Renzo Cini, Rebecca Pogni, Riccardo Basosi, Alessandro Donati, Claudio Rossi, Luciano Sabadini, Libertario Rollo, Sauro Lorenzini, Renata Gelli, Roberto Marcolongo, "Oxygen Radical Scavenger Activity, EPR, NMR, Molecular Mechanics and Extended-Hückel Molecular Orbital Investigation of the Bis(Piroxicam)Copper(II) Complex", Metal-Based Drugs, vol. 2, Article ID 271473, 14 pages, 1995. https://doi.org/10.1155/MBD.1995.43
Oxygen Radical Scavenger Activity, EPR, NMR, Molecular Mechanics and Extended-Hückel Molecular Orbital Investigation of the Bis(Piroxicam)Copper(II) Complex
The oxygen radical scavenger activity (ORSA) of (HPir = Piroxicam = 4-hydroxy -2- methyl -N-2- pyridyl -2H- 1,2-benzothiazine -3- carboxamide 1,1-dioxide) was determined by chemiluminescence of samples obtained by mixing human neutrophils (from healthy subjects) and (DMF = N,N -dimethylformammide) in DMSO/GLY/PBS (2:1:2, v/v) solution (DMSO = dimethylsulfoxide, GLY = 1,2,3-propantriol, PBS = Dulbecco’s buffer salt solution). The ratio of the residual radicals, for the HPir (M) and (M) /HPir (M) systems was higher than 12 (not stimulated) [excess of piroxicam was added (Cu/Pir molar ratio ≈1:10) in order to have most of the metal complexed as bischelate]. In contrast, the ratio of residual radicals for the (M) and (M)/Hpir (M)system was 5. The compound is therefore a stronger radical scavenger than either HPir or . A molecular mechanics (MM) analysis of the gas phase structures of neutral HPir, its zwitterionic and anionic forms, and some -piroxicam complexes based on X-ray structures allowed calculation of force constants. The most stable structure for HPir has a ZZZ conformation similar to that found in the (and complexes) in the solid state as well as in the gas phase. The structure is stabilized by a strong H bond which involves the N(amide)-H and O(enolic) groups. The MM simulation for the complex showed that two high repulsive intramolecular contacts exist between a pyridyl hydrogen atom of one molecule with the O donor of the other ligand. These interactions activate a transition toward a pseudo-tetrahedral geometry, in the case the apical ligands are removed. On refluxing a suspension of in acetone a brown microcystalline solid with the 0.5DMF stoichiometry was in fact prepared. spin-lattice relaxation rates of neutral, zwitterionic and anionic piroxicam, in DMSO solution are explained by the thermal equilibrium between the three most stable structures of the three forms, thus confirming the high quality of the force field. The EPR spectrum of (DMSO/GLY, 2:1, v/v, 298 and 110 K) agrees with a N2O2+O2 pseudo-octahedral coordination geometry. The EPR spectrum of DMF agrees with a pseudo-tetrahedral coordination geometry. The parameters extracted from the room temperature spectra of the solution phases are in agreement with the data reported for powder and frozen solutions. The extended-Hückel calculations on minimum energy structures of and (square planar) revealed that the HOMOs have a relevant character of . On the other hand the HOMO of a computer generated structure for (pseudo-tetrahedral) has a relevant character of atomic orbital. A orbital is better suited to allow a interaction to the anion. Therefore this work shows that the anti-inflammatory activity of piroxicam could be due in part to the formation of chelates, which can exert a SOD-like activity.
Copyright © 1995 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.