Reaction of 1,3-bis(2-pyridinylmethyl)-1H-imidazolium tetrafluoroborate, [H(pyCH(2))(2)im]BF(4), with silver oxide in dichloromethane readily yields [Ag((pyCH(2))(2)im)(2)]BF(4), 1.BF(4)(). 1.BF(4) is converted to the analogous Au(I)-containing species, [Au((pyCH(2))(2)im)(2)]BF(4), 3, by a simple carbene transfer reaction in dichloromethane. Further treatment with two equivalents of AgBF(4) produces the trimetallic species [AuAg(2)((pyCH(2))(2)im)(2)(NCCH(3))(2)](BF(4))(3), 4, which contains two silver ions each coordinated to the pyridine moieties on one carbene ligand and to an acetonitrile molecule in a T-shaped fashion. Monometallic [Ag((py)(2)im)(2)]BF(4), 5, and [Au((py)(2)im)(2)]BF(4), 6, are made analogously to 1.BF(4) and 3 starting from 1,3-bis(2-pyridyl)-imidazol-2-ylidene tetrafluoroborate, [H(py)(2)im]BF(4). Addition of excess AgBF(4) to 6 yields the helical mixed-metal polymer, ([AuAg((py)(2)im)(2)(NCCH(3))](BF(4))(2))(n), 7 which contains an extended Au(I)-Ag(I) chain with short metal-metal separations of 2.8359(4) and 2.9042(4) A. Colorless, monometallic [Hg((pyCH(2))(2)im)(2)](BF(4))(2), 8, is easily produced by refluxing [H(pyCH(2))(2)im)]BF(4) with Hg(OAc)(2) in acetonitrile. The related quinolyl-substituted imidazole, [H(quinCH(2))(2)im]PF(6), is produced analogously to [H(pyCH(2))(2)im]BF(4). [Hg((quinCH(2))(2)im)(2)](PF(6))(2), 9, is isolated in good yield as a white solid from the reaction of Hg(OAc)(2) and [H(quinCH(2))(2)im]PF(6). The reaction of [H(quinCH(2))(2)im]PF(6) with excess Ag(2)O produces the triangulo-cluster [Ag(3)((quinCH(2))(2)im)(3)](PF(6))(3), 11. All of these complexes were studied by (1)H NMR spectroscopy, and complexes 3-9 were additionally characterized by X-ray crystallography. These complexes are photoluminescent in the solid state and in solution with spectra that closely resemble those of the ligand precursor.

Evidence suggests that NK and NKT cells contribute to inflammation and mortality during septic shock caused by cecal ligation and puncture (CLP). However, the specific contributions of these cell types to the pathogenesis of CLP-induced septic shock have not been fully defined. The goal of the present study was to determine the mechanisms by which NK and NKT cells mediate the host response to CLP. Control, NK cell-deficient, and NKT cell-deficient mice underwent CLP. Survival, cytokine production, and bacterial clearance were measured. NK cell trafficking and interaction with myeloid cells was also studied. Results show that mice treated with anti-asialoGM1 (NK cell deficient) or anti-NK1.1 (NK/NKT cell deficient) show less systemic inflammation and have improved survival compared with IgG-treated controls. CD1 knockout mice (NKT cell deficient) did not demonstrate decreased cytokine production or improved survival compared with wild type mice. Trafficking studies show migration of NK cells from blood and spleen into the inflamed peritoneal cavity where they appear to facilitate the activation of peritoneal macrophages (F4-80+GR-1−) and F4-80+Gr-1+ myeloid cells. These findings indicate that NK but not CD1-restricted NKT cells contribute to acute CLP-induced inflammation. NK cells appear to mediate their proinflammatory functions during septic shock, in part, by migration into the peritoneal cavity and amplification of the proinflammatory activities of specific myeloid cell populations. These findings provide new insights into the mechanisms used by NK cells to facilitate acute inflammation during septic shock.

Reaction of the imidazolium N-heterocyclic carbene precursor containing a methyl-substituted pyridyl functionality [HCH3im(CH3py)]PF6, 1, with Ag2O produces the homoleptic Ag(I) complex, [Ag(CH3im(CH3py))2]PF6, 2. In a simple carbene transfer reaction the analogous Au(I) species, [Au(CH3im(CH3py))2]PF6, 3, is formed by treatment of 2 with Au(tht)Cl in dichloromethane. Both 2 and 3 are structurally similar with nearly linearly coordinated NHC ligands. The methyl group appended to the pyridyl ring inhibits rotation of the pyridyl group at room temperature. Addition of AgBF4 to a hot propionitrile solution of 3 followed by crystallization with diethyl ether yields the one-dimensional coordination polymer, {[AuAg(CH3im(CH3py))2(NCCH2CH3)](BF4)2}n, 4, which contains Au-Ag separations of 2.9845(5) and 2.9641(5) A with intermetallic angles of 167.642(14) degrees and 162.081(9) degrees. This material is intensely luminescent in the solid state and exhibits an emission band at 453 nm (lambdaex=350 nm). Nearly colorless [Pd(CH3im(CH3py))2Cl]PF6, 5, is produced upon treatment of 2 with PdCl2(NCC6H5)2. The Pd(II) center in 5 is coordinated to one NHC ligand in a chelate fashion, while the second NHC is bound solely through the carbon center. The X-ray crystal structures of 1-5 are reported.

Several studies indicate that IFN-γ facilitates systemic inflammation during endotoxin-induced shock. However, the pathobiology of IFN-γ in clinically relevant models of septic shock, such as CLP, is not well understood. In this study, the role of IFN-γ in the pathogenesis of CLP-induced septic shock was evaluated by examining IFN-γ production at the tissue and cellular levels. The impact of IFN-γ neutralization on systemic inflammation, bacterial clearance, and survival was also determined. Following CLP, concentrations of IFN-γ in plasma and peritoneal lavage fluid were low in comparison with concentrations of IL-6 and MIP-2, as was IFN-γ mRNA expression in liver and spleen. The overall percentage of IFN-γ+ splenocytes was <5% after CLP and not statistically different from control mice. Intracellular IFN-γ was present in a large proportion of peritoneal exudate cells after CLP, primarily in infiltrating myeloid cells and NK cells. i.p. myeloid cell activation was decreased in IFN-γKO mice, and plasma concentrations of IL-6 and MIP-2 were significantly lower in IFN-γKO mice and in mice treated with anti-IFN-γ compared with controls, but bacterial clearance was not affected. IFN-γKO mice were resistant to CLP-induced mortality when treated with systemic antibiotics. However, neutralization of IFN-γ with blocking antibodies did not improve survival significantly. These studies show that IFN-γ facilitates the proinflammatory response during CLP-induced septic shock. However, neutralization of IFN-γ did not improve survival uniformly.

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Our recent studies indicate that mice depleted of T cells that bear the alphabeta T-cell receptor (alphabeta T cells) show less inflammation, less physiological dysfunction, and improved survival after cecal ligation and puncture (CLP) compared with control mice. Classic CD4(+) and CD8(+) T cells comprise most of the alphabeta T-cell population. We previously showed that CD8(+) T cells, in conjunction with natural killer (NK) cells, participate in CLP-induced inflammation. However, the contribution of CD4(+) T cells to the early inflammatory response caused by CLP is largely undefined. In the present study, we evaluated CLP-induced mortality, bacterial clearance, and inflammation in mice that were depleted of CD4(+) T cells. Compared with control mice, CD4 knockout mice and wild-type mice treated with anti-CD4 did not show significant differences in survival, cytokine production, and systemic bacterial counts. The combined depletion of CD4(+) T and NK cells resulted in improved survival and decreased cytokine production compared with mice possessing a full lymphocyte complement, especially when CD4(+) T and NK cell-deficient mice were treated with imipenem. These improvements were nearly identical to those observed in mice depleted only of NK cells. These studies show that CD4(+) T cells do not seem to play a critical role in facilitating the early inflammatory response caused by CLP.

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