Synthesis, X-ray structural characterization and solution studies of metal complexes containing the anti-inflammatory drugs meloxicam and tenoxicam

Abstract

The reaction of tenoxicam (H 2ten, 4-hydroxy-2-methyl- N-2-pyridyl-2H-thieno[2,3-e]-1,2-thiazine-3-carboxamide-1,1-dioxide), with M(CH 3COO) 2 (M=Cd, Co, Zn; 2:1 molar ratio) in hot methanol produced the microcrystalline compounds: Cd II(Hten) 2·2CH 3OH, 1, Co II(Hten) 2CH 3OH3H 2O, 2, Zn II(Hten) 22CH 3OH, 3. Single crystals of trans, trans-[Cd II(Hten) 2(dmso) 2] 4 (dmso, dimethylsulfoxide) were obtained on cooling hot dmso solutions of 1. trans-[PtCl 2(η 2-C 2H 4)(H 2ten)], 5 and trans-[PtCl 2(η 2-C 2H 4)(H 2mel)]·0.5C 6H 6, 6·0.5C 6H 6 were obtained from the reaction of the Zeise's salt (K[PtCl 3(η 2-C 2H 4)]·H 2O) with tenoxicam and meloxicam (4-hydroxy-2-methyl- N-(5-methyl-2-thiazolyl)-2H-1,2-benzothiazine-3-carboxammide-1,1-dioxide), respectively (1:1 molar ratio) in ethanol solution and subsequent recrystallization from benzene. Microcrystalline Fe II(Hmel) 2·4H 2O·2CH 3OH, 7, was prepared by reacting Fe(CH 3COO) 2 with H 2mel in refluxing methanol at a 1:2 molar ratio, under an atmosphere of ultrapure nitrogen. The X-ray diffraction structure of 4 consists of pseudo-octahedral complex molecules in which the two chelating Hten − anions (trans to each other) occupy the equatorial positions through the O-amide (CdO(15), 2.214(2) Å) and the N-pyridyl (CdN(1′), 2.303(3) Å) atoms. The conformation is ZZZ around the C(3)C(14), C(14)N(16) and N(16)C(2′) bonds. The coordination sphere is completed by two oxygen atoms from two dmso ligands at the apical positions. The sulfur atom from the thieno system as well as the SO 2 function are not involved in any interactions to the metal; they contribute to the crystal packing via S⋯HC and O⋯HC hydrogen bond type interactions. The structures of 5 and 6 are similar each other as regards the coordination mode and overall conformation of the ligands (H 2ten and H 2mel, respectively). The platinum center links the nitrogen atom from pyridyl and thiazolyl rings with PtN bond lengths 2.077(5) and 2.072(13) Å, respectively. The EZE conformation of the neutral ligand molecules facilitates the formation of O(17)H⋯O(15) strong intramolecular hydrogen bonds. The (N(16))H⋯Pt intramolecular contact distances are 2.54(1) ( 5) and 2.93(1) Å ( 6), suggesting that an attractive interactions may exist for 5 on the basis of van der Waals radii for H and Pt. The 1H NMR data for 1 in dmso- d 6 show a general shift towards higher fields for signals of Hten − ligand with respect to those of free H 2ten. On the contrary the signals for H 2ten and H 2mel relevant to 5 and 6 (CDCl 3) undergo significant low field shifts upon the coordination to the platinum center. It is worth note that the signal for the H(16) atom is moved downfield by 1.93 ppm for 5, and this can be related to the short intramolecular Pt⋯H contact distance (see above). The infrared data for 5 and 6 at the solid state show intense and sharp bands at 1524 and 1528 cm −1, respectively, attributable to the CH 2CH 2 stretching vibration coupled to the CH 2 bending mode, some 100 cm −1 lower energy than the band for free ethylene.