Conformation Changes, Complexation, and Phase Transition in Matrix-Assisted Laser Desorption

Abstract

Using molecular dynamics simulations we have demonstrated that the guest species in matrix-assisted laser desorption exhibits significantly different conformations in the gas phase, on the crystal surface, and embedded into the matrix. Our model fully accounted for the internal structure of matrix and guest molecules; thus, we were able to follow the details of conformational changes in the guest molecule within the crystal and throughout the desorption. During the embedding process, simulated by sinapinic acid crystal growth around the substance P guest species, changes in the guest species conformation were investigated. While the guest species placed on the surface of the host crystal exhibited two hydrogen bonds on the backbone and one turn, the conformation of the embedded species contained three hydrogen bonds and two turns. Independent of the burial depth, the conformation of the guest species within the crystal remained the same. After laser heating and during the desorption process, no preferred gas-phase conformation was observed. Investigation of the radius-of-gyration of the guest species originating from different layers of the crystal revealed that, upon desorption, the guest species did not sustain a stable conformation in the gas phase. Liftoff velocities of the guest species embedded in various layers of the host crystal and on the surface were similar to the liftoff velocities of the matrix molecules around them. This is an indication of the entrainment of guest species by the matrix plume. Investigation of the energy histories of the matrix and guest species showed lower internal and kinetic temperatures for the latter, which could explain the absence of fragmentation in MALDI. Results also showed that maximum energy transfer occurred during the phase transition of the host crystal at which time the guest species were released from the crystal. Examining the noncovalent complex of the guest species and sinapinic acid anions showed that the complex remained intact throughout the desorption process. A similar phenomenon is often reflected in MALDI mass spectra, in the form of guest-matrix adduct peaks.

Special Feature: Tutorial

“…No analytes exist as free molecules, they are all embedded into clusters or droplets. The observation that analytes are always ejected parts of clusters of matrix molecules is consistent with other atomistic [42,43] and coarse-grained [9,14] simulations of matrix-assisted laser desorption. Analyte cannot evaporate from a cluster as the matrix molecules do because the net binding energy of a 10-mer is up to 10 times higher than that of a single matrix molecule.…”

“…[9,19 -22] Although more extensive simulations are needed to better understand the role of clusters in MALDI, the current results are quite consistent with analyte entrainment in large clusters early in the plume. [9,14,42,43] As Fig. 12 shows, both short and long laser pulses lead to clusters of matrix with analyte that have total masses of at least 1000 matrix molecules.…”

Fragmentation of leucine enkephalin as a function of laser fluence in a MALDI TOF-TOF

“…Internal energy coupled into the ions produced by these processes has been investigated by Zenobi and coworkers [29] and by Karas' group [25,30]. From a theoretical perspective, molecular dynamics simulations of these processes have been carried out by groups led by Vertes [31][32][33][34], Garrison [35][36][37][38], and Knochenmuss [39]. In addition, Knochenmuss [40] developed an overall quantitative model for ion formation.…”

Computational model for multiscale simulation of laser ablation

“…During the last several years extensive experimental [1][2][3][4][5][6], computational [7][8][9][10][11][12][13][14][15][16], and theoretical [2,17] efforts have resulted in considerable progress in understanding of many aspects of laser ablation of organic materials. In a big part this progress is due to the development of advanced computational methods and their application to various processes induced by pulsed laser irradiation.…”

“…In particular, a molecular-level breathing sphere model has yielded a wealth of information on the microscopic mechanisms of laser ablation [7,9,13], parameters of the ejected plume (velocity distributions of matrix and analyte molecules in MALDI [8,10], cluster ejection [11,12,13]) and their dependence on the irradiation conditions (laser fluence [7,9,11], pulse duration [13], initial temperature of the sample [12]). At smaller time-and length-scales, conventional atomic-level MD simulations have demonstrated the ability of this technique to provide detailed information on the dynamics of intermolecular redistribution of the deposited laser energy [14,16] and conformational changes in the molecules undergoing laser desorption [15]. Atomic-level MD simulation technique has been also applied to laser ablation of inorganic materials and first interesting results have been reported [18,19,20].…”