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

在化学系化学结构动力学和机制-A（CSDM-A）计划的支持下，格鲁吉亚大学的Susanne Ullrich教授和她的团队将研究暴露于UV（紫外线）光后修饰的核碱基的反应。典型的核碱基构成了我们DNA的基石，通过将有害的紫外线能量转化为热量的内部转换过程来保护自己免受光损伤。然而，核碱基的微小变化，例如用氮取代单环碳原子，可以深刻地改变它们的UV光响应并消除它们固有的光保护。根据取代的位置，内部转换过程可能变得不可接近，而是形成长寿命，高反应性的三重激发态。除了对这些氮杂环丁烷的独特的化学物理学的基本兴趣之外，修饰的核碱基在生物学和药理学应用中具有各种用途的期望性质。例如，长寿命的活性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。该项目将培训本科生和研究生以及参与这项研究的暑期实习生。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。具体来说，在这个项目中，Ulrich和她在格鲁吉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azorbide中的超快内部转换和系统间交叉动力学。氮杂环丁烷可以分为两种类型：在1型氮杂环丁烷中，内部转化被淬灭，并且进入三重态歧管的系间交叉变得非常有效。相比之下，2型氮杂环丁烷维持类似于经典核碱基的有效内部转化途径。使用气相实验补充从头计算的分子水平的机制的细节，这种独特的行为将得到。一个新的VUV（真空紫外）源，根据合作者的设计将被集成到现有的实验装置。通过紫外光激发这些分子，并探测与真空紫外激发态的演变，关键信息有关的失活机制可以收集。TR-PES直接观察所有的弛豫路径，并根据它们的光电子谱识别激发态。相反，TR-IY提供了质量信息，有助于根据特征碎片模式识别激发态。补充的理论工作，与教授Barbatti（艾克斯马赛）和冈萨雷斯（维也纳大学）合作，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和模拟TR-PES光谱。比较一个系统的系列azorphins和对比它们的1型和2型行为有可能解开控制其激发态势能表面的复杂细节的电子和结构因素，如激发态之间的耦合，势能势垒，以及圆锥形交叉点和交叉点的可访问性。在这里观察到的内在分子光特性与知识的溶剂效应通过公布的溶液相研究，预计将有助于更好地了解azorphysics在广泛变化的条件下的生物microenvironments.This奖项反映了NSF的法定使命，并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。

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.