Can density functional theory (DFT) be used as an aid to a deeper understanding of tandem mass spectrometric fragmentation pathways?
Prediction of tandem mass spectrometric (MS/MS) fragmentation for non-peptidic molecules based on structure is of immense interest to the mass spectrometrist. If a reliable approach to MS/MS prediction could be achieved its impact within the pharmaceutical industry could be immense. Many publications have stressed that the fragmentation of a molecular ion or protonated molecule is a complex process that depends on many parameters, making prediction difficult. Commercial prediction software relies on a collection of general heuristic rules of fragmentation, which involve cleaving every bond in the structure to produce a list of 'expected' masses which can be compared with the experimental data. These approaches do not take into account the thermodynamic or molecular orbital effects that impact on the molecule at the point of protonation which could influence the potential sites of bond cleavage based on the structural motif. A series of compounds have been studied by examining the experimentally derived high-resolution MS/MS data and comparing it with the in silico modelling of the neutral and protonated structures. The effect that protonation at specific sites can have on the bond lengths has also been determined. We have calculated the thermodynamically most stable protonated species and have observed how that information can help predict the cleavage site for that ion. The data have shown that this use of in silico techniques could be a possible way to predict MS/MS spectra.
Alex
Alexander
A
Pfizer Global Research and Development, Ramsgate Road, Sandwich CT13 9NJ, UK.
Harvey
Sophie
S
Parsons
Teresa
T
Pullen
Frank S
FS
Wright
Patricia
P
Riley
Jo-Anne
JA
D000935:Antifungal Agents / Q000737:chemistry; D015725:Fluconazole / Q000737:chemistry; D015394:Molecular Structure; D011743:Pyrimidines / Q000737:chemistry; D053719:Tandem Mass Spectrometry; D014230:Triazoles / Q000737:chemistry; D065819:Voriconazole
D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; D015725:Fluconazole; D065819:Voriconazole