ABSTRACT
(Acetonitrile-1κN)[µ-1H-benzimidazole-2(3H)-thione-1:2κ(2)S:S][1H-benzimidazole-2(3H)-thione-2κS]bis(µ-1,1-dioxo-1λ(6),2-benzothiazole-3-thiolato)-1:2κ(2)S(3):N;1:2κ(2)S(3):S(3)-dicopper(I)(Cu-Cu), [Cu(2)(C(7)H(4)NO(2)S(2))(2)(C(7)H(6)N(2)S)(2)(CH(3)CN)] or [Cu(2)(tsac)(2)(Sbim)(2)(CH(3)CN)] [tsac is thiosaccharinate and Sbim is 1H-benzimidazole-2(3H)-thione], (I), is a new copper(I) compound that consists of a triply bridged dinuclear Cu-Cu unit. In the complex molecule, two tsac anions and one neutral Sbim ligand bind the metals. One anion bridges via the endocyclic N and exocyclic S atoms (µ-S:N). The other anion and one of the mercaptobenzimidazole molecules bridge the metals through their exocyclic S atoms (µ-S:S). The second Sbim ligand coordinates in a monodentate fashion (κS) to one Cu atom, while an acetonitrile molecule coordinates to the other Cu atom. The Cu(I)-Cu(I) distance [2.6286 (6) Å] can be considered a strong 'cuprophilic' interaction. In the case of [µ-1H-benzimidazole-2(3H)-thione-1:2κ(2)S:S]bis[1H-benzimidazole-2(3H)-thione]-1κS;2κS-bis(µ-1,1-dioxo-1λ(6),2-benzothiazole-3-thiolato)-1:2κ(2)S(3):N;1:2κ(2)S(3):S(3)-dicopper(I)(Cu-Cu), [Cu(2)(C(7)H(4)NO(2)S(2))(2)(C(7)H(6)N(2)S)(3)] or [Cu(2)(tsac)(2)(Sbim)(3)], (II), the acetonitrile molecule is substituted by an additional Sbim ligand, which binds one Cu atom via the exocylic S atom. In this case, the Cu(I)-Cu(I) distance is 2.6068 (11) Å.
ABSTRACT
The proposed curative properties of copper(II)-non-steroidal anti-inflammatory drugs (NSAIDs) have led to the development of numerous copper(II)-NSAID complexes with enhanced anti-inflammatory activity. In this work, the antinociceptive and toxic effects of two new coordination complexes: Cu2(fen)4(caf)2 [fen: fenoprofenate anion; caf: caffeine] and Cu2(fen)4(dmf)2 [dmf: N-N'-dimethylformamide] were evaluated in mice. The antinociceptive effect was evaluated with two models: acetic acid-induced writhing response and formalin test. For the sub-acute exposure, the complexes were added to the diet at different doses for 28days. Behavioral and functional nervous system parameters in a functional observational battery were assessed. Also, hematological, biochemical and histopathological studies were performed. Cu2(fen)4(caf)2 and Cu2(fen)4(dmf)2 significantly decreased the acetic acid-induced writhing response and the licking time on the late phase in the formalin test with respect to the control and fenoprofen salt groups. The sub-acute exposure to Cu2(fen)4(caf)2 complex increased the motor activity, the number of rearings and the arousal with respect to the control and fenoprofen salt groups. These impaired parameters in mice exposed to Cu2(fen)4(caf)2 can be attributable to the presence of caffeine as stimulating agent. On the other hand, all exposed groups decreased the urine pools in the functional observational battery and increased the plasmatic urea. These effects could be due to the decrease in the glomerular filtration caused by NSAIDs. In conclusion, both complexes Cu2(fen)4(dmf)2 and Cu2(fen)4(caf)2 were more potent antinociceptive agents than fenoprofen salt. Sub-acute exposure to different doses of these complexes did not produce significant changes in the parameters that evaluate toxicity.
Subject(s)
Abdominal Pain/drug therapy , Analgesics/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Coordination Complexes/therapeutic use , Fenoprofen/therapeutic use , Inflammation/drug therapy , Abdominal Pain/blood , Abdominal Pain/prevention & control , Abdominal Pain/urine , Analgesics/administration & dosage , Analgesics/adverse effects , Analgesics/chemistry , Animals , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Arousal/drug effects , Caffeine/administration & dosage , Caffeine/adverse effects , Caffeine/chemistry , Caffeine/therapeutic use , Central Nervous System Stimulants/administration & dosage , Central Nervous System Stimulants/adverse effects , Central Nervous System Stimulants/chemistry , Central Nervous System Stimulants/therapeutic use , Coordination Complexes/administration & dosage , Coordination Complexes/adverse effects , Coordination Complexes/chemistry , Copper/administration & dosage , Copper/adverse effects , Copper/chemistry , Dimethylformamide/administration & dosage , Dimethylformamide/chemistry , Dose-Response Relationship, Drug , Female , Fenoprofen/administration & dosage , Fenoprofen/adverse effects , Fenoprofen/chemistry , Hepatic Insufficiency/chemically induced , Inflammation/blood , Inflammation/prevention & control , Inflammation/urine , Mice , Pain Measurement , Random Allocation , Renal Insufficiency/chemically inducedABSTRACT
The title compound, [Cu(2)(C(15)H(13)O(3))(4)(C(3)H(7)NO)(2)], is formed by the chelate coordination of four racemic fenoprofenate (fenoprofenate is 2,3-phenoxyphenyl propionate) anions and two dimethyl-formamide mol-ecules to two copper(II) ions, building a paddle-wheel dinuclear mol-ecule. The distorted square-pyramidal coordination of each Cu(II) atom is made up of four O atoms of the four fenoprofenate units and another O atom from a dimethyl-formamide mol-ecule. The two enanti-omeric forms of the fenoprofenate anions are present in the complex, in an optically inactive centrosymmetric arrangement.
ABSTRACT
The centrosymmetric title compound, [Ag(C(7)H(4)NO(2)S(2))]n, consists of dinuclear units in which two thiosaccharinate anions each bridge two Ag atoms via an endocyclic N atom and an exocyclic S atom across a crystallographic centre of inversion midway between the Ag atoms. The dimeric units are connected via Ag-S(exo) interactions to create two-dimensional networks. The thiosaccharinate anions bridge in a mu3-S:S:N manner. The Ag...Ag distance can be considered a strong argentophilic interaction.
