Mass Spectrometry Overview

How It Works

• Old System and Basic Operation:

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    1. A small droplet of sample is injected, and an electron is removed from the molecules, creating molecular radical cations.
    2. The application of a potential difference accelerates these molecular ion peaks through a slit towards a detection screen.
    3. A magnetic field deflects the course of the ion based on its mass, causing it to arrive at different locations on the phosphorous screen.

• Theory:

  • The mass-to-charge ratio $\frac{m}{z}$ is given by $\frac{m}{z}=\frac{B^2{R}^2}{2V}$, where:
    • (m) is the mass of the ion
    • (z) is the charge of the ion
    • (B) is the applied magnetic field
    • (R) is the radius of deflection
    • (V) is the applied voltage
  • High vacuum conditions are required to prevent intermolecular energy exchanges.
  • The resolution of the mass spectrometer is given by $A=\frac{m}{\mathrm{\Delta }m}$. A resolution greater than 100,000 is considered High-Resolution Mass Spectrometry (HRMS).

Detectors

• Photomultiplier Tube (PMT):

  • PMTs multiply the current produced by incident light, making detection possible.
  • Electrons hit increasingly positive plates, resulting in a detectable current.
  • This method replaces the old phosphorous screen.
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• Double Focusing Mass Spectrometer:

  • Uses an electrostatic analyzer to refocus the spread of masses caused by flight, followed by a slit that further focuses this to the detector.
  • This is used in HRMS and provides extremely high resolution.

• Quadrupole Detector:

  • A quadrupole detector measures mass using an oscillating field.
  • Four voltage-carrying rods run the length of the flight path, creating complex oscillations in the flight path.
  • Only specific $\frac{m}{z}$ ratios oscillate such that they reach the detector, allowing for selective detection by adjusting the voltage.
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• Time-of-Flight Mass Spectrometer (TOF-MS):

  • TOF-MS is based on the principle that different mass particles with the same charge will fly at different speeds through a tube with an applied potential.

Ionization Techniques

• Electron Impact (EI) Ionization:

  • In EI ionization, high-energy electrons impact the sample, causing the ejection of electrons and producing ionized fragments.
  • This method can be too harsh, leading to over-fragmentation or decomposition.
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• Chemical Ionization (CI):

  • CI uses an ionized gas to create quasi-molecular ions.
  • The detected molecular ions are typically M+1 and M+RH, where R is the gas used.

• Electrospray Ionization (ESI):

  • ESI involves spraying molecules from a solution through a charged needle, creating a fine ionized mist where the solvent evaporates quickly.
  • Fragmentation is typically not observed due to the mild conditions.

• Matrix-Assisted Laser Desorption/Ionization (MALDI):

  • MALDI ionizes a sample (often a protein) embedded in a matrix using laser light.
  • It is often coupled with TOF-MS (MALDI-TOF).

Fragmentation Patterns

• Predicting Fragmentation:

  • The most likely fragmentation occurs at the weakest C-C bond.
  • Typically, only one break is made per ionization event.

• Example - Benzene Fragmentation:

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Isotope Patterns

• Calculating Isotope Patterns:
  • Isotope peaks can reveal the elements present in a molecule based on their specific patterns.
  • For example, the isotope pattern for Cl${}_3$Br${}_3$:
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  • Elements like Br and Cl create distinctive patterns:
    • Br: 79/81 amu with 50% abundance each
    • Cl: 35/37 amu with 75%/25% abundance

How to Approach a Mass Spectrum

1. Molecular Ion Peak:

   • Identify the highest mass peak (excluding isotopes).
   • In EI ionization, the M${}^{\cdot +}$ ion is observed, whereas softer methods show MH${}^{+}$ or M(NH${}_4$)${}_2^{+}$, etc.
   • Apply the Nitrogen Rule:
     • If the MI peak is even, the number of nitrogen atoms (N) is 0, 2, 4, etc.
     • If the MI peak is odd, N is 1, 3, 5, etc.
   • Mass to structure calculator

2. Isotope Peaks:

   • Analyze isotope peak patterns to determine elements.
   • Check mass differences and relative intensities.
   • For example, the isotope pattern of 2 Br in a molecule results in a 1:2:1 ratio.

3. Number of Rings and Double Bonds:

   • Calculate using the formula:
     • Rings + Double Bonds $=\frac{2x-y+z+2}{2}$ for $C_x{H}_y{N}_z{O}_n$

4. Common Fragmentation Patterns:

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Resources

• Books and Links:
  • Great overview chapter: Introduction to Organic Spectroscopy
  • Mass to structure calculator