Studying interactions among metal nanoclusters, host ligands and small-molecule analytes

本计画将探讨以核酸为模板的银奈米簇的分子结构与物理性质。银纳米团簇是令人着迷的荧光纳米材料，其颜色往往会对其周围化学环境的细微变化做出反应，使其成为检测小分子（例如，腺苷三磷酸）和重金属（例如，汞和铜）。然而，目前还不知道银纳米团簇如何与这些分析物相互作用并改变其物理或化学性质。此外，尚不清楚为什么某些银簇物种对特定的小分子分析物有强烈反应，但对其他类似化合物没有反应。该项目旨在回答这些基本问题，最终目标是实现银纳米簇传感器的分子和原子水平的理解。了解银纳米团簇的纳米级相互作用也将为各种生物和化学应用创造新的工具，例如检测化学物质。主要研究人员将与当地K-12学生合作开展一项名为“探索纳米医学和光”的推广计划。该外展活动的目标是吸引学生根据对银纳米团簇的新理解开发新工具，并鼓励他们在大学教育中走上科学、技术、工程和数学道路。纳米传感器的未来发展受到阻碍，因为缺乏可以编程以响应特定分析物的功能性纳米材料。Yeh和Brodbelt教授正在使用新的实验（基于芯片的高通量选择）和分析（活化电子光剥离质谱法）方法来筛选大量的银纳米团簇物种，并对它们与宿主配体，小分子分析物和重金属的相互作用进行基本了解。主要研究人员还将利用深度神经网络对银簇对分析物的响应进行分类，并对银纳米簇进行原子建模。银纳米团簇由于其特殊的化学、物理和光学性质，为小分子和重金属的传感提供了新的机会。分析化学、高通量筛选、生物物理表征和深度学习分类的变革性整合不仅可以测试假设（分析物结合通过重新排列银簇周围的核碱基重塑银簇的电子结构），还可以为众多应用创建多功能工具包，包括检测信号分子和检测污染。主要研究人员将与当地K-12学生合作开展一项名为“探索纳米医学和光”的推广计划。该奖项旨在激发学生们在对银纳米团簇的新认识的基础上开发新工具，并鼓励他们在大学教育中走上科学、技术、工程和数学的道路。该奖项反映了NSF的法定使命，并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，被认为值得支持。

This project will investigate the molecular structures and photophysical properties of small metallic nanoparticles encapsulated in nucleic acids, termed DNA-templated silver nanoclusters. Silver nanoclusters are fascinating fluorescent nanomaterials whose colors often respond to subtle changes in their surrounding chemical environment, making them novel sensors for detection of small molecules (e.g., adenosine triphosphate) and heavy metals (e.g., mercury and copper). However, it is not known how silver nanoclusters interact with these analytes and change their physical or chemical properties. In addition, it is not understood why certain silver cluster species respond strongly to specific small-molecule analytes but not to other similar compounds. The project seeks to answer these fundamental questions, with the end goal to achieve molecular and atomic level understanding of silver nanocluster sensors. Understanding the nanoscale interactions of silver nanoclusters will also create new tools for diverse biological and chemical applications, such as detection of chemicals. The principal investigators will work with local K-12 students in an outreach program named “Exploring Nanomedicine and Light”. The goal of the outreach is to intrigue the students to develop new tools based on the new understanding of silver nanoclusters and encourage them into a science, technology, engineering, and mathematics path in their college education.Future development of nanosensors is hampered by the scarcity of functional nanomaterials that can be programmed to respond to specific analytes. Professors Yeh and Brodbelt are using novel experimental (chip-based high-throughput selection) and analytical (activated electron photodetachment mass spectrometry) approaches to screen a large number of silver nanocluster species and develop a fundamental understanding of their interactions with host ligands, small-molecule analytes and heavy metals. The principal investigators will also take advantage of deep neural networks to classify the silver clusters’ responses to analytes and perform atomistic modeling of silver nanoclusters. Silver nanoclusters present new opportunities for small-molecule and heavy metal sensing because of their special chemical, physical and optical properties. The transformative integration of analytical chemistry, high-throughput screening, photophysical characterization and deep learning classification will not only allow the hypothesis to be tested (analyte binding reshapes silver cluster’s electronic structure through rearranging the nucleobases around the silver cluster) but also enable the creation of a versatile toolkit for numerous applications, including detection of signaling molecules and sensing of pollution. The principal investigators will work with local K-12 students in an outreach program named “Exploring Nanomedicine and Light”. The goal of the outreach is to intrigue the students to develop new tools based on the new understanding of silver nanoclusters and encourage them into a science, technology, engineering and mathematics path in their college education.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.