The document summarizes research tuning the redox properties of BODIPY dyes through substituent manipulation. The goals were to create a method to predict BODIPY redox potentials using linear free energy relationships relating substituent Hammett parameters to reduction/oxidation potentials. Various BODIPY dyes with different substituents were synthesized, characterized through cyclic voltammetry, and fitted to equations relating electrochemical values to Hammett coefficients to achieve the goals.

1. Tuning the Fluorogenic Properties of BODIPY Dyes
by the Manipulation of Redox Properties Based on
Linear Free Energy Relationships
Clarissa Ding, Richard Lincoln, Gonzalo Cosa
1

2. Project Goals
2
• Create a method for the prediction of BODIPY redox properties
using linear free energy relationships
• Relate the Hammett parameters of various functional groups to
the reduction and oxidation potentials of a series of BODIPY dyes
• Synthesize and characterize various dyes with different
substituents at the 2, 6 and 8-position
• Perform cyclic voltammetry on these compounds
• Fit the observed electrochemical values to equations relating the
Hammett coefficients of the substituents with the redox
properties

3. General Photophysical Properties of BODIPY Dyes
• Strongly absorbing (ε = 50,000 – 100,000 cm-1M-1)
• High quantum yields (Φ≈ 0.7)
• Small Stokes shifts (ca. 10 nm)
• Photostable (reasonably stable to physiological conditions)
• Little to no solvent dependence on photophysics (relatively insensitive
to pH and polarity of the environment)
Loudet, A.; Burgess, K. Chemical Reviews 2007, 107 (11), 4891-4932.
4-4-difluoro-4-bora-3a, 4a-diaza-s-indacene (BODIPY) core
3

4. 4
BODIPY probes developed in the Cosa group
Oleynik, P.; Ishihara, Y.; Cosa, G. J. Am. Chem. Soc. 2007, 129, 1842.
Krumova, K.; Oleynik, P.; Karam, P.; Cosa, G. J. Org. Chem. 2009, 74 , 3641.
Katchadourian, A.; Krumova, K.; Boridy, S.; Ngo, A.;Maysinger, D.; Cosa, G. Biochemistry, 2009, 48, 5658.

5. Most BODIPY-based Probes Function via a
Photoinduced Electron Transfer (PeT)
Mechanism
A schematic representation of a photoinduced electron transfer process
(a, b) and a non-PET relaxation (c).
5
Krumova, K., Cosa, G., SPR Photochemistry, 2013, DOI: 10.1039/9781849737722-00279
A. P. de Silva, H. Q. N. Gunaratne, T. Gunnlaugsson, A. J. M. Huxley, C. P. McCoy, J. T. Rademacher and T. E. Rice, Chem. Rev., 1997, 97, 1515.
M. Verma, A. F. Chaudhry and C. J. Fahrni, Organic & Biomolecular Chemistry, 2009, 7, 1536.

6. Hammett Parameters of the BODIPY Dyes in This Study
6
aKrumova, K.; Cosa, G. Journal of the American Chemical
Society 2010, 132 (49), 17560-17569.
bTo be synthesized in the future.
cHansch, C.; Leo, A.; Taft, R. W. Chemical Reviews 1991, 91
(2), 165-195.
Verma, M.; Chaudhry, A. F.; Fahrni, C. J.Organic &
Biomolecular Chemistry 2009, 7 (8), 1536-1546.
R1 σR1
a
R2 R3 σR2+R3
a
-0.17 Et Et -0.3
-0.17 H H 0
-0.17 H Cl 0.23
-0.17 Cl Cl 0.46
-0.17 COOEt COOEt 0.9
0 Et Et -0.3
0 H H 0
0 H Cl 0.23
0 Cl Cl 0.46
0 COOEt COOEt 0.9
0.05 Et Et -0.3
0.05 H H 0
0.05 H Cl 0.23
0.05 Cl Cl 0.46
0.05 H CN 0.66
0.05 CN CN 1.32
0 Et Et -0.3
0 H H 0
0 H Cl 0.23
0 Cl Cl 0.46
0 H CN 0.66
0 CN CN 1.32
0.42 Et Et -0.3
0.42 H H 0
0.42 H Cl 0.23
0.42 Cl Cl 0.46
0.42 H CN 0.66
0.42 CN CN 1.32
0.54 Et Et -0.3
0.54 H H 0
0.54 H Cl 0.23
0.54 Cl Cl 0.46
0.54 COOEt COOEt 0.9
-0.83 Et Et -0.3
-0.83 H H 0
-0.83 H Cl 0.23
-0.83 Cl Cl 0.46
-0.83 COOEt COOEt 0.9
CF3
c
N(CH3)2
c
CH3
H
CH2OAcb
CH2OHb
CHOb

7. HOMO-LUMO of the BODIPY Dyes
7
HOMO LUMO
B3LYP/6-31g(d)

8. Synthetic Summary
8
Yang, L.; Simionescu, R.; Lough, A.;
Yan, H. Dyes and Pigments 2011,
91 (2), 264-267.
Nepomnyashchii, A. B.; Bröring,
M.; Ahrens, J.; Bard, A. J. Journal of
the American Chemical Society
2011, 133 (22), 8633-8645.
Wan, C.-W., Burghart, A., Chen, J.,
Bergström, F., Johansson, L.B.Å.,
Wolford, M.F., Kim, T.G., Topp,
M.R., Hochstrasser, R.M. &
Burgess, K. Chemistry – A
European Journal 9, 4430-4441,
2003.
Krumova, K.; Oleynik, P.; Karam, P.;
Cosa, G., The Journal of Organic
Chemistry 2009, 74 (10), 3641-
3651.
Banfi, S.; Nasini, G.; Zaza, S.;
Caruso, E. Tetrahedron 2013, 69
(24), 4845-4856.

9. -0.5
1.5
3.5
5.5
7.5
9.5
400 450 500 550 600 650
NormalizedIntensity
Wavelength (nm)
Spectroscopy of Bodipy Dyes
9
10
9
8
7
6
5
4
3
2
1

10. Lifetime Measurement by Fluorescence
Decay
10
0
5000
10000
15000
20000
25000
30000
9 14 19 24 29 34 39
Intensity
Time (ns)
Photophysical parameters of the dyes prepared. aThe HOMO-LUMO energy, E00, was estimated from the intercept of absorption and
emission spectra. bFluorescence quantum yield determined with PM 605 as the standard. cRadiative decay rate constant: kr = Φf /τav.dNon-
radiative decay rate constant: knr = 1/[τav*(1- Φf)]. eKrumova, K.; Cosa, G., Bodipy Dyes with Tunable Redox Potentials and Functional Groups
for Further Tethering: Preparation, Electrochemical, and Spectroscopic Characterization. Journal of the American Chemical Society 2010, 132
(49), 17560-17569.
Compd ε*103
(M-1
cm-1
) max λabs (nm) max λf (nm) ΔλST (cm-1
) E00
a
(eV) Φf
b
τav (ns) χ2
kr
c
(*108
s-1
) knr
d
(*108
s-1
)
PM 605e
70 542 561 625 2.22 0.72 6.76 NA 1.07 5.28
1 83 514 528 516 2.41 0.84 6.24 1.19 1.27 7.63
2 97 491 498 286 2.53 0.81 5.61 1.10 1.53 12.73
3 73 501 514 505 2.45 0.85 6.02 1.09 1.38 9.77
4 66 514 530 587 2.38 0.69 6.14 1.09 1.22 6.51
5 89 501 516 580 2.48 0.69 6.02 1.07 1.26 6.92
6 96 525 530 180 2.35 0.94 6.36 1.10 1.26 7.86
7 115 501 503 79 2.48 0.91 5.50 1.10 1.47 9.57
8 91 510.5 519 321 2.42 0.87 5.99 1.09 1.29 7.26
9 66 525 534 321 2.38 0.78 6.14 1.12 1.21 6.26
10 126 496 501 201 2.49 0.91 3.96 1.10 2.10 14.85

11. Electrochemistry Study
11
Dye EHOMO
a
(eV) ELUMO
b
(eV) Oxidation Potential (V) Reduction Potential (V)
Et2BCH3 -5.18785 -2.22344 0.7 -1.84
H2BCH3 -5.36336 -2.3127 0.83 -1.73
HClBCH3 -5.53779 -2.53066 0.96 -1.64
Cl2BCH3 -5.69643 -2.74209 1.02 -1.45
(COOEt)2BCH3 -5.78705 -2.75406 1.19 -1.36
H2BH -5.38432 -2.41746 N/A N/A
HClBH -5.57452 -2.62644 N/A N/A
Cl2BH -5.74868 -2.82672 N/A N/A
(COOEt)2BH N/A N/A N/A N/A
Et2BH N/A N/A N/A N/A
Voltammograms were acquired in degassed, Ar-saturated acetonitrile (0.1 M tetrbutylammonium
hexafluorophosphate salt bridge) with 1 mM ferrocene set to zero potential. Scanned clockwise at a rate of 0.2 V/s .
a,b estimated from DFT calculation at B3 LYP/ 6-31G* level
Krumova, K.; Cosa, G., Journal of
the American Chemical Society
2010, 132 (49), 17560-17569.

12. Hammett LFER for Eox and Ered
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Eox (V) = (0.12±0.06)σp(C8)+(0.44±0.03)σp(C2+C6)-(0.83±0.02)
R2=0.92712
Ered (V)= (1.06±0.05)σp(C8)+(0.42±0.02)σp(C2+C6)-(1.49±0.01)
R2=0.97235
Egap (V) = Eox (V) - Ered (V) = (-0.94±0.11) σp(C8) + (0.66±0.03)

13. Conclusion & Future Work
• Linear relationships between the Hammett constants of substituents and
electronic properties of BODIPY dyes was observed
• The reduction and oxidation potentials of the dyes were equally sensitive to
changes at the C2 and C6 positions
• The reduction potentials of the dyes were more sensitive to changes at the C8
position
• Therefore, the gap energy can be related to only the substitution at the C8 position
• Future work will be to prepare and characterize more dyes to determine if the
relation holds for a wider range of Hammett parameters
13

14. Acknowledgements
14
Prof. Gonzalo Cosa
Christina Calver
Viktorija Glembockyte
Robert Godin
Lana Greene
Amani Hariri
Dr. Katerina Krumova
Richard Lincoln
Ryan Marko