Photophysical Processes in Nucleobase Systems

Photophysical processes in nucleobase systems govern how DNA and RNA building blocks interact with ultraviolet and visible light, determining pathways of energy dissipation, photoprotection and photodamage. Upon light absorption, canonical nucleobases primarily deactivate via ultrafast internal conversion back to the ground state, exploiting conical intersections to avoid harmful chemistry. In contrast, modified bases—such as sulphur‐ or selenium‐substituted analogues—favour intersystem crossing into long‐lived triplet states, opening routes to photosensitisation and reactive oxygen generation. Advances in femtosecond spectroscopy, time‐resolved photoelectron and X-ray techniques, combined with quantum‐chemical simulations, have mapped the topography of excited‐state potential energy surfaces and identified key spin–orbit coupling and non-adiabatic coupling mechanisms. These insights underpin applications ranging from photodynamic therapy to the design of organic photoactive materials, and inform our understanding of prebiotic photochemistry and nucleic acid photostability under solar irradiation.

Research from Nature Portfolio

A foundational study uncovered why sulphur substitution in pyrimidine nucleobases yields near-unity triplet-state populations, by combining femtosecond transient absorption with non-adiabatic dynamics on multistate potential energy surfaces. It showed that thionation stabilises critical singlet and triplet crossings and enhances spin–orbit coupling, thereby quenching the intrinsic photostability of canonical bases and promoting ultrafast intersystem crossing. More recently, time-resolved X-ray photoelectron spectroscopy has been applied to 2-thiouracil, directly monitoring charge migration at a sulphur site with femtosecond resolution. This approach revealed a major ground‐state recovery within 220–250 fs and coherent oscillations linked to electronic state exchange, offering a dynamic picture of excited‐state chemical shifts and decay pathways.

Photophysical Processes in Nucleobase Systems publication trend

The graph below shows the total number of articles in photophysical processes in nucleobase systems across all publications each year (not limited to Nature Index journals).

Technical terms

Internal conversion: Radiationless transition between electronic states of the same spin multiplicity, typically S₂→S₁ or S₁→S₀, via conical intersections.

Intersystem crossing: Spin‐forbidden non‐radiative transition between states of different spin multiplicity, for example S₁→T₁, enabled by spin–orbit coupling.

Triplet state: An electronic excited state with two unpaired electrons of parallel spin, often longer lived and capable of sensitising molecular oxygen.

Conical intersection: A point of degeneracy between two electronic potential energy surfaces that facilitates ultrafast non-radiative decay.

Transient absorption spectroscopy: Pump-probe technique that tracks population changes of electronic states over femtosecond to picosecond timescales.

Time-resolved photoelectron spectroscopy: Method that ionises excited states and measures electron kinetic energies to reconstruct potential energy surface dynamics.

Potential energy surface: Multidimensional landscape describing the energy of a molecule as a function of nuclear coordinates for a given electronic state.

References

1. Double Thionated Pyrimidine Nucleobases: Molecular Tools with Tunable Photoproperties. Journal of the American Chemical Society (2023).
2. Disruptive Model That Explains for the Long-Lived Triplet States Observed for 2‑Thiocytosine upon UVA Radiation. ACS Omega (2024).
3. The origin of efficient triplet state population in sulfur-substituted nucleobases. Nature Communications (2016).
4. 2-Thiouracil intersystem crossing photodynamics studied by wavelength-dependent photoelectron and transient absorption spectroscopies. Physical Chemistry Chemical Physics (2017).
5. Following excited-state chemical shifts in molecular ultrafast x-ray photoelectron spectroscopy. Nature Communications (2022).
6. Excited-State Properties and Relaxation Pathways of Selenium-Substituted Guanine Nucleobase in Aqueous Solution and DNA Duplex. The Journal of Physical Chemistry B (2021).