Development and Application of Wave Function Based Methods for the Calculation of Nuclear Magnetic Resonance Scalar Couplings and Chemical Shifts

核磁共振是研究生物分子结构的重要实验技术之一。这些实验中最重要的观察结果是化学位移和间接自旋-自旋耦合。化学位移取决于电子环境，并允许对生物分子的结构进行定量评估。另一方面，间接自旋-自旋耦合描述了束缚电子对磁场中核自旋弛豫的影响。在实验上，这些用于研究生物分子结构的量的解释通常基于经验知识，因为这些光谱的精确计算是不可能的。然而，为了更好地理解实验，这样的计算是非常可取的。该计划的目标是发展计算核磁共振谱的量子化学方法。第一步是开发一个硅核磁共振实验室，它允许通过计算化学位移和自旋-自旋耦合来快速表征大量分子。这些计算所需的核自旋和磁场没有被解析地描述，这将是传统的方法。相反，核自旋是通过有限元素计算的。这个程序允许有效地计算化学位移和自旋-自旋耦合的量子化学方法过剩。在该项目的第二部分，将开发新的量子化学方法，允许以高精度计算化学位移和自旋-自旋耦合。由于精度和计算成本通常是耦合的，感兴趣的系统将被分为两个片段（核心片段和环境）。在小的核心碎片中，高度精确的量子化学方法将用于计算可观测值。为了将计算成本保持在合理的框架内，将使用较便宜的方法来描述环境。这种方法将允许精确计算化学位移和自旋-自旋耦合的生物相关分子。

Nuclear magnetic resonance is one of the most important experimental techniques to investigate the structure of biomolecules. The most important observables in these experiments are chemical shifts and indirect spin-spin couplings. The chemical shifts depend on the electronic environment and allow the quantitative assessment of the structure of the biomolecules. The indirect spin-spin couplings, on the other hand, describe the influence of the binding electrons on the relaxation of the nuclear spins in the magnetic field. Experimentally, the interpretation of these quantities for the investigation of the structure of biomolecules is typically based on empirical knowledge, as the exact calculation of these spectra is not possible. For a better understanding of the experiments, however, such calculations would be highly desirable. The goal of the proposed project is the development of quantum chemical methods for the calculation of nuclear magnetic resonance spectra. The first step is the development of an in silico nuclear magnetic resonance laboratory, which allows the rapid characterization of a large number of molecules by calculating chemical shifts and spin-spin couplings. The nuclear spins and magnetic fields that are needed for these calculations are not described analytically, which would be the traditional approach. Instead, the nuclear spins are calculated via finite elements. This procedure allows the efficient calculation of chemical shifts and spin-spin couplings for a plethora of quantum chemical methods. In the second part of the project, new quantum chemical methods will be developed, which allow the calculation of chemical shifts and spin-spin couplings with high precision. As accuracy and computational cost are typically coupled, the system of interest will be divided into two fragments (core fragment and environment). In the small core fragment, highly accurate quantum chemical methods will be used for the calculation of the observables. In order to keep the computational cost within a reasonable frame, less expensive methods will be used for the description of the environment. This approach will allow the accurate calculation of chemical shifts and spin-spin couplings for biologically relevant molecules.