Stable selones in glutathione-peroxidase-like catalytic cycle of selenonicotinamide derivative

Abstract

Selenonicotinamide, 2,2'-diselenobis[3-amidopyridine] (NictSeSeNict) exhibits glutathione-peroxidase (GPx)-like activity, catalyzing the reduction of hydrogen peroxide (H2O2) by glutathione (GSH). Estimated reactivity parameters for the reaction of selenium species, according to the Dalziel kinetic model, towards GSH (ϕGSH) and H2O2 (ϕH2O2), indicated that the rate constant for the reaction of NictSeSeNict with GSH is higher as compared to that with H2O2, indicating that the activity is initiated by reduction. (77)Se NMR spectroscopy, HPLC analysis, mass spectrometry (MS) and absorption spectroscopy were employed to understand the nature of selenium intermediates responsible for the activity. The (77)Se NMR resonance at 525 ppm due to NictSeSeNict disappeared in the presence of GSH with the initial appearance of signals at δ 364 and 600 ppm, assigned to selone (NictC=Se) and selenenyl sulfide (NictSeSG), respectively. Reaction of H2O2 with NictSeSeNict produced a mixture of selenenic acid (NictSeOH) and seleninic acid (NictSeO2H) with (77)Se NMR resonances appearing at 1069 and 1165 ppm, respectively. Addition of three equivalents of GSH to this mixture produced a characteristic (77)Se NMR signal of NictSeSG. HPLC analysis of the product formed by the reaction of NictSeSeNict with GSH confirmed the formation of NictC=Se absorbing at 375 nm. Stopped-flow kinetic studies with global analysis revealed a bimolecular rate constant of 4.8 ± 0.5 × 10(3) M(-1) s(-1) and 1.7 ± 0.6 × 10(2) M(-1) s(-1) for the formation of NictC=Se produced in two consecutive reactions of NictSeSeNict and NictSeSG with GSH, respectively. Similarly the rate constant for the reaction of NictC=Se with H2O2 was estimated to be 18 ± 1.8 M(-1) s(-1). These studies clearly indicated that the GPx activity of NictSeSeNict is initiated by reduction to form NictSeSG and a stable selone, which is responsible for its efficient GPx activity.

Comparison of the redox chemistry of sulfur- and selenium-containing analogs of uracil

“…Our assignment of the oxidation states of se 2 c 5 Ura oxidized by H 2 O 2 agrees well with work done by Prabhu and coworkers who followed the oxidation of 2,2′-diselenobis(3-amidopyridine), a compound related to se 2 c 5 Ura as both contain a selenoamide [31]. …”

Effect of a Bromo Substituent on the Glutathione Peroxidase Activity of a Pyridoxine-like Diselenide

“…19 The corresponding nicotinic acid (4b)-and nicotinamide (4c)-based diselenides were also found to mimic the GPx-enzymes. 20,21 In the latter case, it was proposed (and corroborated by 77 Se NMR spectroscopy) that a selone was involved in the mechanism responsible for reduction of hydrogen peroxide. In the case of pyridoxine-derived diselenide 3b, such a selone was in fact isolable and the structure determined by X-ray crystallography.…”

An Easy Synthetic Approach to Construct Some Ebselen Analogues and Benzo[b]selenophene Derivatives: Their Antioxidant and Cytotoxic Assessment

“…Synthesis of organoselenium compounds of different classes continues to be a very active research area, because of their distinct chemical and biological properties . In fact, a variety of organoselenium compounds are well known for their antimicrobial, anti‐inflammatory, antioxidant, and biocidal activities . Their practical application in medicine for the treatment of tumors and cancers is a subject of current intense interest .…”