Investigation of Reactive Radical Intermediates for the Development of X-ray Photonanochemistry

我们生命中最重要的分子之一是DNA，它在水中受到强大的、看不见的x射线辐射后会分解成碎片。虽然x射线引起的DNA损伤会对我们的健康造成有害影响，但它也可以在许多应用中得到有益的应用，包括用于癌症治疗的放射治疗。研究发现，微小金属颗粒的存在加速了这种损伤的速度，比如金颗粒，其尺寸相当于人类头发直径的一小部分。然而，DNA损伤速度加快的原因尚不完全清楚。在美国国家科学基金会化学部大分子、超分子和纳米化学项目的支持下，加州大学戴维斯分校的郭教授旨在开发一种新的方法，以更好地理解这一重要而复杂的化学过程。这项研究的结果可以潜在地帮助科学家定制这些重要的反应，应用范围从疾病治疗到合成聚合物的催化裂解。这个跨学科的项目结合了化学、生物学和材料科学，为学生提供了宝贵的研究培训机会，提高了学生的竞争力，包括少数民族学生。一般认为，水中x射线诱导的DNA链断裂过程始于x射线产生活性氧（ROS）。ROS随后与DNA反应形成反应性DNA中间体，随后导致DNA链断裂。虽然最近发现该过程可以在金纳米颗粒的存在下加速，但这种催化过程的机制尚不清楚。为了破译这些重要而复杂的反应，郭教授的团队开发了一种新的方法来生成和监测反应中间体。这种方法的特点是由x射线束照射的纳米反应堆。设计和合成含有催化剂组件的纳米反应器来控制化学环境，并控制x射线照射的时间、x射线束的大小和纳米反应器中催化剂组件的位置，从而使反应中间体向断裂DNA链的转化在空间和时间上与ROS的产生分离。这种分离简化了解释过程，并允许鉴定中间体和测量它们的寿命，从而导致反应机制的阐明。该项目的预期结果是开发一种新技术，该技术不仅可用于阐明x射线诱导的化学反应（如DNA链断裂），还可用于控制化学反应，通过将x射线能量转换为化学能来收集或检测x射线。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。

One of the most important molecules in our life is DNA, which can be broken into pieces in water after exposure to powerful, invisible X-ray radiation. Although X-ray-induced damage to DNA can cause harmful effects to our health, it can also be used beneficially in a number of applications including radiation therapy for cancer treatment. The rate of such damage is found to be accelerated by the presence of tiny metal particles, such as gold particles whose dimensions are on the order of a small fraction of the diameter of a human hair. However, the cause for acceleration in the speed of DNA damage is not fully understood. With the support from the Macromolecular, Supramolecular and Nanochemistry Program of the NSF Division of Chemistry, Professor Guo at the University of California at Davis aims to develop a novel approach to achieve a better fundamental understanding of this important and complex chemical process. The outcome of this research can potentially help scientists tailor these important reactions for applications ranging from disease treatment to catalytic cleavage of synthetic polymers. This interdisciplinary project at the interface of chemistry, biology, and materials science provides valuable research training opportunities and improves competitiveness of students including underrepresented minority students.The X-ray induced DNA strand breaking process in water is generally believed to start with the generation of reactive oxygen species (ROS) by X-rays. The ROS then react with DNA to form reactive DNA intermediates, which subsequently leads to the breaking of the DNA strands. While it was discovered recently that this process can be accelerated in the presence of gold nanoparticles, the mechanism for such catalytic process is not understood. In order to decipher these important and complex reactions, Professor Guo's group develops a novel approach to generate and monitor the reactive intermediates. The approach features nanoreactors irradiated by an X-ray beam. The nanoreactors containing catalyst assemblies are designed and synthesized to control the chemical environment, and the timing of X-ray irradiation, the size of the X-ray beam, and the position of the catalyst assemblies in the nanoreactors are controlled so that the conversion of reactive intermediates to broken DNA strands can be spatially and temporally separated from the production of ROS. Such separation simplifies the interpretation process and allows the identification of the intermediates and measurement of their lifetime, leading to the elucidation of the reaction mechanisms. The anticipated outcome of this project is the development of a novel technique that is useful not only for elucidating X-ray induced chemical reactions (such as DNA strand breakage) but also for controlling chemical reactions that can be used to harvest or detect X-rays through the conversion of X-ray energy to chemical energy.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.