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7BBFM127: The Chemistry of Drugs and Explosives > Mass Spectrometry Fragmentation Mechanisms > Flashcards

Mass Spectrometry Fragmentation Mechanisms Flashcards

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1
Q

LO

A
  • Revision of key learning outcomes
    o Ionisation
    o Mass spectrum
     Molecular ion, isotopic mass
    o General principles of fragmentation
  • Accurate mass
  • Fragmentation
    o Simple fission
     Charge localised on heteroatom
     Cleavage beta-position from heteroatom
  • To be able to interpret the fragmentation of simple mass spectra
  • To be able to confirm the identity of substances
  • To be able to facilitate the identification of unknown substances
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2
Q

What is the molecular ion?

A

Generally, the largest m/z

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3
Q

What must you look for with the molecular ion?

A
  • **Look for unusual losses M+.-4 to M+.-14 **
    o Dot indicates odd number of electrons
    o .H, H2, .H & H2,…
    o (Loss of He, Li, Be, B, C, …CH, ..CH2 does not occur due to the high amount of energy required for this)
    o .CH3 this is a common loss (loss of 15 mass units)
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4
Q

The molecular ion

A
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5
Q

The nitrogen rule

A
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6
Q

Accurate mass

A
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7
Q

How to calculate the Ring and double bond equivalents

A
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8
Q

Calculate the ring and double bond equivalences for the following examples

A
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9
Q

Tell me about the Heterolytic and homolytic cleavage of bonds

A
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10
Q

How would the following circumstances be written following the principles of fragmentation:
* Loss of radical from molecular ion
* Loss of neutral molecules from molecular ions
* Loss of radical from fragment ion
* Loss of neutral molecule from fragment ion

A
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11
Q

Simple fission and hydrocarbons

A
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12
Q

Identify the simple hydrocarbon

A
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13
Q

Identify the simple hydrocarbon

A
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14
Q

Typical features to observe in a mass spectra

A
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15
Q

LO

A
  • Fragmentation- simple fission
    o Charge localised on heteroatom
    o Cleavage beta-position from heteroatom
  • Fragmentation rearrangements
    o Ether re-arrangement
    o McLafferty re-arrangement
  • Summary
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16
Q

Simple fission- heteroatomic compounds

A
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17
Q
A
  • if have N and O in same molecules
    o Localise charge on N or O
    o If on N then end up with species a and if charge on O then end up with species b
    o Both can occur but N is more stable so a is more abundant
    o Mass spec looks at relative abundance
18
Q

Fragmentation of C=X (C=O, C=S, C=NH)

A
19
Q

Aldehydes and Ketones

A
20
Q

Esters

A
21
Q

Unsaturated hydrocarbons

A
22
Q

Atomatic compounds

A
23
Q

Reversed (retro-) Diels-Alder

A
24
Q

What are the
Two general rules for fragmentation in MS?

A

*** McLafferty **
o Stabilisation of charge is the most important factor for determining the fragmentation of a molecules
o Even electron species are most stable than those with an odd number of electrons

*** Stevenson **
o In a fragmentation the charge will go with the fragment with the lower ionisation potential

25
Q

McLafferty Re-arrangement

A
26
Q

Diethyl ether

A
27
Q

Fragmentation of diethyl ether

A
28
Q

Ether (ethyl group) re-arrangement

A
29
Q

Diethylpropion

A
30
Q

Diethylpropion metabolites I and II

A
31
Q

Reflective questions

A
  • Do I understand the difference between simple fission, concerted reactions and rearrangements?
  • How can mass spectrometry help with the identification of drug metabolites?
32
Q

Key LO

A
  • MS is destructive but very sensitive
  • MS is not inherently quantitative
  • MS may be used quantitatively with internal standards that maybe isotopically labelled
  • Spectrum may be library searches and or interpreted
  • Molecular ion
    o Isotopic mass, accurate mass- elemental composition
  • Fragmentation
    o Simple fission, charge localised on heteroatom
    o Re-arrangement, ether, McLafferty
33
Q

Recommended reading

A
34
Q

What is soft ionisation and what typically occurs after it?

A
  • In soft ionisation, such as occurs under electrospray ionisation, the ions produced are even electron species such as protonated molecular ions
  • After soft ionisation, fragmentation is induced (typically in a tandem MS instrument i.e., MS/MS) by accelerating the ions into a collision gas, a process known as collision induced dissociation (CID)
  • After CIS these even electron species mainly fragment by loss of neutrals so that the fragment is also an even electron species
  • An example of ESI fragmentation will be explained with ketamine and hydroxynotketamine
35
Q

An example of ESI fragmentation is Ketamine and hydroxynorketamine, tell me about the structures

A
  • Ketamine has benzene ring with chlorine attached
  • And cyclohexone with methyl amine attached
  • Hydroxynorketamines made by metabolism of ketamine
  • The hydroxy group can be in 4 positions –> 4 possible isomers (phenols)
  • If hydroxyl in cyclohexanone group, they can also be in 4 positions –> 4 isomers
  • Methyl amine is demethylated in the hydroxynorketamines (nor as lost the methyl group)
36
Q

Tell me about
Ketamine- accurate mass and elemental composition

A

*** Ketamine **
o Elemental composition C13H16CINO
o Exact mass=237.09204
o Chlorine-37 isotope to be considered alongside Cl35

*** Protonated ketamine- **when ionised in the MS
protonated ketamine is formed
o Elemental composition C13H17CINO+
o Exact mass= 238.09932 (as protonated the nitrogen rule doesn’t follow)
o 37Cl exact mass 240.09637 (32% relative abundance)

37
Q

Tell me about
Hydroxynorketamines- accurate mass and elemental composition

A

*** Protonated ketamine **
o Elemental composition C13H17CINO+
o Exact mass= 238.09932
o 37Cl exact mass 240.09637 (32% relative abundance)

*** Protonated hydroxynorketamines **
o Elemental composition C12H15CINO2+
o Exact mass= 240.07858 (this is different from integer difference)
o 37Cl exact mass 242.07563 (32% relative abundance)- 2 mass units up from ketamine its self

38
Q

MS/MS spectra of hydroxynorketamines

A
  • A- alcohol hydroxynorketamine
  • B- Phenolic hydroxynorketamine
  • MS/MS can choose the precursor ion to go on and fragment further in second MS
  • This means that what we are looking at is fragments of 240
  • C- instead of 240, collect Cl37 isotope and look at alcohol
  • D- Cl37 isotope and look at phenol
  • C and D have some similarities and differences between isotopes. No 179 and 127 in D and no 143 in D
39
Q

Fragmentation

A

* some fragment of alcohol metabolite in A
o Benzene ring does not contain OH
o Fragment as m/z 125 (as seen in bottom RHS)
o Another ion m/z 222 seen is where the OH has been eliminated by water
o Elemental composition worked out from mass to 5 dp

*** B **
o Phenol in the benzene ring
o Odd m/z as no N so the rule gets reversed from the fragments
o Ion at 141 which did not appear in alcoholic version

40
Q

**Mass spectrometry- fragmentation mechanisms
Relative topics and questions **
* Do I understand the difference between simple fission, concerted reactions, and rearrangements?
* How can mass spectrometry help with the identification of drug metabolites?

A

7BBFM127: The Chemistry of Drugs and Explosives (18 decks)

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