Nuclear Magnetic Resonance (NMR) Spectroscopy

General Chapter <761>

NMR Spectroscopy
Where is it?
1nm 10 102 103 104 105 106 107

(the wave) Frequency (the transition) (spectrometer)

X-ray

UV/VIS

Infrared Vibration

Microwave Rotation

Radio Nuclear NMR

electronic X-ray UV/VIS

Infrared/Raman

Fluorescence

Edward M. Purcell 1912-1997

Felix Bloch 1905-1983

Richard R. Ernst 1933-

Kurt Wuthrich 1938-

CW NMR 40MHz

1960

 Nuclear magnetic resonance (NMR) is a physical phenomenon in which magnetic nuclei in a magnetic field absorb and re-emit electromagnetic radiation. NMR allows the observation of specific quantum mechanical magnetic properties of the atomic nucleus.

 NMR is the most powerful analytical tool currently available to an organic chemist. NMR allows characterization of a very small amount of sample (10mg), and does not destroy the sample (non-destructive technique). NMR spectra can provide vast information about a molecule's structure and can very often be the only way to prove what the compound really is.

NMR spectroscopy important facts:

The number of different absorptions implies how many different types of hydrogens are present. The amount of shielding (chemical shift) is determined by each hydrogen's environment, and so we get information about the local electronic surroundings for each hydrogen.

 The intensities of the signals tell us the number of identical hydrogens. The splittings of each signal tells us about the other groups proximate to the hydrogens in question.

PRINCIPLE OF NMR:
The principle behind NMR is that many nuclei have spin and all nuclei are electrically charged. If an external magnetic field is applied, an energy transfer is possible between the base energy to a higher energy level (generally a single energy gap).

 The energy transfer takes place at a wavelength that corresponds to radio frequencies and when the spin returns to its base level, energy is emitted at the same frequency. The signal that matches this transfer is measured in many ways and processed in order to yield an NMR spectrum for the nucleus concerned.

 Nuclear Magnetic Resonance (NMR) Spectroscopy is a non-destructive analytical technique that is used to probe the nature and characteristics of molecular structure.

Two common types of NMR spectroscopy:

a. 1H NMR is used to determine the type and number of H atoms in a molecule; b. NMR is used to determine the type of carbon atoms in the molecule.
13C

 The source of energy in NMR is radio waves which have long wavelengths, and thus low energy and frequency. When low-energy radio waves interact with a molecule, they can change the nuclear spins of some elements, including 1H and 13C.

The NMR Spectrophotometer

Parts of NMR:
Main features of a basic NMR include:
A radio transmitter coil that produces a short powerful pulse of radio waves A powerful magnet that produces strong magnetic fields The sample is placed in a glass tube that spins so the test material is subject to uniform magnetic field.
Solid samples are dissolved in a solvent that will not give a signal

A radio receiver coil that detects radio frequencies emitted as nuclei relax to a lower energy level A computer that analyses and record the data

What the NMR spectrum tells us?

The number of peaks tell how many different proton environments are in the molecule. The peak area ratio shows the relative numbers of protons in each environment. The chemical shift (measured in ppm) helps to identify each of the different environments and provides information about the functional groups to which the hydrogen is attached. J splitting tells us how many H atoms are on the neighbouring atom according to the rule n+1. This supports the chemical shift data.

General Method of NMR Spectroscopy

1. Selection of solvents

2. Specimen Preparation
The solute concentration depends on the objective of the experiment and on the type of instrument. Detection of minor contaminants requires higher concentration.

 In NMR spectroscopy, the standard is often tetramethylsilane, Si(CH3)4, abbreviated TMS. Tetramethyl silane (TMS) is used as reference because it is soluble in most organic solvents, is inert, volatile, and has 12 equivalent 1H and 4 equivalent 13C. TMS signal is set to 0

3. Procedure
The specimen is place in the magnetic field. The probe contains electronic circuitry including the radio-frequency coils, and is provided with attachments for air supply that spins the specimen tubes.

Steps for analysing NMR spectra

1. Look at the number of peak sets and hence the number of different environments 2. The chemical shift for each peak set 3. The relative number of protons in each peak set (from the relative peak area) 4. The number of fine peaks each major peak set is split into 5. Determine the relative number of hydrogens in each environment 6. The protons responsible for each peak set and the carbon to which they are bonded

Uses of NMR spectroscopy

Nuclear Magnetic Resonance (NMR) spectroscopy is an analytical chemistry technique used in quality control and research for determining the content and purity of a sample as well as its molecular structure.

 Once the basic structure is known, NMR can be used to determine molecular conformation in solution as well as studying physical properties at the molecular level such as conformational exchange, phase changes, solubility, and diffusion.

Advantages of NMR spectroscopy:

Detects many types of molecules (fat, water, ATP, etc) Scans subject non-invasively Good time resolution Absolute quantification of concentration is possible (with appropriate standard solution) Painless to experimental subjects Scans can be localized to specific anatomical regions

Application of NMR:
NMR Spectroscopy is a technique used by most modern chemical laboratories. It has applications in a wide range of disciplines, and development of new applied methods for NMR is an active area of research. Methods in NMR spectroscopy have particular relevance to the following disciplines: Chemical research and development: organic, inorganic and physical chemistry Chemical manufacturing industry Biological and biochemical research Food industry Pharmaceutical development and production Agrochemical development and production Polymer industry

Common applications of NMR Spectroscopy include:

Structure elucidation Compound identification and confirmation Chemical composition determination Analysis of inter- and intramolecular exchange Formulations investigation processes Raw materials fingerprinting Molecular characterization Mixture analysis Reaction kinetics Sample purity examination determination Reaction mechanism Quality assurance and investigation control Quantitative analysis

Figure 14.15

The MRI image of the lower back

Nuclear Magnetic Resonance Spectroscopy

Reference:
Pharmacopeia ( General Chapter NMR <761> http://sydney.edu.au/science/chemistry/~long /applications.html