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

Abstract

Nimesulide, a non-steroidal anti-inflammatory drug, forms semi-oxidized species (λmax = 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 ABTS2-, 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 λmax = 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.