【作者】 陈浩；

【导师】 蔡淑惠；

【作者基本信息】 厦门大学 ， 物理电子学， 2017， 博士

【摘要】 核磁共振(Nuclear Magnetic Resonance,NMR)波谱作为一种无损伤的非侵入性检测技术,业已成为物理、化学、生命科学以及医学等领域研究中一种必不可少的检测手段。高分辨二维谱及多维谱方法可以有效缓解常规一维谱中谱峰拥挤等问题,并获得更多的相关信息,已经成为有机小分子检测以及大分子结构研究中重要的分析工具。然而,高分辨谱图的获取需要有高均匀度的磁场,其空间变化率一般要低于1 ppb/cm3。但受到外磁场不均匀或样品内在磁化率差异等条件的限制,常常无法获得高度均匀的磁场。另外,较长的实验时间也限制了二维谱方法的应用。本论文采用分子间多量子相干技术,并结合时空编码方法,设计了几种新的脉冲序列,能够在不均匀磁场下快速获取高分辨二维谱信息。论文的主要研究成果如下:一、研究了基于同核分子间多量子相干的高分辨方法中选择性脉冲在不均匀磁场中的激发效率。针对选择性脉冲可能诱发多个远程偶极场引起谱峰归属困难,提出了基于异核分子间零量子相干的新方法。结合时空编码和相干转移技术,利用锁场试剂中的氘自旋产生远程偶极场,可以在不均匀磁场下快速获取高分辨二维J分解谱。对氘自旋进行提前激发,能使氘自旋充分编码,序列可以在不均匀度较大的磁场下获取高分辨二维J谱。二、通过分子间零量子相干和J调制采样方法,在不均匀磁场中获取高分辨三维J分解相关谱。分子间零量子相干能有效消除磁场不均匀所引起的相位畸变,使谱线在三个维度均不会出现展宽。新序列采用了时空编码技术,能够在常规二维谱的实验时间内完成三维谱的采样。经过投影可以同时得到高分辨二维J分解谱和化学位移相关谱(COSY)。变换序列中的相干转移模块,还可以获得全相关谱(TOCSY),用以区分化合物的偶合网络,展现了方法的灵活性。三、在磁场强度不均匀的情况下,核磁共振氢谱谱线增宽,使谱峰相互重叠、无法辨识归属,也无法准确测量对应基团质子的纵向弛豫时间(T1)。本文提出了利用分子间二量子相干方法,通过时空编码超快速二维采样方式,仅需单次扫描就能在不均匀磁场下获取高分辨一维氢谱,以区分归属谱峰的化学位移。结合反转恢复法,实现对各基团质子纵向弛豫时间的准确测量。并将新方法测得的T1时间应用于T1加权实验,抑制强信号,也验证了新测量方法的准确性。更多还原

【Abstract】 With the features of non-invasive and non-destructive,nuclear magnetic resonance(NMR)has become an indispensable analytical tool widely used in many disciplines,from physics and chemistry to biology and medicine.High-resolution two-dimensional(2D)NMR can alleviate the jam or even overlapping of resonances in conventional one-dimensional(1D)spectra,and release correlation information.In turn,2D NMR has become a routine analytical tool for the elucidation of small organic molecules and study of macromolecular structures.However,the acquisition of high-resolution spectroscopy relies on the highly homogeneous external magnetic fields,which are inaccessible in many cases,such as poorly shimmed fields or intrinsic heterogeneity of magnetic susceptibility in samples.In addition,the long experiment time hinders further applications of 2D NMR.In this dissertation,based on intermolecular multiple-quantum coherences(iMQC),associated spatiotemporal encoding technique,novel methods are developed to retrieve high-resolution 2D spectra in inhomogeneous fields.The related contents can be summarized as follows:1.The efficiency of selective pulses used in homonuclear iMQC methods,is investigated in inhomogeneous fields.Selective pulses may induce more than one distant dipolar field(DDF),and split the resonances into several groups,leading to difficulties in spectral assignment.In order to circumvent this influence,a new method based heteronuclear intermolecular zero-quantum coherence(iZQC)is proposed.Associated with spatiotemporal encoding and coherence transfer technique,the new method can obtain high-resolution 2D J-resolved spectra in inhomogeneous fields via the DDF originated from 2H spins of deuterium agent.With 2H spins excited in advance,the new method can encode 2H spins sufficiently and achieve high-resolution 2D J-resolved spectra in severe inhomogeneous fields.2.High-resolution three-dimensional(3D)J-resolved correlation spectra are achieved in inhomogeneous fields via intermolecular zero-quantum coherence(iZQC)and J modulation detection method.The dephasing induced by field inhomogeneity can be removed by iZQC,thus the spectrum is free of the influence of line broadening in all three dimensions.Associated with spatiotemporal encoding technique,the acquisition of 3D spectrum can be accomplished within the time for a conventional 2D NMR experiment.A COSY spectrum and J-resolved spectrum can be simultaneous obtained after 2D projection.Furthermore,as TOCSY can be attained by changing the coherence transfer module,the coupling networks of compounds are accessible in inhomogeneous fields.3.The spin-lattice relaxation time(T1)plays a critical role in the study of spin dynamics,signal optimization and data quantification.However,the measurement of chemical shifts specific T1 constants is hampered by the magnetic field inhomogeneity due to poorly shimmed external magnetic field or intrinsic magnetic susceptibility heterogeneity in biological tissues.A new protocol is designed to determine chemical shift specific T1 constants in inhomogeneous fields.Based on intermolecular double-quantum coherences,the new method can resolve overlapped peaks in inhomogeneous fields.The measurement results are in consistent with the measurements in homogeneous fields using conventional method.Since spatial encoding technique is involved,the experimental time for the new method is same to the conventional method.With the aid of T1 knowledge,some concealed information can be exploited by Ti weighting experiment.更多还原