When Push Comes to Shove: Unravelling the Mechanism and Scope

Mar 9, 2015 - We report herein spectroscopy and computational results that illustrate an efficient intramolecular deactivation pathway for meso-unsatu...
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When Push Comes to Shove: Unravelling the Mechanism and Scope of Nonemissive meso-Unsaturated BODIPY Dyes Richard Lincoln,† Lana E. Greene,† Cheryl Bain,† Juan O. Flores-Rizo,†,‡ D. Scott Bohle,† and Gonzalo Cosa*,† †

Department of Chemistry and Center for Self Assembled Chemical Structures, McGill University, 801 Sherbrooke Street West, Montreal, Quebec H3A 2K6, Canada ‡ Departamento de Química, Universidad de Guanajuato, Col. Noria Alta S/N, Guanajuato, Gto 36050, Mexico S Supporting Information *

ABSTRACT: We report herein spectroscopy and computational results that illustrate an efficient intramolecular deactivation pathway for meso-unsaturated boron-dipyrromethene (BODIPY) dyes in their singlet excited state. Our results show that the mechanism hinges on the structural flexibility imparted by the boron atom and on the energetic stabilization conferred by extending the conjugation into the meso substituent, which is otherwise unconjugated in the ground state. Following photoexcitation, rotation along the dihedral angle of the meso-unsaturated group results in its conjugation at the expense of shifting one pyrrole moiety in dipyrrin out of the plane. Internal conversion to an energetically hot, ground-state species efficiently competes with emission. The mechanism applies to meso-vinyl, -formyl, and -iminyl moieties. The presence of methyl groups at positions C1 and C7 exacerbates the energetic penalty toward conjugation of the meso groups leading to a small energy gap between relaxed excited state and ground state and undetected emission quantum yields. Importantly, methyls at C1 and C7 prevent nonradiative deactivation in meso-aryl moieties, illustrating that when push comes to shove, the energetic (kinetic) barrier toward reaching conjugation is too large for aryl moieties but low enough for smaller groups to effectively compete with radiative transitions. Wisely chosen meso-unsaturated BODIPY dyes may serve as richly sensitive platforms for the preparation of novel fluorogenic substrates to monitor chemical reactions or to probe the rigidity of their surrounding environment.

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INTRODUCTION Significant efforts have been devoted over the past decade toward developing fluorogenic probes for reaction screening.1−14 Critical to this work is the design of dyes that upon chemical activation undergo significant emission enhancements following either selective cleavage of a bond of interest or upon formation of a desired new bond. Fluorogenic probes that screen for bond breaking may be readily developed. Here, the rational involves detaching of an intramolecular quenching segment in the reaction of interest, resulting in the concomitant emission enhancement. Designing systems which result in emission enhancement following bond formation is, however, more challenging. One may envision exploiting energy transfer, where a new bond is formed in the reaction of interest with a segment bearing an energy acceptor dye.6 Alternatively, following covalent bond formation/rearrangement, one may rely on electronic changes in the overall probe to render the chromophore emissive. The fluorophore may simply report on electronic changes in a receptor/trap segment (e.g., a redox change following oxidation/reduction or complexation of an analyte of interest) within the probe in two-segment fluorogenic probes.7 Fluorescence may also be activated upon © XXXX American Chemical Society

the direct modification of the dye backbone, which suppresses rapid internal conversion or other deactivation pathways that readily compete with emission.8,10 We recently reported the synthesis and characterization of boron dipyrromethene15 (BODIPY) dyes appended with either a formyl or a hydroxymethyl group at the C8 (meso) position (See Figure 1, structures 1 and 1a, respectively) for synthetic tethering to nucleophiles (1) and electrophiles (1a).16 To our surprise, while the hydroxymethyl dye was highly fluorescent, the meso-formyl dye was not. Upon reaction of the aldehyde moiety with a nucleophile, such as methanol, a fluorescent product was formed. Thus, meso-formyl BODIPY dyes functioned as fluorogenic probes for nucleophilic attack and may be exploited for the detection of target nucleophiles and for high-throughput nucleophilic addition studies. Intrigued by the observed photophysical properties of the new compounds, we sought to elucidate the mechanism accounting for their efficient intramolecular fluorescence quenching, the scope of the process in terms of structural Received: March 3, 2015

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DOI: 10.1021/acs.jpcb.5b02080 J. Phys. Chem. B XXXX, XXX, XXX−XXX

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RESULTS AND DISCUSSION Synthesis of meso-Unsaturated BODIPY Dyes. To explore the scope of the fluorescence quenching mechanism we first reported on the 1,3,5,7-tetramethyl BODIPY scaffold, we prepared two structural analogues of the meso-formyl BODIPY: a meso-iminyl and a meso-vinyl BODIPY dye. The former was prepared by reaction of the aldehyde moiety of 1 with n-butylamine to yield the meso-imine product (2). Synthesis of the vinyl analogue (3) was achieved by reacting 3-bromopropionyl chloride with two equivalents of 2,4dimethylpyrrole to afford the bromo-ethyl-substituted dipyrrin. Addition of diisopropylethylamine and boron trifluoride gave the meso-vinyl BODIPY (see Scheme 1). Scheme 1. Synthesis of meso-Vinyl BODIPY Dye, 3

Figure 1. Structure of the BODIPY dyes studied in this work. Numbering of the BODIPY core shown in green. Photographs show solutions of the unsaturated (left) and saturated (right) dyes under UV light.

Consistent with a versatile intramolecular quenching mechanism that relies on meso unsaturation, both the mesoimine and the meso-vinyl analogues of 1 were nonemissive at room temperature (i.e., ϕf ≤ 1 × 10−5). Reduction of 2 with sodium cyanoborohydride under acidic conditions could be followed through the formation of a fluorescent amine (2a) (ϕf = 1.0 in toluene20). The saturated analogue of compound 3 (3a) was also highly emissive, characterized by a ϕf = 1.0 in acetonitrile (see also Figure 1). Conformational Flexibility of the Unsaturated Moieties. To better understand the quenching mechanism in the family of structurally related meso-unsaturated BODIPY dyes, we utilized a number of spectroscopic and computational techniques to probe both their ground state and excited state conformations, paying special attention to the role of the methyl substituents at positions C1 and C7. Initially, we sought to learn to what extent, if any, the πsystem of the meso group was conjugated with the BODIPY core prior to photoexcitation. Methyl groups on positions C1 and C7 are known to cause steric strain on functional groups at the meso position (C8).21 This results in the propeller-like structure in meso-aryl BODIPY dyes, where the aryl moiety lies orthogonal to the BODIPY plane, preventing the extension of the BODIPY backbone π-system on the meso-aryl group.18 To investigate the conformation of our meso-unsaturated dyes, we obtained X-ray crystal structures. Single crystals of 1− 3 were grown for X-ray diffraction through the slow evaporation of an initial 1:1 solution of dichloromethane and hexanes. Figure 2 depicts the solid-state structures of the BODIPY dyes. The diagrams show that the unsaturated moiety for compounds 1, 2, and 3 lies perpendicular to the BODIPY core and is thus unconjugated. The dihedral angle and C−C bond length between the BODIPY core and the meso-functional groups are given in Table 1. In all three cases, the bond length is consistent with that of a C−C single bond between sp2 carbons, with no conjugation. These results are similar to the observed angle and bond length recorded for meso-aryl dyes featuring C1 and C7 methyl groups, where no delocalization of

analogues, and its positional selectivity (unsaturation at BODIPY positions other than the meso). Recently it was proposed via DFT studies that the mechanism of excited state deactivation may involve conjugation of the meso-formyl group in the excited state, resulting in bending of the dipyrrin to accommodate the van der Waals repulsion of the formyl substituent. Even considering the steric influence of the C1 and C7 methyls in the meso-formyl BODIPY dyes, the mechanism was still operational.17 This new proposal was in line with a previous one enunciated to account for the lack of emission in meso-aryl BODIPY dyes lacking C1 and C7 methyls, where once again, conjugation occurred at the expense of bending the dipyrrin moiety.18,19 The new proposal, however, contradicts the well-established paradigm that meso-aryl BODIPYs bearing methyl groups at C1 and C7 are highly fluorescent dyes since neighboring methyl groups prevent any rearrangement of the meso group in the excited state. Here we show through photophysical, structural, and computational studies that the highly efficient nonemissive deactivation of the meso-formyl-1,3,5,7-tetramethyl BODIPY extends to both the meso-iminyl and vinyl analogues. Our calculations and experimental results further reveal that the C1/ C7 methyl groups play a critical role, enhancing (rather than diminishing, as for meso-aryl BODIPY dyes) the deactivation via nonradiative pathways. Our results indicate that rearrangement along the meso group accounts for the efficient excited state deactivation. Importantly, the positional selectivity for this process dictates that unsaturated groups at other positions along the BODIPY chromophore do not significantly diminish the emission quantum yield of the fluorophore. The mesounsaturated BODIPY dyes provide unique opportunities for the preparation of highly sensitive fluorogenic probes to either monitor chemical reactions or to probe the rigidity of their surrounding environment. B

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Figure 2. ORTEP (http://web.ornl.gov/sci/ortep/ortep.html) diagrams of the meso-unsaturated BODIPY dyes. Thermal ellipsoids are drawn at the 50% probability level.

Table 1. meso-Substituent Structural Data C−C bond length (Å) dihedral angle (deg)

1

2

3

1.493(5) 89.6(3)

1.482(6) 81.9(4)

1.481(2) 76.76(16)

Figure 4). The broadening arises due to the range of ground state conformers accessible in solution at room temperature.

electrons between the BODIPY core and the aryl group was observed.23 From the structural X-ray studies, we therefore conclude that there is little to no conjugation between the unsaturated groups and the BODIPY core in the solid state. To estimate the conformational flexibility of the dyes in solution, we next conducted DFT calculations at the B3LYP/631G(d) level.24,25 We sought to estimate both the minimum energy conformer and the energy barrier of rotation of the unsaturated moiety for the ground-state BODIPY (Figure 3). The presence of the C1 and C7 methyl groups disfavors the conjugation of the meso-moieties and results in the local energy minimum to occur at dihedral angles of 55°, 64°, and 63° for 1, 2, and 3, respectively. The rotational energy barrier for conjugation of the meso-group to the BODIPY core was determined to be smallest for 1 at 2.33 kcal mol−1. At room temperature, the ratio of conformers in planar versus twisted (energy minimum) is thus 1:51 based on a Boltzmann distribution. The barrier for 2 was 5.14 kcal mol−1, yielding a ratio of conformers of 1:122. The largest barrier was for 3, 7.97 kcal mol−1, yielding a ratio of conformers of 1:6.9 × 105. Broadening of the absorption spectra of the BODIPY dyes in solution were consistent with a larger range of conformers explored by 1 vs 2 and 3, as anticipated by the DFT results (see

Figure 4. Room temperature absorption spectra of BODIPY dyes 1−3 and their saturated analogues 1a−3a measured in acetonitrile.

While the spectra of 1−3 and their saturated analogues 1a−3a contain all of the same structural features (a peak in the visible region due to the S0-S1 transition, a higher energy vibronic shoulder, and an absorption band in the ultraviolet region belonging to an S0-S2 transition), only the S0-S1 absorption band of the meso-formyl BODIPY dye shows significant broadening, consistent with the lower-energy barrier to rotation. This broadening is not present in either 2 or 3 due to the higher rotational barriers to yield conjugation. For comparison, no broadening is observed in the saturated analogues 1a−3a. Calculation of Excited-State Structures. We next conducted computational studies in order to explore whether

Figure 3. Computationally derived potential energy surface as a function of the dihedral angle between the BODIPY π system and the meso-π system (blue). Boltzmann distribution of conformers along the dihedral angles calculated at 77 K (red) and 300 K (black). Calculations were conducted at the B3LYP/6-31g(d) level with an applied polarizable continuum model solvation of acetonitrile.22 C

DOI: 10.1021/acs.jpcb.5b02080 J. Phys. Chem. B XXXX, XXX, XXX−XXX

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The Journal of Physical Chemistry B the lack of fluorescence in meso-unsaturated BODIPY dyes is the result of an excited state rearrangement involving twisting along the dihedral angle ⊖ and concomitant bending of the dipyrrin, as reported for meso-aryl dyes lacking C1 and C7 methyls18 and as proposed for compound 1.17 Starting from the optimized ground-state geometry of 1, we first calculated the orbital character of the first excited singlet state. We found that the lowest-energy singlet state involved the electronic π → π* transition. Both the HOMO and LUMO were centered on the BODIPY core, and their shape (the presence of nodal planes) were consistent with the calculated HOMOs and LUMOs of other BODIPY dyes. The LUMO did, however, extend into the aldehyde group. Here, it is important to highlight the location of a nodal plane in the HOMO that bisects the meso position. This node is absent in the LUMO. Therefore, following photoexcitation, favorable interactions are expected between the BODIPY core and the meso substituent. TD-DFT studies yielded the optimized structure of the electronically excited BODIPY dyes (see Figure 5). Calcu-

narrowing of the S0-S1 energy gap by nearly a full 1 eV. This rearrangement of the excited state would ultimately favor the thermal relaxation of the meso-formyl BODIPY dye in the first excited singlet state to an energetically hot, ground state species. TD-DFT studies on the meso-iminyl BODIPY 2 also showed the conjugation of the imine π-system with the BODIPY core while in the excited state. This twisted geometry is highly unstable in the ground state, more so than for its equivalent in 1, consistent with the higher steric strain (rotational barrier) of the imine substituent. The rearrangement in 2 resulted in a narrowing of the S0-S1 gap by ca., 1.3 eV. While calculations on the formyl and iminyl dyes point toward excited state conjugation/twisting and presumably rapid thermal relaxation to a twisted ground state as the deactivation pathway, we could not find a stable minimum for the electronically excited meso-vinyl BODIPY, thus the TD-DFT results for 3 are inconclusive. No excited-state rearrangement of the meso-group was observed upon conducting TD-DFT calculations for the saturated BODIPYs 1a and 3a (see the Supporting Information). Little change in the predicted fluorescence emission wavelength was found for these compounds, relative to their absorption wavelength, consistent with the high fluorescence quantum yield and small Stokes shift observed for these dyes (see also Table 2). The presence of a low-energy photoinduced electron transfer excited state prevented us from obtaining results for 2a. Low-Temperature Spectroscopy. To confirm that the intramolecular deactivation pathway in photoexcited 1−3 fluorescence quenching was the result of an efficient thermal relaxation from a twisted excited singlet state to the twisted ground state, we subsequently prepared vitrified samples of the unsaturated BODIPY dyes 1−3 in 2-methyltetrahydrofuran at 77 K, to restrict molecular motion and eliminate the thermal relaxation pathway. Figure 6 displays the room temperature absorption and 77 K emission spectra of these samples. For comparison, we also include the room temperature spectra of the saturated analogues (1a−3a, respectively) in acetonitrile. The photophysical parameters including fluorescence decay lifetimes (kdec), emission quantum yields (ϕf), and radiative decay lifetimes (krad) are listed in Table 2. The vitrified samples were highly emissive. The emission spectrum of 2 and 3 compare very similarly to those of their saturated analogues, indicating that for these dyes, the meso substituent has very little impact on the nature of the BODIPY chromophore. Thus, the meso-iminyl and -vinyl groups, once restricted by the glass matrix, behaved similarly to the amine and ethyl moieties in solution. However, the emission spectrum of the meso-formyl BODIPY was very different from that of its saturated analogue. The 77 K emission spectrum of 1 showed a

Figure 5. Calculated energy diagrams of 1 (top panel) and 2 (bottom panel)22 at the B3LYP/6-31g(d) level with an applied polarizable continuum model solvation of acetonitrile. Ground state (left) and excited state (right) optimized geometries are shown.

lations for photoexcited 1 showed that its formyl moiety conjugated with the BODIPY chromophore, at the expense of a significant bending of the dipyrrin to accommodate the van der Waals repulsion of the formyl group and methyl groups at C1 and C7. This bending hinged on the movement of the boron atom. The new geometry is highly disfavored in the ground state electronic configuration and results in a significant

Table 2. Photophysical Properties Determined in Acetonitrile at Room Temperature unless Otherwise Indicated abs λmax (nm) 1 2 3 1a 2a 3a a

c

509 503 499 510c 505d 494

em λmax (nm) a

586 539a 526a 523c 524d 502

kdec × 10−8

ϕf a

0.49 0.64a 0.61a 0.98c 1.0d 1.0

1.59, 3.47 1.87a 2.01a 1.50c 1.95d 1.88

a,b

krad × 10−8

ε × 10−3 (M−1 cm−1)

N.A. 1.20 1.23 1.47 1.95 1.88

18c 62 75 100c 83 88

Measured at 77 K in MeTHF. bSee note.26 cTaken from ref 16. dMeasured at room temperature in toluene.20 D

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that there was no significant difference between the groundstate and excited-state structures for these dyes. The above results underscore the importance of steric strain in meso-unsaturated BODIPY dyes. While other positions around the BODIPY scaffold may be substituted with unsaturated moieties, only the meso position experiences sufficient van der Waals repulsions to disfavor ground-state conjugation. Unsaturated groups at either the equatorial (C2) or C3/C5 positions are not hindered in the same manner and are always conjugated with the BODIPY scaffold. At the meso position, conjugation is disfavored in the ground state, especially when methyl groups at C1 and C7 are used but is favored upon photoexcitation due to the increase in electron density at the meso carbon. When push comes to shove, if the energy gain of excited-state conjugation is sufficient to overcome the steric repulsion (as is the case for compounds 1−3), and provided a fast rearrangement is possible, the BODIPY dye will adopt a distorted structure and thermal deactivation of the excited state dramatically outcompetes fluorescence, resulting in emission quantum yields that are undetectable (i.e., no emission).

Figure 6. (Top panel) Room temperature absorption and 77 K emission spectra of the meso-unsaturated BODIPY dyes measured in MeTHF. (Bottom panel) Room temperature absorption and emission spectra of the saturated BODIPY analogues measured in acetonitrile.

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CONCLUSION

Here we show that the long established paradigm of a structural rearrangement for photoexcited meso-aryl BODIPY dyes is a rather universal one also encompassing small unsaturated groups such as formyl, iminyl, and vinyl moieties. Interestingly, while all these moieties may rearrange within the lifetime of the excited state when there is little steric crowding around the meso group (i.e., C1 and C7 bear H atoms), yielding compounds with low-emission quantum yields,30 there is a paradigm shift for those BODIPY dyes bearing methyl groups at C1 and C7. Here, meso-aryl groups become highly emissive, as the kinetic barrier to rotation and BODIPY core distortion is too large for the process to effectively compete with emission. The larger barrier is, however, rapidly surpassed by mesoformyl, -iminyl, and -vinyl groups which readily rearrange into a distorted structure. While meso-alkenyl BODIPY dyes prepared without methyl groups at C1 and C7 exhibit weak fluorescence (ϕf = 0.05 for a meso-propenyl analogue),30 the presence of methyl groups at positions C1 and C7 exacerbates the energetic penalty toward conjugation of the meso groups leading to a small energy gap between relaxed excited state and ground state, and undetected emission quantum yields (i.e., ϕf ≤ 1 × 10−5). We may point out in closing that the 1,7-dimethyl BODIPY scaffold provides the foundation for the preparation of richly sensitive fluorogenic substrates to monitor bond formation or to probe the rigidity of the surroundings. This scaffold provides the optimal steric strain to yield efficient fluorescent deactivation for small unsaturated groups at the meso position, while maintaining maximum fluorescence quantum yields for their saturated analogues. It further enables modifications at the C2 and C6 positions for electronic tuning of the BODIPY core HOMO−LUMO gap and controlling of its reactivity and spectroscopic properties.31 In general, the 1,7-dimethyl BODIPY scaffold may prove also a reliable substrate toward controlling the outcome of photoprocesses within the BODIPY core, where viscosity and the environment may tune the output of the new compounds.

large Stokes shift and significant broadening of the emission spectrum compared to 1a. We hypothesize that the excited state of 1 can undergo rearrangement to yield a conjugated excited state, even in the frozen matrix. A second lifetime was detected for compound 1 (see note 26), primarily on the redshifted shoulder, which we hypothesize is due to aggregation of the formyl-BODIPY. The values we found for the radiative rate constant (krad, calculated from the product of kdec and ϕf) are consistent with an allowed radiative process, indicating that the observed emission of the meso-unsaturated BODIPY dyes arise from the excited singlet state and are not due to phosphorescence (a spin forbidden process). We additionally observed no transient species in laser flash photolysis studies conducted with the meso-formyl BODIPY dye upon excitation at 532 nm. We therefore ruled out intersystem crossing as a potential quenching mechanism for these compounds. Positional Selectivity. An interesting observation arises when comparing compounds 1−3 with BODIPY dyes functionalized with alkenyl and formyl groups at different positions of the BODIPY scaffold (we are unaware of iminyl groups being appended elsewhere on BODIPYs). Aldehyde moieties are easily installed at the C2/C6 and C3/C5 positions of the BODIPY core through the Vilsmeier−Haack reaction,27 or through the oxidation of peripheral alkyl groups.28 However, once installed, they do not significantly reduce the fluorescence output of the BODIPY. Likewise, alkenyl groups may be added to the BODIPY core at the C3/C5 position (for example by Knoevenagel condensation)15 or at the C2−C6 positions via Heck coupling to the appropriate pyrrole.29 Conjugation with the chromophore yields a red-shifted, fluorescent dye in all cases. To understand why the formyl or vinyl groups at other positions do not exhibit the same quenching effect as observed in compound 1, we conducted TD-DFT calculations on BODIPY dyes appended with either formyl or vinyl groups at either C2 or C3 (see the Supporting Information). We found E

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EXPERIMENTAL SECTION Materials. HPLC-grade solvents for spectroscopy and column chromatography were purchased through Fisher Scientific. 8-Formyl-1,3,5,7-tetramethylpyrromethene fluoroborate (1) and 8-hydroxymethyl-1,3,5,7-tetramethylpyrromethene fluoroborate (1a) were synthesized according to previously reported procedures.16 All other chemicals were supplied by Sigma-Aldrich and used without further purification. 8-((Butylimino)methyl)-1,3,5,7-tetramethylpyrromethene Fluoroborate, 2. Compound 1 (140 mg, 0.5 mmol) was dissolved in toluene (10 mL) under argon. N-Butylamine (0.1 mL, 1 mmol) was added to the solution dropwise, and the reaction mixture was stirred at 60 °C for 20 h. Solvent was then removed under reduced pressure. The resulting residue was purified by silica flash column chromatography and eluted with dichloromethane. Compound 2 was obtained as an orange solid (80 mg, 48%). 1H NMR (500 MHz; CDCl3): δ 8.50 (s, 1H), 6.06 (s, 2H), 3.71 (td, J = 7.3, 1.2 Hz, 2H), 2.55 (s, 6H), 2.12 (s, 6H), 1.80−1.74 (m, 2H), 1.50 (dq, J = 15.0, 7.5 Hz, 2H), 1.00 (t, J = 7.4 Hz, 3H).13C NMR (126 MHz; CDCl3): δ 156.7, 156.2, 141.8, 136.2, 130.5, 121.24, 62.2, 32.1, 20.8, 16.6, 14.8, 13.9. HRMS (ESI): for C18H24N3BF2Na (M+) calculated, 354.1927; found, 354.1941. 8-((Butylamino)methyl)-1,3,5,7-tetramethylpyrromethene Fluoroborate, 2a. Compound 2 (28 mg, 0.083 mmol) was dissolved in methanol (5 mL) under argon. NaBH3CN (15 mg, 0.25 mmol) and 3 drops of 1 M HCl was added to the solution. The reaction mixture was stirred at room temperature for 1 h. The reaction mixture was diluted with ethyl acetate and washed with brine. The organic layer was dried with anhydrous sodium sulfate and the solvent was removed under reduced pressure. The resulting residue was purified by silica flash column chromatography and eluted with hexanes/ethyl acetate containing 1% triethylamine. Compound 2a was obtained as red crystals (23 mg, 82%). 1H NMR (500 MHz; CDCl3): δ 6.08 (s, 2H), 3.95 (s, 2H), 2.76 (t, J = 7.1 Hz, 2H), 2.53 (s, 6H), 2.49 (s, 6H), 1.55 (dt, J = 14.7, 7.3 Hz, 2H), 1.39 (dq, J = 15.0, 7.4 Hz, 2H), 0.94 (t, J = 7.3 Hz, 3H). 13C NMR (126 MHz; CDCl3): δ 155.2, 141.2, 132.3, 121.8, 50.1, 45.1, 32.1, 20.5, 15.6, 14.6, 14.0. HRMS (ESI): for C18H27N3BF2 (M+) calculated, 334.2264; found, 334.2269. 8-Vinyl-1,3,5,7-tetramethylpyrromethene Fluoroborate, 3. 2,4-Dimethyl pyrrole (0.46 g, 4.85 mmol, 2 equiv) was dissolved in dry CH2Cl2 under argon. 3-Bromopropionyl chloride (0.46 g, 2.67 mmol, 1.1 equiv) was added to the solution dropwise, and the reaction mixture was refluxed for 3 h. The solvent was removed under reduced pressure, and the mixture was dissolved in 3 mL dry CH2Cl2 and 20 mL of dry toluene. Diisopropylethylamine (2.51 g, 19.4 mmol, 8 equiv) was added, and the reaction was stirred at room temperature for 15 min. BF3OEt2 (10 equiv) was then added, and the reaction was stirred for 15 min. The reaction mixture was diluted with ethyl acetate and washed with water then brine. The organic layer was dried with anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The resulting crude was purified by silica flash column chromatography and eluted with dichloromethane. Compound 3 was obtained as a red solid (98 mg, 15%). 1H NMR (500 MHz; CDCl3): δ 6.77 (dd, J = 17.7, 11.6 Hz, 1H), 6.06 (s, 2H), 5.71 (dd, J = 11.6, 1.6 Hz, 1H), 5.58 (dd, J = 17.6, 1.5 Hz, 1H), 2.55 (s, 6H), 2.25 (s, 6H). 13C NMR (126 MHz; CDCl3): δ 154.9, 142.2, 140.5, 131.2, 130.7, 123.8, 121.1, 17.3, 14.6. HRMS

(ESI): for C15H17N2BF2Na (M+) calculated, 297.1348; found, 297.1352. 8-Ethyl-1,3,5,7-tetramethylpyrromethene Fluoroborate, 3a. 2,4-Dimethyl pyrrole (0.18 g, 1.94 mmol, 2 equiv) was dissolved in dry CH2Cl2 under argon. Propionyl chloride (0.099 g, 1.07 mmol, 1.1 equiv) was added to the solution dropwise, and the reaction mixture was refluxed for 5 h. Diisopropylethylamine (0.50 g, 3.8 mmol, 4 equiv) was added, and the reaction was stirred at room temperature for 15 min. BF3OEt2 (5 equiv) was then added, and the reaction was stirred for 15 min. The reaction mixture was diluted with ethyl acetate and washed with water then brine. The organic layer was dried with anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The resulting crude was purified by silica flash column chromatography and eluted with dichloromethane. Compound 3 was obtained as a red solid (98 mg, 15%). 1H NMR (500 MHz; CDCl3): δ 6.07 (s, 2H), 3.02 (q, J = 7.6 Hz, 2H), 2.54 (s, 6H), 2.46 (s, 6H), 1.33 (t, J = 7.6 Hz, 3H). 13C NMR (126 MHz; CDCl3): δ 153.9, 147.9, 140.3, 131.2, 121.6, 21.3, 16.3, 15.5, 14.5. HRMS (ESI): for C15H19N2BF2Na (M+) calculated, 299.1504; found, 299.1508. Instrumentation. Absorption spectra were recorded using a Hitachi U-2800 UV−vis−NIR spectrophotometer. Room temperature luminescence spectra were recorded using a PTI QuantaMaster spectrofluorimeter using 1 × 1 cm quartz cuvettes and corrected for detector sensitivity. For measurements of emission at 77 K in MeTHF glass matrices, dilute sample solutions (OD < 0.05) were prepared in an NMR tube and suspended in a coldfinger Dewar (custom-made by Ace Glass) filled with liquid nitrogen. Spectra were recorded using a Cary Eclipse Fluorescence Spectrophotometer and corrected for detector sensitivity. 1H NMR and 13C NMR spectra were recorder on a Bruker AV500 instrument at 500 and 125 MHz, respectively. Electrospray ionization (ESI) mass spectra were measured on a Bruker maXis impact. Fluorescence Quantum Yield. Room temperature fluorescence quantum yields were measured using compound 1a in acetonitrile as a reference (ϕf = 0.98). Absorption and emission spectra of 1a and the dye of interest were measured in acetonitrile at different concentrations. The integrated intensity versus absorbance were then plotted and fitted linearly. Relative quantum yields of fluorescence for the unknown with respect to the standard were obtained from eq 1, where ϕ, Δ, and n refer, respectively, to the quantum yield, the slope obtained from the above-mentioned plot and the solvent refractive index for the unknown (x) or standard (st). ϕx = ϕst ×

Δx n2 × x2 Δst nst

(1)

Quantum yields at 77 K in MeTHF glass were measured according to the above procedure, using compound 1a as a reference, assuming a quantum yield of unity. Fluorescence Lifetime Studies. Fluorescence lifetime measurements were carried out using a Picoquant Fluotime 200 Time Correlated Single Photon Counting (TCSPC) setup, employing a LDH 470 diode laser from Picoquant as the excitation source. The laser output was at 466 nm. The excitation rate was 10 MHz, and the laser power was adjusted to ensure that the detection frequency was less than 100 kHz. The laser was controlled by a PDL 88 B picosecond laser driver from Picoquant. Photons were collected at the magic angle of 54.7°. The IRF was 200 ps for our setup. F

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The Journal of Physical Chemistry B

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Crystal Structure Determination. X-ray quality crystals of the meso-unsaturated BODIPY dyes were grown from the slow evaporation of 1:1 hexane/DCM solution. To prevent evaporation of trapped solvent, the crystal of compound 2 was mounted directly from the mother liquor and measured at 100 K. The remaining crystals were measured at room temperature. Crystals were mounted on Mitegen mounts by using Paratone-N from Hampton Research, and X-ray data were collected on a Bruker AXS APEX2 CCD diffractometer by using graphite-monochromated Mo Kα radiation (λ = 071073 Å). The program APEX2 was used to collect the intensity data, indexing, and determination of lattice parameters; SAINT was used for integration of the intensity reflections and scaling. SADABS was used for absorption correction; SHELXTL was used for space group and structure determination and leastsquares refinements against F2. The structures were solved by means of the direct methods followed by Fourier difference maps to locate the light, nonhydrogen atoms. The hydrogen atoms were placed in calculated positions. Compounds 1 and 2 crystallize with two independent molecules per asymmetric unit, and 2 has a disordered hexane located at an inversion center between the channels created by the BF2 units. The structural data has been deposited with the Cambridge Crystallographic Data Centre with CCDC codes 10460742− 1046074 for 1−3, respectively. These data can be obtained free of charge from the Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif. ORTEP diagrams were prepared with Mercury CSD 3.3.32 Only one molecule of the two identical independent molecules are shown for 1 and 2. Computational Methods. All quantum mechanical calculations were performed using Gaussian 09 M.24 All calculations were conducted at the B3LYP 6-31G(d) level25 with an applied polarizable continuum model solvation of acetonitrile. Molecular structures and orbitals were visualized using Gaussview 5.

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ASSOCIATED CONTENT

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H NMR and 13C NMR spectra for compounds 2, 2a, 3, and 3a. Complete ref 24. DFT-derived molecular orbitals of compounds 1 and 2. TD-DFT-derived reaction coordinates. CIF files. This material is available free of charge via the Internet at http://pubs.acs.org.

AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. Notes

The authors declare no competing financial interest.

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REFERENCES

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ACKNOWLEDGMENTS

G.C. and D.S.B. are grateful to the Natural Sciences and Engineering Research Council of Canada (NSERC) and the Canadian Foundation for Innovation (CFI) for funding. R.L. is thankful to NSERC for a postgraduate scholarship; L.E.G. is thankful to Vanier Canada for a postgraduate scholarship. J.O.F.-R. is thankful to CONACyt for a postgraduate scholarship. G

DOI: 10.1021/acs.jpcb.5b02080 J. Phys. Chem. B XXXX, XXX, XXX−XXX

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