Specific Cu2+-induced J-aggregation and Hg2+-induced fluorescence enhancement based on BODIPY

Article abstract of DOI:10.1039/b926300d

A BODIPY derivative with an -NH₂ and -OH substituted meso-phenyl group is reported, which, under biological conditions, exhibits metal-induced J-aggregation in the presence of Cu²⁺ and a specific fluorescence enhancement for Hg²⁺.

Full text of DOI:10.1039/b926300d

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Specific Cu2+−induced J−aggregation and Hg2+−induced
fluorescence enhancement based on BODIPY
Hua Lu, Zhaoli Xue, John Mack, Zhen Shen*, Xiaozeng You and Nagao Kobayashi*.
Electronic Supplementary Information
I. Experimental section
I.1 Synthesis and characterisation……………………………………………………….....S2−S3
I.2 X−ray structure determination………………………………………………………………..S3
I.3 Procedures of metal ion sensing……………………………………………………………..S4
I.4 DFT calculations……………………………………………………………………………….S4
II. Supplementary Figure
Figure S1 (Molecular packing in the crystal structure of 1) …………………………………...S5
Figure S2 (Colour changes in solutions of 1 upon addition of different metals) …………….S6
Figure S3 (Reversibility of J−aggregate formation of [(Cu2+)(1)2]) ……………………………S6
Figure S4 (Frontier π−MOs and TD−DFT spectra of 1 and a model complex) ……………...S7
Figure S5 (Frontier π−MOs and TD−DFT spectra of 1 and a model complex) ……………...S8
Figure S6 (Model diagram for [(Cu2+)(1)2] J−aggregate formation of) …………………….....S9
III. References ……………………………………………………………….…………………....S10
IV. 1H NMR spectra ……………………………………………………………………..…..S11−S12

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I. Experimental Section
All reagents were obtained from commercial suppliers and used without further purification
unless otherwise indicated. Air− and moisture−sensitive reactions were carried out under a
nitrogen atmosphere using oven−dried glassware. Dichloromethane was distilled over
calcium hydride. Triethylamine was obtained by simple distillation. Elemental analyses for
C, H and N were performed on a Perkin−Elmer 240C elemental analyzer. 1H NMR spectra
were recorded on a Bruker DRX500 spectrometer with the residual solvent peaks used as the
reference signals. Mass spectra were measured with a Bruker Daltonics Autoflex IITM
MALDI TOF spectrometer. Luminescence spectra were measured on an Aminco Bowman 2
Luminescence spectrophotometer. The fluorescence quantum yield was calculated using
Rhodamine 6G (φF = 0.88 in EtOH) as a reference.S1
I.1 Synthesis routes and characteristic data
OH
OH
OH
NO2
2,4-dimethylpyrrole
TFA in CH2Cl2
NH2
NO2
Fe, HCl
DDQ
NEt3.BF3 Et2O
CHO
N
N+
B-
N
N+
B-
F F
F F
3
2
1
Scheme S1. The synthetic route for BDP compounds 1 and 2
Synthesis of 8−(3−nitro−4−hydroxyphenyl)−4,4−difluoro−1,3,5,7−tetramethyl 4−bora−3a,
4a−diaza− s−indacene (2)S2
2, 4−dimethylpyrrole (380mg, 4mmol) and 3−nitro−4−hydroxybenzaldehyde (334mg, 2mmol)
were dissolved in dry CH2Cl2 (150mL) under nitrogen. One drop of trifluoroacetic acid (TFA)
was added, and the solution was stirred overnight at ambient temperature in the dark until
TLC indicated complete consumption of the aldehyde. Dichlorodicyanobenzoquinone (DDQ,
442mg, 2mmol) was added, and the mixture was stirred for additional 30 min. The reaction
mixture was then treated with triethylamine (3mL) and stirring was continued for a further 5
min. Boron trifluoride etherate (3mL) was added. After stirring for another 40 min, the dark
brown solution was washed with water (3 × 20mL) and brine (30mL), dried over anhydrous
magnesium sulphate and concentrated at reduced pressure. 2 (150 mg, 19% yield) was

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purified by silica−gel flash column chromatography (silica gel, 10% EtOAc/Petroleum ether)
and recrystallisation (mp > 200 °C (CHCl3/hexane)) yielded red crystals (Found: C, 59.38; H,
4.63; N, 10.93. C19H18N3O3BF2 requires C, 59.25; H, 4.71; N, 10.91); λmax (CHCl3)/nm 479
(ε/dm3 mol−1 cm−1 14 800) and 507 (61 700); νmax(KBr pellet)/cm−1 3447, 2924, 1634, 1548,
1512, 1465, 1415, 1382, 1311, 1192, 1156, 1088 and 937 cm−1; δH(500 MHz; CDCl3) 10.73 (1
H, s), 8.13 (1 H, s), 7.55 (1 H, d, J = 5 Hz), 7.36 (1 H, d, J = 8.5 Hz ), 6.05 (2 H, s), 2.586 (6 H,
s) and 1.49 (6 H, s); m/z (MALDI−TOF) 385.210 [M]+.
Synthesis of 8−(3−amino−4−hydroxyphenyl)−4,4−difluoro−1,3,5,7−tetramethyl 4−bora
−3a, 4a −diaza−s−indacene (1)
BODIPY compound 2 (150mg, 0.39mmol) was dissolved in 5 ml of methanol. Fe (300 mg,
5.4 mmol) in 3ml of H2O was added, the solution was heated to reflux and 2 ml of a 0.6 M
hydrochloric acid solution in methanol was then slowly added dropwise. The solution was
stirred at reflux for 2 h until TLC monitoring indicated complete consumption of the starting
material and was then cooled to room temperature, filtered and concentrated at reduced
pressure. 1 (105 mg, yield 75%) was purified by silica−gel flash column chromatography
(silica gel, 20% EtOAc/Petroleum ether) and recrystallisation (mp > 200 °C (CHCl3/hexane))
yields red crystals (Found: C, 64.43; H, 5.62; N, 11.72. C19H20N3OBF2 requires C, 64.25; H,
5.68; N, 11.83); λmax (CHCl3)/nm 474 (ε/dm3 mol−1 cm−1 12 900) and 502 (56 700); νmax(KBr
pellet)/cm−1 3430, 2923, 1620, 1544, 1507, 1469, 1406, 1382, 1302, 1197, 1158, 1085 and
983; δH(500 MHz; CDCl3) 6.84 (1 H, d, J = 9 Hz), 6.66 (1 H, s), 6.56 (1 H, d, J = 7.5 Hz), 5.99
(2 H, s), 2.56 (6 H, s) and 1.54 (6 H, s); m/z (MALDI−TOF) 355.148 [M]+, 336.157 [M−F]+.
I.2 X−ray structure determination:
A single crystal of compound 1 was selected under a microscope and mounted on a glass
fibre. The unit cell parameters and data were collected on a Bruker Smart Apex CCD
diffractometer with graphite monochromatised Mo Kα radiation (λ = 0.71073 Å) using the
ω−2θ scan mode. The data were corrected for Lorenz and polarisation effects. The
structure was solved by direct methods and refined on F2 by full−matrix least−squares
methods using the SHELXTL−2000 program package.S3
1: C19H20BF2N3O: A red block−like crystal of the approximate dimensions 0.17 × 0.18 ×
0.20 mm3 was measured. Monoclinic, space group P 21/c, a = 15.941(4) Å, b = 7.638(2) Å, c
= 18.761(3) Å, β = 126.05(2)°, V = 1857.7(9) Å3, Z = 4, F(000) = 744, ρ = 1.271 Mgm–3, 2θmax
= 50°, R1 = 0.0701, wR(F2) = 0.2172, GOF = 0.989, residual electron density between 0.378

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and −0.453 eÅ–3.
CCDC 756287 contains the supplementary crystallographic data for this paper. These
data can be obtained free of charge via www.ccdc.cam.ac.uk/conts/retrieving.html (or from
the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax:
(+44)1223–336–033; E−mail: deposit@ccdc.cam.ac.uk).
I.3 Procedures of metal ion sensing
Stock solutions of the metal ions (100 mM and 10 mM) were prepared in deionised water.
A
stock solution of 1 (0.5 mM) was prepared in DMSO. The solution of 1 was then diluted to 5
μM with HEPES buffer solution (50 mM KNO3, 50 mM HEPRS, pH 7.2). During titration
experiments, 2 mL solutions of 1 (5 μM, 0.5 μM) were placed in a 1 cm quartz optical cell and
Cu2+, Hg2+ stock solutions were added gradually with a micropipette. Spectral data were
recorded immediately after each addition. In selectivity experiments, the test samples were
prepared by adding appropriate amounts of the metal ion stock solution into the 2 mL solution
of 1 (5 μM). During fluorescence measurements, the excitation wavelength was 483 nm and
emission spectra were collected between 495 − 600nm.
I.4 DFT Calculation
The G03W software packageS4 was used to carry out a DFT geometry optimisation for 1 and
a model complex with no –NH2 and –OH groups on the phenyl substituent using the B3LYP
functional with 6−31G(d) basis sets. TD−DFT calculations were then carried out using the
same approach.

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II. Supplementary Figure
Fig. S1 The molecular packing viewed along the b−axis in the crystal structure of 1.

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Fig. S2 Colour changes in solutions of 1 (20 μM) upon addition of 100 μM different metal
ions and the further addition of 20 μM of Cu2+ in DMSO/HEPES buffer solution.
Fig. S3 The absorption spectra of 1 (10 μM) in the presence of 1 equiv of Cu2+ and 20 eq of
Na2S.

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1
2nd LUMO 1st LUMO 1st HOMO 2nd HOMO 3rd HOMO 4th HOMO 5th HOMO
(−0.32 eV) (−2.30 eV) (−5.22 eV) (−5.53 eV) (−6.27 ev) (−6.50 ev) (−6.58 ev)
Model complex with no −NH2 and −OH substituents
2nd LUMO 1st LUMO 1st HOMO 2nd HOMO 3rd HOMO 4th HOMO 5th HOMO
(−0.51 eV) (−2.34 eV) (−5.34 eV) (−6.44 eV) (−6.63 ev) (−7.07 eV) (−7.20 ev)
λ / nm
600
500
400
300
0.5
−OH, −NH2
56%, 6%, 10%
81%, 6%
94%
90%
90%, 7%
0.0
0.5
no substituents
65%, 7%
S0 → S1
84%, 4%
90%
30000
99%
0.0
15000
20000
25000
Energy / cm-1
Fig. S4 Frontier π−MOs (TOP) and TD−DFT spectra (BOTTOM) of 1 and a model complex
with an unsubstituted phenyl group at an isosurface value of 0.04 a.u. based on a DFT
geometry optimisation using the B3LYP functional with 6−31G(d) basis sets. The
percentage contribution of one−electron transitions from the first five HOMOs into the 1st
LUMO to the bands predicted in the 300 − 600 nm region is colour coded. The S1 state of 1
is predicted to arise primarily from a 2nd HOMO → 1st LUMO transition (associated with an
occupied MO located primarily on the phenyl substituent), while in the absence of
substituents the dominant contribution is the standard 1st HOMO → 1st LUMO transition of
the BODIPY moiety.

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Fig. S5 Fluorescence spectra (λex = 483 nm) of 5 μM 1 recorded after the addition of 0, 0.1,
0.2, 0.25, 0.3, 0.35, 0.4, 0.45, 0.5, 0.6, 0.8 ,1.0 and 1.2 eq of Hg2+ (LEFT). Variations of
the [Hg2+]/[1] ratio as a function of the fluorescence intensity at 510 nm, the red line
corresponds to the best fit with eq (1) (RIGHT).
2
⎡
⎢
⎤
F − F0
1
FLim − F0
x =
{
+1}
⎥
⎦
2(FLim − F0 ) Ks C0 (FLim − F)
⎣
(1)
where x = [Hg2+]/[1], F is the fluorescence intensity, F0 and C0 are the initial fluorescence
intensity and concentration of 1, respectively, FLim is the limiting fluorescence intensity
value upon full complexation and Ks is the stability constant.S5

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Fig. S6 Model diagram for Cu2+−induced J−aggregation of BDP. The square planar
coordination environment typically adopted by Cu2+ ions due to their d9 configuration can
facilitate the formation of a regular structure containing parallel BODIPY π−system transition
moments.

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III. References
S1 J. Olmsted III, J Phys Chem. 1979, 83, 2581.
S2 H. Lu, L. Xiong, H. Liu, M. Yu, Z. Shen, F. Li and X. You, Org. Biomol. Chem. 2009, 7,
2554.
S3 SMART, SAINT, SADABS and SHELXTL, Bruker AXS Inc., Madison, WI, USA, 2000.
S4 M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman,
J. A. Montgomery, J. T. Vreven, K. N. Kudin, J. C. Burant, J. M. Millam, S. S. Iyengar, J.
Tomasi, V. Barone, B. Mennucci, M. Cossi, G. Scalmani, N. Rega, G. A. Petersson, H.
Nakatsuji, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T.
Nakajima, Y. Honda, O. Kitao, H. Nakai, M. Klene, X. Li, J. E. Knox, H. P. Hratchian, J. B.
Cross, C. Adamo, J. Jaramillo, R. Gomperts, R. E. Stratmann, O. Yazyev, A. J. Austin, R.
Cammi, C. Pomelli, J. W. Ochterski, P. Y. Ayala, K. Morokuma, G. A. Voth, P. Salvador, J.
J. Dannenberg, V. G. Zakrzewski, S. Dapprich, A. D. Daniels, M. C. Strain, O. Farkas, D.
K. Malick, A. D. Rabuck, K. Raghavachari, J. B. Foresman, J. V. Ortiz, Q. Cui, A. G.
Baboul, S. Clifford, J. Cioslowski, B. B. Stefanov, G. Liu, A. Liashenko, P. Piskorz, I.
Komaromi, R. L. Martin, D. J. Fox, T. Keith, M. A. Al−Laham, C. Y. Peng, A. Nanayakkara,
M. Challacombe, P. M. W. Gill, B. Johnson, W. Chen, M. W. Wong, C. Gonzalez and J. A.
Pople, Gaussian 03, Gaussian, Inc., Wallingford CT, 2004.
S5 (a) J. Bourson, J. Pouget and B. Valeur, J. Phys. Chem., 1993, 97, 4552; (b) M. N.
Berberan-Santos, P. Choppinet, A. Fedorov, L. Jullien and B. Valeur, J. Am. Chem. Soc.,
2000, 122, 11876.

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IV. 1H NMR spectra

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