Sensitized photoxygenation of piroxicam in neat solvents and solvent mixtures.
Detection of O(2)(1Delta(g)) phosphorescence emission, lambda(max)=1270 nm, following laser excitation and steady state methods were employed to determine the total rate constant, k(T), for the reaction between the non-steroidal anti-inflammatory drug piroxicam (PRX) and singlet oxygen in several solvents. Values of k(T) ranged from 0.048+/-0.003 x 10(6) M(-1) s(-1) in chloroform to 71.2+/-2.2 x 10(6) M(-1) s(-1) in N,N-dimethylformamide. The chemical reaction rate constant, k(R), was determined by using thermal decomposition of 1,4-dimethylnaphthalene endoperoxide as the singlet oxygen source. In acetonitrile, the k(R) value is equal to 5.0+/-0.4 x 10(6) M(-1) s(-1), very close to the k(T) value. This result indicates that, in this solvent, the chemical reaction corresponds to the main reaction path. Dependence of total rate constant on the solvent parameters pi* and beta can be explained in terms of a reaction mechanism that involves the formation of a perepoxide intermediate. Rearrangement of the perepoxide to dioxetane followed by ring cleavage and transacylation accounts for the formation of N-methylsaccharine and N-(2-pyridyl)oxamic acid, the main reaction products. Data obtained in dioxane-water (pH 4) mixtures with neutral enolic and zwitterionic tautomers of piroxicam in equilibrium show that the zwitterionic tautomer reacts with singlet oxygen faster than the enolic tautomer.
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Universidad de Chile, Facultad de Ciencias Químicas y Farmacéuticas Departamento de Química Orgánica y Fisicoquímica, Casilla 233, Santiago, Chile.
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Günther
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D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D004126:Dimethylformamide / Q000737:chemistry*; D015394:Molecular Structure; D010894:Piroxicam / Q000737:chemistry*; D026082:Singlet Oxygen / Q000737:chemistry*; D012997:Solvents
D000894:Anti-Inflammatory Agents, Non-Steroidal; D012997:Solvents; D010894:Piroxicam; D026082:Singlet Oxygen; D004126:Dimethylformamide