NMR Spectroscopy

Nuclear Magnetic Resonance Spectroscopy

1. Background

Over the past fifty years nuclear magnetic resonance spectroscopy, commonly referred to as nmr, has become the preeminent technique for determining the structure of organic compounds. Of all the spectroscopic methods, it is the only one for which a complete analysis and interpretation of the entire spectrum is normally expected. Although larger amounts of sample are needed than for mass spectroscopy, nmr is non-destructive, and with modern instruments good data may be obtained from samples weighing less than a milligram. To be successful in using nmr as an analytical tool, it is necessary to understand the physical principles on which the methods are based.

The nuclei of many elemental isotopes have a characteristic spin (I). Some nuclei have integral spins (e.g. I = 1, 2, 3 ....), some have fractional spins (e.g. I = 1/2, 3/2, 5/2 ....), and a few have no spin, I = 0 (e.g. ¹²C, ¹⁶O, ³²S, ....). Isotopes of particular interest and use to organic chemists are ¹H, ¹³C, ¹⁹F and ³¹P, all of which have I = 1/2. Since the analysis of this spin state is fairly straightforeward, our discussion of nmr will be limited to these and other I = 1/2 nuclei.

For a table of nuclear spin characteristics Click Here.

The following features lead to the nmr phenomenon:

1. A spinning charge generates a magnetic field, as shown by the animation on the right. The resulting spin-magnet has a magnetic moment (μ) proportional to the spin.
2. In the presence of an external magnetic field (B0), two spin states exist, +1/2 and -1/2. The magnetic moment of the lower energy +1/2 state is alligned with the external field, but that of the higher energy -1/2 spin state is opposed to the external field. Note that the arrow representing the external field points North.
3. The difference in energy between the two spin states is dependent on the external magnetic field strength, and is always very small. The following diagram illustrates that the two spin states have the same energy when the external field is zero, but diverge as the field increases. At a field equal to Bx a formula for the energy difference is given (remember I = 1/2 and μ is the magnetic moment of the nucleus in the field).
Strong magnetic fields are necessary for nmr spectroscopy. The international unit for magnetic flux is the tesla (T). The earth's magnetic field is not constant, but is approximately 10-4 T at ground level. Modern nmr spectrometers use powerful magnets having fields of 1 to 20 T. Even with these high fields, the energy difference between the two spin states is less than 0.1 cal/mole. To put this in perspective, recall that infrared transitions involve 1 to 10 kcal/mole and electronic transitions are nearly 100 time greater. For nmr purposes, this small energy difference (ΔE) is usually given as a frequency in units of MHz (106 Hz), ranging from 20 to 900 Mz, depending on the magnetic field strength and the specific nucleus being studied. Irradiation of a sample with radio frequency (rf) energy corresponding exactly to the spin state separation of a specific set of nuclei will cause excitation of those nuclei in the +1/2 state to the higher -1/2 spin state. Note that this electromagnetic radiation falls in the radio and television broadcast spectrum. Nmr spectroscopy is therefore the energetically mildest probe used to examine the structure of molecules. The nucleus of a hydrogen atom (the proton) has a magnetic moment μ = 2.7927, and has been studied more than any other nucleus. The previous diagram may be changed to display energy differences for the proton spin states (as frequencies) by mouse clicking anywhere within it.
4. For spin 1/2 nuclei the energy difference between the two spin states at a given magnetic field strength will be proportional to their magnetic moments. For the four common nuclei noted above, the magnetic moments are: 1H μ = 2.7927, 19F μ = 2.6273, 31P μ = 1.1305 & 13C μ = 0.7022. These moments are in nuclear magnetons, which are 5.05078•10-27 JT-1. The following diagram gives the approximate frequencies that correspond to the spin state energy separations for each of these nuclei in an external magnetic field of 2.35 T. The formula in the colored box shows the direct correlation of frequency (energy difference) with magnetic moment (h = Planck's constant = 6.626069•10-34 Js).

Read more...

Three scientists share 2009 Nobel Prize in chemistry

The Royal Swedish Academy of Science announces that American scientists Venkatraman Ramakrishnan (L) and Thomas A. Steitz (C), and Ada E. Yonath of Israel won the 2009 Nobel Prize in chemistry "for studies of the structure and function of the ribosome." This is a combo photo of three winners.(Xinhua/Wu Ping)
Three researchers won the 2009 Nobel Prize in chemistry "for studies of the structure and function of the ribosome," the Royal Swedish Academy of Sciences announced Wednesday.

Venkatraman Ramakrishnan, a group leader at the MRC Laboratory of Molecular Biology in Cambridge, England; Thomas A. Steitz, a researcher at Yale University, and Ada E. Yonath, a professor at the Weizmann Institute of Science in Israel, won for their work that has shown what the ribosome looks like and how it functions at the atomic level, the Nobel Committee said.

Scientist Venkatraman Ramakrishnan, along with Israeli scientist Ada Yonath and American scientist Thomas A. Steitz, shares the 2009 Nobel Prize in chemistry on Wednesday.(Xinhua/AFP Photo)
"This knowledge can be put into a practical and immediate use. Many of today's antibiotics cure various diseases by blocking the function of bacterial ribosomes. Without functional ribosomes, bacteria cannot survive," the Nobel Committee said.

The main research breakthrough came in 2000 and each of the three scientists used a method called X-ray crystallography to map the position for each of the hundreds of thousands of atoms that make up the ribosome, the Nobel Committee said.

Ramakrishnan, 56, was born in India and holds American citizenship.

Steitz earned his Ph.D. in Harvard University in 1966 and is the Sterling Professor of Molecular Biophysics and Biochemistry and a Howard Hughes Medical Institute Investigator at Yale.

American scientist Thomas A. Steitz, along with British scientist Venkatraman Ramakrishnan and Ada E. Yonath of Israel shares the 2009 Nobel Prize in chemistry on Wednesday. (Xinhua/AFP Photo)
Yonath, who was born in 1939 in Jerusalem, earned her Ph.D. in X-ray crystallography in 1968 from the Weizmann Institute and became a professor at the same institute.

Yonath said during a telephone interview at the press conference, that she feels "very happy and very thankful" for winning the prize.

The professor said she thought that the research that won the Nobel was very important to life science but there is still lots to learn.

This was the third round of this year's Nobel prizes, which areawarded annually for achievements in science, literature, economics and peace.

Israeli scientist Ada Yonath, along with British scientist Venkatraman Ramakrishnan and American scientist Thomas A. Steitz, shares the 2009 Nobel Prize in chemistry on Wednesday.(Xinhua/Reuters Photo)
All but one of the prizes were established in the will of 19th Century dynamite millionaire Alfred Nobel. The economics award was established by Sweden's central bank in 1968.

The Nobel Prize in Physics on Tuesday went to Charles K. Kao, Willard S. Boyle and George E. Smith, all from the United States.

Each prize consists of a medal, a personal diploma and a cash award of 10 million Swedish kronor (1.4 million U.S. dollars).

Read more...

India-born scientist wins Nobel Prize in Chemistry

WASHINGTON: An India-born structural biologist whose quest for scientific excellence took him from undergraduate schools in India to graduate and

More Pictures

post-doc studies in US and research in UK was jointly awarded the Nobel Prize in Chemistry on Wednesday for work on proteins that control life. ( Watch Video )

Dr Venkatraman ''Venky'' Ramakrishnan, 58, who had his early education in the temple town of Chidambaram, Tamil Nadu, and Vadodra, Gujarat, before he made tracks to the United States, joined the long list of peripatetic Indians who had early education in India but thrived in the western academic eco-system, to have won the Nobel. Also with a chemistry Nobel, Indians or those with an India-connect figure in all prize categories.

The Swedish Nobel Committee awarded the Prize to Dr Ramakrishnan, who is currently affiliated with the MRC Laboratory of Molecular Biology in Cambridge, UK, for his work on protein-producing ribosomes, and its translation of DNA information into life. He will share the Prize with Dr Thomas Steitz of Yale University, Connecticut, and Dr Ada Yonath of Weizmann Institute of Science in Israel.

In a statement following the announcement of the award, Dr Ramakrishnan expressed gratitude to ``all of the brilliant associates, students and post docs who worked in my lab as science is a highly collaborative enterprise.'' He credited the MRC Laboratory of Molecular Biology and the University of Utah for supporting his work and the collegiate atmosphere there that made it all possible. ( Watch Video )

``The idea of supporting long term basic research like that at LMB does lead to breakthroughs, the ribosome is already starting to show its medical importance,'' he said.

The practical importance of Dr Ramakrishnan's work arises from ribosomes being present in all living cells, including those of bacteria. Human and bacterial ribosomes are slightly different, making the ribosome a good target for antibiotic therapy that works by blocking the bacteriums ability to make the proteins it needs to function.

Ramakrishnan, Steitz and Yonath demonstrated what the ribosome looks like and how it functions at an atomic level using a visualisation method called X-ray crystallography to map the position of each of the hundreds of thousands of atoms that make up the ribosome, according to the MRC.

``This year's three Laureates have all generated 3D models that show how different antibiotics bind to the ribosome. These models are now used by scientists in order to develop new antibiotics, directly assisting the saving of lives and decreasing humanity's suffering,'' the Nobel citation explained.

Scientists say growing knowledge of the ribosome has created targets for a new generation of antibiotics. The instruction manual for the creation of proteins is DNA, but the ribosome is the machine which takes information transcribed onto messenger RNA and turns it into proteins.

Elaborating, the MRC said Dr Ramakrishnan's basic research on the arrangement of atoms in the ribosome has allowed his team not only to gain detailed knowledge of how it contributes to protein production but also to see directly how antibiotics bind to specific pockets in the ribosome structure. Dr Ramakrishnan will share the 10 million Swedish kronor ($1.4 million) Nobel Prize money (1/3rd each), in a ceremony in Stockholm on December 10.

Read more...

IUPAC Nomenclature of Organic Chemistry

The main purpose of chemical nomenclature is to identify a chemical species by means of written or spoken words. To be useful for communication among chemists, nomenclature for chemical compounds should additionally contain within itself an explicit or implied relationship to the structure of the compound, in order that the reader or listener can deduce the structure (and thus the identity) from the name. This purpose requires a system of principles and rules, the application of which gives rise to a systematic nomenclature (for examples, see the 1979 Edition of the IUPAC Nomenclature of Organic Chemistry).

In contrast to such systematic names, there are traditional names, semisystematic or trivial, which are widely used for a core group of common compounds. Examples are "acetic acid", "benzene", "cholesterol", "styrene", "formaldehyde", "water", "iron". Many of these names are also part of general nonscientific language and are thus not confined to use within the science of chemistry. They are useful, and in many cases indispensable (consider the alternative systematic name for cholesterol, for example). Little is to be gained, and certainly much to be lost, by replacing such names. Therefore, where they meet the requirements of utility and precision, and can be expected to continue to be widely used by chemists and others, they are retained and, for the most part, preferred in this Guide.

Semisystematic names also exist, such as "methane", "propanol", and "benzoic acid", which are so familiar that few chemists realize that they are not fully systematic. They are retained, and indeed, in some cases there are no better systematic alternatives.

It is important to recognize that the rules of systematic nomenclature need not necessarily lead to a unique name for each compound, but must always lead to an unambiguous one. Lucidity in communication often requires that the rules be applied with different priorities. A comparative discussion of the compounds , , , and , might be easier to follow if they were all named as propenes, even though with the last three, the benzene ring, amino, and hydroxy groups may have seniority over the double bond for citation as a parent or as a suffix. In other cases, a set of rules that generates clear and efficient names for some compounds can lead to clumsy and nearly unrecognizable names for others, even closely related ones. To force the naming of all compounds into the Procrustean bed of one set of rules would not serve the needs of general communication, and the Commission believes that the majority of organic chemists would not accept such a policy for general communication. This situation can be illustrated by a compound that most chemists would probably name as "pentaphenylethane", instinctively, whereas the application of a principle favouring rings over chains leads to a name such as "ethanepentaylpentabenzene". The first name is certainly more easily recognized than the second. Another example is compound (1), which would be named "benzoazete" by application of fusion nomenclature principles, but von Baeyer nomenclature would give the name "7-azabicyclo[4.2.0]octa-1,3,5,7-tetraene". On the other hand, von Baeyer nomenclature is most useful with compounds such as "bicyclo[4.3.2]undecane" (2).

In view of the foregoing considerations, this Guide to IUPAC Nomenclature of Organic Compounds often presents alternative sets of rules, equally systematic, wherever available and justifiable, to enable a user to fit the name to a particular need.

Lastly, the Commission recognizes that for certain types of compounds, there is significant disagreement among chemists in different fields as to what should be the preferred nomenclature. This situation leads to an apparent lack of decisiveness in some of the recommendations in this document. This is unavoidable, because long experience has taught that formulating rules not having general support is a futile exercise; such rules will be widely ignored. Therefore, the Commission's policy is to offer critically examined alternatives, some of which may be new proposals, and to observe how they are accepted and used. If one of the alternatives subsequently becomes preferred to an overwhelming extent by the community of chemists, a future edition of recommendations can reflect that fact.

In this Guide, some practices of the Chemical Abstracts Service and/or of the Beilstein Institute have been mentioned. This is done only for informational purposes, and such instances are not necessarily recommendations of the Commission. The Commission recognized that there are circumstances that require a preferred (i.e., unique) name. These include comprehensive indexing (such as for the volume indexes to Chemical Abstracts) in order to avoid an intolerable amount of cross-indexing and multiple entries. This need is being met in a particular way by Chemical Abstracts Service as in-house procedures designed to place compounds with the same parent skeleton together while at the same time minimizing the number of rules. The Chemical Abstracts Index Guide treats the majority of compounds, but is not complete. There are a number of other in-house procedures applied elsewhere, such as in Beilstein (not yet explicitly published). Specialty files, such as steroids and carbohydrates, have different bases. The result is not always compatible with ease of recognition, ease of generation, or conciseness. Unique names are also very important in legal situations, with manifestation in patents, export-import regulations, health and safety information, etc. These needs are being addressed by other Commission projects. In this Guide, the primary aim is to provide directions for arriving at an unambiguous name, although some guidance is given about establishing preferences (see, for example, Table 10 and Table 16).

The rules given in the Nomenclature of Organic Chemistry, commonly known as the "Blue Book", emphasize the generation of unambiguous names in accord with the historical development of the subject, because the need for a "unique" name was not perceived to be compelling by earlier generations of chemists. The so-called information explosion of recent decades is a major factor in changing this perception. The present matrix of rules, however, cannot easily be overlaid with a simple set of principles for selecting a preferred name among the systematic alternatives, and to declare a preference by arbitrary fiat in each situation would surely lead to widespread rejection. Therefore, the Commission has initiated projects to formulate a comprehensive guide for selecting unique names that will, insofar as feasible, have good recognition value and general acceptance among chemists; the results will be presented in later publications. Further projects, with longer-range objectives of systematizing nomenclature of organic compounds, are also under way.

Finally, those who use this Guide should be aware that the nomenclature in these recommendations is independent of the orientation of the graphic structure (except as stated in the recommendations for nomenclature of fused-ring structures) and of conformation. Furthermore, the nomenclature does not indicate nor imply an electronic structure or spin multiplicity.

Read more...