N-heterocyclic carbenes (NHCs) are shown to be reasonable mimics of imidazole ligands in dinitrosyl iron complexes determined through the synthesis and characterization of a series of {Fe(NO)(2)}(10) and {Fe(NO)(2)}(9) (Enemark-Feltham notation) complexes. Monocarbene complexes (NHC-iPr)(CO)Fe(NO)(2) (1) and (NHC-Me)(CO)Fe(NO)(2) (2) (NHC-iPr = 1,3-diisopropylimidazol-2-ylidene and NHC-Me = 1,3-dimethylimidazol-2-ylidene) are formed from CO/L exchange with Fe(CO)(2)(NO)(2). An additional equivalent of NHC results in the bis-carbene complexes (NHC-iPr)(2)Fe(NO)(2) (3) and (NHC-Me)(2)Fe(NO)(2) (4), which can be oxidized to form the {Fe(NO)(2)}(9) bis-carbene complexes 3(+) and 4(+). Treatment of complexes 1 and 2 with [NO]BF(4) results in the formation of uncommon trinitrosyl iron complexes, (NHC-iPr)Fe(NO)(3)(+) (5(+)) and (NHC-Me)Fe(NO)(3)(+) (6(+)), respectively. Cleavage of the Roussin's Red "ester" (μ-SPh)(2)[Fe(NO)(2)](2) with either NHC or imidazole results in the formation of (NHC-iPr)(PhS)Fe(NO)(2) (7) and (Imid-iPr)(PhS)Fe(NO)(2) (10) (Imid-iPr = 2-isopropylimidazole). The solid-state molecular structures of complexes 1, 2, 3, 4, 5(+), and 7 show that they all have pseudotetrahedral geometry. Infrared spectroscopic data suggest that NHCs are slightly better electron donors than imidazoles; electrochemical data are also consistent with what is expected for typical donor/acceptor abilities of the spectator ligands bound to the Fe(NO)(2) unit. Although the monoimidazole complex (Imid-iPr)(CO)Fe(NO)(2) (8) was observed via IR spectroscopy, attempts to isolate this complex resulted in the formation of a tetrameric {Fe(NO)(2)}(9) species, [(Imid-iPr)Fe(NO)(2)](4) (9), a molecular square analogous to the unsubstituted imidazole reported by Li and Wang et al. Preliminary NO-transfer studies demonstrate that the {Fe(NO)(2)}(9) bis-carbene complexes can serve as a source of NO to a target complex, whereas the {Fe(NO)(2)}(10) bis-carbenes are unreactive in the presence of a NO-trapping agent.

In contrast to the instability of XFe(NO)(3) and [R(3)PFe(NO)(3)](+), the N-heterocyclic carbene (NHC)-containing trinitrosyliron complex (TNIC) [(IMes)Fe(NO)(3)][BF(4)] (1) [IMes =1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene] can be readily isolated and manipulated in solution under ambient conditions. Nevertheless, in the presence of thiolates (SR(-)), this EPR-silent TNIC (denoted {Fe(NO)(3)}(10) in the Enemark-Feltham notation) releases gaseous NO, affording in the case of SR(-) = SPh(-) the EPR-active, neutral dinitrosyliron complex (DNIC) (IMes)Fe(SPh)(NO)(2) (3, {Fe(NO)(2)}(9)). Carbon monoxide enforces a bimolecular reductive elimination of PhSSPh from 3, yielding (IMes)(CO)Fe(NO)(2) (2), a reduced {Fe(NO)(2)}(10) DNIC. The NO released from TNIC 1 in the presence of SPh(-) could be taken up by the NO-trapping agent [(bme-dach)Fe](2) [bme-dach = N,N'-bis(2-mercaptoethyl)-1,4-diazacycloheptane] to form the mononitrosyliron complex (MNIC) (bme-dach)Fe(NO). In the absence of SPh(-), direct mixing of [(bme-dach)Fe](2) with 1 releases both NO and the NHC with formation of a spin-coupled, diamagnetic {Fe(NO)}(7)-{Fe(NO)(2)}(9) complex, [(NO)Fe(bme-dach)Fe(NO)(2)][BF(4)] (4). In 4, the MNIC serves as a bidentate metallodithiolate ligand of Fe(NO)(2), forming a butterfly complex in which the Fe-Fe distance is 2.7857(8) Å. Thus, 1 is found to be a reliable synthon for [{Fe(NO)(2)}(9)](+). The solid-state molecular structures of complexes 1-3 show that all three complexes have a tetrahedral geometry in which the bulky mesitylene substituents of the carbene ligand appear to umbrella the Fe(NO)(2)L [L = NO (1), CO (2), SPh (3)] motif.

The compounds of this study have yielded to complementary structural, spectroscopic (Mössbauer, EPR/ENDOR, IR), and computational probes that illustrate the fine control of electronic and steric features that are involved in the two structural forms of (μ-SRS)[Fe(CO)2PMe3]2(0,+) complexes. The installation of bridgehead bulk in the -SCH2CR2CH2S- dithiolate (R = Me, Et) model complexes produces 6-membered FeS2C3 cyclohexane-type rings that produce substantial distortions in Fe(I)Fe(I) precursors. Both the innocent (Fc(+)) and the noninnocent or incipient (NO(+)/CO exchange) oxidations result in complexes with inequivalent iron centers in contrast to the Fe(I)Fe(I) derivatives. In the Fe(II)Fe(I) complexes of S = 1/2, there is complete inversion of one square pyramid relative to the other with strong super hyperfine coupling to one PMe3 and weak SHFC to the other. Remarkably, diamagnetic complexes deriving from isoelectronic replacement of CO by NO(+), {(μ-SRS)[Fe(CO)2PMe3] [Fe(CO)(NO)PMe3](+)}, are also rotated and exist in only one isomeric form with the -SCH2CR2CH2S- dithiolates, in contrast to R = H ( Olsen , M. T. ; Bruschi , M. ; De Gioia , L. ; Rauchfuss , T. B. ; Wilson , S. R. J. Am. Chem. Soc. 2008 , 130 , 12021 -12030 ). The results and redox levels determined from the extensive spectroscopic analyses have been corroborated by gas-phase DFT calculations, with the primary spin density either localized on the rotated iron in the case of the S = 1/2 compound, or delocalized over the {Fe(NO)} unit in the S = 0 complex. In the latter case, the nitrosyl has effectively shifted electron density from the Fe(I)Fe(I) bond, repositioning it onto the spin coupled Fe-N-O unit such that steric repulsion is sufficient to induce the rotated structure in the Fe(II)-{Fe(I)((•)NO)}(8) derivatives.

[C(4)H(3)N(CH(2)NMe(2))-2]AlMe(2) (1) is prepared in 88% yield by the reaction of substituted pyrrole [C(4)H(4)N(CH(2)NMe(2))-2] with 1 equiv of AlMe(3) in methylene chloride. Reaction of compound 1 with 1 equiv of phenyl isocyanate in toluene generates a seven-membered cycloaluminum compound [C(4)H(3)N[CH(2)NPh(CONMe(2))]-2] AlMe(2) (2). The phenyl isocyanate was inserted into the aluminum and dimethylamino nitrogen bond and induced an unusual rearrangement which results in C-N bond breaking and formation. A control experiment shows that the reaction of substituted pyrrole [C(4)H(4)N(CH(2)NMe(2))-2] with 1 equiv of phenyl isocyanate in diethyl ether yields a pyrrolyl attached urea derivative [C(4)H(3)N(CH(2)NMe(2))-2-[C(=O)NHPh]-1] (3). The demethanation reaction of AlMe(3) with 1 equiv of 3 in methylene chloride at 0 degrees C afforded O-bounded and N-bounded aluminum dimethyl compounds [C(4)H(3)N(CH(2)NMe(2))-2-[C(=O)NPh]-1]AlMe(2) (4a) and [C(4)H(3)N(CH(2)NMe(2))-2-[CO(=NPh)]-1]AlMe(2) (4b) in a total 78% yield after recrystallization. Both 4a and 4b are observed in (1)H NMR spectra; however, the relative ratio of 4a and 4b depends on the solvent used. Two equivalents of AlMe(3) was reacted with 3 in methylene chloride to yield a dinuclear aluminum compound AlMe(3)[C(4)H(3)N(CH(2)NMe(2))-2-[C(=O)NPh]-1] AlMe(2) (5). Reaction of 5 with another equivalent of ligand 3 results in the re-formation of compounds 4a and 4b.

Although MIP-1α is an important chemokine in the recruitment of inflammatory cells, it remains unknown whether MIP-1α plays any role in the development of systemic inflammatory response following trauma-hemorrhage (T-H). C57BL/6J wild type (WT) and MIP-1α-deficient (KO) mice were used either as control, subjected to sham operation (cannulation or laparotomy only or cannulation plus laparotomy) or T-H (midline laparotomy, mean blood pressure 35 ± 5 mmHg for 90 min, followed by resuscitation) and sacrificed 2 h thereafter. A marked increase in serum α-glutathione transferase, TNF-α, IL-6, IL-10, MCP-1, and MIP-1α and Kupffer cell cytokine production was observed in WT T-H mice compared with shams or control. In addition lung and liver tissue edema and neutrophil infiltration (myeloperoxidase (MPO) content) was also increased following T-H in WT animals. These inflammatory markers were markedly attenuated in the MIP-1α KO mice following T-H. Furthermore, compared with 2 h, MPO activities at 24 and 48 h after T-H declined steadily in both WT and KO mice. However, normalization of MPO activities to sham levels within 24 h was seen in KO mice but not in WT mice. Thus, MIP-1α plays an important role in mediating the acute inflammatory response following T-H. In the absence of MIP-1α, acute inflammatory responses were attenuated; rapidly recovered and less remote organ injury was noted following T-H. Thus, interventions that reduce MIP-1α levels following T-H should be useful in decreasing the deleterious inflammatory consequence of trauma.