Structure Determination by NMR
- Introduction to NMR
NMR Spectroscopy May Be Used to Derive Atomic Structures
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Nuclear magnetic resonance (NMR) spectroscopy is the workhorse for determining molecular
structure in chemistry.
Data from NMR spectroscopy characterizes the local environment of atomic nuclei inside
molecules. Certain atomic nuclei have an intrinsic magnetic moment that aligns in a strong
magnetic field.
This alignment may be perturbed by a radio frequency pulse of appropriate wavelength, and
when the nuclei relax to their aligned state, they emit characteristic radio frequency radiation
that reflects the local environment of the atom.
The characteristic NMR spectra have been used extensively in chemistry to define the covalent
and conformational structure of small organic molecules. They are now being used to study
larger molecules, such as small proteins and nucleic acids.
For biomolecules, the spectra get very complex, so more elaborate NMR techniques are needed
to allow study of the many similar atoms in the molecule.
Two-dimensional NMR techniques currently allow determination of structures of small proteins.
In this technique, multiple radio frequency pulses are used to perturb multiple nuclei.
If one nucleus is excited, it will modify the absorption and emission of nuclei in the immediate
vicinity.
Ultimately, these small shifts are used to develop a list of nuclei that are in close proximity in the
molecule.
Refinements in these methods have extended the range of NMR to small and medium-sized
proteins, with 100–250 amino acids.
NMR experiments identify the distances between nuclei that are spatially close to one another
and the local conformation of atoms bonded together.
To determine the structure of the entire biomolecule, these local pieces of information must be
combined into an atomic model.
Summary
There are three primary NMR tools
used to obtain structural information
1) Nuclear Overhauser effect - internuclear distances
2) J Coupling - torsion angles
3) Chemical shift - local nuclear environment
(Chemical exchange can also be monitored by NMR.)