Fragmentation of diketopiperazines from Aspergillus fumigatus by electrospray ionization tandem mass spectrometry (ESI‐MS/MS)

Abstract

Diketopiperazines (DKPs) corresponding to cyclic dipeptides have been reported to exhibit antimicrobial, antitumor, antimutagenic and antiviral properties. These compounds are commonly isolated from microorganisms and sponges and from a variety of tissues and body fluids. In this work, we used electrospray ionization tandem mass spectrometry (ESI-MS/MS) to investigate the fragmentation of a series of DKPs previously isolated from Aspergillus fumigatus, which exhibit the same structural core. Loss of CO directly from the protonated molecule was found to be a fragmentation process common to all the compounds analyzed. However, our results revealed a series of ions that are diagnostic for the substituents at C(4) and C(9). In order to rationalize the differences in the fragmentation pathways of substituted and nonsubstituted DKPs, the relative Gibbs energies (DeltaG) of the product ions and intermediate ions were estimated using the B3LYP/6-31 + + G(d,p) model. The data reported here can be used for the structural elucidation of DKPs from low sample amounts, as an alternative to NMR.

Aplicação da química quântica computacional no estudo de processos químicos envolvidos em espectrometria de massas

“…33 Uma análise dos artigos publicados revela que a maioria dos picos base se refere a íons em cuja estrutura a carga está deslocalizada, como por exemplo íons alílicos ou tropílicos, ou estabilizada pela interação de um orbital não-ligante de um heteroátomo, geralmente N ou O, com o orbital vazio do carbono adjacente, como íons acílios, oxônios e imônios, conforme ilustrado nas Figuras 1 e 2.…”

“…33 Através da análise das funções de Fukui, da topologia dos orbitais HOMO e da energia de Gibbs das moléculas protonadas pode-se concluir que o sítio mais suscetível à protonação é o átomo de nitrogênio sp 3 mais substituído (Figura 9), em concordância com os trabalhos sobre a basicidade de aminas 36 e de nicotinóides 124,125 em fase gasosa. A identificação do sítio de protonação foi uma etapa determinante para se estabelecer o efeito da ativação colisional sobre a migração do próton em experimentos de ESI-CID-EM/EM, possibilitando assim a identificação da estrutura do íon precursor a partir do qual foram formados os íons fragmentos observados no espectro de massas.…”

Electrospray ionization-ion trap mass spectrometry study of PQAAPro and PQProAA mimetic derivatives of the antimalarial primaquine

“…Overall, this work embodies an original and valuable contribution towards a deeper insight into the molecular properties of novel antimalarials, which can be viewed as representative of both the O ver the past decade, electrospray ionization mass spectrometry (ESI-MS) has been used for the most diverse analytical purposes. This technique has provided deeper insight into the structural properties and stability of numerous compounds, from natural products [1][2][3] to synthetic drugs [4][5][6][7][8], peptides [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23], and heterocycles [24][25][26][27][28], among many others. Notwithstanding, little has been done on the application of this technique to the study of relevant antimalarials such as primaquine (PQ, 1) or related structures.…”

Electrospray Ionization Tandem Mass Spectrometry as a Tool for the Structural Elucidation and Dereplication of Natural Products: An Overview

“…UV-DAD has been more and more often applied as a first detection method in dereplication studies using LC because it is rapid and inexpensive, as compared to the other techniques . Liquid chromatography mass spectrometry (LC-MS) is a highly sensitive and selective method for identification of NPs in complex mixtures (Fredenhagen et al, 2005;Furtado et al, 2007). Compounds are separated in the column of the LC system and directed to the mass spectrometer by a flow separator, where they are ionized and further separated in the mass analyzer according to their mass-to-charge (m/z) ratio (Niessen, 2006).…”