Time-resolved spectroscopic and computational study of the initial events in doxazosin photochemistry

Leo Mandić; Ivan Ljubić; Iva Džeba

doi:10.1016/j.saa.2023.123595

Time-resolved spectroscopic and computational study of the initial events in doxazosin photochemistry

Spectrochim Acta A Mol Biomol Spectrosc. 2024 Feb 5:306:123595. doi: 10.1016/j.saa.2023.123595. Epub 2023 Nov 3.

Authors

Leo Mandić¹, Ivan Ljubić², Iva Džeba³

Affiliations

¹ Radiation Chemistry and Dosimetry Laboratory, Division of Materials Chemistry, Ruđer Bošković Institute, Bijenička Cesta 54, 10000 Zagreb, Croatia.
² Theoretical Chemistry Group, Division of Physical Chemistry, Ruđer Bošković Institute, Bijenička Cesta 54, 10000 Zagreb, Croatia. Electronic address: Ivan.Ljubic@irb.hr.
³ Radiation Chemistry and Dosimetry Laboratory, Division of Materials Chemistry, Ruđer Bošković Institute, Bijenička Cesta 54, 10000 Zagreb, Croatia. Electronic address: Iva.Dzeba@irb.hr.

PMID: 37948930
DOI: 10.1016/j.saa.2023.123595

Abstract

Doxazosin is a quinazoline derivative widely used in medicine as a drug. In this study, a combined experimental and computational approach based on the time-dependent density functional theory was used to elucidate the primary events following the photoexcitation of DOX upon interaction with light. The photophysical properties and photochemical reactivity of DOX were investigated by steady-state and time-resolved absorption and fluorescence spectroscopy. DOX in H₂O in S₀ is present in two prototropic forms, with the protonated form dominating (∼91 %, pK_a = 6.75). The computations indicated that the most basic quinazoline nitrogen is at the position 1. Upon excitation, DOX deprotonates in the singlet excited state (pK_a* = 1.31), and the decay times from the singlet excited state of 5 ns and 13 ns are attributed to the non-protonated and protonated forms of DOX, respectively. The quantum yield of fluorescence in H₂O is 0.51 and 0.64 in basic media. The quantum yield of intersystem crossing along with triplet-triplet molar absorption coefficient at 520 nm and the lifetime of the triplet excited state were obtained by LFP, Φ_ISC = 0.17, ε₅₂₀ = 11600 ± 100 M^-1 cm^-1 and τ = 11 μs, respectively. Furthermore, LFP enabled detection of DOX radical formed by the photoinduced intramolecular electron transfer from the benzodioxane-carbamoyl to the protonated aminoquinazoline. Computations were used to back up the assignments of the detected transients and to construct an energy diagram with all plausible photophysical and photochemical pathways. These results elucidated the mechanisms of DOX photochemistry leading to DOX photodegradation which is relevant to environmental studies. They also provided insights into the potential use of such a quinazoline derivative in other applications such as push-pull chromophores or fluorescent probes.

Keywords: Doxazosin (DOX); Laser flash photolysis (LFP); Photoinduced electron transfer (PET); Time-corelated single photon counting (TC-SPC); Time-dependent density functional theory (TD-DFT).