Estimation of the proton affinity values of fifteen matrix-assisted laser desorption/ionization matrices under electrospray ionization conditions using the kinetic method

Abstract

The kinetic method, which is known to be simple, fast and precise, is used for the measurement of proton affinity values of fifteen selected matrix-assisted laser desorption/ionization matrices under electrospray ionization conditions. The stabilization of [ T he most exciting innovations in the last decade for the analysis of non-volatile, high molecular weight compounds is the development of new mass spectral techniques like matrix-assisted laser desorption/ionization (MALDI) [1][2][3] and electrospray ionization (ESI) [4]. MALDI has been successfully applied for the analysis of peptides and proteins [5][6][7][8][9][10][11], oligonucleotides and nucleic acids [12,13], carbohydrates [14 -16], and synthetic polymers [17][18][19][20][21]. Despite its wide range of applications and many fundamental studies [22][23][24][25][26][27][28][29][30], there is a need for better understanding of the MALDI process, to improve ion yields, to gain access to new classes of compounds, and to provide rational guidelines for matrix selection, which play crucial roles in sample analysis. In the discussions of the ionization mechanism, proton-transfer reactions have a very prominent role. The protonated analyte is presumably produced by gas-phase reactions between matrix ions and analyte molecules. Thermochemical data like gas phase basicities (GB) and proton affinities (PA) of the matrices may contribute to better understanding of the MALDI processes.To date, very few studies have been carried out for the measurement of GB and PA of MALDI matrices [31][32][33][34]. The PA values that have been reported for MALDI matrices are inconsistent with one another because of intrinsic errors in the different methods, due to sampling of ions of different internal energy, and because of the use of different ionization techniques in these studies. So far, ESI has not been used for the estimation of PA values of MALDI matrices. In the present study, we estimated PA values of fifteen MALDI matrices under electrospray ionization conditions, which is easier and more broadly applicable than fast atom bombardment or chemical ionization techniques, using the kinetic method [35,36].Estimation of PA values by the kinetic method involves measurement of peak height ratios of the protonated monomers of the compound with unknown PA and that of the reference base with known PA values, generated from the collision induced dissociation of the corresponding proton-bound heterodimers. According to the kinetic method, the ratio of rate constants (k A and k B ) for the competitive dissociation of a cluster ion comprised of the compound of interest and a reference compound, eq 1, can be expressed as eq 2 [37, 38].(1) Experimental MaterialsThe MALDI matrices, 4-hydroxy-␣-cyanocinnamic acid (4HCCA), 2,5-dihydroxy benzoic acid (gentisic acid, GA), 5-methoxysalicylic acid (MSA), trans-3, 5-dimethoxy-4-hydroxycinnamic acid (sinapinic acid, SA), 1,8,9-anthracenetriol (dithranol, DT), 2,4,6-trihydroxyacetophenone (THAP), trans-3-indoleacrylic acid (IAA), 3-hydroxypicoli...

4-Chloro-α-cyanocinnamic acid is an advanced, rationally designed MALDI matrix

“…Within this approach, it becomes possible to describe the analyte ion yield and phenomena such as matrix and analyte suppression, analyte concentration effects, and the formation of multiply charged analyte ions (2,(14)(15)(16). It is assumed that analyte neutrals are ionized by proton transfer from protonated matrix ions, and thus, the role of matrix proton affinity (PA) was investigated (17). PA values have been determined for all common matrices; indeed, all well working matrices exhibit relatively low PA values, with 841 kJ/mol for CHCA being the lowest.…”

“…PA values have been determined for all common matrices; indeed, all well working matrices exhibit relatively low PA values, with 841 kJ/mol for CHCA being the lowest. Using Cook's kinetic method (18,19), we determined a PA of 832 kJ/mol for Cl-CCA by investigating the fragmentation of the CHCA-H ϩ -Cl-CCA mixed dimer and applying the literature value for CHCA of 841 kJ/mol (17). The lower PA of Cl-CCA can be rationalized as follows: For both CHCA and Cl-CCA, the proton will be located either at the carboxylic or at To a first view, it may appear surprising that already a small reduction in the PA can account for the strong effects observed.…”

“…Determination of the PA value of Cl-CCA was carried out by postsource-decay fragmentation (24) of the proton-bound heterodimers (17,19,25) of CHCA and Cl-CCA by using different fluences, followed by a measurement of the peak area ratios of the resulting protonated matrix monomers (Fig. S8).…”

Sodium Cation Affinities of Commonly Used MALDI Matrices Determined by Guided Ion Beam Tandem Mass Spectrometry

“…Limited theoretical and experimental studies of the gas phase properties of MALDI matrices have been reported in the literature. These studies have focused on determining the gas phase proton affinities [43][44][45][46], basicities/acidities [47][48][49][50], and ionization energies of MALDI matrices [43]. Very few studies have reported cation affinities [51][52][53][54][55] of MALDI matrices.…”

A density functional theory (DFT) study on gas-phase proton transfer reactions of derivatized and underivatized peptide ions generated by matrix-assisted laser desorption ionization

“…Many analytes, especially peptides and proteins, are detected predominantly in protonated form. Reactions between peptides/proteins in the gas phase were reported to have proton affinities (PAs) greater than 215 kcal/mol [10], whereas PAs of the most common matrices are between 200 and 215 kcal/mol [11][12][13], making the proton transfer between protonated matrix and neutral analyte favorable. Strong evidence for proton transfer reactions between protonated matrix and analyte was recently reported using mixtures of conventional matrices and various amino acids varying in gas phase basicity [6].…”