[N,P]-pyrrole PdCl2 complexes catalyzed the formation of dibenzo-α-pyrone and lactam analogues.

We herein report the synthesis and catalytic application of a new family of [N,P] ligands based on the pyrrole ring with alpha-phosphine or phosphole units. Their palladium complexes (3a-d) were obtained in very good yields and their catalytic properties were evaluated in the direct intramolecular arylation to obtain both benzopyranones and phenanthridinones. The air stable complex 3a exhibited the best catalytic performance of this series of complexes, using 1 mol% of catalyst in combination with microwaves to promote this reaction.

[Crystallochemistry of copper (II) and zinc (II) chelates by nonsteroidal antiinflammatory drugs]. / Cristallochimie des complexes à visée thérapeutique du cuivre (II) et du zinc (II) par des anti-inflammatoires non-stéroïdiens.

Copper(II) and zinc(II) chelates by some non-steroidal antiinflammatory drugs NSAIDs (niflumic acid, indomethacin) and 3,5-diisopropylsalicylic acid (DIPS) were characterized by single X-ray diffraction methods. Copper(II) complexes by these two types of chelates are binuclear compounds, with Cu(2)(DIPS)(4)L(2) or Cu(2)(AINS)(4)L(2) formula (L=axial non-NSAID ligand such as diethylether, dimethylsulfoxide DMSO). In zinc(II) complex by DIPS, the metal ion is tetrahedrally coordinated and the corresponding compound is mononuclear with Zn(DIPS)(2)(DMSO)(2) formula. These copper(II) and zinc(II) complexes were found to be more active than their parent drugs from the antiinflammatory and anticonvulsant properties. It was pointed out that the Cu(2)(DIPS)(4)L(2) complexes (L=diethylether, N,N-dimethylformamide) exhibited no rotorod toxicity when examined for anticonvulsant activity using the seizure produced by maximal electroshock, following oral administration to rats.

Step-by-step uncoordination of the pyrazolyl rings of hydrotris(pyrazolyl)borate ligands in comlexes of Rh and RhIII.

Compounds of rhodium(I) and rhodium(III) that contain ancillary hydrotris(pyrazolyl)borate ligands (Tp') react with monodentate and bidentate tertiary phosphanes in a step-wise manner, with incorporation of P-donor atoms and concomitant replacement of the Tp' pyrazolyl rings. Accordingly, [Rh(kappa3-TpMe2)(C2H4)(PMe3)] (1b), converts initially into [Rh(kappa2-TpMe2)-(PMe3)2] (3), and then into [Rh(kappa1-TpMe2)-(PMe3)3] (2) upon interaction with PMe3 at room temperature, in a process which can be readily reversed under appropriate experimental conditions. Full disengagement of the Tp' ligand is feasible to give Tp' salts of rhodium(I) complex cations, for example, [Rh(CO)(dppp)2]-[TpMe2,4-Cl] (5; dppp = Ph2P(CH2)3PPh2), or [Rh(dppp)2][TpMe2,4-Cl] (6). Bis(hydride) derivatives of rhodium(III) exhibit similar substitution chemistry, for instance, the neutral complex [Rh(Tp)-(H)2(PMe3)] reacts at 20 degrees C with an excess of PMe3 to give [Rh(H)2-(PMe3)4][Tp] (9b). Single-crystal X-ray studies of 9b, conducted at 143 K, demonstrate the absence of bonding interactions between the [Rh(H)2(PMe3)4]+ and Tp ions, the closest Rh...N contact being at 4.627 A.

Low-temperature crystal structures of tetrakis-mu-3,5-diisopropylsalicylatobis-dimethylformamidodico pper(II) and tetrakis-mu-3,5-diisopropylsalicylatobis-diethyletheratodicopp er(II) and their role in modulating polymorphonuclear leukocyte activity in overcoming seizures.

Two binuclear copper(II) complexes of 3,5-diisopropylsalicylic acid were characterized by single crystal X-ray diffraction methods and examined for anti-inflammatory activity using activated polymorphonuclear leukocytes and for anticonvulsant activities using electroshock and metrazol models of seizures. These complexes were crystallized from dimethylformamide (DMF) or diethylether. Tetrakis-mu-3,5-diisopropylsalicylatobis-dimethylformamidodicop per(II) [Cu(II)2(3,5-DIPS)4(DMF)2] I is in space group P 1; a = 10.393 (2), b = 11.258 (2), c = 12.734 (2) A, alpha = 96.64 (2), beta = 92.95 (2), gamma = 94.90 (2) degrees; V = 1471.7 (4) A3; Z = 1. Tetrakis-mu-3,5-diisopropylsalicylatobis-etheratodicopper(II ) [Cu(II)2(3,5-DIPS)4(ether)2] II is in space group P 1; a = 10.409 (3), b = 11.901 (4), c = 12.687 (6) A, alpha = 91.12 (5), beta = 90.84 (5), gamma = 100.90 (4) degrees; V = 1542 (1) A3; Z = 1. The structure of I was determined at 140 K from 4361 unique reflections (I > 2sigma(1)) and refined on F2 to R1 = 0.04 and wR2 = 0.09. The structure of II was determined at 180 K from 4605 unique reflections (I > 2sigma(I)) and refined on F2 to R1 = 0.05 and wR2 = 0.13. Each compound is a crystallographically centrosymmetric binuclear complex with Cu atoms bridged by four 3,5-diisopropylsalicylate ligands related by a symmetry center [Cu-Cu(i): 2.6139 (9) A in I and 2.613 (1) in II]. The four nearest O atoms around each Cu atom form a nearly rectangular planar arrangement with the square pyramidal coordination completed by the dimethylformamide (or diethylether) oxygen atom occupying an apical position, at a distance of 2.129 (2) A in I and 2.230 (3) A in II. Each Cu atom is displaced towards the DMF (or diethylether) ligand, by 0.189 A in I and 0.184 A in II, from the plane of the four O atoms. The crystal structures of I and II are essentially similar to each other, except for the DMF or diethylether accommodation. Many disorder phenomena were found in the crystal structure of I. Copper(II)2(3,5-DIPS)4(DMF)2 inhibited polymorphonuclear leukocyte (PMNL) oxidative metabolism in vitro. This effect was concentration related and significant for concentrations higher than 10 microg or 0.68 nmol/ml. Copper(II)2(3,5-DIPS)4(DMF)2 was more active than the parent ligand, 3,5-DIPS, as has been demonstrated with copper complexes of other non-steroidal anti-inflammatory drugs. The DMF and diethylether ternary complexes of Cu(II)2(3,5-DIPS)4 were found to have anticonvulsant activity in the maximal electroshock model of grand mal epilepsy in doses ranging from 26 to 258 micromol/kg of body mass following intraperitoneal, subcutaneous, or oral treatment. The DMF ternary complex was also found to be effective in the subcutaneous injection of metrazol model of petit mal epilepsy. We conclude that both ternary copper complexes are lipophilic and bioavailable, capable of facilitating the inflammatory response to brain injury and causing the subsidence of this response in bringing about remission of these disease states.

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 nonsteroidal anti-inflammatory drug niflumic acid {2-[3-(trifluoromethyl)phenyl]aminonicotinic acid} with formula [Cu(niflumato)2L] (L = H2O, 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 P2(1)/n, Z = 2, a = 11.1318(8), b = 17.513(2), c = 15.336(1) A, beta = 103.316(8) degrees, V = 2909.4(4) A3. The structure was refined to R = 0.030 and wR = 0.037 for 3702 reflections with I > sigma (I). It consists of centrosymmetric binuclear units with the Cu-Cui (symmetry code i: 1-x, -y, 1-z) distance between two centrosymmetrically related ions of 2.6272(5) A. Each Cu(II) ion in [Cu2(DMSO)2(mu-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 L-CF3 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 O2- 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.

Crystal structure of 180 degree 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.

Ternary Copper(II) Complexes With Indomethacin, a Potent Non-Steroidal Antiinflammatory Drug. Crystal Structure of Bis (Dimethylformamide)-Tetrakis[1-(4-Chlorobenzoyl)-5-Methoxy-2-Methyl-1-H-Indole-3-Acetato]Dicopper(II). Antiinflammatory Properties and Prevention of Gastrointestinal Side Effects by Nanocapsules.

Two ternary copper(ll) complexes of indomethacin [1-(4-chlorobenzoyl)-5-methoxy-2- methyl-1-H-indole-3-acetic acid] called hereafter lndo, were prepared and characterized by single crystal X-ray diffraction. The first complex Cu(2)(Indo)(4)(DMF)(2) I crystallizes in space group P-1 (a = 10.829(2), b = 13.379(2), c = 16.491(3) A; alpha = 105.58(2), beta = 101.06(2), gamma = 106.96(2) degrees ; V= 2104.6(6) A(3), Z= 1). The title molecule is a centrosymmetric binuclear complex, with Cu atoms bridged by the carboxylate moieties of four indomethacinate ligands. The four nearest O atoms around each Cu atom form a square planar arrangement with the square pyramidal coordination completed by the O atom of N,N'-dimethylformamide. Daily administration for seven days of 1 mg/kg of indomethacin, I and I encapsulated into liposomes induces a weak inflammation of rat gastrointestinal tract. I was less inflammatory than indomethacin but the better protection was brought by encapsulation of the compound. This might be of interest in sustained therapies of chronic inflammatory diseases.