"Position” does matter: The photofragmentation of the nitroimidazole isomers

Experimental and theoretical spectroscopic methods have been combined to disentangle the fundamental mechanism of VUV induced fragmentation of the three isomers of nitroimidazole. P. Bolognesi et al.  J. Chem. Phys., (2016)


Nitroimidazole compounds, i.e. derivatives of imidazole containing one nitro group, are used in radiotheraphy as ‘oxygen mimetic’ radiosensitisers.They increase the effectiveness of a given dose of radiation by reacting with radiation induced DNA radicals and reducing the DNA repairing capabilitiesin otherwise resistant hypoxic tumour cells. Among the different isomers, in clinical trials the 2-nitroimidazole drugs appeared to be more effective than the 5-nitroimidazole ones.
In order to understand the fundamental reasons that could possibly explain such different behavior, we present a joint experimental and theoretical study of the radiation induced fragmentation of 4-, 5- and 2-nitroimidazole isomers. The results suggest that particular neutral products of their decomposition might influence the effectiveness of the radiosensitising action of their derivatives.
The experiments are based on the photofragmentation of isolated 4(5)- and 2- nitroimidazole molecules, where electron-ion coincidence (PEPICO) experiments allow to selectively measure the fragmentation following ionization of individual molecular orbitals.
The non-coincident mass spectra of the isomers recorded at a photon energy of 60 eV shown in the figure are quite different. The most striking difference is in the intensity of the peak [M-NO]+ which is due to the loss of neutral nitric oxide, a very reactive radical. However - as DFT calculated potential energy profiles for 4-, 5- and 2-nitroimidazole show 

- all of the nitroimidazole isomers are likely to release nitric oxide with similar probabilities. Consequently further processes have to be explored to explain the difference. Our results indicate that in 4(5)NI the subsequent fragmentation of the [M-NO]+ intermediate destroys the imidazole ring releasing HCN and CO molecules, while in 2NI the higher stability of the ring leaves the intermediate intact.  The difference in the release of such toxic molecules might also need to be considered when assessing the impact of nitroimidazole isomers in biological media.

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          Communication: “Position” does matter: The photofragmentation of the nitroimidazole isomers
          P. Bolognesi, A. R. Casavola, A. Cartoni, R. Richter, P. Markus, S. Borocci, J. Chiarinelli, S. Tosic, H. Sa'adeh, M. Masic, B.P. Marinkovic, K.C. Prince, L. Avaldi
J. Chem. Phys., (2016) 145, 191102;DOI: http://dx.doi.org/10.1063/1.4967770
Last Updated on Friday, 03 February 2017 08:09