High‐resolution mass spectrometry and hydrogen/deuterium exchange study of mitorubrin azaphilones and nitrogenized analogues

Abstract

Azaphilones represent numerous groups of wild fungal secondary metabolites that exhibit exceptional tendency to bind to nitrogen atoms in various molecules, especially those containing the amine group. Nitrogenized analogues of mitorubrin azaphilones, natural secondary metabolites of Hypoxylon fragiforme fungus, have been detected in the fungal methanol extract in very low concentrations. Positive electrospray ionization interfaced with high-resolution mass spectrometry was applied for confirmation of the elemental composition of protonated species. Collision-induced dissociation (CID) experiments have been performed, and fragmentation mechanisms have been proposed. Additional information regarding both secondary metabolite analogue families has been reached by application of gas-phase proton/deuterium (H/D) exchanges performed in the collision cell of a triple quadrupole mass spectrometer. An incomplete H/D exchange with one proton less than expected was observed for both protonated mitorubrin azaphilones and their nitrogenized analogues. By means of the density functional theory, an appropriate explanation of this behavior was provided, and it revealed some information concerning gas-phase H/D exchange mechanism and protonation sites.

Dereplication, Annotation, and Characterization of 74 Potential Antimicrobial Metabolites from Penicillium Sclerotiorum Using t-SNE Molecular Networks

“…Similarly, propionated compounds 22 and 25 led to losses of 56.0262, 74.0368 and 102.0317 Da, corresponding to the neutral losses of C 3 H 4 O, C 3 H 6 O 2 and C 4 H 6 O 3 , respectively. This observation, supported by the literature evidence for the fragmentation of protonated esters [ 33 , 34 , 35 , 36 ], suggests that the nature of the acyl group can be identified from this typical fragmentation pattern, as described in Figure 4 .…”

“…In contrast, for azaphilone with linear acylation, the acyl moiety is the main neutral loss, and azaphilone is the main ion fragment. This particular fragmentation pathway due to the presence or absence of a labile proton at position α of the carbonyl was previously described for mitorubrin azaphilone [ 35 ].…”

Hydrogen/deuterium exchange mass spectrometry in the world of small molecules

“…However, the negative effect of substituent size observed for mono‐alkyl benzene remains unclear. More recently, the known oxygenized derivatives of mitorubrin azaphilone metabolites and their nitrogenized analogues were distinguished by using ND3 as reagent for HDX processes in the RF‐only collision cell of a TQ instrument (Svilar et al, 2012).…”