1 Ruthenium(III) reacts with nitric oxide (NO) to form stable ruthenium(II) mononitrosyls. Several Ru(III) complexes were synthesized and a study made of their ability to bind NO, in vitro and also in several biological systems following expression of the inducible isoform of nitric oxide synthase (iNOS). Here we report on the properties of two, related polyaminocarboxylate-ruthenium complexes: potassium chloro[hydrogen(ethylenedinitrilo)tetraacetato]ruthenate (=JM1226; CAS no.14741-19-6) and aqua [hydrogen(ethylenedinitrilo)tetraacetato]ruthenium (=JM6245; CAS no.15282-93-6). 2 Binding of authentic NO by aqueous solutions of JM1226 yielded a product with an infrared (IR) spectrum characteristic of an Ru(II)-NO adduct. A compound with a similar IR spectrum was obtained after reacting JM1226 with S-nitroso-N-acetylpenicillamine (SNAP).3 The e ect of JM1226 or JM6245 on nitrite (NO 2 7 ) accumulation in cultures of macrophages (RAW 264 line) 18 h after stimulating cells with lipolysaccharide (LPS) and interferon-g (IFNg) was studied. Activation of RAW264 cells increased NO 2 7 levels in the growth medium from (mean+1 s.e.mean) 4.9+0.5 mM to 20.9+0.4 mM. This was blocked by actinomycin D (10 mM) or cycloheximide (5 mM). The addition of JM1226 or JM6245 (both 100 mM) to activated RAW264 cells reduced NO 2 7 levels to 7.6+0.2 mM and 8.8+0.6 mM, respectively. N G -methyl-L-arginine (L-NMMA; 250 mM) similarly reduced NO 2 7 levels, to 6.1+0.2 mM.4 The e ect of JM1226 or JM6245 on NO-mediated tumour cell killing by LPS+IFNg-activated macrophages (RAW 264) was studied in a co-culture system, using a non-adherent murine mastocytoma (P815) line as the`target' cell. Addition of JM1226 or JM6245 (both 100 mM) to the culture medium a orded some protection from macrophage-mediated cell killing: target cell viability increased from 54.5+3.3% to 93.2+7.1% and 80.0+4.6%, respectively (n=6). 5 Vasodilator responses of isolated, perfused, pre-contracted rat tail arteries elicited by bolus injections (10 ml) of SNAP were attenuated by the addition of JM1226 or JM6245 (10 74 M) to the perfusate: the ED 50 increased from 6.0 mM (Krebs only) to 1.8 mM (Krebs+JM6245) and from 7 mM (Krebs only) to 132 mM (Krebs+JM1226). Oxyhaemoglobin (5 mM) increased the ED 50 value for SNAP from 8 mM to 200 mM. 6 Male Wistar rats were injected with bacterial LPS (4 mg kg 71 ; i.p.) to induce endotoxaemia. JM1226 and JM6245 (both 100 mM) fully reversed the hyporesponsiveness to phenylephrine of tail arteries isolated from animals previously (24 h earlier) injected with LPS. Blood pressure recordings were made in conscious LPS-treated rats using a tail cu apparatus. A single injection of JM1226 (100 mg kg 71 , i.p.) administered 20 h after LPS (4 mg kg 71 , i.p.) reversed the hypotension associated with endotoxaemia. 7 The results show that JM1226 and JM6245 are able to scavenge NO in biological systems and suggest a role for these compounds in novel therapeutic strategies aimed at alleviating NO-mediated disease states.

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A series of [Fe(q-C,H,X)(q-C,H,,X,)] (X = H or Me, n = 0-6) complexes has been prepared. A detailed analysis of their 13C NMR spectra is presented, the assignments being confirmed using distortionless enhancement by polarisation transfer (DEPT) techniques. The co-ordination shift of the cyclohexadienyl ligand shifts are not uniform and these anomalies are discussed in terms of possible bonding schemes. The effect of substitution by chlorine and methyl groups is also included. For the case where X = Me, evidence is presented for the occurrence of conformational isomers due to restricted rotation of the ligands. The ,,Fe Mossbauer parameters are reported as well as a temperature-dependence study. The results are discussed in terms of the somewhat distorted nature of the cyclohexadienyl ligand in these complexes.We have recently reported on correlations of 13C NMR shifts with 57Fe Mossbauer quadrupole splittings (q.s.s) and have shown how such an approach can shed light on the bonding of iron sandwich complexes. In a prior publication a qualitative approach to the understanding of substituent effects on such bonding was presented' again using "Fe Mossbauer parameters as a probe of the iron environment. We have now extended our studies to include (q-cyclohexadienyl)(q-cyclopentadien yl)iron(rI) complexes [Fe(q -C, H ,)(q -C,H 7-nXn)] ( X = Me, n = 0-6; X = C1, n = 1 or 2) and report our findings in this paper.

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