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

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. Copyright © 2009 John Wiley & Sons, Ltd.