Structural and energetic characterization of the emissive RNA alphabet based on the isothiazolo[4,3-d]pyrimidine heterocycle core.
We present theoretical characterization of fluorescent non-natural nucleobases, (tz)A, (tz)G, (tz)C, and (tz)U, derived from the isothiazolo[4,3-d]pyrimidine heterocycle. Consistent with the experimental evidence, our calculations show that the non-natural bases have minimal impact on the geometry and stability of the classical Watson-Crick base pairs, allowing them to accurately mimic 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 are destabilized relative to their natural counterparts. Analysis of the photophysical properties of the non-natural bases allowed us to correlate their absorption/emission peaks to the strong impact of the modification on the energy of the lowest unoccupied molecular orbital, LUMO, which is stabilized by roughly 1.0-1.2 eV relative to the natural analogues, while the highest occupied molecular orbital, HOMO, is not substantially affected. As a result, the HOMO-LUMO gap is reduced from 5.3-5.5 eV in the natural bases to 4.0-4.4 eV in the modified ones, with a consequent bathochromic shift in the absorption and emission spectra.
King Abdullah University of Science and Technology (KAUST), Physical Sciences and Engineering Division, KAUST Catalysis Center, Thuwal 23955-6900, Saudi Arabia. luigi.cavallo@kaust.edu.sa.
Mohit
M
Chawla
Albert
A
Poater
Romina
R
Oliva
Luigi
L
Cavallo
D020029:Base Pairing; D011743:Pyrimidines / Q000737:chemistry*; D012313:RNA / Q000737:chemistry*; D013816:Thermodynamics; D013844:Thiazoles / Q000737:chemistry*
D011743:Pyrimidines; D013844:Thiazoles; D012313:RNA