Why Replacing Different Oxygens of Thymine with Sulfur Causes Distinct Absorption and Intersystem Crossing

Bai, Shuming; Barbatti, Mario

doi:10.1021/acs.jpca.6b05110

Cited by 49 publications

(79 citation statements)

References 56 publications

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“…100 cm −1 ) to 4‐thiothymine (ca. 150 cm −1 ) , which can qualitatively explain the increased rate of intersystem crossing experimentally observed for these two thiobases . Conversely, the spin‐orbit coupling for 2,4‐dithiothymine was calculated to have almost the same magnitude as that calculated for 4‐thiothymine , which does not trend with the experimental observations .…”

Section: Time‐resolved Photophysicsmentioning

confidence: 65%

“…150 cm −1 ) , which can qualitatively explain the increased rate of intersystem crossing experimentally observed for these two thiobases . Conversely, the spin‐orbit coupling for 2,4‐dithiothymine was calculated to have almost the same magnitude as that calculated for 4‐thiothymine , which does not trend with the experimental observations . Further investigations are necessary to understand how the position and degree of thionation regulate the rate of intersystem crossing in the thiothymine and thiouracil derivatives .…”

Section: Time‐resolved Photophysicsmentioning

confidence: 80%

“…The tail redshifts with decreasing solvent polarity, suggesting that it originates from an n S π* transition (B. Ashwood, M. Pollum, C. E. Crespo‐Hernández, unpublished results) . Vertical excitation energies obtained using single‐reference and multiconfigurational computational methods predict that the lowest‐energy absorption maximum is due to a S 2 (π S π*) transition in the thiouracil and thiothymine derivatives , while it has been assigned primarily to a S 4 (π S π*) transition in 2‐thiocytosine . Similarly, the absorption tail has been assigned to a S 1 (n S π*) transition in the thiothymine and thiouracil derivatives, while it has been assigned to a combination of S 2 (π S π*) and S 1 (n S π*) transitions in 2‐thiocytosine .…”

Section: Steady‐state Photophysical Propertiesmentioning

confidence: 98%

“…While the electron density of the LUMO extends over the oxygen atom of the carbonyl group in 2‐thiothymine, it extends over the sulfur atom in 4‐thiothymine (Scheme 4). Thus, the greater redshift in 4‐thiothymine was attributed to the LUMO being localized along the weaker thiocarbonyl bond, whereas the LUMO is localized along the higher energy carbonyl bond in 2‐thiothymine . Manae and Hazra added that the reason behind the localization of the LUMO over the oxygen or the sulfur atom depending on the site of thionation is due to an interplay between two types of electronic delocalization.…”

Section: Steady‐state Photophysical Propertiesmentioning

confidence: 99%

“…That is, the thiothymine series exhibits a 3.5‐fold increase in the rate of intersystem crossing in going from 2‐thiothymine to 2,4‐dithiothymine, whereas a 1.6‐fold increase is observed in going from 2‐thiouracil to 2,4‐thiouracil. Bai and Barbatti have recently made an effort to rationalize the experimental observations by calculating the spin‐orbit coupling between the optimized S 1 state and the triplet states that are at equal or lower in energy than the energy of the S 1 state at its minimum . The spin‐orbit coupling increases in going from 2‐thiothymine (ca.…”

Section: Time‐resolved Photophysicsmentioning

confidence: 99%

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Photochemical and Photodynamical Properties of Sulfur‐Substituted Nucleic Acid Bases,

Ashwood

Pollum

Crespo‐Hernández

2018

Photochem & Photobiology

115

132

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Sulfur-substituted nucleobases (a.k.a., thiobases) are among the world's leading prescriptions for chemotherapy and immunosuppression. Long-term treatment with azathioprine, 6-mercaptopurine and 6-thioguanine has been correlated with the photoinduced formation of carcinomas. Establishing an in-depth understanding of the photochemical properties of these prodrugs may provide a route to overcoming these carcinogenic side effects, or, alternatively, a basis for developing effective compounds for targeted phototherapy. In this review, a broad examination is undertaken, surveying the basic photochemical properties and excited-state dynamics of sulfur-substituted analogs of the canonical DNA and RNA nucleobases. A molecular-level understanding of how sulfur substitution so remarkably perturbs the photochemical properties of the nucleobases is presented by combining experimental results with quantum-chemical calculations. Structure-property relationships demonstrate the impact of site-specific sulfur substitution on the photochemical properties, particularly on the population of the reactive triplet state. The value of fundamental photochemical investigations for driving the development of ultraviolet-A chemotherapeutics is showcased. The most promising photodynamic agents identified thus far have been investigated in various carcinoma cell lines and shown to decrease cell proliferation upon exposure to ultraviolet-A radiation. Overarching principles have been elucidated for the impact that sulfur substitution of the carbonyl oxygen has on the photochemical properties of the nucleobases.

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Section: Time‐resolved Photophysicsmentioning

confidence: 65%

Section: Time‐resolved Photophysicsmentioning

confidence: 80%

Section: Steady‐state Photophysical Propertiesmentioning

confidence: 98%

Section: Steady‐state Photophysical Propertiesmentioning

confidence: 99%

Section: Time‐resolved Photophysicsmentioning

confidence: 99%

See 3 more Smart Citations

Photochemical and Photodynamical Properties of Sulfur‐Substituted Nucleic Acid Bases,

Ashwood

Pollum

Crespo‐Hernández

2018

Photochem & Photobiology

115

132

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Decoding the Molecular Basis for the Population Mechanism of the Triplet Phototoxic Precursors in UVA Light‐Activated Pyrimidine Anticancer Drugs

Martínez‐Fernández

Granucci

Pollum

et al. 2017

Chemistry A European J

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The photosensitization of DNA by thionucleosides is a promising photo-chemotherapeutic treatment option for a variety of malignancies. DNA metabolization of thionated prodrugs can lead to cell death upon exposure to a low dose of UVA light. The exact mechanisms of thionucleoside phototoxicity are still not fully understood. In this work, we have combined femtosecond broadband transient absorption experiments with state-of-the-art molecular simulations to provide mechanistic insights into the ultrafast and efficient population of the triplet state in the UVA-activated pyrimidine anticancer drug 4-thiothymine. The triplet state is thought to act as a precursor to DNA lesions and the reactive oxygen species responsible for 4-thiothymine photocytotoxicity. The electronic-structure and mechanistic results presented in this contribution reveal key molecular design criteria that can assist in developing alternative chemotherapeutic agents that may overcome some of the primary deficiencies of classical photosensitizers.

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Excited‐State Dynamics of Thienoguanosine, an Isomorphic Highly Fluorescent Analogue of Guanosine

Martínez‐Fernández

Gavvala

Sharma

et al. 2019

Chemistry A European J

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Thienoguanosine (thG) is an isomorphic analogue of guanosine with promising potentialities as fluorescent DNA label. As a free probe in protic solvents, thG exists in two tautomeric forms, identified as the H1, being the only one observed in nonprotic solvents, and H3 keto–amino tautomers. We herein investigate the photophysics of thG in solvents of different polarity, from water to dioxane, by combining time‐resolved fluorescence with PCM/TD‐DFT and CASSCF calculations. Fluorescence lifetimes of 14.5–20.5 and 7–13 ns were observed for the H1 and H3 tautomers, respectively, in the tested solvents. In methanol and ethanol, an additional fluorescent decay lifetime (≈3 ns) at the blue emission side (λ≈430 nm) as well as a 0.5 ns component with negative amplitude at the red edge of the spectrum, typical of an excited‐state reaction, were observed. Our computational analysis explains the solvent effects observed on the tautomeric equilibrium. The main radiative and nonradiative deactivation routes have been mapped by PCM/TD‐DFT calculations in solution and CASSCF in the gas phase. The most easily accessible conical intersection, involving an out‐of plane motion of the sulfur atom in the five‐membered ring of thG, is separated by a sizeable energy barrier (≥0.4 eV) from the minimum of the spectroscopic state, which explains the large experimental fluorescence quantum yield.

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Why Replacing Different Oxygens of Thymine with Sulfur Causes Distinct Absorption and Intersystem Crossing

Cited by 49 publications

References 56 publications

Photochemical and Photodynamical Properties of Sulfur‐Substituted Nucleic Acid Bases,

Photochemical and Photodynamical Properties of Sulfur‐Substituted Nucleic Acid Bases,

Decoding the Molecular Basis for the Population Mechanism of the Triplet Phototoxic Precursors in UVA Light‐Activated Pyrimidine Anticancer Drugs

Excited‐State Dynamics of Thienoguanosine, an Isomorphic Highly Fluorescent Analogue of Guanosine

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