CDS&E: Combining Nuclear Magnetic Resonance and Neutron Scattering for Determining Macromolecular and Liquid Structure: Towards Development of the Novel NMR-PNS Technique

在化学系化学测量和成像项目的支持下，罗切斯特理工学院的Michael Kotlarchyk教授及其同事George Thurston和Pratik Dholabhai正在为开发强大的下一代技术奠定基础，以探测分子、分子组装和溶液的结构和动力学。这项目标技术基于核磁共振（NMR）和极化中子散射（PNS）的结合，有可能彻底改变各种材料的详细分子尺度信息，包括液体混合物、催化剂、纳米材料和生物大分子。要获得的信息对于预测和合理化工业、医疗和社会重要性的许多过程至关重要。pi积极参与旨在提高来自代表性不足群体的学生参与STEM的项目，以参与跨学科的最新研究。该项目侧重于计算建模，为未来实验方法的发展奠定基础。该团队正在扩展NMR-PNS的量子力学密度算子处理，以处理自旋松弛，自旋耦合以及原子核与任何量子自旋的结合。这将使溶液中的超极化分子和通过专门的核磁共振协议制备的分子的PNS横截面和信噪比的预测和模拟成为可能。通过可逆交换信号放大（SABRE）对溶液中的分子超极化进行分子动力学模拟，以定量评估溶液中的位点-位点空间相关性，这对于预测PNS信号和对PNS信噪比进行严格的统计分析至关重要。将设计和模拟应用选择性脉冲整形和超极化分子测序的核磁共振协议，从而能够使用相关函数来评估所得到的极化中子散射截面。最后，将对sabre超极化分子的假定NMR-PNS协议进行完整的统计分析。模拟的散射信号将为有效的NMR-PNS仪器和实验的设计提供信息，包括样品环境、波束线和探测器参数。最终目的是确定通过核磁共振自旋操纵选择的原子对之间的结构因素，从亚埃到微米长度尺度，从而提供有关溶液中分子构象和相对取向的有价值的信息。有待开发的SABRE-PNS方法是迈向完全核磁共振- pns的重要基石，其本身也将具有价值。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。

With support from the Chemical Measurement and Imaging Program in the Division of Chemistry, Professor Michael Kotlarchyk and colleagues George Thurston, and Pratik Dholabhai at Rochester Institute of Technology are laying the groundwork for development of a powerful next-generation technique to probe structures and dynamics of molecules, molecular assemblies, and solutions. The targeted technique, based on a combination of Nuclear Magnetic Resonance (NMR) and Polarized Neutron Scattering (PNS), has the potential to revolutionize the detailed, molecular-scale information available for a broad variety of materials, including liquid mixtures, catalysts, nanomaterials, and biological macromolecules. The information to be gained is crucial for predicting and rationalizing many processes of industrial, medical, and societal importance. The PIs are actively engaged in programs seeking to enhance STEM engagement by students from underrepresented groups, for involvement in interdisciplinary state-of-the-art research.The project focuses on calculational modeling as a foundation for future development of experimental methods. The team is extending the quantum-mechanical density-operator treatment of NMR-PNS to treat spin relaxation, spin coupling, and the incorporation of nuclei with any quantum spin. This will enable the prediction and simulation of PNS cross sections and signal-to-noise ratios for hyperpolarized molecules in solution and for molecules prepared via specialized NMR protocols. Molecular dynamics simulations of molecules hyperpolarized in solution via Signal Amplification by Reversible Exchange (SABRE) are being undertaken to permit quantitative evaluations of site-site spatial correlations in solution, which are essential for predicting the PNS signal and for a rigorous statistical analysis of PNS signal-to-noise. NMR protocols that apply selective pulse-shaping and sequencing to hyperpolarized molecules will be designed and simulated, thereby enabling use of the correlation functions to evaluate the resulting polarized neutron scattering cross-sections. Finally, complete statistical analyses of putative NMR-PNS protocols for SABRE-hyperpolarized molecules will be performed. The simulated scattering signals will inform the design of effective NMR-PNS instrumentation and experiments, including sample environment, beamline, and detector parameters. The ultimate aim is to determine structure factors between atomic pairs selected via NMR spin-manipulation, from sub-angstrom to micron length scales, thereby giving valuable information about molecular conformations and relative orientations in solution. The SABRE-PNS methods to be developed are important stepping-stones toward full NMR-PNS and will be valuable in their own right.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.