Three curcumin analogues viz., bisdemethoxy curcumin, monodemethoxy curcumin, and dimethoxycurcumin that differ at the phenolic substitution were synthesized. These compounds have been subjected for free radical reactions with DPPH radicals, superoxide radicals (O₂^•−), singlet oxygen (¹O₂) and peroxyl radicals (CCl₃O₂^•) and the bimolecular rate constants were determined. The DPPH radical reactions were followed by stopped-flow spectrometer, ¹O₂ reactions by transient luminescence spectrometer, and CCl₃O₂^• reactions using pulse radiolysis technique. The rate constants indicate that the presence of o-methoxy phenolic OH increases its reactivity with DPPH and CCl₃O₂^•, while for molecules lacking phenolic OH, this reaction is very sluggish. Reaction of O₂^•− and ¹O₂ with curcumin analogues takes place preferably at β-diketone moiety. The studies thus suggested that both phenolic OH and the β-diketone moiety of curcumin are involved in neutralizing the free radicals and their relative scavenging ability depends on the nature of the free radicals.

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 (ϕ_GSH) and H₂O₂ (ϕ H₂O₂ ), 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. ⁷⁷Se NMR spectroscopy, HPLC analysis, mass spectrometry (MS) and absorption spectroscopy were employed to understand the nature of selenium intermediates responsible for the activity. The ⁷⁷Se 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 (NictCSe) and selenenyl sulfide (NictSeSG), respectively. Reaction of H₂O₂ with NictSeSeNict produced a mixture of selenenic acid (NictSeOH) and seleninic acid (NictSeO₂H) with ⁷⁷Se NMR resonances appearing at 1069 and 1165 ppm, respectively. Addition of three equivalents of GSH to this mixture produced a characteristic ⁷⁷Se NMR signal of NictSeSG. HPLC analysis of the product formed by the reaction of NictSeSeNict with GSH confirmed the formation of NictCSe absorbing at 375 nm. Stopped-flow kinetic studies with global analysis revealed a bimolecular rate constant of 4.8 ± 0.5 × 10³ M⁻¹ s⁻¹ and 1.7 ± 0.6 × 10² M⁻¹ s⁻¹ for the formation of NictCSe produced in two consecutive reactions of NictSeSeNict and NictSeSG with GSH, respectively. Similarly the rate constant for the reaction of NictCSe 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.

Antioxidant activity of organoselenium compounds belonging to different classes i.e. functionalized aliphatic, aromatic and cyclic selenoethers, are compared on the basis of their ability to scavenge reactive oxygen species like hydroxyl and peroxyl radicals and to exhibit glutathione peroxidase (GPx) like catalytic activity. The comparative analysis has revealed that the antioxidant activity of the organoselenium compounds show direct correlation with the energy of the highest occupied molecular orbital (HOMO) and neighboring group participation that stabilizes the reaction intermediate. Finally, structural features responsible for improving the rate of reaction of organoselenium compounds with free radical/molecular oxidants have been discussed on the basis of the compounds screened at our institute.

Selenoethers attached to functional groups through propyl chain viz., bis(3-carboxypropyl)selenide (SeBA), bis(3-hydroxypropyl)selenide (SePOH) and bis(3-aminopropyl)selenide dihydrochloride (SePAm), have been examined for their ability to inhibit peroxyl radical mediated DNA damage, peroxyl radical scavenging ability and glutathione peroxidase (GPx) like activity. The DNA damage was monitored by gel electrophoresis, bimolecular rate constants for scavenging of model peroxyl radical were determined by pulse radiolysis and the GPx activity was followed by their ability to reduce hydrogen peroxide in the presence of glutathione utilizing NADPH decay and HPLC analysis. Among these compounds, SeBA showed maximum DNA protecting activity and it was also the most efficient in scavenging peroxyl radicals with the highest GPx mimicking activity. Quantum chemical calculations confirmed that SeBA with the highest energy level of HOMO (highest occupied molecular orbital) is the easiest to undergo oxidation and therefore exhibits better radical scavenging, GPx mimicking and DNA protecting activity than SePOH or SePAm.