Response to Comment on "Activation of methane to CH3 +: A selective industrial route to methanesulfonic acid".

Roytman and Singleton argue that our proposed electrophilic mechanism for the sulfonation of methane in superacid conditions is "not plausible." We clarify certain terms that might have caused misinterpretation of our proposed mechanism and supplement the discussion. We reaffirm that an electrophilic mechanism may be operative under our reaction conditions.

Activation of methane to CH3 +: A selective industrial route to methanesulfonic acid.

Direct methane functionalization to value-added products remains a challenge because of the propensity for overoxidation in many reaction environments. Sulfonation has emerged as an attractive approach for achieving the necessary selectivity. Here, we report a practical process for the production of methanesulfonic acid (MSA) from only two reactants: methane and sulfur trioxide. We have achieved >99% selectivity and yield of MSA. The electrophilic initiator based on a sulfonyl peroxide derivative is protonated under superacidic conditions, producing a highly electrophilic oxygen atom capable of activating a C-H bond of methane. Mechanistic studies support the formation of CH3 + as a key intermediate. This method is readily scalable with reactors connected in series for prospective production of up to 20 metric tons per year of MSA.

Biological and chemical study of fused tri- and tetracyclic indazoles and analogues with important antiparasitic activity.

A series of fused tri- and tetracyclic indazoles and analogues compounds (NID) with potential antiparasitic effects were studied using voltamperometric and spectroscopic techniques. Nitroanion radicals generated by cyclic voltammetry were characterized by electron spin resonance spectroscopy (ESR) and their spectral lines were explained and analyzed using simulated spectra. In addition, we examined the interaction between radical species generated from nitroindazole derivatives and glutathione (GSH). Biological assays such as activity against Trypanosoma cruzi and cytotoxicity against macrophages were carried out. Finally, spin trapping and molecular modeling studies were also done in order to elucidate the potentials action mechanisms involved in the trypanocidal activity.

ESR and electrochemical study of 1,2-disubstituted 5-nitroindazolin-3-ones and 2-substituted 3-alkoxy-5-nitro-2H-indazoles: reactivity and free radical production capacity in the presence of biological systems.

Two families of 5-nitroindazole derivatives were electrochemically studied in an aprotic solvent using cyclic voltammetry (CV) technique. The produced nitro-anion radical species were characterized using electron spin resonance spectroscopy (ESR). Also, we examined the interaction between the radical species generated from nitroindazole derivatives and glutathione (GSH). Moreover, the capacity of intraparasite and intramammals-free radical production, through ESR spectroscopy, was performed.