Copper(II) complexes of a nonsteroidal anti-inflammatory drug niflumic acid. Synthesis, crystal structure of tetrakis-mu-(2-[3-(trifluoromethyl)phenyl] aminonicotinato)bis(dimethylsulfoxide)-dicopper(II) complex at 190 K. Anti-inflammatory properties

The synthesis and characterization of three complexes with a potent nonster oidal anti-inflammatory drug niflumic acid (2-[3-(trifluoromethyl)phenyl]am inonicotinic acid) with formula [Cu(niflumato)(2)L] (L = H2O, DMSO = dimeth ylsulfoxide, DMF = N,N-dimethylformamide) were investigated. The crystal an d molecular structure of the {Cu(niflumato)(2)(DMSO)}(2) was reported. Crys tallographic data are as follows: monoclinic system, space group P2(1)/n, Z = 2, a = 11.1318(8), b = 17.513(2), c = 15.336(1) Angstrom, beta = 103.316 (8)degrees, V = 2909.4(4) Angstrom(3). The structure was refined to R = 0.0 30 and wR = 0.037 for 3702 reflections with I > a(I). It consists of centro symmetric binuclear units with the Cu-Cu-i (symmetry code i: 1 -x, -y, 1 -z ) distance between two centrosymmetrically related ions of 2.6272(5) Angstr om. Each Cu(II) ion in [Cu-2(DMSO)(2)(mu-niflumato)(4)] is coordinated to a n apical dimethylsulfoxide O atom on the one hand and to the equatorial car bonyl and carboxylic O atoms of two crystallographically independent niflum ate moieties and their centrosymmetric counterparts on the other hand. In s pite of the low-temperature (190 K) crystal measurements, one -CF3 grouping exhibits some disorder. The biological activities of these complexes were compared to that of niflumic acid. Niflumic acid and its various copper com plexes significantly inhibited polymorphonuclear leukocyte (PMNL) oxidative metabolism, as assessed by chemiluminescence and O-2(-) generation measure ment. This effect was dose dependent. All copper complexes exerted a simila r inhibiting effect which was always significantly higher than that exerted by the parent drug. (C) 1999 Elsevier Science Inc. All rights reserved.