Types of ions, fragmentation modes, fragment characterstics, applications

1. Presented By :- RAHUL KRISHNAN.P.R
M.Pharm 1st Year
Dept.Of Pharmaceutics
Mass Spectrometry
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2. Contents
 Introduction of Mass spectrum.
 Types of Ions
 Fragmentation modes
 Fragment characteristics
 Applications
 References
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3. Introduction of MS
 The impact of a stream of high energy electrons causes the
molecule to lose an electron forming a radical cation.
 A species with a positive charge and one unpaired electron
+ e-
H
H C H
H
H
H C H
H
+ 2 e-
3
Molecular ion (M+)
m/z = 16
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4. Introduction of MS
 Only cations are detected.
- Radicals are “invisible” in MS
 The amount of deflection observed depends on the mass to
charge ratio (m/z).
-Most cations formed have a charge of +1 so the amount of
deflection observed is usually dependent on the mass of
the ion.
.
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5. Mass Spectrum
 The resulting mass spectrum is a graph of the mass of each
cation vs. its relative abundance.
 Relative abundance of an ion means the % of total ion
current.
 Mass spectrum is an analytical techniques which can provide
information concerning the molecular structure of organic
comp.
 Base peak is the highest peak or the most intense peak in the
spectrum.
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6. Types of Ion
 Types of ion produced in MS
1.Molecular ions (parent ion)
2.Metastable ions
3.Fragment ions (Dissociation process)
4.Rearrangement ions
5.Multiple charged ions
6.Isotopes ions
7.Negative ions
8.Base peak
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7. Molecular ion
 Molecular ion (parent ion):
-The radical cation corresponding to the mass of the
original molecule
 The molecular ion is usually the highest mass in
the spectrum
H
H C H
H
H H
H C C H
H H
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8. Molecular ion
•When a sample sub.is bombarded with
electrons of energies of 9 to 15eV, the
molecular ions produced by loss of a single
electron.
•This will give rise to a very simple mass
spectrum with essentially all of the ion appearing
in one peak called parent peak.
M + e = M+ + 2e-
Most important ion.
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9. Molecular ion
•The relative height of parent peak decreases in
the following order
aromatic>conjugated olefins>sulphides>
unbranched>hydrocarbon>ketones>amine>est
er> ethers >carboxylic acid>branched
hydrocarbons.
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•If a molecule yields the parent peak due to
molecular ion ,the exact molecular weight can be
calculated.
•The peak intensity of the molecular ion differs from
one compound to other.
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10. The Molecular ion Peak
1
0
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11. Isotope Ion
•Many elements have the natural isotopes.
•For example, Chlorine with mass number 37 exists in
addition to Chlorine 35.
•The presence of isotopes readily produces the isotope
ions in the spectrum accompanied by a main molecular
ion peak and fragment peaks.
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12. Isotope Ion
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13. Fragment ion
•The molecular ion produced in MS is generally
left with considerable excess energy.
•This energy is rapidly lost by the molecular ion
resulting in one or more cleavages in it with or without
some rearrangement.
•One of the fragment retains the charge where as
the remaining fragment may be stable molecule or
radicals.
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14. Fragment ion
•The energy required to remove one electron from
the neutral parent molecule is usually 10eV.
•But the energy of the bombarding electron will be
around 70eV.
•The additional energy is consumed in fragmenting
the parent ion.
E.g. : Ethyl chloride.
CH3-CH2-Cl + e- = CH3-CH2-Cl + + 2e-
CH3-CH2-Cl + = CH3-CH2
+ + Cl. Or
CH2-CH2
+ + HCl. (Fragment ion)
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15. Fragment Ion peak
1
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16. Metastable ion
 The ions in a mass spectrometer that have sufficient
energy to fragment sometime after leaving the ion
source but before arriving at the detector.
 M+
A+ + N


M+ with large amount of internal energy will fragment
in the ionization source, producing “normal” A+ ions.
These A+ ions will be seen as narrow peaks at m/z
values correct for the mass and charge on the ion A+.
M+ having only a small excess of internal energy,
reach detector before decomposition can occur.
Narrow peaks for “normal” M+ appear
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17. Metastable ion
•M+ which posses excesses of internal energy that are
in between the those in above two cases, may
fragment after leaving the ion source and before
reaching the detector. The product ions, A+, are seen
in the mass spectrum as broad peaks, centered at m/z
values that are nor correct for the mass and charge on
the ion A+.
•These broad peaks are called “metastable ion
peaks”.
•The metastable ions are detected differently form
normal ions is due to their different momentum.
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18. Metastable ion Peak
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19. Rearrangement Ion
•These are commonly formed due to the
rearrangement of the fragmented ions.
•In most of the cases, rearrangement takes place with
respect to hydrogen, by a reaction known as
McLafferty Rearrangement.
•It involves the migration of a ϒ hydrogen atom,
followed by cleavage of a β bond.
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20. Multi-charged Ions
•These ions may exist in 2 or 3 charges instead of a
usual single charge.
•These are known as doubly or triply charged ions and
peaks due to these ions are known as multicharged
ion peak.
M + e- → M++ + 3e-
M + e- → M+++ + 4e-
•common in case of the heteroaromatic compounds
•Fixed gases such as co2, N, O etc have measurable
peaks corresponding to co2+2, N+2, O+2
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21. Negative ions
.
•In addition to the positive ions, negative ions are also
formed during the electron bombardment of the
sample.
•This results due to the capture of the electrons during
the bombardment.
•These are not observable with the usual mass
spectrophotometer, unless some modifications are
made, and hence are generally ignored during
studies.
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22. Base Peak
.
•The largest peak in the mass spectrum
corresponding to the most abundant ion or the most
intense peak in the spectrum is known as the base
peak.
•Depending on the nature of the compound, it may be
a fragmented ion peak or parent ion peak.
•Sometimes the molecular ion peak may be the base
peak, and in that case, it is easy to find out the
molecular weight of the compound.
•The base peak will be assigned with a value of 100%
•All other peaks are reported as percentages of base
peak.
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23. Base Peak
.
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24. FRAGMENTATION MODES
•The Relative abundance of fragment ion
formed depends upon
1)The stability of the ion
2)Also the stability of radical lost.
•The radical site is reactive and can form a new bond.
• The formation of a new bond is a powerful driving
force for ion decompositions
•The energy released during bond formation is available
for the cleavage of some bonds in the ion.
.
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25. FRAGMENTATION MODES
1.Simple Clevage
i)Homolytic Clevage
a)Mode1
b)Mode2
c)Mode3
ii)Heterolytic clevage
2.Retro-Diel’s-Alder reaction
3.Hydrogen transfer rearrangements
4.Mc Lafferty Rearrangements
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26. Fragmentation modes
1) Homolytic cleavage :
odd electron ions have unpaired electron which is
capable of new bond formation.
Bond is formed , energy is released , help offset the
energy required for the cleavage of some other bond in
the ion.
Homolytic cleavage reactions are very common.
It is divided into 3:
a. Mode 1
b. Mode 2
c. Mode 3
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27. Mode1
•Operates in compounds where hetero atom is singly
bonded to a carbon atom.
•Parent ion is formed by removal of one electron from hetero
atom.
•New bond is formed with adjacent atom through donation of
the unpaired electron and transfer of electron from adjacent
bond.
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28. Mode 2
•When hetero atom is attached to the carbon atom by double
bond, α clevage is the preferred fragmentation mode.
•It is shown by ketones, aldehydes, esters, amides etc.
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29. Mode 3
•Mainly occurs in the aromatic compounds.
•It involves the cleavage of c-c bond, which is β to the
aromatic ring.
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30. Heterolytic Clevage
•It may be noted the cleavage of C-X (X= 0,N,S,Cl) bond is
more difficult than that of C-C bond.
•In such cleavage , the positive charge is carried by the
carbon atom and not by the heteroatom.
•As size of the halogen atom attached to the carbon atom
increases, the c-x bond becomes very weak, and will
undergo easy fragmentation.
R-CH2-Cl.+ = Cl. + RC+H2
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31. Fragmentation modes
2) Retro –Diels –Alder reaction
•The reaction is an example of multicentre fragmentation
which is characteristic of cyclic olefins.
•It involves the cleavage of two bonds of a cyclic system
which result the formation of 2 stable unsaturated
fragment in which 2 new bonds are formed.
•This process is not accompanied by any hydrogen
transfer rearrangement.
•The charge can be carried by any one of the fragment.
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32. Fragmentation modes
2) Hydrogen ion Transfer Rearrangements
•Transfer of the Hydrogen atom from one part of the
molecule to another.
•Generally the fragmentation occurs through a six
membered transition states.
+
C6H5-NH-C=O C6H5NH2
+ + H2C=O
I
H-CH2
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33. Fragmentation modes
3) Mc Lafferty Rearrangement
• It involves the migration of γ hydrogen atom followed by the
cleavage of β bond.
• To undergo a Mc Lafferty Rearrangement a molecule must
possess
a) An appropriately located heteroatom e.g. O, N
b) A pi electron system ( usually a double bond) &
c) An abstractable hydrogen atom gamma to the C = X system
• Rearrangement leads to the elimination of neutral
molecules from aldehydes, ketones , amines etc.
• Rearrangement proceeds through sterically hindered six
membered transition state. 33
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34. Fragmentation modes
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35. APPLICATIONS
1. Molecular mass determination
2. Isotopic abundance determination.
3. Structural elucidation of organic and biologic
molecules.
4. Detection of impurities.
5. Drug metabolism studies
6. Quantitative analysis of mixtures
7. To detect the distinction between cis and trans isomer
8. Determination of ionization potential
9. Detection of bonding informations.
10.Clinical, toxicological and forensic applications.
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36. References
1. Mass Spectrometry, Second edition by James Barker
2. Elementary organic spectroscopy by Y.R. Sharma
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