A CRITICAL REVIEW ON PHARMACEUTICAL ANALYSIS OF NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY (HETCOR SPECTROSCOPY)

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About Authors:
Reshma. K*, M.Muthukumaran*, B.krishnamoorthy, Amreen Nishat
Montessori Siva sivani Institute of Science&Technology- College Of
Pharmacy
Vijayawada, Andhrapradesh-521 230
reshmakaaja@gmail.com

Abstract
Nuclear magnetic resonance (NMR) has progressed rapidly over the last decade as a result of improved experimental technology and development of novel approaches. NMR spectroscopy has evolved into an important technique in support of structure-based drug design. It was most useful as a technique to provide structural information regarding protein drug targets and target–ligand interactions. More recently, it has been shown that NMR may be used as an alternative method for identification of small molecule ligands that bind to protein drug targets. High throughput implementation of these experiments to screen small molecule libraries may lead to identification of potent and novel lead compounds. NMR as a probe of microscopic dynamic behaviour through relaxation and direct diffusion measurements over a wide temperature range is examined.

REFERENCE ID: PHARMATUTOR-ART-2065

Introduction
Nuclear magnetic resonance spectroscopy, most commonly known as NMR spectroscopy, is a research technique that exploits the magnetic properties of certainatomic nuclei to determine physical and chemical properties of atoms or the molecules in which they are contained. It relies on the phenomenon of nuclear magnetic resonanceand can provide detailed information about the structure, dynamics, reaction state, and chemical environment of molecules. Most frequently, NMR spectroscopy is used by chemists and biochemists to investigate the properties of organic molecules, though it is applicable to any kind of sample that contains nuclei possessing spin. Suitable samples range from small compounds analyzed with 1-dimensional proton or carbon-13 NMR spectroscopy to large proteins ornucleic acids using 3 or 4-dimensional techniques. The impact of NMR spectroscopy on the sciences has been substantial because of the range of information and the diversity of samples, including solutions and solids.

Basic NMR Techniques
When placed in a magnetic field, NMR active nuclei (such as 1H or 13C) absorb electromagnetic radiation at a frequency characteristic of the isotope. The resonant frequency, energy of the absorption, and the intensity of the signal are proportional to the strength of the magnetic field. For example, in a 21 Tesla magnetic field, protons resonate at 900 MHz. It is common to refer to a 21 T magnet as a 900 MHz magnet, although different nuclei resonate at a different frequency at this field strength in proportion to their nuclear magnetic moments.

PRINCIPLE
The only nuclei that exhibit the NMR phenomenon are those for which the spin quantum number I is greater than 0: the spin quantum number I is associated with the mass number and atomic 1number of the nuclei  as follows:

TABLE 1: SPIN QUANTUM NUMBER

Mass number

Atomic number

Spin quantum number

Odd

odd or even

-

Even

Even

0

even 

odd 

1,2,3 

I is associated with the mass number and atomic number of the nuclei as follows:

The nucleus of 1H, the proton, has I = , whereas 12C and 16O have I = 0 and are therefore nonmagnetic. If 12C and 16O had been magnetic, the NMR spectra of organic molecules would have been much more complex.

Other important magnetic nuclei that have been studied extensively by NMR are 1B, 13C, 14N and 15N, 17O, 19F and 31P. Both deuterium (2H) and nitrogen - 14 have l = 1, and the consequences of this observation will become apparent later.

Under the influence of an external magnetic field, a magnetic nucleus can take up different orientatiuons with respect to that field; the number of possible orientations is given by (2l + 1), so that for nuclei with spin 1/2(1H, 13C, 19F, etc.) only two orientations are allowed. Deuterium and 14N have l = 1 and so can take up three orientations: these nuclei do not simply possessing electric quadrupoles can interact with both magnetic and electric field gradients, the relative importance of the two effects being related to their magnetic moments and electric quadrupole moments, respectively.[1]

In an applied magnetic field, magnetic nuclei like the proton precess at a frequency v, which is proportional to the strength of the applied field. The exact frequency is given by where Bo = strength of the applied external field experienced by the proton g = magnetogyric ratio, being the ratio between the nuclear magnetic moment, m, and the nuclear angular momentum, I: g is also called the gyromagnetic ratio.Typical approximate values for v are shown in Table for selected values of field strength Bo, for common magnetic nuclei.

Table 2: Precessional frequencies (in MHz)

Bo/tesla

1.4 

1.9 

2.3 

4.7 

7.1

11.7 

14.1 

Nucleus 








1H

60 

80 

100 

200 

300 

500 

600 

2H

9.2 

12.3 

15.3 

30.6 

46 

76.8 

92 

11B

19.2 

25.6 

32 

64.2 

96.9 

159.8 

192 

13C

15.1 

20.1 

25.1 

50.3 

75.5 

125.7 

151 

15N

6.1

8.1

10.1

20.3

30.4

50.7

61

17O

8.1 

10.8 

13.6 

27.1 

40.7 

67.8 

81 

Free electron

3.9 ´ 104







The strength of the signal, and, hence, the sensitivity of the NMR experiment for a particular nucleus, are related to the magnitude of the magnetic moment, m. The magnetic moments of 1H and 19F are relatively large, and detection of NMR with these nuclei is fairly sensitive. The magnetic moment for 13C is about one-quarter that of 1H; these nuclei are less sensitively detected in NMR. (In contrast, the magnetic moment of the free electron is nearly 700 times that of 1H, and resonance phenomena for free radicals can be studied in extremely dilute solutions).[2]

Nuclei in the lower energy state undergo transitions to the higher energy state; the populations of the two states may approach equality, and if this arises, no further net absorption of energy can occur and the observed resonance signal will fade out. We describe this situation in practice as saturation of the signal. In the recording of a normal NMR spectrum, however, the populations in the two spin states do not become equal, because higher energy nuclei are constantly returning to the lower energy spin state.[3]

The nuclei loss energy - by two radiation less process:
a) spin lattice or longitudinal relaxation process - where the energy is lost by means of translational/vibrational/rotational energy.

b) spin or transverse relaxation process - where the energy is lost to the neighbouring nuclei
Spin lattice relaxation = T1
Spin-spin relaxation    = T2

If T1 and T2 are small we will get broad peaks and if T1 and T2 are large (one second order) sharp peaks are obtained.

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