Structural variation facilitate alkylation: A conceptual DFT study

During alkylation of DNA electron density is shifted towards the drug intermediate (aziridinium ion) from guanine (in DNA), as a result, the tricyclic ring flips to a most stable configuration. [Display omitted] ► Variations of reactivity descriptors of aziridinium ions are studied. ► Ring flipping...

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Bibliographic Details
Published in:Computational and theoretical chemistry 2012-04, Vol.986, p.79-84
Main Authors: Neog, Babul, Sarmah, Nabajit, Kar, Rahul, Bhattacharyya, Pradip Kr
Format: Article
Language:English
Subjects:
Aziridinium ion
DNA alkylation
PCM
Reactivity descriptors
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Summary:During alkylation of DNA electron density is shifted towards the drug intermediate (aziridinium ion) from guanine (in DNA), as a result, the tricyclic ring flips to a most stable configuration. [Display omitted] ► Variations of reactivity descriptors of aziridinium ions are studied. ► Ring flipping is observed as electron density shifted. ► Interaction energy depends on global reactivity descriptor. In this paper, the variation of the DFT-based reactivity descriptors, such as chemical potential, chemical hardness, electrophilicity, Fukui function and local electrophilicity, for a family of anticancer drug intermediate have been analyzed. Based on our findings, we suggest that structural variation in the drug intermediate assist alkylation of DNA. In addition, the interaction energy of the prototype drug intermediates with the GC base pair in gas phase is found to be higher than that in aqueous phase. A linear dependence of interaction energy on the global parameter of the drug intermediate is also observed.
ISSN:2210-271X
DOI:10.1016/j.comptc.2012.02.015