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Nuclear magnetic resonance technology



concept

NMR means nuclear magnetic moments of nuclei is not zero, under the effect of external magnetic field, the nuclear spin energy levels Zeeman splitting (Zeeman Splitting), a resonance absorption physical processes of RF radiation of a specific frequency.

NMR signal is the sum of the contribution of a large number of nuclei.

stimulated emission and stimulated absorption probability of the same subject, in addition, the net effect of the RF field at the transition of the number determined by the difference of vertical level of the population.

development history

NMR history of art

1930's, the physicist Isidor after Rabi found atomic nuclei in the magnetic field direction in a magnetic field was aligned parallel forward or reverse order, the radio wave is applied, the direction of spin nuclei inversion occurs. This is the earliest known human nuclei with the magnetic field and on the applied RF field interactions. Because of this study, Rabbi in 1944 won the Nobel Prize in Physics.

1946 years Bloch and Purcell two American scientists found that having an odd number of nucleons (including protons and neutrons) nuclei in a magnetic field, the RF field to be reapplied specific frequency, phenomenon occurs nuclei absorb RF energy field, which is the people's initial understanding of the phenomenon of nuclear magnetic resonance. To this end they both won the 1950 Nobel Prize in Physics.

works

NMR basic principle is: the nucleus has a spin motion, the constant magnetic field, the spin nuclei will be rotated around the external magnetic field as swing, called precession (precession). Certain precession frequency, which is proportional to the applied magnetic field strength. As an electromagnetic wave based on a fixed frequency, plus, and adjusting the intensity of the external magnetic field, the precession frequency of electromagnetic waves with the same frequency. At this precession nuclei resonance with electromagnetic waves, called nuclear magnetic resonance. Nuclear magnetic resonance, the energy absorbing electromagnetic waves nucleus, the absorption curve is recorded Nuclear magnetic resonance spectrum (NMR-spectrum). As different chemical environment of nuclei in the molecule, it will have a different resonant frequency, resulting in different resonance spectrum. This spectrum can be recorded and determining the relative position of the number of atoms in the molecule which, for performing the analysis and quantitative determination of the molecular weight, and the structural analysis of organic compounds.

Subject branch

NMR There are two main branches of subjects: NMR spectroscopy (Nuclear Magnetic Resonance Spectroscopy) and a magnetic resonance imaging < / b> (Magnetic Resonance Imaging, referred to as MRI). NMR spectroscopy is based on the displacement theoretical chemistry developed, mainly for the determination of chemical composition and molecular structure of the substance. MRI was born in 1973, which is a nondestructive measurement technique, the image can be used to obtain an internal configuration of a plurality of substances. Because of the wealth of information available on MRI, so the wide range of applications, such as analytical chemistry, life sciences, materials testing, petroleum exploration and exploration of water resources and so on.

In all this multi-application, the application of life sciences in recent years, the fastest growing, has become a research focus of NMR techniques. According to incomplete statistics, from 1985 to 2001 and published 602 documents on "Science" with MRI-related, 80% of life sciences.

research and related outcomes

It was found after the magnetic resonance phenomenon soon produced a practical use, chemists Utilization of a hydrogen atom on the molecular structure of the ambient magnetic field generated, developed a NMR spectroscopy is used to analyze the molecular structure, over time, nuclear magnetic resonance spectroscopy technology development, from the initial one-dimensional spectra of hydrogen development to 13C spectra, two-dimensional nuclear magnetic resonance spectroscopy and other senior spectrum, nuclear magnetic resonance analytical molecular capacity of the structure is also growing, after entering the 1990s, people even develop a nuclear magnetic resonance rely on the information to determine the tertiary structure of the protein molecule technology, making accurate determination of the molecular structure of the protein solution phase possible.

On the other hand, medical scientists have found that the hydrogen atoms of water molecules may be nuclear magnetic resonance phenomenon, the use of this phenomenon can obtain information distribution in the body of water molecules, thus rendering accurate internal body structures, in which Based on the 1969 Medical southern new York State University Medical Center in Ann 博士达马迪 to distinguish a theory by measuring the NMR relaxation time successful cancer cells in mice with normal tissue cells area, in the new Damadian inspired technology physicist at Stony Brook State University of New York Paul Lauter Burr was developed in 1973 out of the imaging (MRI) based on nuclear magnetic resonance phenomenon, and the application of his device successfully map out a live clams the internal structure of the image. After Laut Burr, MRI technology matures, increasingly wide range of applications, has become a routine medical testing methods, widely used in Parkinson's disease, multiple sclerosis and other lesions of the brain and spine as well as the treatment and diagnosis of cancer. In 2003, Paul Lauter Burr and the University of Nottingham Professor Peter Mansfield because of their contribution in the technical aspects of magnetic resonance imaging won the Nobel Prize in Physiology or Medicine when the year.

Since the late 1970s, as computer and NMR in theoretical and technical improvement, NMR both in the breadth, depth have gained considerable development, it has become physics, chemistry, biology, medicine and earth science research essential experimental means.

applications in biological research

H, C, P, etc. with non-zero nuclear magnetic spin contained in the biofilm, when the external magnetic field and the RF field interactions, and when the resonance condition is satisfied, the absorbed energy rf field transitions occur between the spin level, which is the basic principles of nuclear magnetic resonance (NMR) is. Since the NMR technique may be non-destructive measurement of aqueous sample, so that observation can be achieved under near physiological conditions, and comprehensive study biofilm H, C and P, in particular, may be provided from the level of the atom or group dynamic information structure and motion of molecules is a powerful tool to study the structure of the biofilm.

biofilm composed mainly of proteins and lipids, complex structure, the phospholipid liposomes was able to exhibit many of the properties of the biofilm structure is an ideal model of biological membranes. Phospholipid liposomes primarily to the presence of a gel phase and a liquid phase, phase, the local motion of molecules in the gel is slow, intermolecular and intramolecular dipole interactions not effectively average, the NMR spectrum is very wide, to give very little information; and in a liquid crystal phase, the molecular movement is restricted locally reduced, faster motion, so that the NMR spectrum narrow, the obtained high-resolution NMR spectroscopy.

NMR techniques in the study of biofilms is widely used. By H, C and P NMR spectra can be identified species of phospholipids. Liquidity can phospholipid bilayer in different parts of the measured time by the process of relaxation. The different positions of the hydrogen molecule selected deuterated phospholipid, fluidity can be studied phospholipid fatty acyl chains with a method and quadrupole splitting H P chemical shift anisotropy, conformation and interactions with other molecules of phospholipid polar group ( proteins, drugs, and metal ions), the P chemical shift anisotropy methods may phospholipid polymorphism study. In recent years, with the development of NMR techniques, two-dimensional (2D) and high resolution solid state NMR techniques are also used in biofilm research, and has become a very important tool. Establishing a chemical bond by using the correlation spectroscopy (e.g. COSY, etc.) may be phospholipids or phospholipid multicomponent mixed with other molecules of each line home system group. The space established through correlation spectroscopy (e.g., NOESY, etc.) may provide direct information about the distance between the groups, lipid membrane structures and powerful tools to study the interaction with other molecules. Technology not only high resolution solid state liquid crystal phospholipid research, but also to a phospholipid gel state.

for a certain kind of the magnetic core, which magnetic moments in the magnetic field can have a different orientation. For protons, it can have two orientations, i.e. parallel and antiparallel to the static magnetic field, the former belongs to a lower energy state, which belongs to the high-energy state. If adding a radiofrequency field in a direction perpendicular to the static magnetic field, when the Larmor frequency of nuclei radio frequency field (nuclear magnetic moments about the field direction of precession frequency) equal, at a lower energy state nuclear will absorb radio frequency energy, transition to a high energy state . After removing the RF field, nuclei by high-energy state back to a lower energy state relaxation process, thereby can be observed NMR signal. Relaxation process, there are two, one is spin - lattice relaxation, this process is represented by Tl; the other is a spin - spin relaxation, represented by T2. T1 is the spin system described will transfer its energy to the energy absorbing ambient restored to its steady state time, T2 internal energy during coupling spin system, no change in the total energy of the spin system. Sports-related relaxation time of the molecule by measuring the relaxation time, the fluidity can be studied various parts of the biofilm.

C and P biofilm chemical shift anisotropy and has a lot of motion. The so-called chemical shift anisotropy, refers to the direction of the static magnetic field in which the core is changed, the resonance frequency of the core (i.e., the chemical shift) change occurs, since I = electron density distribution around the nucleus is spherically symmetric, so if the static magnetic field direction change , the core will change with the effective sensing field, in different forms, which differ motion, thus the chemical shift of the average orientation being different. P can be studied by the chemical shift anisotropy phospholipids pleomorphic; in addition, also be anisotropic with I = H 1 (quadrupole splitting) spectra of phospholipid molecules evenly distributed spatial orientation information.

2D NMR major point different from the conventional one-dimensional (1D) NMR in that 1D NMR refers to only one variable frequency, the absorption peak intensity was plotted on a variable frequency; represents the two 2D NMR TECHNIQUES frequency-independent, it is the absorption peak intensity of the two frequencies variables plotted. The 2D NMR experiments generally divided into four regions, i.e., the period prior to development period (T1), the mixing stage (can not) and the detection period (t2). Preparation of the magnetization vector in order to achieve the appropriate initial state set, followed by development in the evolution of the magnetization vector, the coherent transfer occurs in the spin system during mixing, and finally the signal is detected in the detection period. Sequentially repeated cycles t1 cumulative change, and finally the resulting two Fourier transform data: to obtain 2D NMR TECHNIQUES. 2D NMR TECHNIQUES established can be divided by a chemical bond and two spatial correlation spectrum, two types of 2D NMR TECHNIQUES lines are very important for the home, which biofilms molecular conformation studies also very powerful.

In summary, the application of nuclear magnetic resonance analysis on a biological research mainly in the following aspects:

  • three-dimensional determination of biological macromolecules in solution spatial structure; Nuclear magnetic resonance technology

  • analysis of biological macromolecules in a solution state molecular dynamics;

  • and protein interaction studies mechanism of action of enzymes and the like;

  • the structure was solved and moving the solid membrane proteins and fibrin properties;

  • on protein targets Drug screening and design point;

  • functional activity of the biomolecule in vivo study of physiological and metabolic state.

NMR developments

NMR developments in the 21st century for the following areas:

  • increase the magnetic field strength magnets: NMR spectrometer is expected to be greater than 1GHz of the 21st century there will be, will study the structure of biological macromolecules of a major breakthrough.

  • Development of a three-dimensional nuclear magnetic resonance (3D-NMR) : With the structure of biological macromolecules in the NMR spectrum analysis using, NMR technology provides the number and complexity of the structure information increases exponentially. The interaction between the three-dimensional conformation of macromolecules and small molecules (small molecules or small and Analysis) and the like, two-dimensional NMR (2D-NMR) has become powerless, and therefore to the development of molecular modeling, utilizing the NOE the distance information between the proton in the molecule provided to calculate three-dimensional structure.

  • solid NMR and NMR imaging techniques : This life science, biomedical and materials science will be crucial important, it will be a breakthrough in the molecular structural features and dynamics research.

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