- PAR ID:
- 10161126
- Date Published:
- Journal Name:
- Molecules
- Volume:
- 25
- Issue:
- 3
- ISSN:
- 1420-3049
- Page Range / eLocation ID:
- 584-1 - 584-16
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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null (Ed.)All-organic, heavy-atom-free photosensitizers based on thionation of nucleobases are receiving increased attention because they are easy to make, noncytotoxic, work both in the presence and absence of molecular oxygen and can be readily incorporated into DNA and RNA. In this contribution, the DNA and RNA fluorescent probe, thieno[3,4-d]pyrimidin-4(1H)-one, has been thionated to develop thieno[3,4-d]pyrimidin-4(1H)-thione, which is nonfluorescent and absorbs near-visible radiation with about 60% higher efficiency. Steady-state absorption and emission spectra are combined with transient absorption spectroscopy and CASPT2 calculations to delineate the electronic relaxation mechanisms of both pyrimidine derivatives in aqueous and acetonitrile solutions and to explain the origin of the remarkable fluorescence quenching in the thionated compound. It is demonstrated that thieno[3,4-d]pyrimidin-4(1H)-thione efficiently populates the long-lived and reactive triplet state in hundreds of femtoseconds independent of solvent. Conversely, fluorescence emission in thieno[3,4-d]pyrimidin-4(1H)-one is highly sensitive to solvent, with an order of magnitude decrease in fluorescence yield in going from aqueous to acetonitrile solution. Collectively, the experimental and computational results demonstrate that thieno[3,4-d]pyrimidine-4(1H)-thione stands out as the most promising thiopyrimidine photosensitizer developed to this date, which can be readily incorporated as a photodynamic agent into sequence-specific DNA and RNA sequences for the treatment of skin cancer cells.more » « less
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Abstract Prolonged ultraviolet exposure results in the formation of cyclobutane pyrimidine dimers (CPDs) in RNA. Consequently, prebiotic photolesion repair mechanisms should have played an important role in the maintenance of the structural integrity of primitive nucleic acids. 2,6‐Diaminopurine is a prebiotic nucleobase that repairs CPDs with high efficiency when incorporated into polymers. We investigate the electronic deactivation pathways of 2,6‐diaminopurine‐2′‐deoxyribose and 9‐methyl‐2,6‐diaminopurine in acetonitrile and aqueous solution to shed light on the photophysical and excited state properties of the 2,6‐diaminopurine chromophore. Evidence is presented that both are photostable compounds exhibiting similar deactivation mechanisms upon the population of the S1(ππ* La) state at 290 nm. The mechanism involves deactivation through the C2‐ and C6‐reaction coordinates and >99% of the excited state population decays through nonradiative pathways involving two conical intersections with the ground state. The radiative and nonradiative lifetimes are longer in aqueous solution compared to acetonitrile. While
τ 1is similar in both derivatives,τ 2is ca. 1.5‐fold longer in 2,6‐diaminopurine‐2′‐deoxyribose due to a more efficient trapping in the S1(ππ* La) minimum. Therefore, 2,6‐diaminopurine could have accumulated in significant quantities during prebiotic times to be incorporated into non‐canonical RNA and play a significant role in its photoprotection. -
Photostability is thought to be an inherent property of nucleobases required to survive the extreme ultraviolet radiation conditions of the prebiotic era. Previous studies have shown that absorption of ultraviolet radiation by the canonical nucleosides results in ultrafast internal conversion to the ground state, demonstrating that these nucleosides efficiently dissipate the excess electronic energy to the environment. In recent years, studies on the photophysical and photochemical properties of nucleobase derivatives have revealed that chemical substitution influences the electronic relaxation pathways of purine and pyrimidine nucleobases. It has been suggested that amino or carbonyl substitution at the C6 position could increase the photostability of the purine derivatives more than the substitution at the C2 position. This investigation aims to elucidate the excited state dynamics of 2′-deoxyisoguanosine (dIsoGuo) and isoguanosine (IsoGuo) in aqueous solution at pH 7.4 and 1.4, which contain an amino group at the C6 position and a carbonyl group at the C2 position of the purine chromophore. The study of these derivatives is performed using absorption and emission spectroscopies, broadband transient absorption spectroscopy, and density functional and time-dependent density functional levels of theory. It is shown that the primary relaxation mechanism of dIsoGuo and IsoGuo involves nonradiative decay pathways, where the population decays from the S 1 (ππ*) state through internal conversion to the ground state via two relaxation pathways with lifetimes of hundreds of femtoseconds and less than 2 ps, making these purine nucleosides photostable in aqueous solution.more » « less
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