Chang Xue-Ping, Fan Feng-Ran, Zhang Teng-Shuo, Xie Bin-Bin
College of Chemistry and Chemical Engineering, Xinyang Normal University, Xinyang 464000, China.
College of Chemical Engineering, Zhejiang University of Technology, Hangzhou 310014, China.
Phys Chem Chem Phys. 2023 Oct 4;25(38):26258-26269. doi: 10.1039/d3cp03628f.
The excited state properties and deactivation pathways of two DNA methylation inhibitors, , 5-azacytidine (5ACyd) and 2'-deoxy-5-azacytidine (5AdCyd) in aqueous solution, are comprehensively explored with the QM(CASPT2//CASSCF)/MM protocol. We systematically map the feasible decay mechanisms based on the obtained excited-state decay paths involving all the identified minimum-energy structures, conical intersections, and crossing points driving the different internal conversion (IC) and intersystem crossing (ISC) routes in and between the ππ*, nπ*, ππ*, nπ*, and S states. Unlike the nπ* state below the ππ* state in 5ACyd, deoxyribose group substitution at the N1 position leads to the ππ* state becoming the S state in 5AdCyd. In 5ACyd and 5AdCyd, the initially populated ππ* state mainly deactivates to the S state through the direct ππ* → S IC or mediated by the nπ* state. The former nearly barrierless IC channel of ππ* → S occurs ultrafast the nearby low-lying ππ*/S conical intersection. In the latter IC channel of ππ* → nπ* → S, the initially photoexcited ππ* state first approaches the nearby S/S conical section ππ*/nπ* and then undergoes efficient IC to the nπ* state, followed by the further IC to the initial S state the S/S conical intersection nπ*/S. The nπ*/S conical intersection is estimated to be located 6.0 and 4.9 kcal mol above the nπ* state minimum in 5ACyd and 5AdCyd, respectively, at the QM(CASPT2)/MM level. In addition to the efficient singlet-mediated IC channels, the minor ISC routes would populate ππ* to T(ππ*) through ππ* → T or ππ* → nπ* → T. Relatively, the ππ* → nπ* → T route benefits from the spin-orbit coupling (SOC) of nπ*/ππ* of 8.7 cm in 5ACyd and 10.2 cm in 5AdCyd, respectively. Subsequently, the T system will approach the nearby T/S crossing point ππ*/S driving it back to the S state. Given the ππ*/S crossing point located above the T minimum and the small T/S SOC, , 8.4 kcal mol and 2.1 cm in 5ACyd and 6.8 kcal mol and 1.9 cm in 5AdCyd, respectively, the slow T → S would trap the system in the T state for a while. The present work could contribute to understanding the mechanistic photophysics and photochemistry of similar aza-nucleosides and their derivatives.
采用QM(CASPT2//CASSCF)/MM方法全面探究了两种DNA甲基化抑制剂5-氮杂胞苷(5ACyd)和2'-脱氧-5-氮杂胞苷(5AdCyd)在水溶液中的激发态性质和失活途径。基于所获得的激发态衰变路径，我们系统地描绘了可行的衰变机制，这些路径涉及所有已识别的最低能量结构、锥形交叉点和交叉点，驱动了ππ*、nπ*、ππ*、nπ和S态内部及之间不同的内转换(IC)和系间窜越(ISC)途径。与5ACyd中低于ππ态的nπ态不同，N1位置的脱氧核糖基团取代导致5AdCyd中的ππ态成为S态。在5ACyd和5AdCyd中，最初填充的ππ态主要通过直接的ππ→S IC或由nπ态介导而失活至S态。前者ππ→S的几乎无势垒IC通道在附近的低能ππ*/S锥形交叉点处超快发生。在后者ππ*→nπ*→S的IC通道中，最初光激发的ππ态首先接近附近的S/S锥形截面ππ/nπ*，然后经历高效的IC至nπ态，随后通过S/S锥形交叉点nπ/S进一步IC至初始S态。在QM(CASPT2)/MM水平下，估计5ACyd和5AdCyd中nπ*/S锥形交叉点分别位于nπ态最小值上方6.0和4.9 kcal mol处。除了高效的单线态介导的IC通道外，次要的ISC途径将通过ππ→T或ππ*→nπ*→T使ππ态填充至T(ππ)态。相对而言，ππ*→nπ*→T途径分别受益于5ACyd中8.7 cm和5AdCyd中10.2 cm的nπ*/ππ自旋轨道耦合(SOC)。随后，T体系将接近附近的T/S交叉点ππ/S，将其驱动回S态。鉴于ππ*/S交叉点位于T最小值上方，且T/S SOC较小，5ACyd中分别为8.4 kcal mol和2.1 cm，5AdCyd中为6.8 kcal mol和1.9 cm，缓慢的T→S会使体系在T态中捕获一段时间。本工作有助于理解类似氮杂核苷及其衍生物的光物理和光化学机制。
