<br/>It has been reported that Itraconazole (ITR) would undergo a primary dehalogenation process under the irradiation of UV laser to form a biologically reactive aryl radical, which may induce phototoxicity or photoallergy. The photoinduced dehalogenation of antifungal drug ITR in acetonitrile and acetonitrile/water mixture has been directly investigated using femtosecond and nanosecond transient absorption spectroscopies (TA) and nanosecond time-resolved resonance Raman spectroscopy (ns-TR<sup>3</sup>). The excited resonance energy transfer takes place from 4-phenyl-4,5-dihydro-3H-1,2,4-triazol-3-one terminal to 1,3-dichlorobenzene terminal when ITR is excited by UV light, followed by the primary carbon-halogen bond homogeneous cleavage that leads to the generation of the radical intermediates, which are responsible for the photoallergic reactions of ITR. Density functional theory calculations were also involved. Our results suggested that the photochemistry characters of ITR in the mixed solvent of ACN and water are very different with that in pure aprotic solvent ACN. The concentration of hydrogen ions also has effect on its photoreaction behaviors, it may undergo intramolecular hydrogen transfer. According to the TR3 spectra, we caught the reactive intermediates directly. In addition, the ns-TA and ns-TR3 results provide the direct evidence that a radical intermediate is generated through the homogenous carbon-halogen bond cleavage via singlet excited state pathway in acetonitrile as well as via triplet state pathway in the aqueous solution.

Singlet/Triplet excited state mediated dehalogenation reactions of itraconazole in acetonitrile and aqueous solutions studied by time-resolved spectroscopy

253rd National Meeting (2017)

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