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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

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Project Goals

• 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

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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

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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.

O O

O

N BN

HO

FF

O O

O

N BN

O

FF

OOR

2 ROO ROOH

R

R

R

R

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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).

Krumova, K., Cosa, G., SPR Photochemistry, 2013, DOI: 10.1039/9781849737722-00279A. 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.

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Hammett Parameters of the BODIPY Dyes in This Study

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.

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HOMO-LUMO of the BODIPY Dyes

HOMO LUMO

B3LYP/6-31g(d)

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Synthetic SummaryYang, 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.

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Spectroscopy of Bodipy Dyes10

9

8

7

6

5

4

3

2

1

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Lifetime Measurement by Fluorescence Decay

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.

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Electrochemistry Study

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.

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Hammett LFER for Eox and Ered

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)

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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

Acknowledgements

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Prof. Gonzalo CosaChristina CalverViktorija GlembockyteRobert Godin Lana GreeneAmani HaririDr. Katerina KrumovaRichard LincolnRyan Marko