Switching from ultrafast electron transfer to proton transfer in excited drug–protein complexes upon biotransformation

Abstract

Photosensitization by drugs is directly related with the excited species and the photoinduced processes arising from interaction with UVA light. In this context, the ability of gefitinib (GFT), a tyrosine...

Modulation of the photobehavior of gefitinib and its phenolic metabolites by human transport proteins

“…This result is supported by means of ultrafast spectroscopy and by molecular docking simulations. The photosensitizing damage from both GFT and GFT-M1 in the biological media is consistent with the involvement of a type I mechanism ( Tamarit et al, 2021 ; Tamarit et al, 2022 ; El Ouardi et al, 2023 ).…”

“…Noteworthy, the fluorescence profile of GFT@HSA is very similar to that observed in non-polar solvents such as cyclohexane, where formation of LE states has been demonstrated by means of ultrafast transient absorption spectroscopy. Concerning GFT-M1, although its fluorescence properties in organic solvents are comparable with those of GFT, remarkable differences are noticed after binding with HSA; here, excited state proton transfer (ESPT) to form phenolate-like species, which emit at longer wavelengths (λ max ∼ 430 nm) and higher τ F values (∼2.5 ns) than LE sates, is the predominant process ( Tamarit et al, 2022 ). This result is supported by means of ultrafast spectroscopy and by molecular docking simulations.…”

“…Lapatinib (LAP), which is other TKI currently used for the treatment of lung and breast cancers ( Lin et al, 2008 ; Medina and Goodin, 2008 ; Lin et al, 2009 ), is also a relevant example. In both cases, both the parent drug and their photoactive metabolites can induce damage in cellular milieu ( García-Laínez et al, 2021 ; Tamarit et al, 2021 ; El Ouardi et al, 2023 ); the associated mechanism is related with the excited species that are formed upon irradiation of the supramolecular drug or metabolite@protein complexes with UVA light ( Andreu et al, 2020 ; Vayá et al, 2020 ; Tamarit et al, 2021 ; Tamarit et al, 2022 ).…”

“…Recent publications about the photobehavior of GFT and GFT-M1 within HSA correlate their photophysical properties with their photosensitizing potential ( Tamarit et al, 2021 ; Tamarit et al, 2022 ). In this regard, selective excitation of the protein-bound drug results in emission from locally excited (LE) singlet states; their main features are to display maximum fluorescence at wavelengths ca.…”

Topological effects in ultrafast photoinduced processes between flurbiprofen and tryptophan in linked dyads and within human serum albumin

“…An alternative technique that can in principle be used to investigate the behavior of drugs in solution and in biological media is femtosecond transient absorption spectroscopy. [23][24][25][26][27][28][29][30][31] This technique has proven to be a very sensitive, selective and precise tool that allows investigating processes occurring at the very early stages after excitation, including ultrafast energy and electron transfer or charge separation. 32,33 In this context, it has recently been observed an ultrafast energy transfer from HSA to bound lapatinib (LAP), 25 a drug currently used to treat breast and lung cancer.…”