Theoretical and Experimental Evaluation of the Electronic Relaxation Mechanisms of 2-Pyrimidinone: The Primary UVA Absorbing Moiety of the DNA and RNA (6–4) Photolesion

The (6–4) photolesion is a key photodamage that occurs when two adjacent pyrimidine bases in a DNA strand bond together. To better understand how the absorption of UVB and UVA radiation by the 2-pyrimidinone moiety in a (6–4) lesion can damage DNA, it is important to study the electronic deactivation mechanism of its 2-pyrimidinone chromophore. This study employs theoretical (MS-CASPT2/cc-pVDZ level) and experimental (steady state and femtosecond broadband spectroscopic) methods to elucidate the photochemical relaxation mechanisms of 2-(1H)-pyrimidinone and 1-methyl-2-(1H)-pyrimidinone in aqueous solution (pH 7.4). In short, excitation at 320 nm leads to the population of the S₁ ¹(ππ*) state with excess vibrational energy, which relaxes to the S₁ ¹(ππ*) minimum in one picosecond or less. A trifurcation event in the S₁ ¹(ππ*) minimum ensued, leading to radiative and nonradiative decay of the population to the ground state or the population of the long-lived and reactive T₁ ³(ππ*) state in hundreds of picoseconds. Collectively, the theoretical and experimental results support the idea that in DNA and RNA, the T₁ ³(ππ*) state of the 2-pyrimidinone moiety in the (6–4) lesion can further participate in photosensitized chemical reactions increasing DNA and RNA damage.