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.

在化学系化学结构动力学和机理(CSDM-A)计划的支持下，佐治亚大学的Susanne Ullrich教授和她的团队将研究修饰的碱基在紫外线(UV)光照射下的反应。构成我们DNA的基石的标准碱基，通过将有害的紫外线能量转化为热能的内部转换过程来保护自己免受光损伤。然而，碱基的微小变化，如用氮取代单环碳原子，可以深刻地改变它们的紫外光响应，并消除它们固有的光保护。根据取代位置的不同，内部转换过程可能变得不可访问，而是形成长寿命、高活性的三重态激发态。除了对这些氮基的独特光物理有基本的兴趣外，修饰的碱基还具有在生物和药理学应用中的各种用途的理想性质。例如，长寿命的反应三重态是某些形式的癌症治疗、抗病毒和抗微生物药物以及光动力疗法的关键。该项目将培训参与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日活动和科学表演向公众广泛传播。具体地说，在这个项目中，佐治亚大学的Ulrich和她的团队将应用时间分辨光电子能谱(tr-PES)和离子产额(tr-IY)测量来研究一系列氮化物的超快内部转换和系统间交叉动力学。氮基化合物可分为两种类型：在类型1氮化物中，内部转换是猝灭的，而进入三重态流形的系间交叉变得高效。相反，类型2氮基维持类似于经典核碱基的有效的内部转换途径。利用气相实验，辅以从头计算，将得到支配这一独特行为的分子水平的机制细节。一种新的VUV(真空紫外线)源，基于合作者的设计，将被集成到现有的实验装置中。通过用紫外光激发这些分子，并用真空紫外光探测激发态的演化，可以收集到与它们的失活机制有关的关键信息。TR-PES能直接观察到所有的弛豫路径，并根据它们的光电子能谱识别激发态。取而代之的是，TR-IY提供了大量信息，这些信息有助于根据特征碎片模式识别激发态。与Barpai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-轨道耦合的动力学模拟，并模拟tr-PES谱。系统地比较一系列氮氧化物，对比它们的类型1和类型2的行为，有可能揭开控制其激发态势能面的复杂细节的电子和结构因素，如激发态之间的耦合，势垒，以及锥形交叉点和交叉点的可达性。这里观察到的内在分子光性质，结合通过已发表的溶液相研究收集的关于溶剂影响的知识，有望有助于更好地理解生物微环境条件变化较大的氮杂酶光物理。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。