The chemical properties accounting for the operation of a valuable matrix used in matrix-assisted laser desorption ionization (MALDI) to perform mass spectrometry imaging (MSI), namely 3-(4,5-bis(dimethylamino)napthalen-1-yl)furan-2,5-dione (4-maleicanhydridoproton sponge, MAPS), have been elucidated also by comparison with the parent molecule 1,8-bis(dimethylamino) naphthalene (so-called proton sponge, PS). Both compounds present the bis(dimethylamino) groups, apt to efficiently trap a proton imparting positive charge. Only MAPS, though, owns the maleicanhydrido function acting as electrophile and yielding covalently bound adducts with a variety of analytes. In this way, MAPS performs as "carrier" for the analyte (A) of interest, at the same time minimizing the presence of useless, background ions. The covalent character of the adducts, [MAPS+H + A]+, is testified by their collision-induced dissociation pattern, quite distinct from the one displayed by [PS + H]+, while PS does not form any [PS + H + A]+, thus confirming the key role of the maleicanhydrido functionality of MAPS. Vibrational spectroscopy of [MAPS+H + A]+ adducts (A = H2O, NH3) provided further structural evidence. The presence of a mobile proton on A was found to be a requisite for adduct formation by electrospray ionization of acetonitrile solutions, pointing to a possible role of MAPS in discriminating competing analytes based on molecular features. The performance of MAPS has been verified in MALDI-MSI of Atropa belladonna berries, exploiting MAPS binding to atropine. Graphical abstract ᅟ.