Pure Shift Based Phase-Sensitive J-Resolved Diffusion Order NMR Spectroscopy And Its Applications

Molecular diffusion mechanism based diffusion order spectroscopy(DOSY)is regarded as a powerful tool for studying complex mixtures systems,which can realize"virtual" separation of mixture solution in the sample tube by the difference of diffusion coefficient without physical and chemical separation of the sample.However,typical DOSY technology is often limited by two main problems in practical applications.It is firstly limited by the interference of NMR crowded spectra,mainly caused by the limited spectrum frequency range of proton and the complex peak splittings due to J couplings.By eliminating peak splitting in chemical shift dimension,pure shift DOSY can overcome spectra congestions to achieve high-resolution detection.But the elimination of J couplings makes it impossible to obtain the information of the multiplet splittings directly related to the molecular coupling network.High-dimensional DOSY technology can alleviate spectral congestion and retain J couplings information,but the absolute value display mode reduces the resulting spectral resolution and restricts its application in complex mixture samples.In addition,typical DOSY technology is also limited by the interference of inhomogeneous magnetic fields leading to broadened peak in the chemical shift dimension,which make it impossible to get the correct diffusion coefficients and the corresponding diffusion ordering function.In this thesis,combining the above-mentioned technical characteristics of pure shift DOSY and highdimensional DOSY,we propose a pure shift based high-resolution three-dimensional phase-sensitive J-resolved DOSY spectrum method,which effectively solves the problem of spectra congestions and retains J couplings structure information.In the meantime,our proposed J-resolved DOSY spectrum method,based on small voxel signal excitation,can also be applied for high-resolution detection in inhomogeneous magnetic fields and heterogeneous samples,providing a new way for high-resolution analytical separation of complex solution mixtures.The thesis comprises:First,this thesis sorts out some important points in NMR history development,and analyzes the principle and technique of several key pure shift methods,such as bilinear rotational decoupling,slice-selective decoupling and small angle scanning frequency pulse decoupling,and discusses the sensitivity difference and application range of these methods.We also discuss the basic principles and application features of the DOSY methods,and briefly review the spin echo DOSY method and the stimulated echo DOSY method,and introduce two DOSY methods that can defeat the eddy current effect.Second,we propose a method pure shift based 3D phase-sensitive J-resolved diffusion order NMR spectroscopy,PS2DJ-DOSY,by combining PSYCHE,Oneshot and echo-train.In this chapter,we focus on the basic principles of the pulse sequence,theoretically deduce the signal evolution process,and apply this method to complex mixture system to verify the feasibility and applicability.It has been proved to achieve complex mixture separation and obtain J couplings information that is used to analyze multiplet splittings structure of each component.Third,in this chapter,we explore the capacity of ZS(Zangger-Sterk)decoupling method to overcome field homogeneity through focusing on small voxel slice-selection excitation,and analyze the influence of the ZS slice-selective gradient on the evolution of diffusion ordered,and finally propose a high-resolution 3D phase-sensitive Jresolved diffusion order method that focuses on ZS decoupling module and fits in heterogeneous magnetic field named ZS2DJ-DOSY.We introduce its technical characteristics and deduce relative theoretical signal expressions.At the same time,through experiments,we verify the comparative results of complex mixtures system detection of this method applied under homogeneous and inhomogeneous magnetic fields,which provides a new inspiration for high-resolution DOSY complex mixtures and separation of complex mixtures under non-ideal magnetic fields.