Transcript Document

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
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/tools/ionization_maldi.html
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

Proposed Mechanisms

Cluster Ionization
– Ionization occurs after desorption from the
matrix
– Proton transfer occurs in the gas-phase or
in small matrix clusters
Proposed Mechanisms

Photoionzation
– Multiple matrix molecule photon absorption
– Energy transferred to the analyte in the
solid-phase or the gas-phase
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-reactioncoordinate electronic
structure studies for a test
set of amino acid/benzoic
acid derivatives
Methods
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

Special Thanks…