1. Photophysics and 1O2 Sensitization Characteristics of BODIPY Dyes for
Photodynamic Therapy
Department of
CHEMISTRY
Keenan Komoto* and Tim Kowalczyk
Department of Chemistry, Advanced Materials Science & Engineering Center, and Institute for Energy Studies, Western Washington University, Bellingham, WA 98225
Introduction
With the high volume of cancer rates throughout the world, people are looking to find more efficient ways to treat the disease. One
promising method is photodynamic therapy (PDT), which is a process that involves illuminating a chromophore, which
subsequently causes a reaction which generates singlet oxygen (1O2), a reactive form of oxygen that destroys cancer cells. To
accelerate the progress made in the field of PDT, this study aims to provide useful information to those researching candidate
chromophores for use in PDT
Overview:
• Compare time-dependent density functional theory (TDDFT) and restricted open-shell Kohn-Sham (ROKS) excitation & emission
energies of BODIPY dyes (figure 1a) to experiment
• Compute excitation & emission energies using TDDFT & ROKS, compare values to experiment1
• Use molecular dynamics (MD) sampling to characterize the nonparallelity between the TDDFT and ROKS descriptions of the S1
potential energy surface (PES) for a particular chromophore (figure 1b)
• Examine the conformational dependence of O2 around
a BODIPY chromophore
• Study the electronic states involved in 1O2
sensitization, and compute the energies & coupling
between them using constrained DFT (CDFT)
Figure 1. (a) BODIPY derivatives used for excitation/emission energy comparison, and (b) BODIPY derivative used for PES characterization
Figure 2. Schematic of PES showing the excitation (i.e. absorbance) &
emission energy gaps between the S0 ground state and S1 excited state
Excitation/Emission & Nonparallelity
All calculations were performed with the B3LYP functional and the 6-31G(d) basis set. The MD simulations were
performed at 300K with a 40 a.u. time step and the 3-21G basis set, but the snapshots extracted were performed at the 6-
31G(d) basis.
Figure 3. Excitation and Emission energies for a set of 26 BODIPY derivatives, compared to experiment1. The best linear fit (red line), best linear fit assuming a slope
of 1 (dotted green), and hypothetical perfect agreement (dashed blue line) are provided for reference. Pearson’s r values (top to bottom, right to left) = 0.55, 0.53, 0.98,
0.83, 0.64, 0.90
Figure 4. Molecular dynamics snapshot energies
using ROKS MD (top left) and TDDFT MD
(bottom left). The best linear fit (red line) and
hypothetical perfect agreement (dashed blue) are
provided for reference). (left side) is a schematic
of the PESROKS
TDDFT
Figure 5. Comparison of S1 PES projected onto modes along which ROKS and TDDFT sampled configurations most significantly differ. Sin𝜃=0 is the
minimum energy while Sin𝜃=±1 are the turning points along the mode.
• TDDFT systematically overestimates Eex by ~0.4eV
• ROKS underestimates Eex by ~0.15eV
• Both methods show weak correlation to experiment but strong
correlation to each other
• Similar capabilities in computational screening of BODIPY
derivatives
• ROKS MD
 TDDFT predicts higher S1 energies
 Constant offset of ~0.5eV from perfect agreement
 High correlation indicating region of PES sampled is more parallel
• TDDFT MD
 Weak correlation but no significant energy gap
 Sampled region of PES with greater nonparallelity but smaller
displacement
1O2 Photosensitization of BODIPY Chromophore
Separate systems containing a single O2 molecule and a BODIPY chromophore were optimized to give
orientations and energies in figure 6. Electronic states in figure 7 were calculated using CDFT with the ωB97X-
D exchange and 6-31G(d) basis set. Couplings were calculated using the same parameters but with the SCF
convergence set to 10-5.
Figure 6. Optimized geometry of BODIPY + O2 configurations. Purple, green and maroon dots are O2 molecules (1 dot=1 oxygen atom on a molecule), orange
dots are atoms on the BODIPY dye. Ball & stick model is for orientation reference.
Figure 7. Jablonski diagram (left) of electronic states involved in 1O2 generation. CDFT
calculated values (right) for electronic states in terms of total occurrence at a specific energy.
PS=photosensitizer (BODIPY)
• O2 molecules oriented on sides of BODIPY have high
energy
 Face-on orientations have lower energy
• Electronic states show two peaks further backing the
conformational dependence on energy
• This dependence is shown clearly in figure 8, where the log
of the coupling between the 1PS+1O2 and 3PS+3O2 states is
clearly split between high and low energy depending on the
O2 orientation.
Figure 8. Plot of the log of the coupling between the 1PS+1O2 and 3PS+3O2 states, color
coded to match the orientations in figure 6.
Summary and Future Work
Excitation/Emission & MD: TDDFT overestimates excitation and emission energy while ROKS underestimates
by a lower margin, and both methods have a strong correlation to each other. ROKS and TDDFT sample different
regions of the PES when performing MD sampling. ROKS samples parallel region with an energy offset, while
TDDFT samples a region with less of an energy gap but greater nonparallelity.
1O2 photosensitization: O2 molecules tend to aggregate around the sides and top/bottom of the plane of the
BODIPY chromophore where the energy is split between high (side) and low (top/bottom) energies. This trend is
also seen when calculating the different electronic states involved in 1O2 sensitization as well as the coupling
between states.
Continuation: We plan to extend this study by calculating the coupling between all directly connected electronic
states (Jablonski diagram in figure 7), then solve for the rates between the states. Further down we hope to calculate
the rate of 1O2 generation in the dyes.
Acknowledgements
The author would like to thank Dr. Tim Kowalczyk for all of the wise advisement and extra time spent in the lab to
give help with issues. Thanks to the entire research group for the support and sanity check. Finally, thanks to the
support and funding through Western Washington University Department of Chemistry, Institute for Energy
Studies, and Advanced Materials Science and Engineering Center.
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