Metal ion attachment to the matrix meso‐tetrakis(pentafluorophenyl)porphyrin, related matrices and analytes: an experimental and theoretical study

Abstract

In a previous study [van Kampen et al. Analytical Chemistry 2006; 78: 5403], we found that meso-tetrakis (pentafluorophenyl)porphyrin (F20TPP), in combination with lithium salts, provides an efficient matrix to cationize small molecules by Li+ attachment and that this combination can be successfully applied to the quantitative analysis of drugs, such as antiretroviral compounds using matrix-assisted laser desorption ionization in conjunction with a time-of-flight analyzer (MALDI-TOF). In the present study, we further explore the mechanism of metal ion attachment to F20TPP and analytes by MALDI-FTMS(/MS). To this end, we have studied the interaction of F20TPP and analytes with various mono-, di- and trivalent metal ions (Li+, Na+, K+, Rb+, Cs+, Co2+, Cu2+, Zn2+, Fe2+, Fe3+ and Ga3+). For the alkali cations, we find that F20TPP forms complexes only with Li+ and Na+; in addition, model analyte molecules such as poly(ethyleneglycol)s, mixed with F20TPP and the alkali cations, also only form Li+ and Na+ adducts. This contrasts sharply with the commonly used matrix 2,5-dihydroxybenzoic acid, where analytes are most efficiently cationized by Na+ or K+. Reasons for this difference are delineated. Ab initio calculations on porphyrin itself reveal that even the smallest alkali cation, Li+, does not fit in the porphyrin cavity, but lies on top of it, pushing the 21H and 23 H hydrogen atoms out of and below the plane with concomitant bending of the porphyrin skeleton in the opposite direction, i.e. toward the cation. Thus, the Li+ ion is not effectively sequestered and is in fact exposed and thus accessible for donation to analyte molecules. Interaction of F20TPP with di- and trivalent metal ions leads to protoporphyrin-metal ions, where the metal ion is captured within the protoporphyrin dianion cavity. The most intense signal is obtained when F20TPP is reacted with CuCl2 and then subjected to laser ablation. This method presents an easy general route to study the metal containing protoporphyrin molecules, which could all act as potential MALDI matrices.

Biomedical application of MALDI mass spectrometry for small‐molecule analysis

“…leads to an observed optimum affinity for K þ (van Kampen et al, 2008aKampen et al, , 2009a. The optimum affinity for K þ is indeed the case when 2,5-DHB is used as the matrix.…”

“…5). Furthermore, the binding efficiencies of Li þ towards LMW PEGs strongly depend on the number of sites where the Li þ ion can interact (Bogan & Agnes, 2002;van Kampen et al, 2009a). The intensity order of F20TPP itself cationized by various alkali metals is very similar to that of the LMW PEGs; that is, Li…”

“…Sometimes, we test for matrix properties of molecules when they have favorable UVlight absorption profiles; that process led to the discovery of the novel matrix HFMC (van Kampen et al, 2008b). Ab initio calculations were used to create new hypotheses of how matrices act in MALDI such as in the case of porphyrin matrices (van Kampen et al, 2009a). A breakthrough in finding matrices for MALDI was the rational design of the new matrix 4-chloro-acyanocinnamic acid (Jaskolla, Lehmann, & Karas, 2008).…”

Making the invisible visible: improved electrospray ion formation of metalloporphyrins/-phthalocyanines by attachment of the formate anion (HCOO−)

“…In fact, Pors have been successfully used as matrix materials themselves for the MALDI analysis of other materials. [25][26][27][28][29] For MALDI, solubility is not a prerequisite, 30,31 which accommodates the often only poorly soluble Pors. ESI, on the other hand, is a softer approach, which is advantageous for the analysis of Pors bearing more fragile substituents, but it requires solubility.…”

Screening Analysis of 10 Adrenal Steroids by Matrix-Assisted Laser Desorption Ionization-Tandem Mass Spectrometry

“…2) Alkali metal ions are preferred in MALDI analysis of molecules lacking basic sites. 9 3) A binary matrix mixture with different proton affinity has been used to reduce background noise and in consequence improve detection sensitivity. In this manner, the conventional matrix such as CHCA (α-cyano-4-hydroxycinnamic acid) owns an acidic group site which makes it ideal for analyte protonation, whereas the amine group of 9-AA (9-aminoacridine) is easily protonated and helps to produce negatively charged species.…”