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Mechanism of Ionization in Matrix-Mechanism of Ionization in Matrix-Assisted Laser Desorption Ionization Assisted Laser Desorption Ionization
(MALDI):(MALDI):
How does proton transfer occurHow does proton transfer occurAjax Group
http://pslc.ws/mactest/maldi.htm
Joshua P. Layfield Jordan C. Vincent
Desiree M. Bates Ashley K. Tucker
Sara E. Ray Ron C. Estler
MALDI OverviewMALDI 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/tools/ionization_maldi.html
AdvantagesAdvantages Used for Disease Used for Disease
DiagnosisDiagnosis Able to Ionize Large Able to Ionize Large
moleculesmolecules Accurate / Rapid Accurate / Rapid
AnalysisAnalysis Fast TechniqueFast Technique
MALDI OverviewMALDI Overview
DisadvantagesDisadvantages Lack of ReproducibilityLack of Reproducibility
– Sample Hot SpotsSample Hot Spots Lack of proper Matrix Lack of proper Matrix
MoleculesMolecules Poor Fundamental Poor Fundamental
Understanding of the Understanding of the MechanismMechanism
Lack of Rational Lack of Rational DesignDesign
Cluster IonizationCluster Ionization– Ionization occurs after desorption Ionization occurs after desorption
from the matrix from the matrix – Proton transfer occurs in the gas-Proton transfer occurs in the gas-
phase or in small matrix clustersphase or in small matrix clusters
Proposed MechanismsProposed Mechanisms
PhotoionzationPhotoionzation– Multiple matrix molecule photon Multiple matrix molecule photon
absorptionabsorption– Energy transferred to the analyte in Energy transferred to the analyte in
the solid-phase or the gas-phasethe solid-phase or the gas-phase
Proposed MechanismsProposed Mechanisms
MethodsMethods Run a MD canonical Run a MD canonical
simulation (CHARMM) to simulation (CHARMM) to determine the general determine the general structure of the matrix structure of the matrix protein interactionsprotein interactions
Optimize the structures of Optimize the structures of potentially relevant potentially relevant matrix/analyte matrix/analyte conformations using conformations using electronic structure theoryelectronic structure theory
Study the energetics of Study the energetics of the proton transfer the proton transfer reactions using intrinsic-reactions using intrinsic-reaction-coordinate reaction-coordinate electronic structure electronic structure studies for a test set of studies for a test set of amino acid/benzoic acid amino acid/benzoic acid derivativesderivatives
MethodsMethods
Future ChallengesFuture Challenges
Move beyond pure molecular Move beyond pure molecular mechanicsmechanics
Investigate other possibilities for Investigate other possibilities for matrix moleculesmatrix molecules
Move beyond the gas phase for the Move beyond the gas phase for the MD simulationsMD simulations
Testing new matrix molecules for Testing new matrix molecules for predictive recommendations to predictive recommendations to experimentalists experimentalists
Special Thanks…Special Thanks…