October 10, 2006

Theoretical principles of NMR

Nuclear Magnetic Resonance spectroscopy is a powerful and theoretically complex analytical tool. On this page, we will cover the basic theory behind the technique. It is important to remember that, with NMR, we are performing experiments on the nuclei of atoms, not the electrons. The chemical environment of specific nuclei is deduced from information obtained about the nuclei.
Nuclear spin and the splitting of energy levels in a magnetic field

Subatomic particles (electrons, protons and neutrons) can be imagined as spinning on their axes. In many atoms (such as 12C) these spins are paired against each other, such that the nucleus of the atom has no overall spin. However, in some atoms (such as 1H and 13C) the nucleus does possess an overall spin. The rules for determining the net spin of a nucleus are as follows;

1. If the number of neutrons and the number of protons are both even, then the nucleus has NO spin.
2. If the number of neutrons plus the number of protons is odd, then the nucleus has a half-integer spin (i.e. 1/2, 3/2, 5/2)
3. If the number of neutrons and the number of protons are both odd, then the nucleus has an integer spin (i.e. 1, 2, 3)

The overall spin, I, is important. Quantum mechanics tells us that a nucleus of spin I will have 2I + 1 possible orientations. A nucleus with spin 1/2 will have 2 possible orientations. In the absence of an external magnetic field, these orientations are of equal energy. If a magnetic field is applied, then the energy levels split. Each level is given a magnetic quantum number, m.

When the nucleus is in a magnetic field, the initial populations of the energy levels are determined by thermodynamics, as described by the Boltzmann distribution. This is very important, and it means that the lower energy level will contain slightly more nuclei than the higher level. It is possible to excite these nuclei into the higher level with electromagnetic radiation. The frequency of radiation needed is determined by the difference in energy between the energy levels.
Calculating transition energy

The nucleus has a positive charge and is spinning. This generates a small magnetic field. The nucleus therefore possesses a magnetic moment, m, which is proportional to its spin,I.

The constant, g, is called the magnetogyric ratioand is a fundamental nuclear constant which has a different value for every nucleus. h is Plancks constant.
The energy of a particular energy level is given by;

Where B is the strength of the magnetic field at the nucleus.

The difference in energy between levels (the transition energy) can be found from

This means that if the magnetic field, B, is increased, so is DE. It also means that if a nucleus has a relatively large magnetogyric ratio, then DE is correspondingly large.

If you had trouble understanding this section, try reading the next bit (The absorption of radiation by a nucleus in a magnetic field) and then come back.
The absorption of radiation by a nucleus in a magnetic field

In this discussion, we will be taking a “classical” view of the behaviour of the nucleus – that is, the behaviour of a charged particle in a magnetic field.

Imagine a nucleus (of spin 1/2) in a magnetic field. This nucleus is in the lower energy level (i.e. its magnetic moment does not oppose the applied field). The nucleus is spinning on its axis. In the presence of a magnetic field, this axis of rotation will precess around the magnetic field;

The frequency of precession is termed the Larmor frequency, which is identical to the transition frequency.

The potential energy of the precessing nucleus is given by;

E = - m B cos q

where q is the angle between the direction of the applied field and the axis of nuclear rotation.

If energy is absorbed by the nucleus, then the angle of precession, q, will change. For a nucleus of spin 1/2, absorption of radiation “flips” the magnetic moment so that it opposes the applied field (the higher energy state).

It is important to realise that only a small proportion of “target” nuclei are in the lower energy state (and can absorb radiation). There is the possibility that by exciting these nuclei, the populations of the higher and lower energy levels will become equal. If this occurs, then there will be no further absorption of radiation. The spin system is saturated. The possibility of saturation means that we must be aware of the relaxation processes which return nuclei to the lower energy state.
Relaxation processes

How do nuclei in the higher energy state return to the lower state? Emission of radiation is insignificant because the probability of re-emission of photons varies with the cube of the frequency. At radio frequencies, re-emission is negligible. We must focus on non-radiative relaxation processes (thermodynamics!).

Ideally, the NMR spectroscopist would like relaxation rates to be fast – but not too fast. If the relaxation rate is fast, then saturation is reduced. If the relaxation rate is too fast, line-broadening in the resultant NMR spectrum is observed.

There are two major relaxation processes;

  • Spin – lattice (longitudinal) relaxation
  • Spin – spin (transverse) relaxation

Spin – lattice relaxation
Nuclei in an NMR experiment are in a sample. The sample in which the nuclei are held is called the lattice. Nuclei in the lattice are in vibrational and rotational motion, which creates a complex magnetic field. The magnetic field caused by motion of nuclei within the lattice is called the lattice field. This lattice field has many components. Some of these components will be equal in frequency and phase to the Larmor frequency of the nuclei of interest. These components of the lattice field can interact with nuclei in the higher energy state, and cause them to lose energy (returning to the lower state). The energy that a nucleus loses increases the amount of vibration and rotation within the lattice (resulting in a tiny rise in the temperature of the sample).

The relaxation time, T1 (the average lifetime of nuclei in the higher energy state) is dependant on the magnetogyric ratio of the nucleus and the mobility of the lattice. As mobility increases, the vibrational and rotational frequencies increase, making it more likely for a component of the lattice field to be able to interact with excited nuclei. However, at extremely high mobilities, the probability of a component of the lattice field being able to interact with excited nuclei decreases.

Spin – spin relaxation
Spin – spin relaxation describes the interaction between neighbouring nuclei with identical precessional frequencies but differing magnetic quantum states. In this situation, the nuclei can exchange quantum states; a nucleus in the lower energy level will be excited, while the excited nucleus relaxes to the lower energy state. There is no net change in the populations of the energy states, but the average lifetime of a nucleus in the excited state will decrease. This can result in line-broadening.
Chemical shift

The magnetic field at the nucleus is not equal to the applied magnetic field; electrons around the nucleus shield it from the applied field. The difference between the applied magnetic field and the field at the nucleus is termed the nuclear shielding.

Consider the s-electrons in a molecule. They have spherical symmetry and circulate in the applied field, producing a magnetic field which opposes the applied field. This means that the applied field strength must be increased for the nucleus to absorb at its transition frequency. This upfield shift is also termed diamagnetic shift.

Electrons in p-orbitals have no spherical symmetry. They produce comparatively large magnetic fields at the nucleus, which give a low field shift. This “deshielding” is termed paramagnetic shift.

In proton (1H) NMR, p-orbitals play no part (there aren’t any!), which is why only a small range of chemical shift (10 ppm) is observed. We can easily see the effect of s-electrons on the chemical shift by looking at substituted methanes, CH3X. As X becomes increasingly electronegative, so the electron density around the protons decreases, and they resonate at lower field strengths (increasing dH values).

Chemical shift is defined as nuclear shielding / applied magnetic field. Chemical shift is a function of the nucleus and its environment. It is measured relative to a reference compound. For 1H NMR, the reference is usually tetramethylsilane, Si (CH3)4.
Spin – spin coupling

Consider the structure of ethanol;

The 1H NMR spectrum of ethanol (below) shows the methyl peak has been split into three peaks (a triplet) and the methylene peak has been split into four peaks (a quartet). This occurs because there is a small interaction (coupling) between the two groups of protons. The spacings between the peaks of the methyl triplet are equal to the spacings between the peaks of the methylene quartet. This spacing is measured in Hertz and is called the coupling constant, J.

To see why the methyl peak is split into a triplet, let’s look at the methylene protons. There are two of them, and each can have one of two possible orientations (aligned with or opposed against the applied field). This gives a total of four possible states;

In the first possible combination, spins are paired and opposed to the field. This has the effect of reducing the field experienced by the methyl protons; therefore a slightly higher field is needed to bring them to resonance, resulting in an upfield shift. Neither combination of spins opposed to each other has an effect on the methyl peak. The spins paired in the direction of the field produce a downfield shift. Hence, the methyl peak is split into three, with the ratio of areas 1:2:1.

Similarly, the effect of the methyl protons on the methylene protons is such that there are eight possible spin combinations for the three methyl protons;

Out of these eight groups, there are two groups of three magnetically equivalent combinations. The methylene peak is split into a quartet. The areas of the peaks in the quartet have the ration 1:3:3:1.

In a first-order spectrum (where the chemical shift between interacting groups is much larger than their coupling constant), interpretation of splitting patterns is quite straightforward;

  • The multiplicity of a multiplet is given by the number of equivalent protons in neighbouring atoms plus one, i.e. the n + 1 rule
  • Equivalent nuclei do not interact with each other. The three methyl protons in ethanol cause splitting of the neighbouring methylene protons; they do not cause splitting among themselves
  • The coupling constant is not dependant on the applied field. Multiplets can be easily distinguished from closely spaced chemical shift peaks.

Review your learning

You should now be familiar with the basic principles of NMR spectroscopy, such as the splitting of nuclear energy levels in a magnetic field and how a transition between the levels can be induced. You should understand the mechanisms by which an excited nucleus can return to the lower energy level. You should also understand how the chemical environment of a nucleus gives rise to chemical shift and spin-spin splitting patterns.

June 06, 2006

Magnetic nanoparticles for potential cancer treatment

Writing about web page http://www.physorg.com/news6097.html

_Virginia Commonwealth University researchers have created highly magnetized nanoparticles based on metallic iron that could one day be used in a non–invasive therapy for cancer in which treatment would begin at the time of detection.

“We envision a potential for these materials to combine both detection and treatment into a single process,” said Everett E. Carpenter, Ph.D., an assistant professor of chemistry at VCU.

Carpenter is discussing his ongoing work of the synthesis and characterization of these functional magnetic nanoparticles for use in biomedical applications at the 2005 American Chemical Society National Meeting & Exposition in Washington, D.C., which began Aug. 28 and continues through Sept. 1.

More than 12,000 researchers from across the country are presenting new multidisciplinary research and highlighting important advances in biotechnology, nanoscience, nanotechnology, and defense and homeland security.

“Eventually, our goal is to use the scientific understanding of the growth mechanisms of these nanoparticles to develop materials for biomedical applications,” said Carpenter. “By engineering the magnetic properties of enhanced ferrites it is possible to develop materials for the treatment of various cancers, such as breast cancer.”

Carpenter and his team are working to determine how to best construct the core–shell structure and learn which shell materials are most ideal for biomedical applications such as magnetodynamic therapy (MDT), or as MRI contrast enhancement agents.

According to Carpenter, in the future it may be possible for a patient to be screened for breast cancer using MRI techniques with engineered enhanced ferrites as the MRI contrast agent. He said if a tumor is detected, the doctor could then increase the power to the MRI coils and localized heating would destroy the tumor region without damage to the surrounding healthy cells.

Another promising biomedical application is MDT, which employs magnetic nanoparticles that are coupled to the radio frequency of the MRI. This coupling converts the radio frequency into heat energy that kills the cancer cells. European researchers studying MDT have shown that nanoparticles are able to target tumor cells. Carpenter said that because the nanoparticles target tumor cells and are substantially smaller than human cells, only the very few tumor cells next to the nanoparticles are killed, which greatly minimizes damage to healthy cells.

“Our goal is to tailor the properties of the nanoparticles to make the use of MDT more universal,” said Carpenter. “The only thing slowing down the development of enhanced ferrites for 100 megahertz applications is a lack of understanding of the growth mechanisms and synthesis–property relationships of these nanoparticles.

“By studying the mechanism for the growth of the enhanced ferrites, it will be possible to create shells that help protect the metallic core from oxidation in biologically capable media,” he said.

Enhanced ferrites are a class of ferrites that are specially engineered to have enhanced magnetic or electrical properties and are created through the use of core–shell morphology. He said that in this approach the core can be a highly magnetic material like iron or iron alloys, while the shell can be a mixed metal ferrite with tailored resistivity.

“Ferrites (iron oxides) are used in many applications that require both a high magnetization and high electrical resistance; properties which are typically mutually exclusive,” said Carpenter. “These two properties are tied not only to the structure of the material but also to the way in which the material is synthesized and processed.”

Today, polymer encapsulated iron oxide particles are used in biomedical applications. However, Carpenter said that the high magnetization of the enhanced ferrite nanoparticles may potentially improve the absorption of the radio frequency, thereby providing better detection of tumor regions and the use of less MRI contrast re–agent.

In 2002, Carpenter invented a new material based on metallic iron. He said the magnetic power of the iron nanoparticles he created is 10 times greater than that of the currently available iron oxide nanoparticles, which translates to a substantial reduction in the amount of iron needed for imaging or therapy.

This work is supported by a grant from the American Cancer Society and the VCU Department of Chemistry.

Source: Virginia Commonwealth University

Nanotechnology : August 29, 2005 _


Writing about web page http://www.wisegeek.com/what-is-molecular-nanotechnology.htm

_Molecular nanotechnology ("MNT") is an anticipated manufacturing technology that would allow precise control and positional assembly of molecule–sized building blocks through the use of nano–scale manipulator arms. Molecular nanotechnology is usually considered distinct from the more inclusive term "nanotechnology", which is now used to refer to a wide range of scientific or technological projects that focus on phenomena or properties of the nanometer scale (around 0.1–100nm). Nanotechnology is already a blossoming field, but molecular nanotechnology – the goal of productive, molecular–scale machine systems – is still in the preliminary research stage.

Nanotechnology was first introduced in 1959, in a talk by the Nobel Prize–winning physicist Richard Feynman, entitled "There's Plenty of Room at the Bottom". Feynman proposed using a set of conventional–sized robot arms to construct a replica of themselves, but one–tenth the original size, then using that new set of arms to manufacture an even smaller set, and so on, until the molecular scale is reached. If we had many millions or billions of such molecular–scale arms, we could program them to work together to create macro–scale products built from individual molecules – a "bottom–up manufacturing" technique, as opposed to the usual technique of cutting away material until you have a completed component or product – "top–down manufacturing".

Feynman's idea remained largely undiscussed until the mid–80s, when the MIT–educated engineer K. Eric Drexler published "Engines of Creation", a book to popularize the potential of molecular nanotechnology. Because MNT would allow manufacturers to fabricate products from the bottom up with precise molecular control, a very wide range of chemically possible structures could be created. Since MNT systems could put every molecule in its specific place, molecular manufacturing processes could be very clean and efficient. Also, because every little bit of matter in an molecular nanotechnology system would be part of a nano–scale manipulator, nanotechnological systems could be far more productive and maintain much higher throughputs than modern manufacturing techniques, which use macro–scale manipulators to fabricate products.

To initiate an MNT revolution would require an "assembler" – a reprogrammable nano–scale manipulator capable of creating a wide range of molecular structures, including a complete copy of itself. The first assemblers will only function effectively in lab–controlled environments, such as a vacuum. The advent of self–replicating molecular nanomachines could quickly lead to "desktop nanofactories", tabletop appliances that consume modest amounts of power and contain the software required to manufacture an interesting range of useful products. The arrival of MNT would revolutionize wide sectors of human activity, including manufacturing, medicine, scientific research, communication, computing, and warfare. When full–blown molecular nanotechnology will arrive is currently unknown, but many experts foresee its arrival between 2010 and 2020. _

December 20, 2005

Important Postgraduate Dates

This is the timetable for postgraduate progress monitoring.
All items should be handed in to Jan Spencer in the Department Office P566.
All potential excuses should be tried out on David Leadley.
MSc Project Outline Fri. 21 Oct

Progress report and thesis plan Fri 31 March

Viva with Director of Graduates Thur 6 April

PhD year 1 Project Outline Fri 21 Oct

1st Year Report Mon 3 April

Viva with Director of Graduates Thur 27 or Fri 28 April

PhD year 2 Progress Report and Research PlanFri 21 Oct

Poster Presentation Tues 23 May

PhD year 3 Progress Report and Research PlanFri 21 Oct

Thesis Plan Tues 28 Feb

Interview with Head of Department Tues 7 March

PhD year 4 Progress report Fri 21 Oct

Interview with Head of Department Tues 1 Nov

Last chance to submit!4 years after start date

All dates apply to students who started a PhD between 1st June and 30th November. Progress monitoring dates for students who started their studi es o utside this period will be arranged on an individual basis.

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