Topology and Excited State Multiplicity as Controlling Factors in the Carbazole-Photosensitized CPD Formation and Repair

Abstract

Photosensitized thymine<>thymine (Thy<>Thy) formation and repair can be mediated by carbazole (Cbz). The former occurs from the Cbz triplet excited state via energy transfer, while the latter takes place from the singlet excited state via electron transfer. Here, fundamental insight is provided into the role of the topology and excited state multiplicity, as factors governing the balance between both processes. This has been achieved upon designing and synthesizing different isomers of trifunctional systems containing one Cbz and two Thy units covalently linked to the rigid skeleton of the natural deoxycholic acid. The results shown here prove that the Cbz photosensitized dimerization is not counterbalanced by repair when the latter, instead of operating through-space, has to proceed through-bond.

Scheme 1. Reagents and Conditions: (i) Cbz-CH₂CH₂OH, TBTU, DIEA, and DMF (67%); (ii) Thy-CH₂COOH, Et₃N, 2,4,6-Trichlorobenzoyl Chloride, 4-DMAP, and THF (77%)^a, (56%)^b, and (60%)^c; (iii) Benzyl Bromide, DBU, and DMF (57%); (iv) LiAlH₄ and Refluxing THF (87%); (v) Cbz-CH₂CO₂H, TBTU, DIEA, and DMF (43%)

Figure 1

Top: UV–vis spectra of 2 recorded at different irradiation times. Middle: UV–vis spectra of 6 recorded at different irradiation times. Bottom: Photoreaction kinetics of Thy (as ThyCH₂CO₂H) (black inverted triangle), Cbz (as Cbz-CH₂CH₂OH) (*), the intermolecular 2Thy:1Cbz mixture (open circle), and the intramolecular systems 2 (black circle) and 6 (diamond). All reactions were performed upon irradiation at 350 nm, in deaerated 4CH₃CN:1H₂O.

Figure 2

X-ray crystal structure (thermal ellipsoids drawn at the 50% probability level) of the Thy<>Thy 8 resulting from irradiation (λ_max = 350 nm) of 6 in CH₃CN under N₂, and the detail of the cyclobutane fragment. CCDC 2159900 contains the supplementary crystallographic data for this paper. These data are provided free of charge by The Cambridge Crystallographic Data Centre.

Scheme 2. Irradiation (λ_max = 350 nm) in Deaerated CH₃CN of 2 (Top) to Give 7 (>99%) and 6 (Bottom) to Give 8 (68%)

Figure 3

LFP decays obtained upon selective excitation of Cbz at 308 nm and monitored at 420 nm in deaerated 4CH₃CN:1H₂O. Top: Cbz (as Cbz-CH₂CH₂OH) (black circle) and the intermolecular mixtures, 1Thd:1Cbz (pink triangle), 2Thd:1Cbz (green square), and 3Thd:1Cbz (violet star) in deaerated 4CH₃CN:1H₂O. Inset: Stern–Volmer plot for the quenching of ³Cbz* by Thd. Bottom: Traces recorded at 420 nm upon excitation of Cbz at 308 nm for 5 (blue), 2 (pink), and 6 (green).

Figure 4

Kinetics of the evolution of 7 (left) and 8 (right) upon increasing irradiation times (λ_exc = 350 nm), at 0.2 mM in aerated 4CH₃CN:1H₂O. (A, D) Changes in the absorbance spectra (inset: relative absorbance changes); (B, E) changes in the steady-state emission spectra, λ_exc = 340 nm (inset: relative emission changes); (C, F) changes in the time-resolved emission, λ_exc = 340 nm (inset: relative lifetime changes). Pink (in A–C) and green (in D–F) traces correspond to 2 and 6, respectively.

Figure 5

HPLC Chromatograms (top) and conversion rate (bottom) for 7 (left) or 8 (right) upon increasing irradiation times (λ_exc = 350 nm), at 0.2 mM in aerated 4CH₃CN:1H₂O. The chromatograms corresponding to 2 (pink trace, left) and 6 (green trace, right) are shown for comparison.

Figure 6

Left: Histogram of chromophore–chromophore distances of 2 and 6. Right: Histogram of chromophore–chromophore Thy-Cbz distances of 7 and 8. Results were in all cases obtained from molecular dynamics during 3 ns at 298 K in a 4:1 acetonitrile:water solvent. Each plot has been calculated using 300,000 configurations.

Figure 7

Configuration of molecules 2, 6, 7, and 8 showing the distances between chromophore groups (dotted lines).

Scheme 3. Postulated Mechanism to Explain Intramolecular Photosensitized Dimer Formation (TS Energy Transfer) and Repair (TB Electron Transfer)