The 4,4-difluoro-4-bora-3a,4a-diaza-indacene (BODIPY) dyes ^{[1, 2, 3]},firstly discovered as early as 1968 by Treibs and Kreuzer ^[4], are valuable class of fluorophore because of their outstanding attributes,such as good photostability,high molar extinction coefficients and fluorescence quantum yields,as well as narrow emission bands. Up to now,thousands of papers were published that described the multifarious applications of BODIPY dyes. The diversity of available BODIPYs could be achieved by ingenious chemical modification and synthetic strategies,such as nucleophilic/ electrophilic substitutions at the pyrrole rings,replacement of fluorine atoms with carbon or oxygen centred substituent groups,insertion of donor/accepter groups,extension of π conjugated structure and formation of dimers ^{[5, 6, 7, 8, 9, 10, 11]}. The versatility of synthetic strategies to the BODIPYs allows the creation of a perfect fit between the structure of the dyes and their desired photophysical properties,making BODIPYs attractive for wide applications in fields as fluorescent probes ^{[12, 13, 14, 15, 16, 17, 18, 19, 20, 21]},bioimaging ^{[22, 23, 24, 25, 26, 27, 28, 29]} and photodynamic therapy ^{[30, 31]}.

Among the BODIPY derivatives reported to date,the construction of 3,5-dichloroBODIPYs,originally introduced by Dehaen and Boens,is an efficient pathway to direct linking of substitution to the BODIPY core. The electron deficiency at the 3,5-postions enables the replacement of chlorine efficiently via nucleophilic aromatic substitution reactions (S_NAr) or palladium-catalyzed cross-coupling reactions. Mono- or di-substitution products can be prepared with carbon,nitrogen,oxygen,sulfur,selenium,tellurium centred nucleophiles by careful tuning the reaction conditions ^{[32, 33]}. Hence 3,5-dichloroBODIPYs are useful for access to heterosubstituted BODIPYs,which are difficult to obtain by other routes and thus enrich the BODIPY family. On the other hand,introducing new substitution groups at the 3,5-positions by replacement of chlorine has a large effect on the spectroscopic and photophysical properties,shifting both absorption and/or emission spectra,and changing the fluorescence quantum yields ^[2].

Efficient preparation and tunable properties make 3,5-dichloroBODIPY a good candidate for the design of novel fluorescent sensors. Our group has developed a series of fluorescent sensors for highly sensitive and selective detection of thiols and heavy metal ions based on 3,5-dichloroBODIPY ^{[34, 35, 36, 37, 38]}. As part of our work on construction of BODIPY based sensors,a hydroxy group wasattempted to introduce to the 3- or 5-position of the BODIPY core. In the previous reports,8-hydroxy-BODIPY was obtained by Hg²⁺ promoted hydrolysis of 8-methylthio-BODIPY ^[39]. Zhao and coworkers reported 6-hydroxyindole based BODIPY for developing fluorescent sensors ^{[40, 41, 42]}. Gabbaı¨ and co-workers found boron hydroxide BODIPY derivatives in which the hydroxyl group could be easily substituted by fluoride under acidic condition ^{[43, 44]}. However,as far as we know,no literature has ever reported such a structure that hydroxy group is directly attached to the 3- or 5-position of BODIPY core. Herein,we report an interesting BODIPY analogue which was obtained from the 3- hydroxy-BODIPY under basic condition.

The reaction precursor 3,5-dichloroBODIPY was synthesized according to the reported literature methods ^{[45, 46]}. The hydroxy substituted BODIPY was expected by the reaction of 3,5- dichloroBODIPY with an excess of sodium hydroxide in methanol or dimethylformamide (DMF) (Scheme 1). After reaction overnight, TLC analysis of crude reaction mixture indicated the formation of one major product. The crude product was subjected to silica gel column chromatographic purification by using petroleum ether/ acetone as eluent to afford pure product in 70% yield. To our surprise,the product had poor solubility in chloroform,dichloromethane and toluene,but easily dissolved in acetone,ethyl acetate and tetrahydrofuran,which was significantly different from the common BODIPY dyes.

For purposes of comparison,3-chloro-5-methoxy-BODIPY (BDPOMe) was also prepared (details please see the Supporting information). BDPOMe was deemed to possess similar skeleton to the product. But they displayed quite different signals for pyrrole rings in the ¹H NMR spectroscopy. The four pyrrole hydrogen atoms of BDPOMe exhibited four well-defined signals in aromatic region in acetone-d₆. However,for the product,these signals shifted to upfield and coalesced into two sets (Fig. S1 in Supporting information). This observation implied different conjugation properties involving the pyrrole fragments between the product and BDPOMe.

Scheme 1

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Scheme 1.The proposed reaction process for the formation of BDPONa.

The reaction between 3,5-dichloroBODIPY and sodium hydroxide most probably proceeds by the proposed process as shown in Scheme 1. A tautomerization reaction of the product was occurred subsequently to the substitution of chlorine by hydroxy group and deprotonation of hydroxy group to result in the keto-form product BDPONa,in which the BODIPY core was negatively charged with sodium ion as counter-ion. The formation of keto-form product was further supported by high-resolution mass spectrum (Fig. S4 in Supporting information) and X-ray crystallographic analysis.

Single crystals of BDPONa were successfully grown by slow diffusion of n-hexane into ethyl acetate and n-pentane into acetone respectively over a period of one week (CCDC 1003302 and 1003303). Bond lengths involving the two pyrrole rings and the C- O bond lengths were examined. The distance of C9-O is 1.259Å ,shorter than that of C-O single bond (～1.43Å ),indicating the C=O double bond character. Unlike the common BODIPY derivatives which have a fully delocalized π system within the pyrrole rings, the bond lengths involving two pyrrole rings of BDPONa behave more like an alternation between C=C double bond and C-C single bond (Fig. 1),confirming the rearrangement of the chromophoric p system of BODIPY core,which is consistent with the result reflected in the ¹H NMR spectroscopy. The pyrrole-pyrrole dihedral angle is 4.47°,similar to that of common BODIPYs reported in the literature,indicating that the rearrangement of BODIPY core causes no structural distortion of the planar core structure. The boron centre displays a slightly disordered tetrahedral geometry,with the two fluorine atoms being arranged orthogonal to the BODIPY cores. And the B-N bonds,ranging from 1.52Å to 1.53Å ,are similar to the common BODIPYs.

Fig. 1

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Fig. 1.ORTEP view of BDPONa showing 50% probability ellipsoids. The benzyl and pyrrole ring hydrogen atoms and solvent molecules are omitted for clarity. Selected bond lengths (Å) are C9-O,1.259(3); C9-C8,1.460(3); C8-C7,1.344(3); C7 C6,1.447(3); C6-C5,1.365(3); C5-C4,1.443(3); C4-C3,1.389(3); C3-C2,1.406(4); C2-C1,1.365(4); C1-N1,1.368(3); C9-N2,1.365(3); B-N1,1.533(3); B-N2,1.527(3); B-F1,1.401(3) and B-F2,1.415(3).

Both in acetone/n-pentane and ethyl acetate/n-hexane systems, BDPONa crystallizes in the triclinic space group P-1. Sodium atoms were doped in the crystal lattice,adopting six-coordinated with octahedron geometry. Fluorine and oxygen atoms in each BODIPY ligand participated in coordination,as well as the carbonyl oxygen atoms of the solvent molecules (Fig. 2). The bond lengths for both Na-O and Na-F bonds are ranging from 2.2Å to 2.7Å ,comparable with the sum of ionic radius of the corresponding elements. Four BDPONa constitute one unit cell,packing in a head-to-head way. The BODIPY cores are connected via sodium atoms to form polymer chain along the a-direction for the crystal obtained from ethyl acetate (Fig. 3). However,the packing structure performs in a quite different way for the crystal from acetone/n-pentane. Every four BDPONa are connected via sodium atoms,forming one group independently and packing along the b-direction (Fig. S5 in Supporting information). In both crystal lattices,two adjacent BODIPY cores adopt unparallel packing behaviour,with dihedral angle 6.71° for crystal from acetone and 19.84° for crystal from ethyl acetate. The distances between the closest overlapping π-conjugation systems are 7.566Å and 13.650Å respectively,indicating the presence of negligible π-stacking interactions in the solid state.

Fig. 2

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Fig. 2.The coordinated modes of sodium with the BODIPY ligands in the crystal structure from acetone/n-pentane (a) and ethyl acetate/n-hexane (b) respectively. Part of bonds involving sodium in (b) are artificially omitted for clarity. The selected bond lengths (Å) are (a) Na1-F2,2.253; Na1-F3,2.313; Na1-F4,2.717; Na1-O1,2.384; Na1-O2, 2.317; Na1-O5,2.309; Na2-F1,2.431; Na2-F4,2.414; Na2-O1,2.367; Na2-O1,2.409; Na2-O2,2.451,Na2-O11,2.303; (b) Na1-F2,2.375; Na1-O1,2.452; Na1-O1,2.350;Na1-O2,2.568; Na1-O4,2.290; Na1-F4,2.353; Na2-O1,2.363; Na2-O2,2.512; Na2-O2,2.307; Na2-F1,2.233; Na2-F3,2.268; Na2-F4,2.399.

Fig. 3

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Fig. 3.Views of the packing structure of crystal obtained from ethyl acetate (top,side view; bottom,view along a-direction). Hatoms were omitted for clarity. Colour coding: nitrogen,blue; oxygen,red; boron,yellow; fluorine,green; chlorine,darkgreen; sodium,blue-green[1TD$DIF].

The spectroscopic and photophysical properties of BDPONawere investigated. In different solvents,BDPONa exhibits an absorbance (Fig. S6 in Supporting information) in the range from 410 nm to 440 nm,with molar extinction coefficients ～10⁴ mol^-1 cm^-1, which are typical for BF₂ compounds. The emission spectra (Fig. 4a) of BDPONa display broad and structureless bands between 475 nm and 505 nm,with high fluorescence quantum yields (0.35 in THF). Both absorption and emission spectra of BDPONa have a remarkable blue-shift property compared to the common BODIPY dyes.With UV lamp illumination at 365 nm,the BDPONa in acetone solution exhibits blue-green fluorescence, while green fluorescence of BDPOMe in acetone is observed(Fig. 4b). The blue shift is more prominent in the absorption spectra than in the emission spectra,leading to a clear increment in the Stokes shift. Moreover,measurements of the fluorescence full width at half-maximum (fwhm) (Table S1 in Supporting information) peak heights show that BDPONa has greater halfwidth than that of common BODIPYs.

Fig. 4

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Fig. 4.(a) Normalized emission spectra of BDPONa in different solvents at the concentration of 20 μmol/L at 298 K.(b) Normalized emission spectra of BDPONa (red line) and BDPOMe (black line) in acetone at room temperature. The inset shows the fluorescence of both compounds in acetone under UV lamp illumination at 365 nm.

The reason why BDPONa gives rise to spectral bands in blue region of the visible spectrum could refer to the systematic work on 8-aminoBODIPYs from Cabrera and co-workers ^{[47, 48, 49, 50]}. Upon theoretical simulations,they attributed the blue fluorescence of 8- aminoBODIPYs to the fact that the amino group at 8-position generates an increase of the energy of the LUMO state while leaving the HOMO unaltered. It may also apply to our system. As depicted in X-ray crystallographic analysis,BDPONa is a crossconjugated structure,where the push-pull interaction of the pyrrole nitrogen atoms is interrupted. This factor reduces the delocalization of the electronic p system between the two pyrrole groups and causes a widened HOMO-LUMO gap,resulting in the observed blue shift in both absorption and emission spectra.

Fluorescence lifetimes were also recorded in different solvents. In all cases,lifetimes are in the nanosecond regime (Table S1 in Supporting information),confirming the singlet emission nature of BDPONa.

In conclusion,we discovered a new blue-emitting BODIPY analogue with interesting structural property. The introduction of hydroxy group to the 3- or 5-position of BODIPY resulted in an unexpected structural rearrangement in the BODIPY core,leading to the keto-form product BDPONa. The core of BDPONa is an anion with sodium ion as counter-ion. BDPONa with significant blueemitting property,enriches the BODIPY family and may have potential applications in blue-emitting materials,fluorescent probes and biological imaging.

This work was financially supported by the 973 program (Nos. 2013CB933800,2013CB834505),National Natural Science Foundation of China (Nos. 21222210,21102155,91027041),and the Chinese Academy of Sciences (100 Talents Program).