vinylthienyl)-substituted BOPHY derivatives 41 and 42 in yields of 29% and 21%, respectively, by using harsh Knoevenagel conditions (Scheme [8b]). A power-conversion efficiency of 4.3% and an external quantum efficiency in excess of 70%, were achieved in the spectral band from 580 to 720 nm by using 41 as the donor in bulk heterojunction solar cells.[33]
#
#
#
# 3
BOPPY and BOPYPY Fluorophores
3.1Discovery of BOPPY and BOPYPY, and Their Fundamental Properties
In 2018, Jiao and Hao disclosed a series of nonsymmetrical and highly fluorescent bisBF2 BOPPY fluorophores (Figure [5]), easily obtainable from commercially available 2-formylpyrroles and N-heteroarene derivatives. The simple one-pot reaction is diversity-oriented and efficient. Due to the adequate rigidity of the skeleton, this fluorophore manifests a large molar absorption coefficient, a large Stokes shift, outstanding photostability, and insensitivity to pH, while retaining a distinct fluorescence quantum yield in both solution and solid states.[21] These unique asymmetric structures generally exhibit diverse structures, strong solid-state emissions, and two-photon absorptions.
The BOPPY fluorophores 43 were first isolated in yields 23–54% (Scheme [9a]) by the reaction of formylpyrrole derivatives with commercially available N-heteroarene derivatives such as 2-hydrazinopyridine, 2-chloro-6-hydrazinopyridine, or 2-hydrazino-1,3-benzothiazole in the presence of p-toluenesulfonic acid (PTSA) and then DIPEA–BF3·Et2O.
These BOPPY dyes generally exhibit excellent optical properties with a strong broad absorption and intense emission in the visible region in several solvents. For example, the parent BOPPY 43aa in DCM displays two well-split absorptions with maxima at 393 and 413 nm (Figure [6]), respectively, and large molar extinction coefficients of 4.48 × 104 and 4.43 × 104 M–1 cm–1 (Table [3]). BOPPY 43aa in DCM also exhibits dual fluorescence with maxima at 432 and 462 nm (Figure [6]) and a fluorescence quantum yield of 0.79 (Table [3]). Similar dual absorption and emission maxima are observed for most other BOPPY dyes. These dyes exhibit large Stokes shifts, ranging from 2427 to 4463 cm–1. Gradual absorption and emission red-shifts were observed on introducing electron-rich alkyl substituents at the pyrrolic position or an electron-deficient chloro group on the pyridyl ring. For example, the absorption bands of 2,4-dimethyl-3-ethyl-substituted 43ca were red-shifted to 411 and 430 nm, whereas the bands of chloro-substituted 43cb were red-shifted to 422 and 442 nm in comparison with 43aa (Table [3]).
Most of these BOPPYs exhibit a strong solid-state fluorescence with high fluorescence quantum yields of 0.09–0.48. Their broad emission bands with maxima in the range 466 to 625 nm in the solid state are red-shifted with respect to the corresponding bands in solution. For example, 43aa and 43ab display emission maxima at 484 and 557 (Figure [6]) and at 500, 528 nm, respectively, and the solid-state fluorescent quantum yields are 0.21 and 0.48, respectively (Table [3]).
a Data correspond to the strongest absorption (or emission) peaks.
b Absolute fluorescence quantum yield.
In 2019, Jiang and co-workers[22] developed a family of nonsymmetric bisBF2 fluorescent dyes containing pyrrole and 5,6,5,6-tetracyclic pyrazine moieties, known as BOPYPYs (Scheme [9b]). The synthetic pathway for the pyrazine-fused asymmetric bisBF2 fluorescent BOPYPYs is similar to that used in the synthesis of BOPPY, except that 2-hydrazinopyrazine is used instead of 2-hydrazinopyridine in the condensation reaction with pyrrole-2-carboxaldehyde. First, 44a was synthesized by treating pyrrole-2-carboxaldehyde with 2-hydrazinopyrazine with a subsequent BF3·OEt2 complexation in the presence of Et3N. The absorption and emission spectra of 44a show two main peaks with absorption maxima at 443 and 467 nm and emission maxima at 490 and 522 nm; these represent remarkable bathochromic shifts in comparison with those of the pyridine-fused BOPPY 43ba reported by the group of Jiao and Hao[21] (λabs = 408 and 428 nm; λem =447, 478 nm; Table [3]). The obvious red-shifts can be ascribed to the strong electronegativity of the odd N atom in the pyrazine segment instead if the C atom in the pyridine segment. To better bathochromically shift the absorption and emission, aryl-containing formylpyrroles were used to synthesize the BOPYPYs 44b–f in yields of 23–54% (Scheme [9b]). Because of the extended π-conjugation of the aryl-containing pyrroles, 44b–f exhibit longer-wavelength absorptions, ranging from 498 to 546 nm, and their emissions reach into the red region, ranging from 560 to 610 nm. The series of BOPYPYs possess large molar extinction coefficients and Stokes shifts, and show modest fluorescence quantum yields.
# 3.2
Synthesis and Properties of Benzo-Fused BOPPYs from Isoindoles
Owing to the important advantages discussed above, asymmetric bisboron-anchoring BOPPY chromophores quickly attracted attention because of their advantageous photophysical properties and their promising framework as building blocks and functional materials.[47] [48] [49] [50] For example, in 2022, Ono and co-workers[47] reported a new family of BOPPY dimers as flag-hinge chromophores; these were synthesized from premodified diformyl-2,2′-bipyrroles, and showed good multicolor and circularly polarized emission. Shen and co-workers[48] developed B–O–B-bridged BOPPY dimers by reacting 3,5-dimethylpyrrole-2-carbaldehyde with 2,3-dihydrazinoquinoxaline, with subsequent boron complexation. They found that the two diastereomeric isomers undergo a feasible cis–trans interconversion in weak acids owing to a possible acid-catalyzed B–N bond cleavage.[48]
The short emission wavelength of the BOPPY fluorophore[21] dramatically restricts its range of applications in biomedical fields. Thus, synthesizing BOPPY dyes with long-wavelength emissions is highly desirable. Inspired by the success of works with BOPHY, Yu, Hao, and co-workers[50] prepared a new family of a-benzo-fused BOPPYs 45a–e in isolated yields of 42–68% and b-benzothiophene-fused BOPPYs 46a–c in isolated yields of 68–79% by reacting 2-chloro-6-hydrazinopyridine with various formylated isoindole derivatives (Scheme [10a]) or thieno[3,2-g]indoles (Scheme [10b]) in the presence of DIPEA–BF3·Et2O. The efficient fusion of a-benzo and b-benzothiophene markedly extended the π-conjugation of the parent BOPPY; meanwhile, formylated isoindole functionalized with a 2-hydroxyphenyl group gave BOPPY 45e (Scheme [10a]), which has both an a-benzo-fusion and a conformation-restricted boron fusion. These double fusions made BOPHY 45e red emitting, as manifested by the presence of spectral bands that were more red-shifted than those of other a-benzo-fused BOPPYs.[50] The chlorine atom in the pyridine ring of the BOPPY chromophore also provides a convenient means for introducing various functional groups.
Importantly, all of these aromatic-ring-fused BOPPY dyes show bright emissions and moderate to high absolute fluorescence quantum yields of up to 0.92 in DCM, together with intense emissions ranging from the visible to the NIR region (Table [3]). In particular, 45c with a triphenylamino group exhibits a bright NIR emission in the solid state with a maximum at 748 nm (Figure [7]) and a high fluorescence quantum yield of 21% (Table [3]).
# 3.3
Nucleophilic Substitution and Cross-Coupling Reactions of Halogenated BOPPYs
Halogen groups on BOPPY fluorophores provide valuable reactive sites for straightforward postfunctionalization with various groups by nucleophilic substitution reactions or metal-catalyzed cross-coupling reactions, similar to those of BOPHYs. For example, compound 43bb readily underwent nucleophilic substitution and Stille cross-coupling reactions to give 47 in 82% yield and thiophene-substituted 48 in 91% yield, respectively (Scheme [11a]). By using nucleophilic substitution reaction, Yu and Hao[50] developed two organelle-specific probes, 49a with a morpholine group and 49b with benzenesulfonamide group (Scheme [11b]), based on a conformation-restricted a-benzo-fused BOPPY. These were used to selectively light-up the two corresponding subcellular organelles at ultralow concentrations, as expected.
# 3.4
Knoevenagel Reaction
The first successful Knoevenagel reaction of this type of asymmetrical fluorophore was achieved through the reaction of 44a with 4-(dimethylamino)benzaldehyde (Scheme [12]). The resulting 4-(dimethylamino)styryl-substituted product 50 was then used in the development of a pH-turn-on-type fluorescent sensor for detecting pH values.
#
# 4
BOAPY and BOPAHY Fluorophores
In 2020, our research group[23] and that of Dehaen[24] independently developed new BOPHY-like bisBF2 fluorophores: BOAPYs 51a–f (Scheme [13a]) and BOPAHY 52a–e (Scheme [13b]). These were prepared by anchoring two BF2 motifs in a simple one-pot process involving condensation of 2-formylpyrroles and acylhydrazines with various groups, and subsequent fluorine–boron coordination. With two BF2 units anchored through N–B–N and N–B–O bridges, rotation of the C=N bonds of the ligand frameworks were largely restricted, providing adequate rigidity. These dyes all exhibited large Stokes shifts, excellent chemical stability, high solution quantum yields of 0.88, and solid-state fluorescence quantum yields of 0.64.[23]
Once the reaction conditions for the synthesis of BOAPY 51a had been optimized, it was found that 51a could be generated in 46% yield in dry toluene in a sealed reaction tube in an oil bath at 125 °C.[23] By reacting commercially available benzoylhydrazine, 4-(dimethylamino)benzoylhydrazide, 1H-pyrrole-2-carbohydrazide, thiophene-2-carbohydrazide, or salicylhydrazide with the corresponding formylpyrroles in the presence of PTSA, with subsequent treatment by Et3N-BF3·OEt2, the BOAPY fluorophores 51b–f were isolated in yields of 40–53% (Scheme [13a]). Interestingly, in 51f, the additional OH group of the o-phenol was chelated with the boron atom through an O–N–B-linked six-membered-ring to generate a new N2O-type BF complex. All these BOAPYs were stable toward a 365 nm UV lamp, daylight, air, and humidity.
Most of the BOAPYs show a dual-emission shape with bright blue fluorescence. For example, 51b in toluene displays dual emissions with a maximum at 481 nm and a shoulder peak of 460 nm (Figure [8]); the fluorescence quantum yield is 0.77 (Table [4]). These BOAPY dyes show quite large Stokes shifts, ranging from 2453 to 5773 cm–1. Gradual absorption and emission red-shifts of these dyes were observed on the introduction of electron-donating groups at the pyrrolic position and/or the aryl group of the arylhydrazide unit. For example, the emission bands for 51a were red-shifted to 510 nm in acetonitrile, and the emission bands for 51c at 471 and 494 nm in toluene were red-shifted in comparison with those of 51b (Table [4]).
a Data correspond to the strongest absorption (or emission) peaks.
b Absolute fluorescence quantum yields.
In great contrast to the BODIPY dyes, which are barely emissive in the solid state, the nonsymmetrical BOAPYs 51a–f show intense fluorescence with maxima in the visible range from 462 to 533 nm and high solid-state emission quantum yields of up to 0.64 (Table [4]). Their solid-state emission bands are tunable by changing the substituents on the pyrrolic or aryl group. For example, strong solid-state emissions are observed with maxima at 456 and 508 nm (φ = 0.32) for 51a, 462 nm (φ = 0.64, Figure [8]) for 51b, and 473, 492, and 531 nm (φ = 0.09) for 51c (Table [4]). The high level of solid-state fluorescence of these BOAPYs perfectly matches their crystal-packing structures. An absence of π–π interactions in their packing and the presence of slip angles of 18.3–50.4° are observed for their coplanar inclined arrangements, corresponding to a J-type case.
# 5
Conclusion
In this review, we have summarized the key synthetic strategies used in the preparation of the hydrazine-inserted pyrrole-based bisboron fluorophores BOPPY, BOPYPY, BOPAHY, and BOAPY, while drawing attention to the effects of various modifying groups on their photophysical properties in solution and in the solid state. BOPHY chemistry has made vital progress in relation to structural modifications and tunable properties. The premodification approach provides aromatic ring-fused BOPHYs, for example, with a/b bond aromatic-ring-fusion or conformationally restricted boron-fusion. The postmodification approach can provide, for example, halogenated BOPHYs that can undergo nucleophilic substitution, cross-coupling reactions, or Knoevenagel condensations, among others. However, to take advantage of the full potential of the chromophores to meet the needs of a wide variety of applications, synthetic strategies for diversity-oriented BOPHYs and other hydrazine-inserted pyrrole-based bisboron fluorophores remain in high demand; however, these are still underdeveloped, in comparison with BODIPY chemistry. Nevertheless, the available pyrrole-based hydrazine-inserted bisBF2 fluorophores, such as asymmetric BOPPYs and BOAPYs, display large molar absorption coefficients, large Stokes shifts, distinct photostability and chemical stability as well as insensitivity to pH, while retaining outstanding fluorescence quantum yields in the solution and solid states. All these remarkable properties, together with their easy synthesis, suggest an ever-increasing fame and a bright future as functional dyes for these hydrazine-inserted pyrrole-based bisboron fluorophores.
#
#
Conflict of Interest
We declare no competing financial interest.
-
References and Notes
- 1 Rao Y, Zhou W, Xu L, Zhou M, Yin B, Tanaka T, Osuka A, Song J. J. Am. Chem. Soc. 2019; 141: 18836
- 2 Li Z, Zhang L, Wu Q, Li H, Kang Z, Yu C, Hao E, Jiao L. J. Am. Chem. Soc. 2022; 144: 6692
- 3 Schrage BR, Nemykin VN, Ziegler CJ. Org. Lett. 2021; 23: 1076
- 4 Luo J, Xie Z, Zou J, Wu X, Gong X, Li C, Xie Y. Chin. Chem. Lett. 2022; 33: 4313
- 5 Krzeszewski M, Gryko D, Gryko DT. Acc. Chem. Res. 2017; 50: 2334
- 6 Li J, Dong Y, Wei R, Jiang G, Yao C, Lv M, Wu Y, Gardner SH, Zhang F, Lucero MY, Huang J, Chen H, Ge G, Chan J, Chen J, Sun H, Luo X, Qian X, Yang Y. J. Am. Chem. Soc. 2022; 144: 14351
- 7 Bera MK, Prasanta Pal P, Malik S. J. Mater. Chem. C 2020; 8: 788
- 8 Boens N, Verbelen B, Ortiz MJ, Jiao L, Dehaen W. Coord. Chem. Rev. 2019; 399: 213024
- 9 Hirai M, Tanaka N, Sakai M, Yamaguchi S. Chem. Rev. 2019; 119: 8291
- 10 Lu H, Mack J, Yang Y, Shen Z. Chem. Soc. Rev. 2014; 43: 4778
- 11 Wang S, Wang Z, Gao H, Jiang L, Liu H, Wu F, Zhao Y, Chan KS, Shen Z. Chem. Commun. 2021; 57: 1758
- 12 Frath G, Massue J, Ulrich G, Ziessel R. Angew. Chem. Int. Ed. 2014; 53: 2290
- 13 Yu C, Fang X, Wang H, Guo X, Sun L, Wu Q, Jiao L, Hao E. J. Org. Chem. 2021; 86: 11492
- 14 Liu H, Lu H, Zhou Z, Shimizu S, Li Z, Kobayashi N, Shen Z. Chem. Commun. 2015; 51: 1713
- 15 Li H.-J, Fu W.-F, Li L, Gan X, Mu W.-H, Chen W.-Q, Duan X.-M, Song H.-B. Org. Lett. 2010; 12: 2924
- 16 Wang L, Xiong Z, Ran X, Tang H, Cao D. Dyes Pigm. 2022; 198: 110040
- 17a Patalag LJ, Jones PG, Werz DB. Angew. Chem. Int. Ed. 2016; 55: 13340
- 17b Patalag LJ, Jones PG, Werz DB. Chem. Eur. J. 2017; 23: 15903
- 17c Freese T, Patalag LJ, Merz JL, Jones PG, Werz DB. J. Org. Chem. 2021; 86: 3089
- 18 Shimogawa H, Murata Y, Wakamiya A. Org. Lett. 2018; 20: 5135
- 19 Tamgho I.-S, Hasheminasab A, Engle JT, Nemykin VN, Ziegler CJ. J. Am. Chem. Soc. 2014; 136: 5623
- 20 Yu C, Jiao L, Zhang P, Feng Z, Cheng C, Wei Y, Mu X, Hao E. Org. Lett. 2014; 16: 3048
- 21 Yu C, Huang Z, Wang X, Miao W, Wu Q, Wong WY, Hao E, Xiao Y, Jiao L. Org. Lett. 2018; 20: 4462
- 22 Jiang X, Yue S, Chen K, Shao Z, Li C, Su Y, Zhao J. Chin. Chem. Lett. 2019; 30: 2271
- 23 Yu C, Fang X, Wu Q, Jiao L, Sun L, Li Z, So PK, Wong WY, Hao E. Org. Lett. 2020; 22: 4588
- 24 Parambil SP, de Jong F, Veys K, Huang J, Veettil SP, Verhaeghe D, Van Meervelt L, Escudero D, Van der Auweraer M, Dehaen W. Chem. Commun. 2020; 56: 5791
- 25 Boodts S, Fron E, Hofkens J, Dehaen W. Coord. Chem. Rev. 2018; 371: 1
- 26 Bismillah AN, Aprahamian I. Chem. Soc. Rev. 2021; 50: 5631
- 27 Shamova LI, Zatsikha YV, Nemykin VN. Dalton Trans. 2021; 50: 1569
- 28 Wang J, Wu Q, Yu C, Wei Y, Mu X, Hao E, Jiao L. J. Org. Chem. 2016; 81: 11316
- 29 Zhou L, Xu D, Gao H, Zhang C, Ni F, Zhao W, Cheng D, Liu X, Han A. J. Org. Chem. 2016; 81: 7439
- 30 Zhang G, Wang M, Bobadova-Parvanova P, Fronczek FR, Smith KM, Vicente MG. H. Chem. Eur. J. 2022; 28: e202200421
- 31 Wang J, Fang X, Guo X, Wu Q, Gong Q, Yu C, Hao E, Jiao L. Org. Lett. 2021; 23: 4796
- 32 Huaulmé Q, Mirloup A, Retailleau P, Ziessel R. Org. Lett. 2015; 17: 2246
- 33 Mirloup A, Huaulmé Q, Leclerc N, Lévêque P, Heiser T, Retailleau P, Ziessel R. Chem. Commun. 2015; 51: 14742
- 34 Rhoda HM, Chanawanno K, King AJ, Zatsikha YV, Ziegler CJ, Nemykin VN. Chem. Eur. J. 2015; 21: 18043
- 35 Cui T.-F, Zhang J, Jiang X.-D, Su Y.-J, Sun C.-L, Zhao J.-L. Chin. Chem. Lett. 2016; 27: 190
- 36 Li X, Ji G, Son Y.-A. Dyes Pigm. 2016; 124: 232
- 37 López-Calixto CG, Liras M, de la Peña O’Shea V, Pérez-Ruiz R. Appl. Catal., B 2018; 237: 18
- 38 Zhang C, Zhao J. J. Mater. Chem. C 2016; 4: 1623
- 39 Li Y, Zhou H, Yin S, Jiang H, Niu N, Huang H, Shahzad SA, Yu C. Sens. Actuators, B 2016; 235: 33
- 40 Boodts S, Hofkens J, Dehaen W. Dyes Pigm. 2017; 142: 249
- 41 Lv X, Li T, Wu Q, Yu C, Jiao L, Hao E. J. Org. Chem. 2018; 83: 1134
- 42a López-Calixto CG, Cabrera S, Pérez-Ruiz R, Barawi M, Alemán J, de la Peña O’Shea V, Liras M. Appl. Catal., B 2019; 258: 117933
- 42b López-Calixto CG, Barawi M, Gomez-Mendoza M, Oropeza FE, Fresno F, Liras M, de la Peña O’Shea V. ACS Catal. 2020; 10: 9804
- 43 Ponce-Vargas M, Azarias C, Jacquemin D, Le Guennic B. J. Phys. Chem. B 2017; 121: 10850
- 44 Jiang X.-D, Su Y, Yue S, Li C, Yu H, Zhang H, Sun C.-L, Xiao L.-J. RSC Adv. 2015; 5: 16735
- 45 Cheng D, Liu X, Xie Y, Lv H, Wang Z, Yang H, Han A, Yang X, Zang L. Sensors 2017; 17: 2517
- 46 He C, Zhou H, Yang N, Niu N, Hussain E, Li Y, Yu C. New J. Chem. 2018; 42: 2520
- 47 Cui L, Shinjo H, Ichiki T, Deyama K, Harada T, Ishibashi K, Ehara T, Miyata K, Onda K, Hisaeda Y, Ono T. Angew. Chem. Int. Ed. 2022; 61: e202204358
- 48 Wang S, Wang Z, Song W, Gao H, Wu F, Zhao Y, Chan KS, Shen Z. Dalton Trans. 2022; 51: 2708
- 49 Elek M, Dubiel M, Mayer L, Zivkovic A, Müller TJ. J, Stark H. Bioorg. Med. Chem. Lett. 2022; 59: 128573
- 50 Yu C, Sun Y, Fang X, Li J, Wu Q, Bu W, Guo X, Wang H, Jiao L, Hao E. Inorg. Chem. 2022; 61: 16718
Corresponding Authors
Publication History
Received: 07 February 2023
Accepted after revision: 01 March 2023
Accepted Manuscript online:
01 March 2023
Article published online:
05 April 2023
© 2023. Thieme. All rights reserved
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
-
References and Notes
- 1 Rao Y, Zhou W, Xu L, Zhou M, Yin B, Tanaka T, Osuka A, Song J. J. Am. Chem. Soc. 2019; 141: 18836
- 2 Li Z, Zhang L, Wu Q, Li H, Kang Z, Yu C, Hao E, Jiao L. J. Am. Chem. Soc. 2022; 144: 6692
- 3 Schrage BR, Nemykin VN, Ziegler CJ. Org. Lett. 2021; 23: 1076
- 4 Luo J, Xie Z, Zou J, Wu X, Gong X, Li C, Xie Y. Chin. Chem. Lett. 2022; 33: 4313
- 5 Krzeszewski M, Gryko D, Gryko DT. Acc. Chem. Res. 2017; 50: 2334
- 6 Li J, Dong Y, Wei R, Jiang G, Yao C, Lv M, Wu Y, Gardner SH, Zhang F, Lucero MY, Huang J, Chen H, Ge G, Chan J, Chen J, Sun H, Luo X, Qian X, Yang Y. J. Am. Chem. Soc. 2022; 144: 14351
- 7 Bera MK, Prasanta Pal P, Malik S. J. Mater. Chem. C 2020; 8: 788
- 8 Boens N, Verbelen B, Ortiz MJ, Jiao L, Dehaen W. Coord. Chem. Rev. 2019; 399: 213024
- 9 Hirai M, Tanaka N, Sakai M, Yamaguchi S. Chem. Rev. 2019; 119: 8291
- 10 Lu H, Mack J, Yang Y, Shen Z. Chem. Soc. Rev. 2014; 43: 4778
- 11 Wang S, Wang Z, Gao H, Jiang L, Liu H, Wu F, Zhao Y, Chan KS, Shen Z. Chem. Commun. 2021; 57: 1758
- 12 Frath G, Massue J, Ulrich G, Ziessel R. Angew. Chem. Int. Ed. 2014; 53: 2290
- 13 Yu C, Fang X, Wang H, Guo X, Sun L, Wu Q, Jiao L, Hao E. J. Org. Chem. 2021; 86: 11492
- 14 Liu H, Lu H, Zhou Z, Shimizu S, Li Z, Kobayashi N, Shen Z. Chem. Commun. 2015; 51: 1713
- 15 Li H.-J, Fu W.-F, Li L, Gan X, Mu W.-H, Chen W.-Q, Duan X.-M, Song H.-B. Org. Lett. 2010; 12: 2924
- 16 Wang L, Xiong Z, Ran X, Tang H, Cao D. Dyes Pigm. 2022; 198: 110040
- 17a Patalag LJ, Jones PG, Werz DB. Angew. Chem. Int. Ed. 2016; 55: 13340
- 17b Patalag LJ, Jones PG, Werz DB. Chem. Eur. J. 2017; 23: 15903
- 17c Freese T, Patalag LJ, Merz JL, Jones PG, Werz DB. J. Org. Chem. 2021; 86: 3089
- 18 Shimogawa H, Murata Y, Wakamiya A. Org. Lett. 2018; 20: 5135
- 19 Tamgho I.-S, Hasheminasab A, Engle JT, Nemykin VN, Ziegler CJ. J. Am. Chem. Soc. 2014; 136: 5623
- 20 Yu C, Jiao L, Zhang P, Feng Z, Cheng C, Wei Y, Mu X, Hao E. Org. Lett. 2014; 16: 3048
- 21 Yu C, Huang Z, Wang X, Miao W, Wu Q, Wong WY, Hao E, Xiao Y, Jiao L. Org. Lett. 2018; 20: 4462
- 22 Jiang X, Yue S, Chen K, Shao Z, Li C, Su Y, Zhao J. Chin. Chem. Lett. 2019; 30: 2271
- 23 Yu C, Fang X, Wu Q, Jiao L, Sun L, Li Z, So PK, Wong WY, Hao E. Org. Lett. 2020; 22: 4588
- 24 Parambil SP, de Jong F, Veys K, Huang J, Veettil SP, Verhaeghe D, Van Meervelt L, Escudero D, Van der Auweraer M, Dehaen W. Chem. Commun. 2020; 56: 5791
- 25 Boodts S, Fron E, Hofkens J, Dehaen W. Coord. Chem. Rev. 2018; 371: 1
- 26 Bismillah AN, Aprahamian I. Chem. Soc. Rev. 2021; 50: 5631
- 27 Shamova LI, Zatsikha YV, Nemykin VN. Dalton Trans. 2021; 50: 1569
- 28 Wang J, Wu Q, Yu C, Wei Y, Mu X, Hao E, Jiao L. J. Org. Chem. 2016; 81: 11316
- 29 Zhou L, Xu D, Gao H, Zhang C, Ni F, Zhao W, Cheng D, Liu X, Han A. J. Org. Chem. 2016; 81: 7439
- 30 Zhang G, Wang M, Bobadova-Parvanova P, Fronczek FR, Smith KM, Vicente MG. H. Chem. Eur. J. 2022; 28: e202200421
- 31 Wang J, Fang X, Guo X, Wu Q, Gong Q, Yu C, Hao E, Jiao L. Org. Lett. 2021; 23: 4796
- 32 Huaulmé Q, Mirloup A, Retailleau P, Ziessel R. Org. Lett. 2015; 17: 2246
- 33 Mirloup A, Huaulmé Q, Leclerc N, Lévêque P, Heiser T, Retailleau P, Ziessel R. Chem. Commun. 2015; 51: 14742
- 34 Rhoda HM, Chanawanno K, King AJ, Zatsikha YV, Ziegler CJ, Nemykin VN. Chem. Eur. J. 2015; 21: 18043
- 35 Cui T.-F, Zhang J, Jiang X.-D, Su Y.-J, Sun C.-L, Zhao J.-L. Chin. Chem. Lett. 2016; 27: 190
- 36 Li X, Ji G, Son Y.-A. Dyes Pigm. 2016; 124: 232
- 37 López-Calixto CG, Liras M, de la Peña O’Shea V, Pérez-Ruiz R. Appl. Catal., B 2018; 237: 18
- 38 Zhang C, Zhao J. J. Mater. Chem. C 2016; 4: 1623
- 39 Li Y, Zhou H, Yin S, Jiang H, Niu N, Huang H, Shahzad SA, Yu C. Sens. Actuators, B 2016; 235: 33
- 40 Boodts S, Hofkens J, Dehaen W. Dyes Pigm. 2017; 142: 249
- 41 Lv X, Li T, Wu Q, Yu C, Jiao L, Hao E. J. Org. Chem. 2018; 83: 1134
- 42a López-Calixto CG, Cabrera S, Pérez-Ruiz R, Barawi M, Alemán J, de la Peña O’Shea V, Liras M. Appl. Catal., B 2019; 258: 117933
- 42b López-Calixto CG, Barawi M, Gomez-Mendoza M, Oropeza FE, Fresno F, Liras M, de la Peña O’Shea V. ACS Catal. 2020; 10: 9804
- 43 Ponce-Vargas M, Azarias C, Jacquemin D, Le Guennic B. J. Phys. Chem. B 2017; 121: 10850
- 44 Jiang X.-D, Su Y, Yue S, Li C, Yu H, Zhang H, Sun C.-L, Xiao L.-J. RSC Adv. 2015; 5: 16735
- 45 Cheng D, Liu X, Xie Y, Lv H, Wang Z, Yang H, Han A, Yang X, Zang L. Sensors 2017; 17: 2517
- 46 He C, Zhou H, Yang N, Niu N, Hussain E, Li Y, Yu C. New J. Chem. 2018; 42: 2520
- 47 Cui L, Shinjo H, Ichiki T, Deyama K, Harada T, Ishibashi K, Ehara T, Miyata K, Onda K, Hisaeda Y, Ono T. Angew. Chem. Int. Ed. 2022; 61: e202204358
- 48 Wang S, Wang Z, Song W, Gao H, Wu F, Zhao Y, Chan KS, Shen Z. Dalton Trans. 2022; 51: 2708
- 49 Elek M, Dubiel M, Mayer L, Zivkovic A, Müller TJ. J, Stark H. Bioorg. Med. Chem. Lett. 2022; 59: 128573
- 50 Yu C, Sun Y, Fang X, Li J, Wu Q, Bu W, Guo X, Wang H, Jiao L, Hao E. Inorg. Chem. 2022; 61: 16718