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Rationalizing the environment-dependent photophysical behavior of a DNA luminescent probe by classical and non-adiabatic molecular dynamics simulations

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Abstract

Environment-sensitive fluorescent nucleoside analogs are of utmost importance to investigate the structure of nucleic acids, their intrinsic flexibility, and sequence-specific DNA- and RNA-binding proteins. The latter play indeed a key role in transcription, translation as well as in the regulation of RNA stability, localization and turnover, and many other cellular processes. The sensitivity of the embedded fluorophore to polarity, hydration, and base stacking is clearly dependent on the specific excited-state relaxation mechanism and can be rationalized combining experimental and computational techniques. In this work, we elucidate the mechanisms leading to the population of the triplet state manifold for a versatile nucleobase surrogate, namely the 2-thienyl-3-hydroxychromone in gas phase, owing to non-adiabatic molecular dynamics simulations. Furthermore, we analyze its behavior in the B-DNA environment via classical molecular dynamics simulations, which evidence a rapid extrusion of the adenine facing the 2-thienyl-3-hydroxychromone nucleobase surrogate. Our simulations provide new insights into the dynamics of this family of chromophores, which could give rise to an integrated view and a fine tuning of their photochemistry, and namely the role of excited-state intramolecular proton transfer for the rational design of the next generation of fluorescent nucleoside analogs.

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Acknowledgements

The authors thank GENCI and Explor computing centers for computational resources. A.M. thanks ANR and CGI for their financial support of this work through Labex SEAM ANR 11 LABX 086, ANR 11 IDEX 05 02. The support of the IdEx “Université Paris 2019” ANR-18-IDEX-0001 is also acknowledged. ED is grateful for a support from the Institut Universitaire de France.

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Authors and Affiliations

  1. Université Paris Cité and CNRS, ITODYS, 75006, Paris, France

    Antonio Monari

  2. Institut de Chimie de Nice, UMR 7272, Université Côte d’Azur, CNRS, 06108, Nice, France

    Alain Burger & Elise Dumont

  3. Institut Universitaire de France, 5 Rue Descartes, 75005, Paris, France

    Elise Dumont

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  1. Antonio Monari
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  2. Alain Burger
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Correspondence to Antonio Monari or Elise Dumont.

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43630_2023_431_MOESM1_ESM.pdf

Supplementary file1 (PDF 810 KB) RESP charges for the M chromophore at the ωB97Xd/6-311+G(d,p) vs. B3LYP/6-31G(d,p) levels of theory. Library file for the non-canonical M and M’ chromophores obtained for the GAFF parameters are available at: https://github.com/elisejdumont/3HC-parametrization. Distribution of the torsion angle of the -OH moiety along the Wigner distribution (100 generated structures). TDDFT benchmark for M in gas phase and with a PCM implicit solvation, with and without one water molecule at the ωB97Xd/6-311+G(d,p)//ωB97Xd/6-311+G(d,p) and M06-2X/6-311+G(d,p)//ωB97Xd/6-311+G(d,p) levels of theory. TDDFT calculations for the uracil-M’ system

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Monari, A., Burger, A. & Dumont, E. Rationalizing the environment-dependent photophysical behavior of a DNA luminescent probe by classical and non-adiabatic molecular dynamics simulations. Photochem Photobiol Sci 22, 2081–2092 (2023). https://doi.org/10.1007/s43630-023-00431-3

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