Photophysics and Photochemistry of Canonical Nucleobases’ Thioanalogs: From Quantum Mechanical Studies to Time Resolved Experiments

Abstract

Interest in understanding the photophysics and photochemistry of thiated nucleobases has been awakened because of their possible involvement in primordial RNA or their potential use as photosensitizers in medicinal chemistry. The interpretation of the photodynamics of these systems, conditioned by their intricate potential energy surfaces, requires the powerful interplay between experimental measurements and state of the art molecular simulations. In this review, we provide an overview on the photophysics of natural nucleobases’ thioanalogs, which covers the last 30 years and both experimental and computational contributions. For all the canonical nucleobase’s thioanalogs, we have compiled the main steady state absorption and emission features and their interpretation in terms of theoretical calculations. Then, we revise the main topographical features, including stationary points and interstate crossings, of their potential energy surfaces based on quantum mechanical calculations and we conclude, by combining the outcome of different spectroscopic techniques and molecular dynamics simulations, with the mechanism by which these nucleobase analogs populate their triplet excited states, which are at the origin of their photosensitizing properties.

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

“…The calculations also reveal relaxation pathways that satisfactorily explain two distinctive properties of the thiobases―one of the fastest intersystem‐crossing lifetimes measured to date among bioorganic molecules and have near‐unity triplet yields, compared to nearly zero triplet yields of the DNA and RNA nucleobases in aqueous solution . As summarized in this section, and in greater detail elsewhere , the primary relaxation mechanisms leading to the ultrafast population of the triplet state in the thiobase derivatives are now reasonably well understood.…”

“…It is crucial to investigate and understand the photochemistry of these unnatural bases because, as shown herein and elsewhere , thionation of a carbonyl group is expected to significantly modulate the photochemistry and reactivity of organic molecules. Hence, the photochemical properties of dNaM, d5SICS and dTPT3 have recently been studied in solution .…”

“… *See previous reviews for absorption and emission properties in other solvents and temperatures . † Wavelength of lowest‐energy absorption band maximum.…”

“…The localization of the nπ* transition on the sulfur atom is responsible for its significant redshift relative to analogous transitions in the canonical nucleobases . A compilation of the vertical excitation energies calculated at different levels of theory can be found in a recent review by Corral and co‐workers .…”

A Unified Experimental/Theoretical Description of the Ultrafast Photophysics of Single and Double Thionated Uracils

“…Thiobases are nucleobase derivatives obtained by the replacement of oxygen atoms in the canonical exocyclic carbonyl group with sulfur . Thionation redshifts the absorption spectra and radically changes the photophysics of sulfur‐substituted bases.…”