Vitamin B₂-sensitised photooxidation of the ophthalmic drugs Timolol and Pindolol: kinetics and mechanism

Abstract

The kinetics and mechanistic aspects of the riboflavin-photosensitised oxidation of the topically administrable ophthalmic drugs Timolol (Tim) and Pindolol (Pin) were investigated in water-MeOH (9:1, v/v) solution employing light of wavelength > 400 nm. riboflavin, belonging to the vitamin B(2) complex, is a known human endogenous photosensitiser. The irradiation of riboflavin in the presence of ophthalmic drugs triggers a complex picture of competitive reactions which produces the photodegradation of both the drugs and the pigment itself. The mechanism was elucidated employing stationary photolysis, polarographic detection of dissolved oxygen, stationary and time-resolved fluorescence spectroscopy, and laser flash photolysis. Ophthalmic drugs quench riboflavin-excited singlet and triplet states. From the quenching of excited triplet riboflavin, the semireduced form of the pigment is generated, through an electron transfer process from the drug, with the subsequent production of superoxide anion radical (O(2)(*-)) by reaction with dissolved molecular oxygen. Through the interaction of dissolved oxygen with excited triplet riboflavin, the species singlet oxygen (O(2)((1)Delta(g))) is also generated to a lesser extent. Both O(2)(*-) and O(2)((1)Delta(g)) induce photodegradation of ophthalmic drugs, Tim being approximately 3-fold more easily photooxidisable than Pin, as estimated by oxygen consumption experiments.

A Comparative Kinetic and Mechanistic Study Between Tetrahydrozoline and Naphazoline Toward Photogenerated Reactive Oxygen Species

“…3 and Table 1). The fluorescence decay of Rf in MeOH was monoexponencial with a value 1 τ o of 5.4 ns, in excellent agreement with previous published data (33,34). The quenching of 1 Rf* by IDs was only observed at relatively high IDs concentrations.…”

“…Under identical conditions but in the presence of 5.0 m m NPZ ( ca. 95% 3 Rf* quenched by NPZ), the shape of the long‐lived absorption spectrum is in good agreement with that reported for the RfH • , a pH 5.1 (26,30,34,35). Besides, the spectrum showed three new peaks centered at 345, 370 and 385 nm, in MeOH.…”

“…Transient absorption spectrum of Rf, obtained in MeOH 10 μs after the laser pulse (Fig. 4), is similar to the reported one for 3 Rf* in MeOH (34). Under identical conditions but in the presence of 5.0 m m NPZ ( ca.…”

“…†Value taken from Sortino and Scaiano (21). (26,30,34,35). Besides, the spectrum showed three new peaks centered at 345, 370 and 385 nm, in MeOH.…”

Antioxidant capacity of (+)-catechin visible-light photoirradiated in the presence of vitamin B2

“…5 ns). 38,39 Therefore these species cannot be intercepted by dCTQ at concentration range employed in our experiments (ca. 0.4 mM).…”