Pulse-radiolysis studies of nimesulide in aqueous solution: effect of microheterogeneous media

Nimesulide, a non-steroidal anti-inflammatory drug, forms semi-oxidized species (_max = 350 nm) on reaction with N·₃ and CCl₃OO· in aqueous solution. Their oxidizing nature is confirmed by their ability to undergo an electron-transfer reaction with ABTS^2-, the rate constant for the reaction k = 4.7 × 10⁹ dm³ mol^-1 s^-1. ·OH-adduct constitutes about 94% of the species formed on reaction with ·OH radicals, the remaining 5-6% species are oxidizing in nature. The rate constant for the formation of ·OH-adduct, i.e. k(·OH + Nim-NO₂) = 2.8 × 10¹⁰ dm³ mol^-1 s^-1. Oxygen adds to both e^- _aq and ·OH-adducts of nimesulide with rate constants of 9.5 × 10⁶ dm³ mol^-1 s^-1 and 1.4 × 10⁷ dm³ mol^-1 s^-1, respectively. In the presence of cyclodextrins the nature of the transient species formed is much the same. Binding constants of the drug with CDs are generally quite low in comparison to BSA and range between 37 and 390 dm³ mol^-1. Hydrated electrons add on to nimesulide at the nitro group forming a semi-reduced species with _max = 320 and 500 nm. The rate constant k for this reaction is 1.4 × 10¹⁰ dm³ mol^-1 s^-1. The transient species formed on reaction of e^- _aq or (CH₃)·₂COH radicals with nimesulide seem to be identical, as is seen from their decay rates. The reduction potential of nimesulide for the couple (Nim-NO₂/Nim-NO·₂ ^-) is found to be -0.52 V vs. NHE at pH 7, by cyclic voltammetric and pulse radiolysis techniques.