Neighboring Effect in Fragmentation Pathways of Cage Guanylhydrazones in the Gas Phase

Abstract

ESI-MS/MS investigation of the mono- and bis(guanylhydrazone) derivatives 1-5 based on adamantane and pentacycloundecane (PCU) skeleton was described. Elimination of neutral guanidine is the most abundant reaction channel in the case of 2,4-adamantyl and PCU derivatives 4 and 5, while the elimination of CH2N2 fragment is preferred for other compounds. This was attributed to the cage opening of adamantane or PCU skeletons in the former case leading to the formation of the cyclohexyl- or cyclopropylcarbinyl carbocation stabilized by the conjugation with the guanylhydrazone subunit. The main fragmentation pathways observed experimentally were analyzed by using DFT calculations. All investigated bis(guanylhydrazone)s formed dications and their abundances were found to be proportional to the interguanidine distance in the considered ions. Calculation of the first and the second proton affinities supported qualitative interpretation of the dication abundance. Close contact of two guanidine subunits is thus confirmed to be crucial in determining preferential fragmentation pathway and to suppress formation of the dication.

Mechanistic investigation of charge‐remote and charge‐driven fragmentation processes in 2,5‐diphenyl‐3,4‐ethylenedioxythiophene diamidines

“…Tautomerism of the molecular ion [A1] 2+ → [A2] 2+ ( m / z 190) appears to be a prerequisite for ammonia loss and formation of the fragment ion [A3] 2+ ( m / z 181). A similar tautomerism is reported by Šekutor et al ., where the authors showed that one of the three fragmentation pathways of adamantyl guanylhydrazones includes the tautomeric shift of a proton from one of the nitrogen atoms to another in a singly protonated molecule of guanylhidrazone. DFT calculations showed that the activation energy for this process is 47.8 kcal mol −1 , whereas the energy difference between the two tautomers was 33.8 kcal mol −1 .…”

A Multidisciplinary Approach to the Study of Adamantyl Aminoguanidines – A New Class of Potentially Bioactive Compounds

“…3 This further encouraged us to undertake a systematic study of this type of compounds, covering various aspects of their nature and properties. [4][5][6][7][8] The most facile way to synthesize adamantyl guanylhydrazones was to use the corresponding adamantyl ketones as a key starting material. On the other hand, in order to prepare adamantyl aminoguanidines we used the corresponding adamantyl amines (Scheme 1).…”

“…The studies we conducted included a structural characterization of all the possible compound geometries using a computational approach, [4][5][6] fragmentation studies in the gas phase, 4 oxo-anion binding studies, 7 enzyme-inhibition testing, 8 and their incorporation into the liposomes. 5 We calculated the enthalpies for compounds 1-12 and for all of their isomers using B3LYP/6-311+G (d,p) level of theory.…”

“…5 We calculated the enthalpies for compounds 1-12 and for all of their isomers using B3LYP/6-311+G (d,p) level of theory. [4][5][6] From the guanylhydrazone series, only compounds 2, 4, and 6 possess diastereoisomers and when comparing them we found that the most stable structures were the ones where the functional groups were the fur-…”

“…thest apart from each other (Figure 2). 4 That could be explained by the diminution of the repulsions, resulting in less system destabilization. In the adamantyl aminoguanidine series no diastereoisomers are possible due to the symmetry of the prepared molecules, although the corresponding compound pairs can be regarded as constitutional isomers (7 and 8, 9 and 10, 11 and 12, respectively).…”