定义Definition
二维核磁共振是把核磁共振信号在两个频率维度上展开的技术，通过交叉峰揭示原子核之间的耦合（通过化学键）或空间接近（通过空间）关系，是解析复杂有机分子、天然产物和生物大分子结构的关键工具。
Two-dimensional NMR spreads NMR signals over two frequency axes, with cross peaks revealing which nuclei are coupled through bonds or close in space. It is a key tool for solving the structures of complex organic molecules, natural products and biomacromolecules.
原理Principle
基本脉冲序列包括预备期、演化期 t₁、混合期和检测期 t₂。系统地改变 t₁ 并记录一系列信号，对 t₁ 和 t₂ 两个时间变量分别作傅里叶变换，得到二维谱。对角峰对应一维谱，交叉峰表示两核之间存在磁化转移，即有相关关系。
A basic pulse sequence has preparation, evolution (t₁), mixing and detection (t₂) periods. Incrementing t₁ systematically and recording a series of signals, then Fourier-transforming over both t₁ and t₂, gives a two-dimensional spectrum. Diagonal peaks correspond to the one-dimensional spectrum, and cross peaks show magnetisation transfer, that is, a correlation, between two nuclei.
常用实验Common experiments
COSY（¹H–¹H 相关）：显示通过 2–3 个键耦合的氢，追踪自旋体系；TOCSY：显示同一自旋体系中所有氢，常用于识别氨基酸残基和糖环；HSQC/HMQC（¹H–¹³C 单键相关）：确定每个氢连在哪个碳上；HMBC（¹H–¹³C 远程相关，2–3 个键）：连接分子片段、确定季碳位置；NOESY/ROESY（空间相关，< 5 Å）：确定相对构型、构象和蛋白质三维结构。
COSY (¹H–¹H) shows protons coupled through two or three bonds and traces spin systems; TOCSY shows all protons in a spin system, used to identify amino-acid residues and sugar rings; HSQC/HMQC (one-bond ¹H–¹³C) shows which carbon each proton is attached to; HMBC (long-range ¹H–¹³C over two or three bonds) links fragments and places quaternary carbons; and NOESY/ROESY (through-space, under 5 Å) establish relative configuration, conformation and protein three-dimensional structure.
由来Origin
1971 年比利时物理学家让·耶纳在一次暑期学校上提出二维 NMR 的设想。1976 年瑞士的理查德·恩斯特团队实现了二维傅里叶变换 NMR，恩斯特因此获 1991 年诺贝尔化学奖。库尔特·维特里希利用 NOESY 等多维 NMR 测定了溶液中的蛋白质结构，获 2002 年诺贝尔化学奖。
In 1971 the Belgian physicist Jean Jeener proposed two-dimensional NMR at a summer school. In 1976 Richard Ernst's group in Switzerland realised two-dimensional Fourier-transform NMR, and Ernst received the 1991 Nobel Prize in Chemistry. Kurt Wüthrich used NOESY and other multidimensional methods to determine protein structures in solution, sharing the 2002 Nobel Prize in Chemistry.
年表Timeline
- 1971
耶纳提出二维 NMR
Jeener proposes 2D NMR
- 1976
恩斯特实现二维傅里叶变换 NMR
Ernst realises 2D Fourier-transform NMR
- 1985
维特里希用 NMR 测定首个蛋白质溶液结构
Wüthrich determines the first protein structure in solution by NMR
- 1991
恩斯特获诺贝尔化学奖
Ernst receives the Nobel Prize in Chemistry