Resolving Ultrafast Photoinitiated Dynamics of the Hachimoji 5-Aza-7-Deazaguanine Nucleobase: Impact of Synthetically Expanding the Genetic Alphabet

August 17, 2022

Title

Resolving Ultrafast Photoinitiated Dynamics of the Hachimoji 5-Aza-7-Deazaguanine Nucleobase: Impact of Synthetically Expanding the Genetic Alphabet

Author

Sarah E. Krul, Gustavo J. Costa, Sean J. Hoehn, Danillo Valverde, Leonardo M. F. Oliveira, Antonio Carlos Borin, Carlos E. Crespo-Hernández

Year

2022

Journal

Photochemistry and photobiology

Abstract

The guanine derivative, 5-aza-7-deazaguanine (5N7CG) has recently been proposed as one of four unnatural bases, termed Hachimoji (8-letter) to expand the genetic code. We apply steady-state and time-resolved spectroscopy to investigate its electronic relaxation mechanism and probe the effect of atom substitution on the relaxation mechanism in polar protic and polar aprotic solvents. Mapping of the excited state potential energy surfaces is performed, from which the critical points are optimized by using the state-of-art Extended Multi-State Complete Active Space Second-Order Perturbation Theory. It is demonstrated that excitation to the lowest energy 1ππ* state of 5N7CG results in complex dynamics leading to ca. 10 to 30-fold slower relaxation (depending on solvent) compared to guanine. A significant conformational change occurs at the S1 minimum, resulting in a 10-fold greater fluorescence quantum yield compared to guanine. The fluorescence quantum yield and S1 decay lifetime increase going from water to acetonitrile to propanol. The solvent-dependent results are supported by the quantum chemical calculations showing an increase in the energy barrier between the S1 minimum and the S1/S0 conical intersection going from water to propanol. The longer lifetimes might make 5N7CG more photochemical active to adjacent nucleobases than guanine or other nucleobases within DNA.

Instrument

V-730

Keywords

DNA, Ultrafast Photoinitiated Dynamics, Genetic Alphabet