Effect of spirocyclopiperazinium salt compound LXM-15 on spinal nerve injury in rats.

BACKGROUND: Currently available therapies for neuropathic pain show limited efficacy. This study aimed to investigate the anti-nociceptive effect of the spirocyclopiperazinium salt compound LXM-15 in spinal nerve ligation (SNL) rats and to explore the potential mechanisms. METHODS: Mechanical allodynia and thermal hyperalgesia tests were used to evaluate the effects of LXM-15 in SNL rats. The expression of CaMKIIα, CREB, JAK2, STAT3, c-fos and TNF-α was detected by western blotting, ELISA or qRT-PCR analysis. Receptor blocking test was performed to explore possible target. RESULTS: Administration of LXM-15 (1, 0.5, 0.25 mg/kg, i.g.) dose-dependently attenuated mechanical allodynia and thermal hyperalgesia in rats subjected to SNL (p < 0.01, p < 0.05), and the effects were completely blocked by peripheral α7 nicotinic or M4 muscarinic receptor antagonist (p > 0.05). LXM-15 significantly decreased the overexpression of phosphorylated CaMKIIα, CREB, JAK2 and STAT3 proteins and the mRNA levels of TNF-α and c-fos (p < 0.01, p < 05). All of the effects could be blocked by α7 or M4 receptor antagonist. Furthermore, LXM-15 reduced the protein expression of TNF-α and c-fos (p < 0.01, p < 0.05). No significant acute toxicity or abnormal hepatorenal function was observed. CONCLUSIONS: This is the first study to report that LXM-15 exerts significant anti-nociceptive effect on SNL rats. This effect may occur by activating peripheral α7 nicotinic and M4 muscarinic receptors, further inhibiting the CaMKIIα/CREB and JAK2/STAT3 signalling pathways, and finally inhibiting the expression of TNF-α and c-fos. SIGNIFICANCE: Existing treatments for neuropathic pain show limited efficacy with severe adverse reactions. This paper is the first to report that LXM-15, a new spirocyclopiperazinium salt compound, exerts a significant anti-nociception in SNL rats without obvious toxicity. The underlying mechanisms include activating peripheral α7 nicotinic and M4 muscarinic receptors, then inhibiting the signalling pathways of CaMKIIα/CREB and JAK2/STAT3 and the expressions of TNF-α and c-fos. This study sheds new light on the development of novel analgesic drugs with fewer side effects.

Electrochemical fluorosulfonylation of styrenes.

An environmentally friendly and efficient electrochemical fluorosulfonylation of styrenes has been developed. With the use of sulfonylhydrazides and triethylamine trihydrofluoride, a diverse array of ß-fluorosulfones could be readily obtained. This reaction features mild conditions and a broad substrate scope, which could also be conveniently extended to a gram-scale preparation.

Anti-arthritic Effect of the Spirocyclopiperazinium Salt Compound LXM-15 in Rats and Its Underlying Mechanism.

In this study, we aimed to evaluate the effects of the spirocyclopiperazinium salt compound LXM-15 on rheumatoid arthritis induced by complete Freund's adjuvant (CFA) in rats and investigate the underlying mechanism. The results showed that LXM-15 significantly inhibited the paw edema and ankle swelling, and alleviated the mechanical allodynia and thermal hyperalgesia responses in the CFA rats. The histopathological results revealed that LXM-15 ameliorated the infiltration of inflammatory cells and joint destruction. The micro-CT scan showed that LXM-15 alleviated bone erosion and increased BMD in the ankle joints of the CFA rats. Western blot analyses showed that LXM-15 significantly reduced the upregulation of phospho-JAK2, phospho-STAT3, phospho-IκBα, and phospho-NF-κBp65, and the overexpression of BDNF in the dorsal root ganglions. ELISA result showed that the protein level of TNF-α in the paw tissue was decreased upon LXM-15 treatment. RT-PCR analysis showed that the mRNA expression levels of c-fos and BDNF were reduced in the dorsal root ganglions by LXM-15 treatment. The LXM-15-mediated anti-arthritic effects were abolished by treatment with hexamethonium (a peripheral nicotinic receptor antagonist), atropine methylnitrate (a peripheral muscarinic receptor antagonist), methyllycaconitine citrate (a selective α7 nicotinic receptor antagonist), and tropicamide (a selective M4 muscarinic receptor antagonist). Collectively, our results demonstrate that LXM-15 exerts anti-arthritic effects in CFA rats. The underlying mechanism may be related to the activation of the peripheral α7 nicotinic receptor and M4 muscarinic receptor by LXM-15, further suppressing the activation of the JAK2/STAT3 and IκBα/NF-κBp65 signaling pathways and, eventually, inhibiting the expression levels of TNF-α, BDNF, and c-fos.

Renal blood perfusion in GK rats using targeted contrast enhanced ultrasonography.

OBJECTIVE: To explore application of targeted contrast enhanced ultrasonography in diagnosis of early stage vascular endothelial injury and diabetic nephropathy. METHODS: Targeted SonoVue-TM microbubble was prepared by attaching anti-TM monoclonal antibody to the surface of ordinary microbubble SonoVue by biotin - avidin bridge method and ultrasonic instrument was used to evaluate the developing situation of targeted microbubble in vitro. Twenty 12-week-old male GK rats and 20 Wistar rats were enrolled in this study, and were randomly divided into targeted angiography group and ordinary angiography group. Targeted microbubbles SonoVue-TM or general microbubble SonoVue were rapidly injected to the rats via tail vein; the developing situation of the two contrast agents in rats kidneys was dynamically observed. Time-intensity curve was used to analyze rat kidney perfusion characteristics in different groups. RESULTS: Targeted ultrasound microbubble SonoVue-TM was successfully constructed, and it could be used to develop an external image. Targeted microbubbles SonoVue-TM enabled clear development of experimental rat kidney. Time-intensity curve shapes of rat kidney of the two groups showed as single apex with steep ascending and slowly descending branch. Compared with the control group, the rising slope of the GK rat renal cortex, medulla in targeted angiography group increased (P < 0.05); the peak intensity of medulla increased (P < 0.05), and the total area under the curve of medulla increased (P < 0.05). Compared with control group, the ascending branch of the GK rat in renal cortex, medulla in ordinary angiography group increased (P < 0.05). The peak intensity of the curve increased (P < 0.05), and the total area under the curve increased (P < 0.05). Compared with the ordinary angiography group, the peak of GK rat medulla curve in targeted angiography group intensity increased (P < 0.05), and the total area under the curve increased (P < 0.05). CONCLUSIONS: Targeted microbubbles SonoVue-TM can make a clear development of experimental rat kidney, its stable performance meet the requirement of ultrasonic observation time limit, and it can reflect early changes of blood perfusion in GK rat kindey.

Triaqua-(cyclo-hex-4-ene-1,2-dicarboxyl-ato-κO(1))(1,10-phenanthroline-κ(2)N,N')cobalt(II).

In the title compound, [Co(C(8)H(8)O(4))(C(12)H(8)N(2))(H(2)O)(3)], the Co(II) atom is coordinated by two N atoms from a bidentate 1,10-phenanthroline ligand, one O atom from a monodentate 4-cyclo-hexene-1,2-dicarboxyl-ate ligand and three water O atoms in a distorted octa-hedral geometry. The mononuclear mol-ecules are engaged in extensive intra- and inter-molecular O-H⋯O hydrogen-bonding inter-actions and π-π stacking inter-actions [centroid-centroid distance = 3.784 (3) Å], forming a three-dimensional supra-molecular network.

1-[2-(Pyrazin-2-ylsulfan-yl)eth-yl]pyrazine-2(1H)-thione.

The title multifunctional twisted organic ligand, C(10)H(10)N(4)S(2), contains a short C=S bond [1.671 (2) Å]. The dihedral angle between the two pyrazine rings is 39.83 (6)°. In the crystal, inter-molecular C-H⋯N and C-H⋯S hydrogen bonds result in the formation of a supra-molecular network.

Reversible shuttle action upon dehydration and rehydration processes in cationic coordinatively-bonded (4,4) square-grid nets threaded by supramolecular bonded anions, {[Cu(II)(4,4'-bpy)2(H2O)][Cu(II)(2-pySO3)3](NO3)}·H2O.

{[Cu(II)(4,4'-bpy)(2)(H(2)O)][Cu(II)(2-pySO(3))(3)](NO(3))}·H(2)O, obtained serendipitously by the reaction of the constituents in water, consists of parallel coordinatively bonded cationic (4,4) corrugated square-grids polymer of {[Cu(II)(4,4'-bpy)(2)(H(2)O)](2+)}(n) threaded by π-π and H-bonded supramolecular chains of [Cu(II)(2-pySO(3))(3)](-) through the open squares. A single-crystal to single-crystal transformation takes place upon removal of the noncoordinated water by controlled heating. The resulting structure exhibits a rearrangement of the coordination of the copper atoms in the grids, where the Cu-H(2)O bond is elongated from 2.250(3) to 2.628(3) Å while the Cu-NO(3) is shortened from 3.122(3) to 2.796(1) Å. This process is reversible as demonstrated by the single crystal structure after rehydration with corresponding bond distances of 2.224(3) and 3.152(3) Å. Such a cooperative effect may be associated with the Jahn-Teller distortion of the copper(II) ion accompanying the shuttle action of the hydrogen-bonded water and nitrate moiety.

Piperazine-2,3,5,6-tetra-one.

The mol-ecule of the title compound, C(4)H(2)N(2)O(4), is located around an inversion center and the four O atoms are in the 2,3,5,6-positions of the piperazine ring. In the crystal, bifurcated N-H⋯O hydrogen bonds link the mol-ecules into a corrugated layer parallel to (101).

Anti-tumor effect of Liqi, a traditional Chinese medicine prescription, in tumor bearing mice.

BACKGROUND: Liqi, an herbal preparation used in traditional Chinese medicine, has been used to treat cancer in China for centuries. We investigated the anti-tumor effects of liqi and their mechanisms in mice that had been xenografted with tumors. METHODS: Sarcoma 180 tumor, Lewis lung carcinoma, and SGC-7901 cells were implanted in BALB/c mice, C57BL/6 mice, and BALB/c nude mice, respectively. Liqi was administered to subgroups of these mice. The tumor weight and size were measured. Cell cycle analysis and T lymphocyte subsets were determined by flow cytometry. The activity of NK cells and TNF was tested using cytotoxicity assay on YAC-1 cells and L929 cells, respectively, and the activity of IL-2 was tested with an IL-2-dependent CTLL-2 cell proliferation assay. Platelet aggregation was monitored by measuring electric impedance, and the levels of thromboxane A2 (TXA2) and prostacyclin (PGI2) in blood were measured by 125I-TXB2 and 125I-Keto-PGF1alpha radioimmunoassay. RESULTS: The results showed that liqi inhibited tumor growth in tumor-implanted mice and arrested the cell proliferation in the G0/G1 phase and reduced the portion of cells in S and G2/M phase for SGC-7901 cells. Liqi increased the activity of NK cells and TNF-alpha, stimulated IL-2 production and activity, and regulated T lymphocyte subpopulations. Liqi inhibited the Lewis lung carcinoma metastasis by inhibiting platelet aggregation and normalizing the balance between TXA2 and PGI2. CONCLUSION: All these findings demonstrated that liqi has an anti-tumor effect in vivo. The mechanism may be related to immune regulation and anticoagulation effects.

Bis[2-(2-pyridylmethyl-eneamino)benzene-sulfonato-κN,N',O]manganese(II) dihydrate.

The title complex, [Mn(C(12)H(9)N(2)O(3)S)(2)]·2H(2)O, is isotypic with the previously reported Zn(II) and Cd(II) species. The complex was prepared by the reaction of the potassium salt of 2-(2-pyridylmethyl-eneamino)benzene-sulfonic acid with MnCl(2)·6H(2)O in methanol. The complex displays twofold symmetry, with the ligands coordinated in a tridentate meridional-like arrangement through pyridyl N, imine N, and sulfonate O atoms. The metal center has a strongly distorted octa-hedral coordination geometry. The uncoordin-ated water mol-ecules and the complexes participate in a hydrogen-bonding network, forming a two-dimensional structure parallel to the ab plane.

Triaqua(2-{[(E)-5-formyl-2-oxidobenzyl-idene]amino}ethanesulfonato)cobalt(II) dihydrate.

The title compound, [Co(C(10)H(9)NO(5)S)(H(2)O)(3)]·2H(2)O, is a cobalt-Schiff base complex derived from taurine. There are two complex mol-ecules and four solvent water mol-ecules in the asymmetric unit. The central Co atom is six coordinated by two O atoms and one N atom of the ligand and three O atoms of water mol-ecules, forming a slightly distorted octa-hedral geometry. The crystal structure is stabilized by several O-H⋯O hydrogen bonds.

Bis[2-(2-pyridylmethyl-eneamino)benzene-sulfonato]-κN,N',O;κN,N'-copper(II).

In the mononuclear title compound, [Cu(C(12)H(9)N(2)O(3)S)(2)], the copper(II) salt of 2-(2-pyridylmethyl-eneamino)benzene-sulfonic acid, the Cu(II) atom is coordinated by one O and two N atoms from a monoanion as well as by two N atoms from another monoanion in a distorted trigonal-bipyramidal environment.

Chloridotetra-kis(pyridine-4-carb-alde-hyde-κN)copper(II) chloride.

In the mol-ecular structure of the title compound, [CuCl(C(6)H(5)NO)(4)]Cl, the Cu(II) atom is coordinated by four N atoms of four pyridine-4-carboxaldehyde ligands and one chloride anion in a slightly distorted square-pyramidal coordination geometry. There is also a non-coordinating Cl(-) anion in the crystal structure. The Cu(II) atom and both Cl atoms are situated on fourfold rotation axes. A weak C-H⋯Cl inter-action is also present.

Bis[2-(2-pyridylmethyl-eneamino)benzene-sulfonato-κN,N',O]cobalt(II) dihydrate.

The title complex, [Co(C(12)H(9)N(2)O(3)S)(2)]·2H(2)O, has site symmetry 2 with the Co(II) cation located on a twofold rotation axis. Two tridentate 2-(2-pyridylmethyl-eneamino)benzene-sulfonate (paba) ligands chelate to the Co(II) cation in a distorted octa-hedral geometry. The pyridine and benzene rings in the paba ligand are oriented at a dihedral angle of 42.86 (13)°. Inter-molecular O-H⋯O and C-H⋯O hydrogen bonding is present in the crystal structure.

Crystalline-state guest-exchange and gas-adsorption phenomenon for a "soft" supramolecular porous framework stacking by a rigid linear coordination polymer.

A 1D rigid, linear coordination polymer, (4,4'-bipyridine)(2-pyridylsulfonate)copper, has been applied for the controlled-assembly of a new porous host that generates 1D channels by an interdigitated packing through the recognition of hydrogen bonding and pi-pi stacking interactions. The porous structure is architecturally robust when it reversibly uptakes water molecules and exchanges guest small molecules (MeOH, i-PrOH) from solution as determined by single-crystal-to-single-crystal transformation studies. Moreover, the open-channel solid displays irreversible benzene and toluene vapor sorption behaviors attributed to a widening of the channel cross-section that fetters the larger guest molecules, resulting from the dynamic, "soft" supramolecular framework.

Bis[2-(2-pyridylmethyl-eneamino)benzene-sulfonato-κN,N',O]zinc(II) dihydrate.

In the title complex, [Zn(C(12)H(9)N(2)O(3)S)(2)]·2H(2)O, the Zn(II) ion lies on a crystallographic inversion center and is coordinated by four N atoms and two O atoms from two tridentate 2-(2-pyridylmethyl-eneamino)benzene-sulfonate ligands in a slightly distorted octa-hedral environment. In the crystal structure, the complex forms a two-dimensional network through inter-molecular O-H⋯O and C-H⋯O hydrogen bonds.

Bis[2-(2-pyridylmethyl-eneamino)benzene-sulfonato-κN,N',O]cadmium(II) dihydrate.

The title complex, [Cd(Paba)(2)]·2H(2)O or [Cd(C(12)H(9)N(2)O(3)S)(2)]·2H(2)O, was synthesized by the reaction of the potassium salt of 2-(2-pyridylmethyl-eneamino)benzene-sulfonic acid (PabaK) with CdCl(2)·2.5H(2)O in methanol. The Cd(II) atom lies on a crystallographic twofold axis and is coordinated by four N atoms and two O atoms from two deprotonated tridentate 2-(2-pyridylmethyl-eneamino)benzene-sulfonate ligands in a slightly distorted octa-hedral environment. There are extensive hydrogen bonds of the type O-H⋯O between the uncoordinated water molecules and the sulfonate O atoms, through which the complex forms a layered structure parallel to (001).

A novel helical copper complex: catena-poly[[[aquacopper(II)]-micro-N-(3-carboxy-2-oxidobenzylidene-kappaO2)glycinato-kappa3N,O':O'] monohydrate].

In the polymeric title compound, [[Cu(C(10)H(7)NO(5))(H(2)O)].H(2)O](n), the Cu atom adopts a square-based pyramidal coordination involving a N,O,O'-tridentate glycine dianionic ligand, a water O atom and an apical bridging carboxylate O atom from an adjacent ligand. The title compound also adopts a carboxylate-bridged chain structure. The molecular chain propagates in a helical fashion along the b axis of the monoclinic unit cell. Neighbouring chains are linked together to form a three-dimensional network via hydrogen-bonding interactions between coordinated and uncoordinated water molecules and O atoms of the bridging carboxylate groups.

Di-mu-hydroxo-bis[aqua(1,10-phen-anthroline-kappa2N,N')copper(II)] trans-bis(2-([(E)-5-formyl-2-oxido-kappaO-benzylidene]amino-kappaN)ethanesulfonato(2-))copper(II) hexahydrate.

The title compound, [Cu(2)(OH)(2)(C(12)H(8)N(2))(2)(H(2)O)(2)][Cu(C(10)H(9)NO(5)S)(2)].6H(2)O, is comprised of a copper-centred complex cation and a copper-centred complex anion; the cation lies about an inversion centre and in the anion the Cu atom lies on an inversion centre. In the doubly charged bridged dicopper cation, each Cu centre has distorted square-pyramidal geometry. In the square-planar dianion, two sulfonate ligands are trans coordinated to the Cu atom via a deprotonated hydroxyl O atom and an imine N atom, forming two six-membered chelate rings. The structure is stabilized by an extensive hydrogen-bond system and aromatic-ring stacking interactions.

Numerical modeling method on the movement of water flow and suspended solids in two-dimensional sedimentation tanks in the wastewater treatment plant.

Taking the distributing calculation of velocity and concentration as an example, the paper established a series of governing equations by the vorticity-stream function method, and dispersed the equations by the finite differencing method. After figuring out the distribution field of velocity, the paper also calculated the concentration distribution in sedimentation tank by using the two-dimensional concentration transport equation. The validity and feasibility of the numerical method was verified through comparing with experimental data. Furthermore, the paper carried out a tentative exploration into the application of numerical simulation of sedimentation tanks.