Electronic and Structural Factors Governing the Intersystem Crossing and Internal Conversion Dynamics of Aza-Substituted Nucleobases

控制氮杂取代核碱基的系统间交叉和内部转换动力学的电子和结构因素

• 批准号: 2154852
• 负责人: Susanne Ullrich
• 金额: $ 49.88万
• 依托单位: University of Georgia Research Foundation Inc
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2154852&HistoricalAwards=false
• 关键词: Electronic; Structural; Factors; Governing; Intersystem

With support of the Chemical Structure Dynamics and Mechanisms-A (CSDM-A) program of the Chemistry Division, Professor Susanne Ullrich and her team at the University of Georgia will study the response of modified nucleobases upon exposure to UV (ultraviolet) light. The canonical nucleobases, which form the building blocks of our DNA, protect themselves against photodamage through internal conversion processes that dissipate harmful UV energy into heat. However, minor changes to the nucleobases, such as substitution of a single ring carbon atom with nitrogen, can profoundly alter their UV photo-response and eliminate their inherent photo-protection. Depending on the position of substitution, internal conversion processes can become inaccessible and instead long-lived, highly reactive triplet excited states are formed. Besides fundamental interest in the unique photophysics of these azabases, modified nucleobases have desirable properties for various uses in biological and pharmacological applications. For example, long-lived reactive triplet states are key to some forms of cancer treatments, antiviral and antimicrobial medicines, and photodynamic therapies. The project will train undergraduate and graduate students as well as summer interns who participate in this research. Outcomes of the project will be broadly disseminated to the public through open house activities and science show performances. Specifically, in this project, Ulrich and her team at the University of Georgia will apply time-resolved photoelectron spectroscopy (TR-PES) and ion yield (TR-IY) measurements to the study of ultrafast internal conversion and intersystem crossing dynamics in a series of azabases. Azabases can be classified into two types: In type 1 azabases, internal conversion is quenched and intersystem crossing into the triplet manifold becomes highly efficient. In contrast, type 2 azabases maintain efficient internal conversion pathways similar to the classic nucleobases. Using gas-phase experiments supplemented by ab initio calculations the molecular-level mechanistic details governing this unique behavior will be derived. A new VUV (vacuum ultraviolet) source, based on a collaborator’s design will be integrated into the existing experimental setup. Through photo-exciting these molecules with UV radiation and probing the evolution of the excited states with VUV, critical information pertaining to their deactivation mechanisms can be gleaned. TR-PES directly observes all relaxation pathways and identifies excited states based on their photoelectron spectra. TR-IY instead provides mass information that helps identify excited states based on characteristic fragmentation patterns. Supplemental theoretical efforts, in collaboration with Professors Barbatti (Aix Marseille) and González (University of Vienna), will go beyond simple static pictures, using dynamics simulations with non-adiabatic and spin-orbit couplings and simulating TR-PES spectra. Comparing a systematic series of azabases and contrasting their type 1 and type 2 behavior has the potential to unravel the electronic and structural factors that control intricate details of their excited state potential energy surfaces such as couplings between excited states, potential energy barriers, and accessibility of conical intersections and crossing points. The intrinsic molecular photoproperties observed here combined with knowledge of solvent effects gleaned through published solution-phase studies, are expected to contribute to a better understanding of azabase photophysics under the widely varying conditions of biological microenvironments.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

在化学部化学结构动力学和机理- a （CSDM-A）项目的支持下，乔治亚大学的Susanne Ullrich教授和她的团队将研究修饰核碱基暴露在紫外线（紫外线）光下的反应。典型的核碱基，构成了我们DNA的基石，通过内部的转换过程将有害的紫外线能量转化为热量，保护自己免受光损伤。然而，核碱基的微小变化，如单环碳原子被氮取代，可以深刻地改变它们的紫外线光响应并消除它们固有的光保护作用。根据取代的位置，内部转换过程可以变得难以接近，而形成长寿命，高反应性的三重态激发态。除了对这些氮杂基独特的光物理特性的基本兴趣外，修饰的核碱基在生物和药理学应用中具有各种理想的特性。例如，长寿命的反应三重态是某些形式的癌症治疗、抗病毒和抗菌药物和光动力疗法的关键。本项目将培养参与本研究的本科生、研究生以及暑期实习生。计划的成果将透过开放日活动及科学表演向公众广泛传播。具体来说，在这个项目中，Ulrich和她在佐治亚大学的团队将应用时间分辨光电子能谱（TR-PES）和离子产率（TR-IY）测量来研究一系列azabase的超快内部转换和系统间交叉动力学。azabase可分为两种类型：在1型azabase中，内部转换被淬灭，系统间交叉到三重流形变得高效。相比之下，2型azabase保持与经典核碱基相似的有效内部转化途径。利用气相实验辅以从头算计算，将推导出控制这种独特行为的分子水平机理细节。一个新的真空紫外线源，基于合作者的设计，将被整合到现有的实验装置中。通过紫外辐射光激发这些分子并探测其激发态的演变，可以收集有关其失活机制的关键信息。TR-PES直接观察所有的弛豫路径，并根据它们的光电子能谱识别激发态。相反，TR-IY提供大量信息，帮助识别基于特征碎片模式的激发态。与Barbatti教授（Aix Marseille）和González教授（维也纳大学）合作的补充理论工作将超越简单的静态图片，使用非绝热和自旋轨道耦合的动态模拟并模拟r - pes光谱。比较系统的一系列azabase，并对比它们的1型和2型行为，有可能揭示控制其激发态势能表面复杂细节的电子和结构因素，如激发态之间的耦合、势能障碍、锥形交叉点和交叉点的可达性。本研究中观察到的分子固有的光性质，结合通过发表的溶液相研究收集到的溶剂效应知识，有望有助于更好地理解在广泛变化的生物微环境条件下的氮杂基光物理。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。