Unit 13: Mass Spectrometry (MS)

Weighing molecules and their fragments to determine molecular mass and structure.

13.14 Basic Principles (Ionization, Fragmentation)

Mass Spectrometry (MS) is a powerful analytical technique that measures the mass-to-charge ratio (m/z) of ions. Unlike other forms of spectroscopy, it does not use electromagnetic radiation to probe the sample. Instead, it effectively "weighs" molecules and their pieces.

A mass spectrometer works in several key stages:

  1. Vaporization: The sample is injected and heated to turn it into a gas.
  2. Ionization: The gaseous molecules are bombarded with high-energy electrons. This knocks an electron off a molecule, creating a positively charged molecular ion ($M^+$), which is also a radical ($M^{+\bullet}$).
  3. Fragmentation: The high energy of the ionization process causes the unstable molecular ion to break apart into smaller, positively charged fragments and neutral radicals.
  4. Acceleration: The positive ions (both the molecular ion and the fragments) are accelerated by an electric field so they all have the same kinetic energy.
  5. Deflection: The ions then travel through a magnetic field, which deflects them. The amount of deflection depends on their mass-to-charge ratio (m/z). Lighter ions are deflected more than heavier ions.
  6. Detection: A detector measures the m/z ratio and the relative abundance of each ion that strikes it.

The output is a mass spectrum, which is a graph of relative abundance versus m/z.

Solved Examples:
  1. What does a mass spectrometer measure?
    Solution: It measures the mass-to-charge ratio (m/z) of ions.
  2. What is the purpose of bombarding the sample with high-energy electrons?
    Solution: To ionize the molecules by knocking off an electron, creating a positive ion that can be accelerated and detected.
  3. What is fragmentation in mass spectrometry?
    Solution: It is the process where the high-energy molecular ion breaks apart into smaller, positively charged fragments and neutral radicals.
  4. In the deflection stage, which ion is deflected more: a heavy one or a light one (assuming they have the same charge)?
    Solution: The lighter ion is deflected more by the magnetic field.
  5. What is the charge (z) on most ions detected in a standard mass spectrometer?
    Solution: The charge is typically +1. Therefore, the m/z value is effectively equal to the mass of the ion.
  6. Why must the sample be in the gas phase?
    Solution: So that the individual molecules can be ionized and travel through the vacuum of the spectrometer without colliding with each other.
  7. What is the molecular ion?
    Solution: It is the ion formed when the entire molecule loses one electron but does not fragment.
  8. Are the neutral fragments formed during fragmentation detected by the mass spectrometer?
    Solution: No. Only the positively charged ions are accelerated, deflected, and detected.
  9. What are the five main stages of mass spectrometry?
    Solution: Vaporization, Ionization, Acceleration, Deflection, and Detection.
  10. Why is the inside of a mass spectrometer kept under a high vacuum?
    Solution: To prevent the ions from colliding with air molecules, which would interfere with their path to the detector.

13.15 Molecular Ion Peak (M⁺) & Isotope Patterns

The molecular ion peak (M⁺) is one of the most important signals in a mass spectrum. It is the peak caused by the intact molecule that has lost only one electron. The m/z value of the molecular ion peak is equal to the relative molecular mass (Mr) of the compound. It is usually the peak with the highest m/z value in the spectrum.

Isotope Patterns

Many elements exist naturally as a mixture of isotopes. Mass spectrometry is sensitive enough to distinguish between these isotopes. This gives rise to characteristic patterns for molecules containing certain elements.

  • Chlorine: Chlorine has two common isotopes, ³⁵Cl (75% abundance) and ³⁷Cl (25% abundance). A molecule containing one chlorine atom will show two molecular ion peaks: an M⁺ peak (for the molecule with ³⁵Cl) and an M+2 peak (for the molecule with ³⁷Cl) that is about one-third the height of the M⁺ peak.
  • Bromine: Bromine has two isotopes, ⁷⁹Br (~50.5% abundance) and ⁸¹Br (~49.5% abundance). A molecule containing one bromine atom will show an M⁺ peak and an M+2 peak that are of nearly equal height.

These distinct isotope patterns are powerful tools for identifying the presence of chlorine or bromine in an unknown compound.

Solved Examples:
  1. The mass spectrum of a compound shows the molecular ion peak at m/z = 58. What is the relative molecular mass of the compound?
    Solution: The relative molecular mass is 58.
  2. A mass spectrum has a peak at m/z = 78 and another peak at m/z = 80, with the peak at 80 being about one-third the height of the peak at 78. What element does the molecule likely contain?
    Solution: The M+2 peak with a 1/3 ratio is the characteristic isotope pattern for chlorine.
  3. The mass spectrum of bromoethane ($CH_3CH_2Br$) shows two peaks of almost equal height at m/z = 108 and m/z = 110. Explain these peaks.
    Solution: These are the molecular ion peaks. The peak at m/z = 108 corresponds to the molecule containing the ⁷⁹Br isotope. The peak at m/z = 110 corresponds to the molecule containing the ⁸¹Br isotope. Because the two isotopes are in roughly a 1:1 abundance, the peaks are nearly equal in height.
  4. What is the M+1 peak?
    Solution: It is a small peak one mass unit higher than the molecular ion peak, caused by the natural 1.1% abundance of the ¹³C isotope.
  5. Why might the molecular ion peak be very small or absent in some spectra?
    Solution: If the molecular ion is very unstable (e.g., in tertiary alcohols), it may fragment so completely that very few or no intact molecular ions reach the detector.
  6. A compound is known to be a chloroalkane. Its mass spectrum shows a molecular ion peak at m/z = 64. What is its molecular formula?
    Solution: The molecular mass is 64. The chlorine atom (³⁵Cl) has a mass of 35. The remaining mass is 64 - 35 = 29. This corresponds to an ethyl group ($C_2H_5$). The formula is $C_2H_5Cl$.
  7. What would the isotope pattern look like for a molecule containing two chlorine atoms, like dichloromethane ($CH_2Cl_2$)?
    Solution: It would be more complex. There would be an M⁺ peak (for two ³⁵Cl atoms), an M+2 peak (for one ³⁵Cl and one ³⁷Cl), and an M+4 peak (for two ³⁷Cl atoms). The ratio of heights would be approximately 9:6:1.
  8. How can high-resolution mass spectrometry help determine a molecular formula?
    Solution: High-resolution MS can measure m/z values to several decimal places. This allows it to distinguish between compounds with the same nominal mass but different formulas (e.g., CO and N₂, both have Mr ≈ 28, but their exact masses are different).
  9. The mass spectrum of an unknown compound shows two major peaks of equal height at m/z = 156 and 158. What can you deduce?
    Solution: The M⁺ and M+2 peaks of equal height strongly indicate the presence of one bromine atom in the molecule. The molecular mass is 156 (using the lighter isotope).
  10. Where would you find the molecular ion peak on a mass spectrum?
    Solution: It is the peak with the highest mass-to-charge ratio (the furthest to the right), ignoring any small M+1 or M+2 isotope peaks.

13.16 Fragmentation Patterns & Interpretation

When the molecular ion breaks apart, it forms a unique set of fragment ions. The pattern of these fragments provides clues to the molecule's structure. The most abundant fragment ion produces the tallest peak in the spectrum, which is called the base peak.

By analyzing the difference in mass between the molecular ion and a fragment ion, we can deduce the structure of the neutral piece that was lost.

Common Neutral Fragments Lost:
Mass Lost (M - fragment) Neutral Fragment Lost Structure
15 Methyl radical $\cdot CH_3$
29 Ethyl radical $\cdot CH_2CH_3$
43 Propyl radical $\cdot C_3H_7$
18 Water $H_2O$ (from alcohols)
45 Carboxyl group $\cdot COOH$ (from carboxylic acids)

The stability of the resulting carbocation fragment influences its abundance. For example, the fragmentation of branched alkanes often occurs at the branch point to form the most stable (e.g., tertiary) carbocation.

Solved Examples:
  1. What is the base peak in a mass spectrum?
    Solution: It is the tallest peak in the spectrum, corresponding to the most abundant (most stable) fragment ion. It is assigned a relative abundance of 100%.
  2. The mass spectrum of propane ($CH_3CH_2CH_3$) has a molecular ion peak at m/z = 44. A major fragment peak is seen at m/z = 29. What neutral fragment was lost?
    Solution: The mass lost is 44 - 29 = 15. This corresponds to the loss of a methyl radical ($\cdot CH_3$).
  3. An alcohol shows a prominent peak at M-18. What does this indicate?
    Solution: An M-18 peak is characteristic of the loss of a molecule of water ($H_2O$), which is a common fragmentation pathway for alcohols.
  4. The mass spectrum of pentane has its base peak at m/z = 43. What is the likely structure of this fragment?
    Solution: The molecular mass of pentane ($C_5H_{12}$) is 72. A peak at 43 corresponds to a loss of 72 - 43 = 29, which is an ethyl radical. The fragment ion with m/z = 43 is therefore the propyl cation ($[C_3H_7]^+$).
  5. How can fragmentation patterns help distinguish between isomers?
    Solution: Isomers have the same molecular mass and thus the same molecular ion peak. However, they have different structures and will break apart in different ways, leading to different and unique fragmentation patterns (different fragment peaks and/or different base peaks).
  6. A compound has a molecular ion at m/z = 88. Its IR spectrum shows it is a carboxylic acid. The mass spectrum shows a prominent peak at m/z = 43. What is the structure of the compound?
    Solution: The peak at m/z = 43 corresponds to a loss of 88 - 43 = 45. A loss of 45 from a carboxylic acid is characteristic of losing the -COOH group. The remaining fragment, $[C_3H_7]^+$, has a mass of 43. The acid is therefore butanoic acid.
  7. What is the likely fragment lost to produce a peak at m/z = 57 from a molecular ion of octane (Mr = 114)?
    Solution: The mass lost is 114 - 57 = 57. This corresponds to a butyl radical ($\cdot C_4H_9$).
  8. Why is the base peak not always the molecular ion peak?
    Solution: Because the molecular ion is often unstable and fragments readily. One of the resulting fragment ions may be more stable and therefore more abundant than the molecular ion.
  9. A mass spectrum shows a molecular ion at m/z = 60 and a base peak at m/z = 45. What neutral fragment is lost?
    Solution: The mass lost is 60 - 45 = 15. This corresponds to the loss of a methyl radical ($\cdot CH_3$).
  10. What information does the fragmentation pattern provide?
    Solution: It provides clues about the structure of the molecule by showing how it breaks apart into smaller, stable pieces.

13.17 Applications of Mass Spectrometry

Mass spectrometry is a highly sensitive and versatile technique used in many scientific fields.

  • Molecular Mass Determination: The most fundamental application is to find the precise relative molecular mass of a compound from the molecular ion peak.
  • Structure Elucidation: The fragmentation pattern, combined with data from IR and NMR, is essential for determining the structure of unknown compounds.
  • Drug Testing and Forensics: MS is used to detect and identify tiny amounts of drugs, explosives, or other substances in samples from crime scenes or in an athlete's urine. The fragmentation pattern provides a definitive fingerprint for identification.
  • Environmental Analysis: Used to detect and quantify pollutants like pesticides and dioxins in water, soil, and air samples at very low concentrations.
  • Space Exploration: Miniaturized mass spectrometers are sent on space probes (e.g., to Mars) to analyze the composition of planetary atmospheres and soils.
Solved Examples:
  1. Why is mass spectrometry so useful in forensic science?
    Solution: Because it is extremely sensitive and can identify a substance from a very small sample size. The unique fragmentation pattern provides a very reliable identification.
  2. How can MS be used in airport security?
    Solution: Swabs from luggage can be analyzed in a mass spectrometer to detect trace amounts of explosive residues.
  3. A new natural product is isolated from a plant. What is the first piece of information a chemist would want from its mass spectrum?
    Solution: The relative molecular mass, which is given by the m/z value of the molecular ion peak.
  4. How does a breathalyzer for alcohol work?
    Solution: While older models used chemical reactions, modern police breathalyzers often use a form of infrared spectroscopy or a fuel cell. Mass spectrometry is used in the more accurate blood tests performed at the station.
  5. What is a major advantage of mass spectrometry over other techniques?
    Solution: Its incredible sensitivity, allowing for the detection of substances at the parts-per-billion level or even lower.
  6. Can MS distinguish between isomers?
    Solution: Yes. While isomers have the same molecular ion peak, they will produce different fragmentation patterns.
  7. How is MS used to determine the age of ancient artifacts?
    Solution: A specialized technique called Accelerator Mass Spectrometry is used for carbon dating. It directly counts the ratio of ¹⁴C to ¹²C isotopes, which is a very accurate way to determine the age of organic materials.
  8. What is a GC-MS instrument?
    Solution: It is a powerful combination where a Gas Chromatograph (GC) first separates a complex mixture into its individual components, and then a Mass Spectrometer (MS) analyzes each component to identify it.
  9. How can MS be used to detect food contaminants?
    Solution: It can identify trace amounts of harmful substances like pesticides, illegal dyes, or toxins in food samples.
  10. In medicine, how might MS be used?
    Solution: It is used in newborn screening to detect metabolic disorders, in toxicology to identify poisons, and in clinical labs to analyze biomarkers for diseases.

🧠 Quiz

Answer: Its mass-to-charge ratio (m/z).

Answer: The molecular ion peak (M⁺).

Answer: The base peak.

Answer: Bromine.

Answer: The breaking apart of the molecular ion into smaller charged fragments.

Answer: The relative molecular mass (Mr).

Answer: A methyl radical ($\cdot CH_3$, mass = 15).

Answer: A peak two mass units higher than the molecular ion, caused by the presence of a heavier isotope like ³⁷Cl or ⁸¹Br.

Answer: Because they have no charge and cannot be accelerated or deflected by the electric and magnetic fields.

Answer: Drug testing, forensics, environmental analysis, or structure elucidation.

Answer: Approximately one-third (1/3).

Answer: +1.

Answer: A water molecule ($H_2O$).

Answer: 100%.

Answer: They will produce different fragmentation patterns.

Answer: They are bent into a curved path by a magnetic field.

Answer: An ethyl radical ($\cdot C_2H_5$).

Answer: The presence of the ¹³C isotope in the molecule.

Answer: Gas Chromatography-Mass Spectrometry (GC-MS).

Answer: Vaporization of the sample.
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