Singlet Oxygen: Rates Strongly Depend on Geometry

Simulations show how to maximize reaction rates for singlet oxygen generation.

In brief:

Reaction rates for ¹O₂ generation were computed with the DtC model.
Rates were determined as a function of the geometry of the PS-O₂ complex, spanning 15 different conformations.
The rates mapped in this way change over five orders of magnitude between the largest and the smallest ones.
¹O₂ generation is maximized when O₂ directly interacts with the PS region with highest spin density.

Singlet oxygen (¹O₂) is a central component for photodynamical therapy and diverse groups have been searching for the best photosensitizers (PS) to produce ¹O₂. In the most relevant channel in solution, ¹O₂ generation takes place through the reaction

¹[³PS+³O₂] → ¹[¹PS+¹O₂], (1)

in which a singlet complex (with each monomer in the triplet state) converts to another singlet state of the complex, but now with the spin of the monomers flipped to the singlet.

Shuming Bai and I have been developing a long-term project to explain the ¹O₂ formation photosensitized by thiothymines. Sooner this year, we proposed a computational model, name Dived-to-Conquer (DtC), to calculate kinetic rates for reaction (1). In our most recent work [1], we have employed the DtC model to investigate how the ¹O₂ generation rate depends on the spatial conformation of the PS-O₂ complex.

We mapped the rates for fifteen different directions and orientations for the incidence of O₂ on PS. These directions span the whole conformational space around PS, allowing to know exactly which regions should maximize or minimize the singlet oxygen production. The rates, computed for ¹O₂ formation in the ¹Σ_g⁺ and ¹Δ_g states of oxygen, are shown in the figure below.

The rates strongly depend on the direction, spanning five orders of magnitude between the largest and the lowest. All productive directions feature out-of-plane (-o) incidence, having atoms C4/C5/N6 as targets, exactly where the highest spin density of triplet PS peaks. This finding implies that orbital overlap is a necessary condition for effective photosensitization and indicates the relative importance of different conformers. For 6-aza-2-thiothymine, for instance, singlet oxygen production is maximized for an O₂ attack from above (or below) the aromatic ring. O₂ attack on the ring plan (-i) renders low rates.

For the most productive directions, rates for forming ¹Σ_g⁺ are larger than to form ¹Δ_g by 10 to 60%. This means that the direct formation of the final singlet oxygen product (¹Δ_g) should occur mainly via internal conversion from ¹Σ_g⁺, but still with significant amounts of the direct formation.

The calculations also revealed that formation of ¹O₂ in the ¹Σ_g⁺ and ¹Δ_g states have different underlying mechanisms: ¹Σ_g⁺ is formed with low activation energy and small diabatic couplings, while ¹Δ_g is formed with high activation energies and large diabatic couplings.

These results were recently published in the J. Phys. Chem. Letters [1].

Reference

[1] Shuming Bai and Mario Barbatti, Spatial Factors for Triplet Fusion Reaction of Singlet Oxygen Photosensitization, J. Phys. Chem. Letters doi:10.1021/acs.jpclett.7b02574 (2017).