Theoretical Characterization of Sulfur-to-Selenium Substitution in an Emissive RNA Alphabet: Impact on H-bonding Potential and Photophysical Properties

Mohit Chawla, Albert Poater, Pau Besalu-Sala, Kanav Kalra, Romina Oliva, Luigi Cavallo

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

We employ density functional theory (DFT) and time-dependent DFT (TDDFT) calculations to investigate the structural, energetic and optical properties of a new computationally designed RNA alphabet, where the nucleobases,tsA, tsG, tsC, and tsU (ts-bases), have been derived by replacing sulfur with selenium in the previously reported tz-bases, based on the isothiazolo[4.3-d]pyrimidine heterocycle core. We find out that the modeled non-natural bases have minimal impact on the geometry and energetics of the classical Watson-Crick base pairs, thus potentially mimicking the natural bases in a RNA duplex in terms of H-bonding. In contrast, our calculations indicate that H-bonded base pairs involving the Hoogsteen edge of purines are destabilized as compared to their natural counterparts. We also focus on the photophysical properties of the non-natural bases and correlate their absorption/emission peaks to the strong impact of the modification on the energy of the lowest unoccupied molecular orbital. It is indeed stabilized by roughly 1.1-1.6 eV as compared to the natural analogues, resulting in a reduction of the gap between the highest occupied and the lowest unoccupied molecular orbital from 5.3-5.5 eV in the natural bases to 3.9-4.2 eV in the modified ones, with a consequent bathochromic shift in the absorption and emission spectra. Overall, our analysis clearly indicates that the newly modelled ts-bases are expected to exhibit better fluorescent properties as compared to the previously reported tz-bases, while retaining similar H-bonding properties. In addition, we show that a new RNA alphabet based on size-extended benzo-homologated ts-bases can also form stable Watson-Crick base pairs with the natural complementary nucleobases.
Original languageEnglish (US)
Pages (from-to)7676-7685
Number of pages10
JournalPhysical Chemistry Chemical Physics
Volume20
Issue number11
DOIs
StatePublished - 2018

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