1、核磁共振技術及其應用進展商武 201120118853化學與化工學院 化學工程摘要：核磁共振技術已經成為現(xiàn)代科學中一種非常重要的測定儀器，其獨特的優(yōu)點，有著不可替代的作用，本文主要介紹了核磁共振技術的發(fā)展、原理，以及儀器和其應用進展。NMR techniques and their application progress Abstract: nuclear magnetic resonance (NMR) has now become a very important analytical tool in modern science, because of its unique advan

2、tages and the irreplaceable role. This paper mainly describes the development of NMR technology, principle, instrumentation and the application progress.Keywords: nuclear magnetic resonance(NMR); principle; application progress 關鍵詞：核磁共振 NMR 原理 應用引言核磁共振是一種利用原子核在磁場中的能量變化來獲得關于核的信息的技術，已廣泛應用于物理、化學、生物、醫(yī)學、

3、地質等各個領域和工業(yè)、農業(yè)、商業(yè)、有機化工等各個部門， 例如用高分辨核磁共振技術研究液相生物大分子的空間構象, 用固體NMR方法研究材料等, 核磁共振成像技術則已廣泛用于醫(yī)療診斷, 測試大腦功能活動等方面1?？梢哉f核磁共振技術已成為現(xiàn)代科學不可或缺的一種分析和測量手段。IntroductionNMR is a technology by utilizing the energy change of the nuclei in a magnetic field to obtain technical information on nuclear, it has widely applied in

4、 various fields such as physics, chemistry, biology, medicine, geology, and in various sectors of industry, including agriculture, commerce, and organic chemical. For examples, using high-resolution nuclear magnetic resonance to research the space conformation of liquid biological macromolecules, st

5、udy materials with solid-state NMR methods. magnetic resonance imaging technology has been widely used in medical diagnostics, and testing the functional activity of the brain. It can be said that NMR technology has become an indispensable analysis and measurements in modern science. 1. 核磁共振基本概念和原理

6、原子核磁性的大小一般用磁矩表示,具有方向性,=hI, h是普朗克常數(shù),I 為自旋量子數(shù), 簡稱自旋。旋磁比實際上是原子核磁性大小的度量,值大表示原子核的磁性強, 反之亦然. 在天然同位素中,以氫原子核(質子)的值最大( 42.6MHz/T) , 因此檢測靈敏度最高, 這也是質子首先被選擇為NMR研究對象的重要原因之一。 當把有磁矩的核(I0) 置于某磁場中, 該原子核在磁場的行為就好似陀螺的運動拉莫爾進動, 其頻率由下式決定: =2, 式中為角頻率,為拉莫爾進動頻率. 當外加射頻場的頻率與原子核的拉莫爾頻率相等時, 處于低能態(tài)的核便吸收射頻能, 從低能態(tài)躍遷到高能態(tài)即發(fā)生核磁共振現(xiàn)象. 沒有自

7、旋的原子核(I=0) 沒有磁矩, 這類核觀察不到NMR信號, 如12C、16O、32S等，I=1/2的原子核是NMR中研究的最多的核，如：1H、13C、19F、15N、29Si、31P等。1. NMR basic concepts and principlesNuclear magnetic size is generally measured by magnetic moment:,with a directional. There is an equation: =hI ,where h is Planck constant, I is spin quantum number. gyrom

8、agnetic ratio is actually a measurement of nuclear magnetic size. The larger value of v indicates the magnetic of atomic nuclei is stronger, and vice versa. In natural isotope, hydrogen nuclei (proton) has the maximum value of gyromagnetic ratio(42.6MHz/T). So its detection sensitivity is highest,wh

9、ich is also one of the important reasons why the proton is firstly selected for the NMR study.When a atomic nuclei with magnetic moments placed into a magnetic field, the nucleus in the magnetic field acts like a gyroscope movement- Larmor precession.Its frequency is determined by: =2,where angular

10、frequency, andis Larmor prescession frequency. When the frequency of the applied RF field is equal with the nuclear Larmor frequency, the nuclear in the low-energy state will absorb radio frequency energy and then transit from low to high-energy statethat is, nuclear magnetic resonance phenomenon oc

11、curs. The nucleus with no spin (I = 0) has no magnetic moment, such nuclear wont produce NMR signal, such as 12C、16O、32S and etc. Nucleus with I=1/2 is most frequent during NMR study, such as 1H、13C、19F、15N、29Si、31P and etc. 2. 核磁共振儀 實現(xiàn)核磁共振可采取兩種途徑: 一種是保持外磁場不變,而連續(xù)地改變入射電磁波頻率; 另一種是用一定頻率的電磁波照射, 而調節(jié)磁場的強弱

12、。圖1 為核磁共振現(xiàn)象的裝置示意圖, 采用調節(jié)入射電磁波頻率的方法來達到核磁共振。樣品裝在小瓶中, 并置于磁鐵兩極之間, 瓶外繞有線圈, 通有由射頻振蕩器輸出的射頻電流。于是, 由線圈向樣品發(fā)射電磁波。調制振蕩器的作用是使射頻電磁波的頻率在樣品共振頻率附近連續(xù)變化, 當頻率正好與核磁共振頻率吻合時, 射頻振蕩器的輸出就會出現(xiàn)一個吸收峰, 這可以在示波器上顯示出來, 同時由頻率計即刻讀出這時的共振頻率值。 圖1 核磁共振實驗裝置示意圖核磁共振儀主要部件：超導磁體，射頻發(fā)射接收機柜，高分辨液體探頭，工作站，低溫附件，液氦傳輸管。磁體的功用是產生一個恒定的磁場; 探頭置于磁極之間, 用于探測核磁共振

13、信號。隨著核磁共振技術的發(fā)展, 已研制出各種類型的核磁共振儀。2. Nuclear Magnetic Resonance Spectrometernuclear magnetic resonance can be taken by two ways: one is to keep the external magnetic field unchanged,but continuously change the frequency of the incident electromagnetic wave; another is to adjust the strength of the magn

14、etic field with a certain frequency of electromagnetic radiation. Figure 1 shows the NMR device schematic, nuclear magnetic resonance is attained by adjusting the frequency of the electromagnetic wave. Samples were packed in vials,and placed between the magnetic poles, out of bottles around the coil

15、 ,the RF current in the coil was output by RF oscillator. Thus,electromagnetic wave was emitted from coil to samples. Role of the modulation oscillator is to make RF electromagnetic wave frequency continuously change around the samples resonance frequency, when the frequency is just consistent with

16、the NMR frequency, the RF oscillator output appears an absorption peak , which can be displayed on an oscilloscope,while read out the value of the resonance frequency by the frequency meter instantly. Figure 1 NMR device schematicThe main components of the NMR: superconducting magnets, radio frequen

17、cy transmitting and receiving cabinets, high-resolution liquid probes, workstations, low-temperature attachment, liquid helium transfer tube.The function of the magnet is to produce a constant magnetic field; probe placed between the poles, used to detect the NMR signal. With the development of NMR

18、techniques, there have been developed various types of NMR. 3. 核磁共振技術的應用3.1 核磁共振技術在化學中的應用3.1.1在分子結構的測定中的應用 核磁共振技術是測定分子結構的有效工具, 現(xiàn)在已經測定了萬余種有機化合物的核磁共振圖。對分子結構的測定, 包括對有機化合物絕對構型的測定和對復雜化合物結構的解析。應用核磁共振技術測定有機化合物的絕對構型, 主要是測定R和(或)S手性試劑與底物反應的產物的1H 或13C NMR 化學位移數(shù)據,得到值與模型比較來推斷底物手性中心的絕對構型。有的情況下, 我們要做更多的譜才能確定一個分子的結

19、構, 包括: 1D 只要有氫譜、碳譜、極化轉移譜; 2D 有氫- 氫化學位移相關譜、碳-氫化學轉移相關譜、遠程化學位移相關譜以及J-分解譜等。對復雜化合物結構解析是核磁共振技術最為主要的應用4。利用這項技術可以獲得化合物豐富的分子結構信息, 廣泛應用于天然產物的結構解析。3. The application of NMR techniques3.1 Application of NMR techniques in chemistry 3.1.1 Application in the determination of the molecular structure The NMR techniq

20、ue is an effective tool for determination of molecular structure, is now determined more than 10,000 kinds of organic compounds by proton NMR. Molecular structure determination, includes the determination of absolute stereochemistry of organic compounds and resolving the structure of complex compoun

21、ds. Determining the absolute configuration of organic compounds mainly determines the NMR chemical shift data of 1H or 13C in the products reacted by R or S chiral reagent and substrate. Then it could infer the absolute configuration of substrates chiral center by comparing the attained value and mo

22、del. In some cases, we need to do more spectrum in order to determine a molecular structure, including: 1D hydrogen spectrum, 13C NMR, polarization transfer spectrum; 2D hydrogen - hydrogen chemical shift correlation spectroscopy, carbon - hydrogen chemical transfer correlation spectroscopy, remote

23、chemical shift correlation spectroscopy and J-decomposition spectrum. Structural analysis of complex compounds is the most major applications of NMR techniques. It could obtain abundant information about molecular structure by this technology, so its widely used in the structure elucidation of natur

24、al products.3.1.2 在有機合成反應中的應用 核磁共振技術在有機合成中, 不僅可對反應物或產物進行結構解析和構型確定, 在研究合成反應中的電荷分布及其定位效應、探討反應機理等方面也有著廣泛應用5。核磁共振譜能夠精細地表征出各個H 核或C 核的電荷分布狀況, 通過研究配合物中金屬離子與配體的相互作用, 從微觀層次上闡明配合物的性質與結構的關系。對有機合成反應機理的研究主要是對其產物結構的研究和動力學數(shù)據的推測來實現(xiàn)的。另外, 通過對有機反應過程中間產物及副產物的辨別鑒定, 可以研究有關有機反應歷程及考察合成路線是否可行等問題。3.1.2 Application in organic

25、 synthesis reactions NMR technique can not only determine the structural elucidation and conformation about reactants or products in organic synthesis, but also has a wide range of applications in studying charge distribution and orientation effect in the synthesis reaction,as well as in investigati

26、ng the reaction mechanism. NMR spectroscopy can finely characterize the charge distribution of the H-nuclear or C-nuclear, and it can clarify the relationship between nature and structure of a complex from the micro-level by investigating the interaction between the metal ions and ligands. The study

27、 of organic reaction mechanism is mainly achieved by the speculation of products structure and kinetic data. In addition, it can study on the feasibility of an organic reaction and the synthesis route through the identification of intermediates and byproducts during an organic reaction. 3.1.3 在定量分析和

28、分子量測定中的應用 核磁共振譜峰的面積( 積分高度) 正比于相應質子數(shù), 這不僅用于結構的分析中, 同樣可用于定量分析。用NMR 定量分析的最大優(yōu)點就是不需要引進任何校正因子或繪制工作曲線, NMR 可以用于多組分混合物分析、元素的分析、有機物中活潑氫及重氫試劑的分析等。3.1.3 Application in quantitative analysis and determination of molecular weight NMR peak area (integral height) is proportional to the corresponding number of prot

29、ons, which is not Only used for the analysis of the structure, but can be used for quantitative analysis. The biggest advantage of NMR quantitative analysis is that there is no need to introduce any correction factors or to drow the working curve. NMR can be used for multi-component mixture analysis

30、, element analysis, analysis of the active hydrogen and deuterium in the organic reagent. 3.1.4 在高分子化學中的應用 聚合物固體寬譜線NMR 可以提供有關結晶度、聚合物取向、玻璃化溫度(T)等有關信息。還可以通過研究聚合反應過程NMR 譜線寬度的變化,了解反應過程中正在生長聚合物鏈的活動度變化, 從而獲得有關聚合反應動力學方面的信息。聚合物液體高分辨NMR 可以提供聚合物的信息有: 聚合物類型的鑒定; 有關聚合物鏈的異構化信息; 通過13C-NMR譜可以分別研究其不同單元組的序列分布、交替度和不同反

31、應條件下聚合過程鏈活動度變化等聚合物微觀結構信息。3.1.4 Application in polymer chemistryPolymer solid wide lines NMR can provide information on the crystallinity , the polymers orientation, the glass transition temperature(T) and other relevant information. It can understand the activity changes of the growing polymer chain

32、 through the width changes of NMR line during polymerization reaction, so that it can obtain relative information about polymerization kinetics. Polymer liquid high-resolution NMR can provide following information about polymers: The identification of polymer type; information about the isomerizatio

33、n of related polymer chains; it can study the sequence distribution of different unit groups, alternating degrees and the activity changes of polymer chain under different reaction conditions. 3.2 核磁共振技術在其它領域的應用3.2.1 核磁共振技術在找水探深方面應用 核磁共振找水方法是利用水中的氫核在磁場的激發(fā)下會產生核磁共振現(xiàn)象的原理來進行地下水的勘探的一種地球物理方法。核磁共振找水的方法是核磁共

34、振技術應用的新領域，是目前唯一可用來直接尋找地下水的物探新方法，若存在有水（自來水）就會有核磁共振信號反應，測量結果不受地質因素的影響。在三峽滑坡監(jiān)測和秦始皇陵勘測中，就運用了核磁共振找水的方法，已經取得了中外矚目的科研成果。3.2 The application of NMR techniques in other areas 3.2.1 Application of NMR techniques in finding and exploring the deep of waterThe method to find water by NMR technique is a geophysic

35、al method, which use that hydrogen nuclei in the water will produce NMR phenomenon under the excitation of the magnetic to explore groundwater. The method to find water by NMR technique is new fields of application of NMR, and till now it is only new method which can be directly used to explore grou

36、ndwater. When there is water (tap water), it will has a magnetic resonance signal response. The measurement results wont be influenced by geographical factors. During monitoring the Three Gorges landslide and investigating Qin Shi Huang Mausoleum, this method has been used, and great scientific achi

37、evement has been made. 3.2.2 核磁共振技術在生物醫(yī)學方面的應用 核磁共振作為一種對人體無創(chuàng)、無電離輻射的診斷工具,不僅適合做結構成像, 還可以做功能性成像, 因而使之和X射線、CT 、超聲成像等一道, 成為當今幾大最常用的醫(yī)學成像技術。但是, 核磁共振成像的一個重要不足是不能給出足夠的信息說明正常組織與病理組織之間細胞代謝的區(qū)別。在組織中存在多種化合物( 代謝作用產物) , 無損提取這些化合物信息, 不僅有利于疾病的診斷和治療, 同時對闡明代謝的生理過程十分重要。核磁共振技術在藥物研發(fā)過程中也有著重要的應用, 它可以提供藥物設計的結構信息, 還可以通過NMR 技術進

38、行配體的篩選, 從而在確定藥物的有效性等方面有著廣泛的應用6。 核磁共振分析技術可以無侵入的獲取活體生物系統(tǒng)的信息, 使NMR 技術在活體應用方面的研究進展迅速。NMR 技術可以用于分析生物細胞系統(tǒng)的代謝途徑, 包括分析細胞內的pH 值、分析乳酸菌糖份的分解以及分析轉基因生物的代謝過程等。NMR 技術還可以用于生物反應器系統(tǒng)的優(yōu)化, 將NMR 成像技術與代謝NMR 技術結合起來用于設計生物反應器, 目前是一個全新的領域NMR 技術還可用于結構基因組學, 可以方便的獲取蛋白質、DNA 等的三級結構。3.2.2 Application of NMR in biomedicalNMR ,as a d

39、iagnostic tool with non-invasive and no ionizing radiation to human,is not only suitable for structural imaging, but also suitable for functional imaging, so it has become one of todays most commonly medical imaging technologies,as well as X-ray, CT and ultrasonic imaging. However, an important defi

40、ciency of MRI is that it could not give sufficient information about the difference of cell metabolism between normal tissue and pathology. There are a variety of compounds (metabolism products) in the organization, so non-destructive extraction the information about these compounds is not only bene

41、ficial to the diagnosis and treatment of disease, but also is very important to clarify the physiological processes of metabolism. NMR technique has important applications in the drug development process. It can provide structural information of drug design, screen ligand by NMR, so it has wide appl

42、ication in determining the effectiveness of drugs and other aspects.NMR analysis techniques can be access to the information systems of living organisms with non-invasive, so that it has gained rapid progress in vivo application. NMR techniques can be used for metabolic pathway analysis of biological cells system, including analysis the