Singlet molecular oxygen generation and quenching by the antiglaucoma ophthalmic drugs, Timolol and Pindolol

Abstract

The dye sensitized photooxidation in water (pH 6), of the pharmaceutical topical antiglaucoma drugs, Timolol and Pindolol, which act as β-adrenergic receptor antagonists, were studied by means of static and time-resolved spectroscopic methods and polarographic determinations. O₂(¹Δ_g)-mediated photooxidation of Timolol and Pindolol takes place with quantum efficiencies of 0.035 and 0.16, respectively, which raises concern about the possible day-light-mediated photodamaging of the drugs, in the presence of sensitizing agents. Pindolol behaves kinetically as a typical indole derivative, for which the intermediacy of a polar complex is proposed. Solvent effects on the kinetics of photooxidation suggests that the same mechanism could operate for the case of Timolol. Upon direct ultraviolet-light irradiation Timolol and Pindolol generate O₂(¹Δ_g), with quantum yields of 0.027 and 0.11 respectively. The former comprises three desirable properties for an external-use ocular drug: a reduced efficiency of O₂(¹Δ_g) photooxidation, a relatively high power as O₂(¹Δ_g) physical deactivator and a relatively low propensity to O₂(¹Δ_g) generation upon direct light irradiation.