Photophysics of BODIPY-Based Photosensitizer for Photodynamic Therapy: Surface Hopping and Classical Molecular Dynamics

Abstract

Halogenated BODIPY derivatives are emerging as important candidates for photodynamic therapy of cancer cells due to their high triplet quantum yield. We probed fundamental photophysical properties and interactions with biological environments of such photosensitizers. To this end, we employed static TD-DFT quantum chemical calculations as well as TD-DFT surface hopping molecular dynamics on potential energy surfaces resulting from the eigenstates of the total electronic Hamiltonian including the spin−orbit (SO) coupling. Matrix elements of an effective one-electron spin− orbit Hamiltonian between singlet and triplet configuration interaction singles (CIS) auxiliary wave functions are calculated using a new code capable of dealing with singlets and both restricted and unrestricted triplets built up from up to three different and independent sets of (singlet, alpha, and beta) molecular orbitals. The interaction with a biological environment was addressed by using classical molecular dynamics (MD) in a scheme that implicitly accounts for electronically excited states. For the surface hopping trajectories, an accelerated MD approach was used, in which the SO couplings are scaled up, to make the calculations computationally feasible, and the lifetimes are extrapolated back to unscaled SO couplings. The lifetime of the first excited singlet state estimated by semiclassical surface hopping simulations is 139 ± 75 ps. Classical MD demonstrates that halogenated BODIPY in the ground state, in contrast to the unsubstituted one, is stable in the headgroup region of minimalistic cell membrane models, and while in the triplet state, the molecule relocates to the membrane interior ready for further steps of photodynamic therapy.

Mechanistic Understanding from Molecular Dynamics in Pharmaceutical Research 2: Lipid Membrane in Drug Design

“…Previous reviews [222,223], Chlorambucil [199], Camptothecin [224], Ohmline [225] Photosensitizer used in cancer treatment Tetra-phenylporphyrin [169,183], Hematoporphyrin [130], 1-BODIPY (6,7-dibromo-2-ethyl-1,3-dimethyl-4,4-difluoro-4-bora-3a,4a-diaza-s-indacene) [226],…”

Theoretical Investigation of the Effect of Alkylation and Bromination on Intersystem Crossing in BODIPY-Based Photosensitizers

“…Therefore, the design of new photosensitizers with well-tuned properties is a critical issue for the development of efficient PDT. Recently, we employed a combination of various-level molecular modeling and theoretical chemistry methods to study a potential photosensitizer molecule, 1-BODIPY, both in the context of its photophysics and accumulation in models of biological membranes . We demonstrated that this molecule is potentially a good photosensitizer due to its strong spin–orbit coupling (SOC) as well as good accumulation in lipid phases.…”

“…Since 1-BODIPY studied in our previous work has both alkyl and bromine substituents, we now aim to find out their respective effects on ISC in substituted BODIPY derivatives. In this work, we perform further calculations of SOCs between five excited singlet and triplet states in the four molecules shown in Figures – at the B3LYP/aug-cc-pVDZ and B3LYP/cc-pVDZ levels of theory.…”

Increased photoluminescence and photodynamic therapy efficiency of hydroxyapatite-β-cyclodextrin-methylene blue@carbon powders with the favor of hydrogen bonding effect

“…For this type II photosensitized oxygenation reaction, PDT efficiency is closely relied on the generation ratio of singlet oxygen molecule, whose low intra-tumoral yield is a major limitation for traditional and available photosensitizers [12][13][14] with requirements of high absorption coefficient [4,15] and monomer state of these lipophilic dyes without dimeric aggregation [16][17][18]. Many efforts are devoted to increase generation efficiencies of singlet oxygen molecules through promoting intersystem crossing processes by spin coupling of heavy atom effect [19][20][21][22][23], optimizing state energy levels through fine-tuned absorption wavelengths [20,22] or employing Förster resonance energy transfer pairs with photoinduced charge transfer [24][25][26]. Structural modifications [22] or sulfur substitutions of carbonyl thionaphathalimides at 2-and 6-positions [20] endow remarkable fluorescence quenching and tremendous enhancement in the rate constant of intersystem crossing, due to the significant increase of spin-orbit coupling constant and decrease of singlet-triplet energy gap [20,22].…”