Nuclear magnetic resonance (NMR) spectroscopy allows scientists to see fine details of molecular structure by placing a molecular sample into an ultra-high magnetic field created by the NMR magnet. Once in the magnetic field, atoms in the molecule interact with the magnetic field, creating an energy which can then be detected. Through observing and measuring this energy, researchers are able to determine the molecule's structure and bow it interacts with other molecules. NMR spectroscopy is reliable, predictable, and reproducible. "NMR is the best non-destructive technique for the study of molecular bonding and conformation in solution and also a very powerful method in solids," says R.N. Sheppard, of the Cross-Faculty NMR Center at Imperial College London, UK.
"NMR spectroscopy is a powerful tool, which gives a unique insight into the structure and dynamics of a wide variety of materials," agrees Rob Law, senior lecturer in the chemistry department at Imperial College. "It is particularly useful, in the solid state, for both liquid crystalline and amorphous materials, because more conventional scattering techniques only give very limited information."
NMR spectroscopy can also be used in the field of metabolism.
"NMR gives a highly reliable metabolic fingerprint of the major metabolic species in the body--it also allows you to study reaction dynamics non-invasively," says J.K. Nicholson, head of the department of biomolecular medicine at Imperial College.
Because NMR spectroscopy is so widely used, cross-disciplinary NMR centers have been formed to take advantage of the ubiquitous technology.
Imperial College commits to NMR
The Cross-Faculty NMR Center at Imperial College London was officially opened in September 2006. At that time, Steve Matthews from the division of molecular biosciences stated, "NMR holds the key to unprecedented insight into fundamental processes in medicine, biology, chemistry, and materials. Our new NMR spectrometer here at Imperial is extremely powerful and will enable researchers from across the College to understand molecular structures and dynamics in greater detail than ever before."
As its name states, the Cross-Faculty NMR facility is used across many disciplines at Imperial College, including the departments of molecular biosciences, biomolecular medicine, chemistry, materials, chemical engineering, and cell and molecular biology.
The department of biomolecular medicine covers a wide range of interdisciplinary research themes in biochemistry, systems biology, toxicology, disease etiology, functional genomics, xenobiotic metabolism, and environmental issues. In particular, the group has beenpivotal in founding the new science of NMR-based metabonomics that has evolved out of more than two decades of assiduous research. The department now has one of the world's largest research teams in metabolic science, led by Nicholson. The group has performed pioneering research in NMR spectroscopy of biofluids and tissues and is a world leader in the application of hyphenated NMR and mass spectrometry (MS) techniques in drug metabolism and drug metabolite reactivity studies.
"Metabonomics is a top-down systems biology tool for studying the multiplicity of metabolic responses to stressors--NMR/MS and mathematical tools are employed to create the models" explains Nicholson.
"We are using NMR to study a variety of major problems in human and animal metabolism relating to diabetes, obesity, nutrition, mammalian-microbial symbiosis, neuropsychiactric diseases, drug toxicity and metabolism, cancer, environmental problems, and clinical diagnostics, etc.," he continues. "We also do state-of-the-art MS and mathematical modeling to understand biological mechanisms for disease."
The department of chemistry also uses NMR for a wide variety of investigations. "I investigate phase separation in biological liquid crystals with J.M. Seddon, of the dept. of chemistry, and bioactive amorphous solids with R.G. Hill, of the dept. of materials," says Law.
Other analytical techniques are often employed with NMR. "Other techniques we use with NMR are MS linked with chromatography--especially UPLC-MS (ultra performance liquid chromatography-mass spectrometry). Within the 800 MHz NMR facility is the Waters Laboratory of Molecular Spectroscopy," says Nicholson. [see sidebar]
"Other techniques I use with NMR are thermal calorimetry, fluorescence spectroscopy, and x-ray scattering," says Law.
The NMR Center has a variety of NMR instruments used for different purposes. "The NMR Center has three 400 MHz machines which employ open access for research, a 500-and a 400-MHz machine we operate as a service, and an 800-MHz system used for biological applications," says Sheppard.
The high field NMR facilities include:
* Bruker DRX-600
* Bruker Efficient Sample Transferring (BEST) system
* LC-NMR (MS) system
* Bruker AV-400
* Other facilities:
--BPSU-36 system for pre-NMR and"loop transfer" experiments
--Bruker BPSU-12 pea storage unit for preparation and teaching
The Cross-Faculty NMR center at Imperial College is a shining example of what multidisciplinary research centers can accomplish. In the U.S., two such research facilities dedicated to NMR are following similar paths in cross-disciplinary research.
Improving N M R technology
The National Magnetic Resonance Facility at Madison (NMRFAM) is a state-of-the-art NMR facility located in the department of biochemistry at the Univ. of Wisconsin-Madison. NMRFAM equipment and resources are available to all scientists both within and outside of the university.
Research at NMRFAM includes biomacromolecular research, protein research, metabolomics, determination of diffusion coefficients, and imaging. In addition, NMRFAM has five core research projects:
1. Fast data collection and automated data analysis.
2. Technology for larger biomolecules and complexes.
3. NMR and computation investigations of paramagnetic iron-sulfur proteins.
4. Integrated platform for macromolecular dynamics.
5. Novel methods for RNA.
The equipment used at NMRFAM includes:
* Bruker DMX 400 WB
* Bruker DMX 500i
* Bruker DMX 500i with Cryoprobe
* Bruker DMX 600i with Cryoprobe
* Varian Unity INOVA 600ii with Cold Probe
* Varian NMR System 600iii with Cold Probe
* Bruker DMX 750 with Cryoprobe
* Varian Unity INOVA 800 with Cold Probe
* Varian Unity INOVA 900 with Cold Probe
NMR in the desert
The Magnetic Resonance Research Center (MRRC) at Arizona State Univ., Tempe, is a regional Southwest resource for characterization and structure determination of proteins, DNA, drugs, natural products, chemical compounds, and materials by NMR. The facility contains 800-and 500-MHz NMR spectrometers (Varian 800 and INOVA 500) optimized for protein and DNA structure studies and 300- and 400-MHz wide-bore systems (Varian 400 wide bore, INOVA 400, and Gemini 300) for solid-state NMR, diffusion, and exotic NMR experiments. The Varian 800 has dual solids/liquids capabilities, including the world's fastest magic-angle spinning (MAS) probes.
The MRRC is located in a 418-[m.sup.2] laboratory in the basement of the Interdisciplinary Science and Technology building I (ISTB I). The MRRC supports collaborative research and training in NMR across disciplines and provides a special emphasis for support of projects at the interfaces of molecular medicine, bio-engineering, bio-inspired chemistry and physics, and materials research.
The future of NMR
Although NMR spectroscopy is a good technique, it still has drawbacks. It is not particularly sensitive; however, recent advances in the technology have improved the ability to detect signals from samples at fairly low concentrations. In addition, NMR machines are large and expensive.
Researchers would like to see advances in the technology. "One improvement I would like in NMR is a higher field magnet, maybe 1 GHz," says Law.
"Some improvements I would like to see include higher sensitivity, automation, higher fields at affordable price," says Sheppard.
Improvements I would like to see in NMR are more sensitivity and smaller machines--both are on their way," agrees Nicholson.
NMR is a robust technique that will continue to keep pace with scientific needs. "In the future, NMR within my field will be used for the localization of molecular species in complex cellular environments;' says Nicholson.
"It is very hard to predict how NMR might be used in the future, as it is an incredibly versatile technique with an enormous range of applications," explains Law. "However, one of the most important areas it will have application to is that of membrane proteins, these are very hard to crystallize, and understanding the structure and dynamics of these in the membrane will be its biggest challenge."
Collaborative science
The Waters Laboratory of Molecular Spectroscopy was launched along with the Cross Faculty NMR Center on Sept. 26, 2006, at Imperial College London, UK. The Waters Laboratory contains high-end equipment for mass spectroscopy which complements the NMR facility's work in defining the structure of molecules.
The lab is named for Waters Corp., Milford, Mass., which funded $1 million in spectroscopy equipment for the lab.
"[Waters'] investment in the new mass spectrometry laboratorytogether with our new NMR facility-means that the College has a uniquely powerful new facility for molecular structure elucidation, which will enable researchers here in the future to develop new disease diagnostics based on small molecule biomark ers and to understand molecular mechanism of disease," says Jeremy Nicholson, head of Imperial's department of biomolecular medicine.
Waters equipped the lab with the ACQUITY UPLC System, the QT of Premier Mass Spectrometer, and the GCT Premier Mass Spectrometer.
The collaboration and new facility will allow researchers at Waters and Imperial to address fundamental medicinal-biology problems, which in turn will pave the way for a better understanding of the underlying causes of disease and the effect of lifestyle and diet on health and overall well-being. It is hoped that the work done at this laboratory will provide the tools necessary to make significant steps toward the goal of personalized medicine.
CryoProbes enhance NMR
Bruker BioSpin offers CryoProbes for their NMR spectrometers. The 5 mm QNP CryoProbe, pictured here, is used for multipurpose NMR measurements of four different nuclei--carbon, phosphorus, fluorine and hydrogen. This general purpose, cryogenically cooled CryoProbe is automated to easily switch between these nuclei, eliminating the need to change probes. Phosphorus, carbon, fluorine and hydrogen are present individually or together in a majority of organic, biological, and inorganic compounds. The direct observation of these nuclei can provide quantitative information in addition to small molecule structural data.
The QNP CryoProbe enables more complete characterization of molecules that contain any of these four nuclei. It is available for Bruker BioSpin Avance III 400-MHz and 500-MHz NMR spectrometers.
Standard-size 5 mm CryoProbes improve the signal-to-noise ratio by three to four times, as compared to non-cryogenically cooled conventional probes. As a result, they are capable of measuring lower concentrations and enable experiments to be completed as much as 16 times faster. While CryoProbes typically have been aimed at molecular biology research, the QNP CryoProbe is designed for applications in organic, medicinal and inorganic chemistry.
RESOURCES
* Bruker BioSpin, Billerica, Mass., 978-667-9580, www.bruker-biospin.com
* Cross-Faculty NMIR Center at Imperial College London, UK, +44 (0)207 5945336, www3.imperial.ac.uk/nmrcentre
* MRRC at Arizona State Univ., Tempe, 480-965-3613, http://nmr.asu.edu
* NMRFAM at Univ. of Wisconsin-Madison, www.nmrfam.wisc.edu
* Varian, Inc., Pale Alto, Calif., 650-213-8000, www.varianinc.com
* Waters Corp., Milford, Mass., 508-478-2000, www.waters.com
Gale Document Number:A168548506