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.
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On the Origin of the Photostability of DNA and RNA Monomers: Excited State Relaxation Mechanism of the Pyrimidine Chromophore
Today’s genetic composition is the result of continual refinement processes on primordial heterocycles present in prebiotic Earth and at least partially regulated by ultraviolet radiation. Femtosecond transient absorption spectroscopy and state-of-the-art ab initio calculations are combined to unravel the electronic relaxation mechanism of pyrimidine―the common chromophore of the nucleobases. Excitation of pyrimidine at 268 nm populates the S1(nπ*) state directly. A fraction of the population intersystem crosses to the triplet manifold within 7.8 ps, partially decaying within 1.5 ns, while another fraction recovers the ground state in >3 ns. The pyrimidine chromophore is not responsible for the photostability of the nucleobases. Instead, C2 and C4 amino and/or carbonyl functionalization is essential for shaping the topography of pyrimidine’s potential energy surfaces, which present accessible conical intersections between the initially populated electronic excited state and the ground state.
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- Award ID(s):
- 1800052
- NSF-PAR ID:
- 10161128
- Date Published:
- Journal Name:
- The Journal of Physical Chemistry Letters
- ISSN:
- 1948-7185
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Ultraviolet radiation (UVR) from the sun is essential for the prebiotic syntheses of nucleotides, but it can also induce photolesions such as the cyclobutane pyrimidine dimers (CPDs) to RNA or DNA oligonucleotide in prebiotic Earth. 2,6-Diaminopurine (26DAP) has been proposed to repair CPDs in high yield under prebiotic conditions and be a key component in enhancing the photostability of higher-order prebiotic DNA structures. However, its electronic relaxation pathways have not been studied, which is necessary to know whether 26DAP could have survived the intense UV fluxes of the prebiotic Earth. We investigate the electronic relaxation mechanism of both 26DAP and its 2′-deoxyribonucleoside (26DAP-d) in aqueous solution using steady-state and femtosecond transient absorption measurements that are complemented with electronic-structure calculations. The results demonstrate that both purine derivatives are significantly photostable to UVR. It is shown that upon excitation at 287 nm, the lowest energy 1 ππ* state is initially populated. The population then branches following two relaxation coordinates in the 1 ππ* potential energy surface, which are identified as the C2- and C6-relaxation coordinates. The population following the C6-coordinate internally converts to the ground state nonradiatively through a nearly barrierless conical intersection within 0.7 ps in 26DAP or within 1.1 ps in 26DAP-d. The population that follows the C2-relaxation coordinate decays back to the ground state by a combination of nonradiative internal conversion via a conical intersection and fluorescence emission from the 1 ππ* minimum in 43 ps and 1.8 ns for the N9 and N7 tautomers of 26DAP, respectively, or in 70 ps for 26DAP-d. Fluorescence quantum yields of 0.037 and 0.008 are determined for 26DAP and 26DAP-d, respectively. Collectively, it is demonstrated that most of the excited state population in 26DAP and 26DAP-d decays back to the ground state via both nonradiative and radiative relaxation pathways. This result lends support to the idea that 26DAP could have accumulated in large enough quantities during the prebiotic era to participate in the formation of prebiotic RNA or DNA oligomers and act as a key component in the protection of the prebiotic genetic alphabet.more » « less
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null (Ed.)The Watson–Crick A·T and G·C base pairs are not only electronically complementary, but also photochemically complementary. Upon UV irradiation, DNA base pairs undergo efficient excited-state deactivation through electron driven proton transfer (EDPT), also known as proton-coupled electron transfer (PCET), at a rate too fast for other reactions to take place. Why this process occurs so efficiently is typically reasoned based on the oxidation and reduction potentials of the bases in their electronic ground states. Here, we show that the occurrence of EDPT can be traced to a reversal in the aromatic/antiaromatic character of the base upon photoexcitation. The Watson–Crick A·T and G·C base pairs are aromatic in the ground state, but the purines become highly antiaromatic and reactive in the first 1 ππ* state, and transferring an electron and a proton to the pyrimidine relieves this excited-state antiaromaticity. Even though proton transfer proceeds along the coordinate of breaking a N–H σ-bond, the chromophore is the π-system of the base, and EDPT is driven by the strive to alleviate antiaromaticity in the π-system of the photoexcited base. The presence and absence of alternative excited-state EDPT routes in base pairs also can be explained by sudden changes in their aromatic and antiaromatic character upon photoexcitation.more » « less
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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(3H)-one, has been thionated to develop thieno[3,4-d]pyrimidin-4(3H)-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. It is demonstrated that thieno[3,4-d]pyrimidin-4(3H)-thione efficiently populates the long-lived and reactive triplet state generating singlet oxygen with a quantum yield of about 80% independent of solvent. It is further shown that thieno[3,4-d]pyrimidin-4(3H)-thione exhibits high photodynamic efficacy against mono-layer melanoma cells and cervical cancer cells both under normoxic and hypoxic conditions. Our combined spectroscopic, computational, and in vitro data demonstrate the excellent potential of thieno[3,4-d]pyrimidin-4(3H)-thione as a heavy-atom-free PDT agent and paves the way for further development of photosensitizers based on the thionation of thieno[3,4-d]pyrimidine derivatives. Collectively, the experimental and computational results demonstrate that thieno[3,4-d]pyrimidine-4(3H)-thione stands out as the most promising thiobase photosensitizer developed to this date.more » « less
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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
- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1021/acs.jpclett.0c00935
