Georges Morgant

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

Abstract The synthesis and characterization of three complexes with a potent nonsteroidal anti-inflammatory drug niflumic acid {2-[3-(trifluoromethyl)phenyl]aminonicotinic acid} with formula [Cu(niflumato) 2 L] (L=H 2 O, DMSO=dimethylsulfoxide, DMF= N , N -dimethylformamide) were investigated. The crystal and molecular structure of the {Cu(niflumato) 2 (DMSO)} 2 was reported. Crystallographic data are as follows: monoclinic system, space group P 2 1 / n , Z =2, a =11.1318(8), b =17.513(2), c =15.336(1) A, β =103.316(8)°, V =2909.4(4) A 3 . The structure was refined to R =0.030 and w R =0.037 for 3702 reflections with I > σ ( I ). It consists of centrosymmetric 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) A. Each Cu(II) ion in [Cu 2 (DMSO) 2 (μ-niflumato) 4 ] is coordinated to an apical dimethylsulfoxide O atom on the one hand and to the equatorial carbonyl and carboxylic O atoms of two crystallographically independent niflumate moieties and their centrosymmetric counterparts on the other hand. In spite of the low-temperature (190 K) crystal measurements, one –CF 3 grouping exhibits some disorder. The biological activities of these complexes were compared to that of niflumic acid. Niflumic acid and its various copper complexes significantly inhibited polymorphonuclear leukocyte (PMNL) oxidative metabolism, as assessed by chemiluminescence and O − 2 generation measurement. This effect was dose-dependent. All copper complexes exerted a similar inhibiting effect which was always significantly higher than that exerted by the parent drug.

Synthesis, structural analysis and anticonvulsant activity of a ternary Cu(II) mononuclear complex containing 1,10-phenanthroline and the leading antiepileptic drug valproic acid

The synthesis and characterization of the binary complex of copper(II) with the antiepileptic drug valproic acid sodium salt (Valp) and the related ternary complex with 1,10-phenanthroline (phen) are reported, as well as the anticonvulsant properties of the latter. The characterization was carried out by means of elemental analyses, infrared (IR), UV-visible (UV-vis) spectrophotometry and Electron Paramagnetic Resonance (EPR). The X-ray crystal structure of the mononuclear complex bis(2-propylpentanoate)(1,10-phenanthroline)copper(II) [Cu(Valp)(2)phen] is showed for the first time. It crystallized in C2/c space group with unit cell dimensions of a = 14.939(1) A, b = 19.280(1) A, c = 9.726(1) A, beta = 97.27(2) degrees , V = 2778.8(4) A(3) and Z = 8. The carboxylates bond in an asymmetric chelating mode and the copper atom adopts a highly distorted octahedral coordination, characterized by the sum of the angles of 365.9 degrees around Cu(II) and its nearest atoms in the CuN(2)O(2) + O(2) chromophore instead of the expected 360 degrees for a basal square planar geometry found in most Cu(II) complexes. Molecules assemble three by three through slipped pi-pi stacking of the aromatic phen with respectively 3.519 and 3.527 A distances, in a head-to-tail arrangement. Studies of the anticonvulsant properties of this bioligand chelate evidenced its lack of efficacy in preventing MES-induced seizures. Interestingly, complex 4 protected mice against the Minimal Clonic seizures at doses that do not cause Rotorod toxicity, with an ED(50) documenting very potent anticonvulsant activity in this model of seizure, a particularly useful pharmacological profile of activity for the treatment of Petit Mal seizures.

Crystal structure at 180°K of bis-3,5-diisopropylsalicylatobisdimethylsulfoxidozinc(II) and the inhibition of seizures and polymorphonuclear leukocyte chemiluminescence

Dimethylsulfoxide (DMSO) formed a ternary complex when mixed with a Zn-3, 5-diisopropylsalicylate complex of unknown structure. The structure of this new ternary complex was characterized in an initial effort to understand the nature of this compound. Since the original complex is known to have anticonvulsant activity, the new ternary complex was also examined for anticonvulsant activity. The original complex was examined for inhibition of the polymorphonuclear leukocyte (PMNL) respiratory burst in an effort to mechanistically account for zinc complex mediated anticonvulsant activity. Dissolving the structurally unknown complex in DMSO gave crystals of a characterizable complex with an empirical formula C30H46O8S2Zn. Crystallographic data: P 1, Z = 2, a = 8.06(1), b = 12.452(2), c = 17.951(2) A, alpha = 74.42(l), beta = 77.07(1), gamma = 89.50(1) degree. The structure was refined to R = 0.03, RW = 0.04 for 3815 independent reflections with I > 2 sigma(I). This complex is mononuclear, with two 3,5-diisopropylsalicylate ligands and two bonded DMSO ligands, Zn(II)(3,5-DIPS)2(DMSO)2, Zn(II) is coordinate covalently bonded to four O atoms in a strongly distorted tetrahedral arrangement. Each DMSO ligates via its sulfoxide O atom while each 3,5-diisopropylsalicylate ligand is monodentate The non-ligating carbonyl O atom of each 3,5-DIPS is free except for an intramolecular hydrogen bond from the hydroxy group of the same ligand. Both 3,5-DIPS acid and Zn(II)(3,5-DIPS)2(DMSO)2 were examined for anticonvulsant activity in the Maximal Electroshock (MES) and Metrazol (MET) models of seizures and found to prevent both types of seizures. The Zn complex was qualitatively and quantitatively more effective than treatment with the free ligand. The influence of a Zn 3,5-DIPS complex and of the ligand 3,5-DIPS on PMNL oxidative metabolism was also studied to help understand the mechanism of anticonvulsant activity of these compounds. A dose-related and significant decrease in chemiluminescent (CL) response to opsonized Zymosan was observed, and the Zn complex was significantly more effective than the free ligand. It is concluded that mononuclear Zn complexes have anticonvulsant activity in Grand Mal and Petit Mal models of seizure possibly due to inhibition of the synthesis of superoxide or down-regulation of Nitric Oxide Synthase in activated phagocytic cells of the central nervous system.

Solvent-free one-pot synthesis and crystal structure of a spiro[indole-thiazine]

An improved facile one-pot synthesis of 3′-(fluorophenyl)-spiro[3H-indole-3,2′-tetrahydro-1,3-thiazine]-2,4′(1H)-dione is reported using an environmentally friendly green chemistry procedure under microwave irradiation. The crystal structure of the reported compound has been determined by a X-ray diffraction. The molecule is largely planar and has cell parameters of a = 11.181(9) Å, b = 11.06(1) Å, c = 12.715(12) Å, α = 90°, β = 98.31(7)°, γ = 90°.

Synthetic approaches to Cinchona alkaloids: the C-8/C-9 disconnection strategy

When conducted in DMSO, the Hunigs base-promoted condensation of 3-quinuclidinone with quinoline-4-carboxaldehyde gave an equimolar mixture of epimeric aldols 8 with an excellent yield.

Reinvestigation of the fluoride-triggered condensation of allyltrimethylsilane with cinnamonitrile: ‘abnormal Sakurai’ and sequential ‘abnormal Sakurai’–Michael–Thorpe Ziegler side reactions☆

Abstract Together with the expected 1,4-adduct, three by-products are generated in the fluoride-triggered condensation of allyltrimethylsilane with cinnamonitrile: the 1,3 adduct, an acyclic dinitrile and a cyclopentenaminonitrile issuing, respectively, from ‘abnormal Sakurai’, ‘abnormal Sakurai’–Michael and ‘abnormal Sakurai’–Michael–Thorpe Ziegler side reactions.

An unprecedented outcome of the lithium-ammonia reduction of enones: the formation of cyclopropanols

Abstract An unusual process takes place during the lithium–ammonia reduction of a variety of cyclic enones bearing an ester group in the γ-position, furnishing cyclopropanols. The reason for this unprecedented outcome has been attributed to the through-space stabilization of a developing cyclopropyl radical by interaction with the neighboring ester substituent.

2‐(2‐Aminophénylthio)‐2‐(2‐thiényl)éthyl 2‐Thiényl Cétone

The X-ray structure of the title compound, C17H15NOS3, unambiguously establishes the nature of the unexpected and non-cyclized compound obtained by reacting 2-aminobenzenethiol with 1-(2-thienyl)-3-(2-thienyl)-2-propen-1-one. The molecule as a whole is not planar, the two thienyl rings, P1 and P2, and the phenyl ring, P3, are planar and make (P1, P2), (P1, P3) and (P2, P3) dihedral angles of 75.9 (2), 31.9 (2) and 70.7 (1)°, respectively. Atoms S1 and O exhibit a Z conformation around the C10—C14 bond.

Tetraaqua-bis(3-hydroxy-4-nitrobenzoato) Co(II) and Ni(II) complexes and diaqua-bis(2-hydroxy-4-methoxybenzoato) Zn(II) complex: crystal structure and thorough metal-coordination investigation

Reactions of Co(II) and Ni(II) salts with the monosodium salt of 3-hydroxy-4-nitrobenzoic acid (3) in aqueous solution resulted in isomorphous covalent complexes 3C and 3D, of centrosymmetric geometries. In similar conditions, 2-hydroxy-4-methoxybenzoic acid (5) led to the covalent Zn(II) complex 5A, exhibiting a marked dissymmetric geometry. The present crystallographic data with structural data for a series of closely related metal complexes previously reported allow a tentative rationalization of the solid-state architecture of such complexes. The dissymmetry in 5A was interpreted on the basis of a mixed (monodentate and bidentate) metal-ligation mode and a pyramidal coordination at the metal.