Elucidation of the influence of tautomerization on the physicochemical stability of photoactive anticancer drug Vemurafenib in Solutions: Computational insights

Elucidating the physicochemical properties of pharmaceutical materials is crucial for targeted enhancement, including tautomerization and photoconversion reactions. Photostability and phototoxicity are major concerns for medications like Vemurafenib (VFB), a photosensitive anticancer drug approved for advanced melanoma treatment. Recent reports highlight VFB’s phototoxicity linked to its physicochemical properties. To explore VFB’s stability in aqueous solutions, we used computational methods, focusing on tautomeric transitions and intermolecular hydrogen bonding with DMF. Results show a preference for the keto-amine tautomer over the enol-imine counterpart in implicit aqueous conditions, with a tautomerization energy of 20.7 kcal/mol. Both tautomers can bind to DMF via hydrogen bonding, with bond lengths ranging from 1.5 to 1.9 Å. Intermolecular hydrogen bonding significantly influences VFB’s tautomeric forms within VFB:DMF complexes. This study elucidates the complex relationship between molecular configurations and hydrogen bonding in VFB’s simulated biological environment, providing insights into its interactions with peptide-like substances.

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Published in: Computational and Theoretical Chemistry
License: http://creativecommons.org/licenses/by/4.0/
See article on publisher's website: https://dx.doi.org/10.1016/j.comptc.2024.114754