Mechanism of Ionization in Matrix-Assisted Laser Desorption Ionization (MALDI):

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• Mechanism of Ionization in Matrix-Assisted Laser
  Desorption Ionization (MALDI)
• How does proton transfer occur

Ajax Group
Joshua P. Layfield Jordan C. Vincent Desiree M.
Bates Ashley K. Tucker Sara E. Ray Ron C.
Estler
http//pslc.ws/mactest/maldi.htm
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MALDI Overview

• MALDI is a soft ionization technique that has
  revolutionized high-molecular weight mass
  spectrometry
• Technique used to measure the molecular weights
  of a number of systems
• Proteins
• Polysaccharides
• Glyco-lipids
• Synthetic Polymers
• Nobel Prize Awarded to Fenn and Tanaka in 2002
  for the development of soft ionization techniques

http//www.magnet.fsu.edu/education /tutorials/too
ls/ionization_maldi.html
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MALDI Overview

• Advantages
• Used for Disease Diagnosis
• Able to Ionize Large molecules
• Accurate / Rapid Analysis
• Fast Technique

• Disadvantages
• Lack of Reproducibility
• Sample Hot Spots
• Lack of proper Matrix Molecules
• Poor Fundamental Understanding of the Mechanism
• Lack of Rational Design

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Proposed Mechanisms

• Cluster Ionization
• Ionization occurs after desorption from the
  matrix
• Proton transfer occurs in the gas-phase or in
  small matrix clusters

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Proposed Mechanisms

• Photoionzation
• Multiple matrix molecule photon absorption
• Energy transferred to the analyte in the
  solid-phase or the gas-phase

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Methods

• Run a MD canonical simulation (CHARMM) to
  determine the general structure of the matrix
  protein interactions
• Optimize the structures of potentially relevant
  matrix/analyte conformations using electronic
  structure theory
• Study the energetics of the proton transfer
  reactions using intrinsic-reaction-coordinate
  electronic structure studies for a test set of
  amino acid/benzoic acid derivatives

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Methods
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Future Challenges

• Move beyond pure molecular mechanics
• Investigate other possibilities for matrix
  molecules
• Move beyond the gas phase for the MD simulations
• Testing new matrix molecules for predictive
  recommendations to experimentalists

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Special Thanks