jp058257c_si_001.pdf (791.1 kB)
Computational Study of Matrix−Peptide Interactions in MALDI Mass Spectrometry: Interactions of 2,5- and 3,5-Dihydroxybenzoic Acid with the Tripeptide Valine−Proline−Leucine
journal contribution
posted on 2006-03-16, 00:00 authored by Faten H. Yassin, Dennis S. MarynickThe mechanism of matrix-to-analyte proton transfer in matrix-assisted laser desorption and ionization mass
spectrometry (MALDI-MS) has been investigated computationally by modeling the matrix−analyte interaction
of potential MALDI matrixes such as 2,5-dihydroxybenzoic acid (2,5-DHB) and 3,5-DHB with the tripeptide
valine−proline−leucine (VPL). A combination of molecular dynamics/simulated annealing calculations
followed by density functional theory geometry optimization using a reasonably large basis set has been
done on a large number of clusters in an attempt to study the ionization energy of each matrix in the cluster
environment and the intracluster proton transfer from the matrix to the tripeptide. The calculations show a
substantial reduction in the IP for both matrixes in their cluster environments. In the 2,5-system, proton
transfer can sometimes occur in the neutral clusters (preformed ions), whereas proton transfer in the cationic
clusters, which is actually a double proton transfer, is spontaneous and exoergic. Even though it is more
acidic from a thermodynamic perspective, the radical cation of 3,5-DHB is a less efficient proton donor to
VPL. The thermodynamics of proton transfer in the cationic clusters is discussed in detail.