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.

在化学司的化学结构动力学和机制-A（CSDM-A）计划的支持下，佐治亚大学苏珊·乌尔里希（Susanne Ullrich）教授及其团队将研究暴露于紫外线（紫外线）光线后修饰的​​核碱基的反应。构成我们DNA的构建块的规范核碱基通过内部转换过程来保护自己免受光损伤，从而将有害的紫外线耗散成热量。然而，核盆地的微小变化，例如用氮代替单个环碳原子，可以深刻地改变其紫外线响应并消除其固有的照片保护。根据替代的位置，内部转换过程可能无法访问，而是形成了长期，高反应性的三胞胎激发态。除了对这些Azabase独特的光体物理学的基本兴趣外，经过修改的核盆地具有可取的特性，用于生物和药物应用中的各种用途。例如，长寿命的反应三胞胎状态是某些形式的癌症治疗，抗病毒药和抗菌药物以及光动力疗法的关键。该项目将培训参加这项研究的本科生和研究生以及暑期实习生。该项目的成果将通过开放式活动和科学表演表演广泛传播给公众。具体而言，在这个项目中，乌尔里希（Ulrich）和她在佐治亚大学（University of Georgia）的团队将在一系列Azabases中应用时间分辨的光电子光谱（TR-PES）和离子产量（TR-IY）测量。 Azabase可以分为两种类型：在类型的Azabase中，内部转换被淬灭，并在三胞胎歧管中交叉时，内部转换变得高效。相比之下，2型Azabase保持有效的内部转换途径，类似于经典的核基础。使用从头开始计算补充的气相实验，将得出控制这种独特行为的分子级机械细节。基于合作者设计的新的VUV（真空紫外线）将集成到现有的实验设置中。通过将紫外线辐射的这些分子兴奋，并通过VUV探测激发态的演变，可以收集与其失活机制有关的关键信息。 TR-PE直接观察所有弛豫途径，并根据其光电子光谱识别激发态。 TR-IY提供的质量信息可以帮助根据特征性碎片模式识别令人兴奋的状态。补充理论努力与巴巴蒂教授（Aix Marseille）和冈萨雷斯（维也纳大学）合作，将超越简单的静态图片，并使用具有非绝热和旋转轨道耦合的动态模拟以及模拟TR-PES光谱。比较一系列系统的Azabase和对比其1型和2型行为，有可能揭示电子和结构性因素，这些因素控制了其激发状态势能表面的复杂细节，例如激动人心的状态，势能障碍以及临床交叉点的可及性和交叉点之间的耦合。此处观察到的固有分子光早期与通过已发表的解决方案相研究收集的效果的知识相结合，有望有助于更好地理解生物微环境的广泛变化条件下的阿扎比斯摄影，这是NSF的法定任务，反映了NSF的法定效果，并通过评估范围进行了评估，并概述了基金会的支持。