Table 2. TDDFT-Calculated Excitation Energies for the Lowest
Transition (eV, nm), Oscillator Strengths (f), and Experimental
Absorption Maxima (exp)
E
exp
dye
state
S1
excitation
(eV, nm)
f
(eV, nm)
KFL4
Hf L (103%)
1.87 (662)
1.72 (718)
1.73 (717)
1.78 (697)
1.71 (723)
1.64 (757)
1.66
1.72
(723)
1.69
8
S1
S1
S1
S1
S3
H f L (81%)
H f L (96%)
H f L (22%)
H f L (97%)
H2 f L (79%)
0.47
1.28
0.54
1.23
0.40
(731)
1.68
9
(738)
1.72
10
11
12
(720)
1.66
Figure 4. Photobleaching kinetics of mTHPC and mTHPBC
(in MeOH) and compounds 8ꢀ12 (in THF) using a xenon arc
lamp (400ꢀ800 nm, 100 mW/cm2) over a period of 60 min.
(746)
1.61
(766)
solutions for 1 h. The first-order kinetics for the compounds
that generated singlet oxygen was compared with mTHPBC
and mTHPC (Figure 4). The first-order rate constant k
(minꢀ1) in the DPBF solution with dye 10 was ꢀ0.001, and
that of 12 was comparable with that of mTHPC at ꢀ0.0033.
Dye 9 showed bleaching with a k value of ꢀ0.0055 over the
period with the others remaining highly resistant to photo-
bleaching. It is important to note that under the irradiation
conditions mTHPBC photobleached much more rapidly
than all the BODIPY analogues.
To gain insight into the excited state in predicting the
absorption behavior of these compounds, theoretical char-
acterization by density functional theory (DFT) was
used.20 Geometry optimizations of these compounds were
performed using the 6-311 G* basis set while the electronic
excitations corresponding to the absorption spectra were
calculated using time-dependent-DFT (TDDFT) and the
PBEPBE correlation functional in vacuo as expressed by
Gaussian 09.21 The TD-DFT calculations predicted strong
absorption maxima of compounds 8ꢀ12 in the NIR region
with relatively small deviations from the experimental data
(ΔE = 0.03ꢀ0.15 eV)22 (Table 2). The observed trend seen
in calculated excitation energies in vacuo was consistent
with the experimental data obtained from absorption
spectra (Figure S3, Supporting Information). The solvent
effect might have increased the spectral shifts, resulting in
the differences observed.
In conclusion, we developed new BODIPY analogues
that absorb (720ꢀ766 nm) and emit (738ꢀ820 nm) in the
NIR region of the electromagnetic spectrum. Compounds
10 and 12 displayed good singlet oxygen generation com-
parative to CMP and a relatively high resistance to photo-
bleaching, showing promise of use as NIR photosensitizers
in PDT. In particular, compound 10 showed high bright-
ness (BT = ε ꢁ Φf), 40050 and 10880 Mꢀ1 cmꢀ1 in CHCl3
and THF, respectively, in addition to efficient generation
of singlet oxygen. Such chromophores could be useful for
dual purposes: imaging and PDT. Relatively consistent
predictions of absorption bands by DFT calculation sup-
port it as a good tool in the design of new BODIPY
analogues with tuned absorption bands. Work is under-
way on the synthesis and characterization of more water-
soluble derivatives to understand their biological effects
and potential PDT applications.
Acknowledgment. We wish to acknowledge the South
Dakota Board of Regents and the BCAAP (Biological
Control and Analysis by Applied Photonics) Center at
SDSU and College of Pharmacy at OUHSC for financial
support. We also thank Dr. Tymish Y. Ohulchanskyy
(SUNY at Buffalo) and Dr. Susan Nimmo (University of
Oklahoma) for their helpful discussions on singlet oxygen
detection and NMR experiments. Helpful discussions with
Dr. Seth Darling (Argonne National Laboratory) are also
appreciated. Use of the Center for Nanoscale Materials
was supported by the U.S. Department of Energy, Office
ofScience, Officeof Basic Energy Sciences, under Contract
No. DE-AC02-06CH11357.
(20) Quartarolo, A. D.; Russo, N.; Sicilia, E. Chem.;Eur. J. 2006,
12, 6797.
(21) Frisch, M. J. T., G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb,
M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci, B.;
Petersson, G. A.; Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H. P.;
Izmaylov, A. F.; Bloino, J.; Zheng, G.; Sonnenberg, J. L.; Hada, M.;
Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima,
T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Montgomery, Jr.,
J. A.; Peralta, J. E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers,
E.; Kudin, K. N.; Staroverov, V. N.; Kobayashi, R.; Normand, J.;
Raghavachari, K.; Rendell, A.; Burant, J. C.; Iyengar, S. S.; Tomasi,
J.; Cossi, M.; Rega, N.; Millam, N. J.; Klene, M.; Knox, J. E.; Cross,
J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann,
R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.;
Martin, R. L.; Morokuma, K.; Zakrzewski, V. G.; Voth, G. A.; Salvador, P.;
Supporting Information Available. Available experi-
mental details and characterization data of new com-
pounds were reported. This material is available free of
€
Dannenberg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas, O.; Foresman, J. B.;
Ortiz, J. V.; Cioslowski, J.; Fox, D. J. Gaussian 09, Revision A.1; Gaussian,
Inc.: 2009.
(22) Fabian, J. Dyes Pigm. 2010, 84, 36.
Org. Lett., Vol. 13, No. 15, 2011
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