Photochemical Electron Transfer Reactions of Tirapazamine¶

Abstract

The absorption and fluorescence spectra of 3‐aminobenzo‐1,2,4‐triazine di‐N‐oxide (tirapazamine) have been recorded and exhibit a dependence on solvent that correlates with the Dimroth ET30 parameter. Time‐dependent density functional theory calculations reveal that the transition of tirapazamine in the visible region is π→π* in nature. The fluorescence lifetime is 98 ± 2 ps in water. The fluorescence quantum yield is ∼0.002 in water. The fluorescence of tirapazamine is efficiently quenched by electron donors via an electron‐transfer process. Linear Stern–Volmer fluorescence quenching plots are observed with sodium azide, potassium thiocyanate, guanosine monophosphate and tryptophan (Trp) methyl ester hydrochloride. Guanosine monophosphate, tyrosine (Tyr) methyl ester hydrochloride and Trp methyl ester hydrochloride appear to quench the fluorescence at a rate greater than diffusion control implying that these substrates complex with tirapazamine in its ground state. This complexation was detected by absorption spectroscopy.

Photodegradation of the Benzotriazine 1,4-Di-N-Oxide Hypoxia-Activated Prodrug SN30000 in Aqueous Solution

“…Both 3‐alkyl‐substituted di‐oxides are clearly much more photosensitive than TPZ ( 1 ), which may reflect the influence of the more strongly electron‐donating 3‐amino group disfavouring formation of an oxaziridine intermediate. We note, however, that photolysis of TPZ in the presence of an electron donor (not provided in the present study) does have the potential to generate the corresponding 1‐oxide via a free radical intermediate, and that there is at least a theoretical possibility of photo‐sensitisation by BTOs through a photolytically generated free radical.…”

Toxic metabolites, MAPK and Nrf2/Keap1 signaling pathways involved in oxidative toxicity in mice liver after chronic exposure to Mequindox

“…Apart from the deoxidation rate of QdNOs 6 , the appearance of ROS and unstable oxygen–sensitive radical intermediates during N → O reduction of QdNOs is considered to play a critical role in the DNA damage 1 18 63 64 . Previously, the production of oxygen–sensitive radical intermediates during QdNOs metabolism was thought to explain the mutagenicity 18 , antibacterial activity 1 and hypoxic cytotoxin induced by these compounds 63 65 .…”

Reactions of Excited States of Phenoxazin‐3‐one Dyes with Amino Acids¶

“…This points to a higher reactivity of the excited dye involving the N‐oxide moiety. Photo‐induced electron transfer also has been proposed for the singlet quenching of acridine by sulfur‐containing amino acids (19), and for the quenching of tirapazamine, an N‐oxide compound, by tryptophan and tyrosine (20).…”