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Introduction. The definitive management of R/R FL remains controversial due to various treatment options, including chemoimmunotherapy, pathway inhibitors, and autologous stem cell transplantation (auto-SCT). These options can provide prolonged progression-free survival (PFS). Allogeneic hematopoietic stem cell transplantation (allo-SCT) remains the sole curative therapy for FL. Herein, we report the long term outcome of the largest sample of allo-SCT for FL ever studied as well as the identification of patient and disease related factors that were significantly associated with treatment failure. Patients. Eligible were adult patients with R/R FL having received a first allo-SCT between 2001 and 2011 from an HLA identical sibling donor (SIB) or a well-matched unrelated donor (MUD). Patients with transformed lymphoma were excluded from the analysis as well as planned second transplants, allotransplants from cord blood, mismatched donors, and transplants with ex vivo T cell depletion (TCD). Results. 1567 patients met the eligibility criteria (EBMT, n = 1115; CIBMTR, n = 452). Demographics separated by data source demonstrate some differences in transplant practices between the two regions. The CIBMTR cohort had a higher proportion of MUD recipients [167 (37%) vs 252 (23%), p < 0.001], more cases with chemoresistant disease [113 (25%) vs 145 (13%), p < 0.001], less patients having received a prior auto-SCT [53 (12%) vs 403 (36%), p < 0.001], more use of myeloablative conditioning (MAC) (145 (32%) vs 220 (20%), p < 0.001) and less use of alemtuzumab in-vivo TCD [29 (6%) vs 201 (18%), p < 0.001] compared to the EBMT cohort. Median (range) follow up of survivors in months was 58 (3 - 130) and 54 (3 - 160) for CIBMTR and EBMT patients, respectively. Cumulative incidence of acute (grades II-IV) graft versus host disease (GVHD) was 20% (18-22) at 100 days and of chronic GVHD 45% (42-48) and 55% (52-58) at 1 and 3 years, respectively for the whole series; this risk was slightly but significantly reduced in the EBMT cohort. All major outcomes [non-relapse mortality (NRM), relapse/progression (R/P), overall survival (OS) and PFS] were comparable between the CIBMTR and EBMT samples (Table 1). Table 1. Outcomes CIBMTR EBMT p-value NRMN@ 1 y@ 3 y@ 5 y 45021 (17-25)27 (23-32)31 (26-35) 108819 (16-21)24 (21-27)28 (25-31) 0.3630.1720.114 R/PN@ 1 y@ 3 y@ 5 y 45013 (10-16)16 (13-20)17 (13-21) 108813 (11-15)18 (15-20)21 (18-23) 0.8740.4800.114 PFSN@ 1 y@ 3 y@ 5 y 45066 (62-71)56 (52-61)52 (47-57) 108869 (66-72)58 (55-61)52 (48-55) 0.3750.4950.792 OSN@ 1 y@3 y@ 5 y 45274 (70-78)65 (60-69)61 (56-65) 110475 (72-78)67 (64-70)62 (59-65) 0.5890.4550.695 Multivariate analysis indicated that NRM was significantly affected by age (HR 1.04, 1.02-1.05, p < 0.0001), chemoresistant disease (HR 1.61, 1.28-2.03, p < 0.0001), >= 5 lines of prior CT (vs 3-4) (HR 1.62, 1.20-2.19, p=0.0015) and Karnofsky performance score (KPS) < 80 (HR 2.05 (1.32-3.19, p=0.0014); R/P was significantly affected by grade 3 histology (HR 1.63, 1.16-2.26, p=0.0049) and chemoresistant disease (HR 1.46 (1.07-1.97), p=0.0156); PFS by grade 3 histology (HR 1.42, 1.15-1.76, p=0.0012), chemoresistant disease (HR 1.54, 1.28-1.86, p= 5 lines of prior CT (vs 3-4) (HR 1.45, 1.13-1.85, p=0.0031), MAC (HR 1.36, 1.14-1.63, p=0.0008) and KPS < 80 (HR 1.78, 1.23-2.58, p =0.0022) and OS by age (HR 1.03, 1.02-1.04, p= 5 lines of prior CT (vs 3-4) (HR 1.63, 1.25-2.13, p=0.0003), MAC (HR 1.42, 1.16-1.73, p=0.0006) and KPS < 80 (HR 2.23, 1.52-3.25, p Conclusions. This study represents an example of a fruitful cooperation between two important scientific transplant societies, the EBMT and CIBMTR. Despite significant differences in patient characteristics and transplant strategies between these 2 hitherto largest samples on allo-SCT for R/R FL, long-term disease control was similar and remarkably good with an R/P risk of about only 20% at 5 years. Chemoresistant disease, higher age, multiple pretreatment lines, poor KPS, and MAC all were predictors for an adverse outcome, whereas MUD, TCD, and prior auto-SCT had no impact on any survival endpoint. Disclosures Sureda: Takeda: Consultancy, Honoraria, Speakers Bureau. Fenske:Celgene: Honoraria; Millennium/Takeda: Research Funding; Pharmacyclics: Honoraria; Seattle Genetics: Honoraria. Smith:Celgene: Consultancy; Pharmacyclics: Consultancy.

Introduction: Allogeneic hematopoietic stem cell transplantation (alloHSCT) is currently considered the standard of care for those patients with HL that relapse after autologous HSCT. Several studies have shown that fit patients with chemosensitive disease can benefit from alloHSCT using and identical sibling (SIB) or matched-unrelated (MUD) donors. Recently, encouraging results have been obtained using haploidentical donors (HAPLO) and post-transplantation cyclophosphamide (ptCY) as graft-versus-host disease prophylaxis (GVHD). Because information regarding the results of alloHSCT using alternative donors is still scarce, we aimed to compare outcome of umbilical cord blood (UCB) and HAPLO transplants with conventional SIB and MUD for HL. Patients and methods: Information of patients older than 17y with HL who received an alloHSCT from a SIB, MUD (8/8 antigen matched), UCB or a ptCY-based HAPLO between 2010-2013 was downloaded from the EBMT and GETH databases. Results: 773 patients with HL were identified meeting the inclusion criteria. 339 received a transplant from a SIB donor, 276 from a MUD, 101 from HAPLO, and 47 from UCB. A significant higher number of patients treated with alloHSCT from UCB and HAPLO donors received reduced intensity (RIC) regimens in comparison to SIB and MUD (76% and 88% vs. 69% and 69%, respectively, p=0.001). Bone marrow was more frequently used as source of stem cells in the HAPLO group in relation to SIB and MUD (61% vs 10% and 11%, respectively, p=0.001), Other variables such as sex, age, performance status, chemorefractory disease, and previous autologous SCT were balanced. Median follow-up after alloHSCT for all patients was 12 months (1-60). The 1-year probabilities of overall survival (OS) and progression-free survival (PFS) were 80% and 49% after SIB transplant, 69% and 54% after MUD, 65% and 40% after UCB, and 73% and 56% after HAPLO, respectively. The 1-year probabilities of non-relapse mortality (NRM) and relapse rate (RR) were 12% and 38% after SIB, 21% and 25% after MUD, 20% and 40% after UCB, and 18% and 27% after HAPLO. Multivariate analysis showed that, in comparison with standard SIB alloHSCT, UCB was associated with a trend to a higher NRM (p=0.08) and RR (p=0.06), leading to a significant lower OS and PFS (p=0.009, HR 2.1, 95% CI 1.2-3.6; p=0.02, HR 1.6, 95% CI 1.1-2.3; respectively). NRM was also significantly higher after MUD (p=0.004, HR 1.8, 95% CI 1.2-2.6), but in contrast, RR was lower (p=0.003 HR 0.6, 95%CI 0.5-0.9) with a lower OS (p=0.002, HR 1.6, 95% CI 1.2-2.1) and no significant differences in PFS. No significant differences were observed between HAPLO and SIB in NRM, RR, PFS and OS. Conclusions: This registry study suggests that in adults with advanced HL, the outcome of pt-CY-based HAPLO HSCT may be comparable to that of conventional SIB alloHSCT and MUD across multiple centers and conditioning regimens. These findings need to be corroborated by longer follow-up. Figure 1. Figure 1. Disclosures Peggs: Autolus: Consultancy, Equity Ownership; Cellectis: Research Funding. Milpied:Celgene: Honoraria, Research Funding. Afanasiev:CELLTRION, Inc.: Research Funding. Russell:Therakos: Other: shares. Sureda:Takeda: Consultancy, Honoraria, Speakers Bureau.

Inhibition of avb3 or avb5 integrin function has been reported to suppress neovascularization and tumor growth, suggesting that these integrins are critical modulators of angiogenesis. Results. We ...

The aim of our lab is to understand the contributions made by cell adhesion molecules in the processes of disease. Much of our recent work has focused on the role played by beta3-integrin in mediating pathological angiogenesis. It is fair to state that without the ability to manipulate the mouse genome, and specifically to create knockout mice, the advances we have made in this field would not be nearly as significant as they are. The ability to generate knockout mice depends on the two technological breakthroughs of the ability to isolate and culture mouse embryonic stem (ES) cells and the methods employed for achieving targeted gene replacement in these cells by homologous recombination. Here, we present the methods we have found to be successful, and that we routinely employ to grow and manipulate ES cells, as well as those to screen and identify homologous recombinants.

Objective— β3-integrin deficiency has been implicated in increasing levels of Flk-1 expression on endothelial cells and enhancing vascular endothelial growth factor (VEGF)-induced angiogenesis. We determined the role of β3-integrin in mediating VEGF-A–induced blood vessel permeability through Flk-1. Methods and Results— Using the Miles assay, we demonstrated that VEGF-A–induced plasma leakage was enhanced in β3-null mice when compared with wild-type controls. This was not caused by any changes in blood vessel structure (as detected by light or electron microscopy) or by changes in endothelial cell–cell adhesion proteins (as determined by Western blot analysis, flow cytometry, and immunofluorescence). Circulating levels of VEGF, baseline blood vessel leakage, and leakage in response to an acute inflammatory stimulus were identical in wild-type and β3-null mice. However, VEGF-A–induced leakage was abolished in β3-null mice by the inhibition of Flk-1, indicating that the elevated levels of Flk-1 on β3-null endothelial cells enhance VEGF-A–induced permeability. Conclusions— β3-integrin–deficiency increases the sensitivity of endothelial cells to VEGF-A by elevating Flk-1 expression and, as a consequence, enhances VEGF-A–mediated permeability.

The synthesis and X-ray crystal structures of the acetamidinato complexes (M = Ru, Rh) and the triazenido complexes and are reported.

Background: Allogeneic stem cell transplantation (SCT) can provide long-term disease control in selected patients with relapsed refractory NHL. Restricted availability of a matched sibling donor limits its use especially for patients with rapidly progressing disease in whom unrelated donor search cannot be awaited and in patients from ethnic minorities. Donor sources such as haplo-identical relatives or cord blood represent reasonable alternatives but data of alternative donor transplants in lymphoma is sparse. We therefore intended to compare outcome after transplants performed with sibling or fully matched unrelated donors with alternative sources such as cord blood and haplo-identical donors. Methods: Information of patients with mantle cell lymphoma (MCL), DLBCL, T-cell lymphoma (TCL) and follicular lymphoma (FL) who received an SCT from a sibling donor (SIB), 10/10 matched unrelated donor (MUD), haplo-identical donor (HAPLO) or cord blood (CORD) between 2007 and 2012 was downloaded from the EBMT database. Comparisons of outcome after transplants from different donors were performed with regard to overall survival (OS), non relapse mortality (NRM), relapse (REL) and acute GVHD incidence. For comparisons between donors SIB has been chosen as the reference group. Results: 2798 patients with NHL were identified in the EBMT database meeting the inclusion criteria. 2065 received a transplant from a SIB, 447 from a MUD, 167 from CORD (18 MCL, 36 DLBCL, 43 FL, 70 TCL) and 119 from a HAPLO donor (16 MCL, 30 DLBCL, 22 FL, 51 TCL). 66% were male and 34% female patients. Median age at transplant was 49 years (range: 18-72). 24% (n=684) had DLBCL, 27% (n=755) FL, 17% (n=464) MCL and 32% (n=895) TCL. 56% received their transplant in CR, 17% in PR and 27% had active disease at SCT. Active disease was more common in the HAPLO group (p Median follow-up after SCT was 27 month (CI 25 to 29). OS of patients who received an alloSCT from a SIB or MUD was not significantly different, whereas OS of HAPLO and CORD transplants was significantly worse than SIB transplants (HR 1.9 CI 1.5 -2.5, HR 1.8 CI 1.4 -2.2, p < 0.0001, Figure 1). Worse OS after alternative donor transplant (reference SIB) was observed across all studied disease entities. Relapse incidence after conventional transplants (SIB, MUD) and alternative donor transplants (HAPLO, CORD) was not significantly different within the whole group (HAPLO: HR 1.2 95% CI 0.9-1.8 p= 0.23; CORD: HR 1.1 95% CI 0.7-1.4, p=0.74; Figure 1) and across all studied disease entities. In contrast, whereas NRM incidence was not significantly different between SIB and MUD, it was, but significantly higher with alternative donor transplants (HAPLO: HR 1.8 95% CI 1.3-1.8, p80%) and conditioning intensity (RIC vs. MAC) confirmed worse OS for HAPLO (HR 1.5 CI 1.2-2.0, p=0.003) and CORD (HR 1.6 CI 1.3-2.0, p Conclusions: Alternative donor transplants are a valuable option if no suitable SIB or MUD donor is available. With the limited number of patients studied here, relapse incidence after alternative donor transplants was not significantly different from conventional transplants. Higher NRM incidence in alternative donor transplants might be improved with increasing refinement of the procedure, such as post-transplant cyclophosphamide approaches. Figure 1) Outcome (OS, Rel, NRM) after alloSCT with different donors Figure 1). Outcome (OS, Rel, NRM) after alloSCT with different donors Disclosures No relevant conflicts of interest to declare.

Peatlands are a particularly good medium for trapping and preserving tephra, as their surfaces are wet and well vegetated. The extent of tephra-depositing events can often be greatly expanded through the observation of ash in peatlands. This paper uses the presence of the White River tephra layer (1200 B.P.) in peatlands to extend the known distribution of this late Holocene tephra into the Mackenzie Valley, northwestern Canada. The ash has been noted almost to the western shore of Great Slave Lake, over 1300 km from the source in southeastern Alaska. This new distribution covers approximately 540 000 km² with a tephra volume of 27 km³. The short time span and constrained timing of volcanic ash deposition, combined with unique physical and chemical parameters, make tephra layers ideal for use as chronostratigraphic markers.

Ground penetrating radar (GPR) surveying has been used by the Geological Survey of Canada (GSC) to provide continuous profiles of shallow ground properties for a variety of permafrost-related applications. Permafrost often provides ideal ground conditions for GPR, owing primarily to low signal attenuation. Results from surveys examining zones of thaw along a pipeline route, discontinuously frozen peatlands, and stratigraphy and massive ground ice within an outwash complex are presented.

Amides, NH2COR (R = CF3, Ph), undergo metallation reactions to form mono- and bi-nuclear ruthenium(II) amido complexes, notably [Ru(NHCOCF3)2(H2O)(CO)(PPh3)2], the cyclometallated (N,C) benzamido derivative [Ph3P)(OC)[graphic omitted]6H4-o)(µ-NHCOPh)(µ-H)Ru(CO)(PPh3)2] and the quadruply bridged species [Ru2(µ-Cl)(µ-H)(µ-NHCOCF3)2(PPh3)4] all of which have been characterised by X-ray diffraction methods.

We extend our previous analyses of mice deficient in selectins by describing the generation and comparative phenotype of mice lacking one, two, or three selectins after sequential ablation of the murine genes encoding P-, E-, and L-selectins. All mice deficient in selectins are viable and fertile as homozygotes. However, mice missing both P- and E-selectins (PE−/−), and mice missing all three selectins (ELP−/−) develop mucocutaneous infections that eventually lead to death. Mice deficient in multiple selectins display varying degrees of leukocytosis, resulting in part from alterations in leukocyte rolling and recruitment.PE−/−mice,ELP−/−mice, and mice missing both P- and L-selectins (PL−/−) show drastic reductions in leukocyte rolling and in extravasation of neutrophils in thioglycollate-induced peritonitis. In a separate inflammatory model (ragweed-induced peritoneal eosinophilia), we demonstrate P-selectin to be both necessary and sufficient for the recruitment of eosinophils. The phenotype of mice missing both E- and L-selectins (EL−/−) is less severe than those seen in the other double knockouts. Comparisons among the double knockouts suggest that P-selectin normally cooperates with both E- and L-selectins. Our results indicate a preeminent role for P-selectin in regulating leukocyte behavior in mice. Data from theELP−/−mice indicate, however, that all three selectins are important to leukocyte homeostasis and efficient neutrophil recruitment.

In b3-floxed/Pdgfb.Creert2 positive mice treated with tamoxifen, allograft tumours grow significantly smaller when compared to their growth in Cre negative littermate controls. This correlates with decreased microvascular density observed in Cre-postive compared to Cre-negative tumour sections. In contrast, constitutive deletion of endothelial b3-integrin via Tie1.Cre leads to enhanced tumour angiogenesis. These findings are re-capitulated in the aortic ring model. VEGF-induced microvessel sprouting is inhibited in b3-floxed/Pdgfb.Creert2 positive mice compared to Cre-negative littermates. In marked contrast, sprouting is enhanced in b3-floxed/Tie1.Cre positive mice compared to b3-floxed/Tie1.Cre negative mice. Conclusions These findings strengthen the argument that endothelially-expressed b3-integrin remains a valid target of antiangiogenic tumour therapy. However, taken together, these data suggest that the timing and length of exposure to b3-integrin endothelial genetic inhibition impacts on the angiogenic response. These data highlight the need to enhance our understanding of the molecular basis of angiogenesis in order to develop improved therapeutic treatments.

Angiogenesis, the formation of new blood vessels from pre-existing ones, is vital for tumor growth and spread. A better understanding of angiogenic processes, particularly cell-cell adhesion, is required for the development of effective anti-angiogenic drugs. Claudin-14 (Cldn14) is a component of Tight Junctions (TJ) and its function in angiogenesis is not yet known. Other TJ molecules such as JAMs are known to be involved in angiogenesis; for example, we have identified a novel dosage-dependent role for JAM-B in the regulation of angiogenesis in the context of trisomy of human chromosome 21 (Hsa21) genes (Reynolds et al. Nature 2010); Cldn14 is also present on Hsa21. Therefore we hypothesise that Cldn14 may also play a role in the regulation of angiogenesis. Here we show that depletion of Cldn14 enhances VEGF-stimulated angiogenesis in the ex vivo aortic ring assay and increases primary mouse lung endothelial cell proliferation via changes in downstream signalling. Viable Cldn14 knockout mice exhibit normal vasculature in unchallenged organs, suggesting that the effect may be specific to pathological states. These data reveal novel regulatory roles for Cldn14 and future work will characterise further the functions of Cldn14 in angiogenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3479. doi:10.1158/1538-7445.AM2011-3479

In dryland agricultural systems, efficient farm management requires a degree of flexibility according to variations in climate from year to year. Tactical adjustments to the mix of farm enterprises can capitalize on good growing conditions and minimise losses under poor growing conditions. In this paper, a discrete stochastic programming model of dryland wheat-sheep farms in Western Australia is used to identify optimal tactical adjustments to climate and to calculate the value of these tactical adjustments. The model, MUDAS, includes nine discrete season types with a wide range of options for tactical adjustments in each. In the standard model, optimal tactical responses increase expected net cash surplus by approximately 22% relative to a fixed or inflexible strategy. In most season types, changes to the long term farm strategy are made on less than 10% of the farm area, although in some seasons over 25% of the farm can require adjustments to the enterprise selected. The benefits of flexibility are not evenly distributed across different season types but occur predominantly in the best and worst seasons. The magnitude of benefits is affected differently by different commodity prices. Benefits of flexibility are due to capitalizing on knowledge about the greater volatility of profits from cropping than from livestock production. Deterministic models and even stochastic models which don't include activities for tactical adjustments miss this key feature of the system.

Mononuclear rhodium(II) dithiocarbamato complexes ‘Rh(S 2 CNR 2 ) 2 (PPh 3 )’ and ‘Rh(S 2 CNR 2 ) 2 ’, (R=Me, Et) have been shown to be mixtures of various rhodium(III) dithiocarbamato complexes.

The ruthenium and osmium complexes [MH(Cl)(CO)(PPh3)3](M = Ru or Os) each react with benzotriazole (Hbta) in cold benzene to form a pair of geometrical isomers [MH(Cl)(Hbta)(CO)(PPh3)2](H trans to Hbta or Cl). The dihydrides [MH2(CO)(PPh3)3] react with excess of benzotriazole in boiling benzene (M = Ru) or toluene (M = Os) to afford products of the form [MH(bta ⋯ H–bta)(CO)(PPh3)2] containing a hydrogen-bonded benzotriazole–benzotriazolate pair co-ordinated as an NN′ chelate ligand. Similar chelate ligands are found in the products trans-[M(bta ⋯ H–bta)2(Hbta)(PPh3)] obtained from [RuH2(PPh3)4] and Hbta in boiling benzene, or from [MCl2(PPh3)3], Hbta, and triethylamine in boiling benzene (M = Ru) or toluene (M = Os). Isomeric forms of the complexes trans-[M(bta ⋯ H–bta)2(Hbta)(PPh3)] are thought to involve N2- or N3-co-ordinated Hbta ligands. Treatment of [IrCl(CO)(PPh3)2] with Hbta leads to reversible formation of the oxidative-addition product [IrH(Cl)(bta)(CO)(PPh3)2] in solution. The same reagents in the presence of NEt3 afford the known complex [Ir(bta)(CO)(PPh3)2]. Benzotriazole also reacts with mer-[IrH3(PPh3)3] to form [IrH2(bta ⋯ H–bta)(PPh3)2] and with [Pt(PPh3)4] to generate [Pt(bta)2(PPh3)2]. The nature of the hydrogen-bonded composite (bta ⋯ H–bta) ligand has been confirmed by an X-ray diffraction study on the osmium complex [OsH(bta ⋯ H–bta)(CO)(PPh3)2]. The crystals are triclinic, space group P, with a= 10.059(4), b= 11.876(1), c= 20.629(3)A, α= 74.57(1), β= 83.08(2), γ= 65.96(2)°, and Z= 2. A parallel series of complexes have been obtained using 5,6-dimethylbenzotriazole.

Reactions of 4,6-dimethylpyrimidine-2-thiol (Me 2 pymSH) and its oxidation product bis(4,6-dimethylpyrimidine-2-yl)disulphide (Me 2 pymSSpymMe 2 ) with a range of platinum metal complexes are described. The chlorohydrides [MHCl(CO)(PPh 3 ) 3 ] (M=Ru, Os) react with Me 2 pymSH in refluxing toluene to afford [RuCl(Me 2 pymS)(CO)(PPh 3 ) 2 ] and [OsH(Me 2 pymS)(CO)(PPh 3 ) 2 ] (two isomers). A similar reaction in cold benzene affords the substitution product [RuH(Cl)(Me 2 pymSH)(CO)(PPh 3 ) 2 ] (two isomers). Reaction of the precursors [MH 2 (CO)(PPh 3 ) 3 ] (MRu, Os) and [Ru(CO) 3 (PPh 3 ) 2 ] in boiling toluene afford [MH(Me 2 pymS)(CO)(PPh 3 ) 2 ] (two isomers) and [Ru(Me 2 pymS) 2 (CO)(PPh 3 )] (two isomers) respectively whilst the reaction of [Ru(CO) 3 (PPh 3 ) 2 ] with Me 2 pymSSpymMe 2 yields a mixture of [Ru(Me 2 pymS) 2 (CO) 2 (PPh 3 )] and [Ru(Me 2 pymS) 2 (CO)(PPh 3 )]. In the presence of the base (NEt 3 ) the dichlorides [MCl 2 (PPh 3 ) 3 ] (M=Ru, Os) react with Me 2 pymSH to afford the bis-chelates [M(Me 2 pymS) 2 (PPh 3 ) 2 ]. Reactions between Me 2 pymSH and the precursors [IrCl(CO)(PPh 3 ) 2 ] and [IrH(CO)(PPh 3 ) 3 ] at ambient temperature or below afford [IrH(Cl)(Me 2 pymS)(CO)(PPh 3 ) 2 ] and [IrH 2 (Me 2 pymS)(CO)(PPh 3 ) 2 ] respectively, the same ligand reacts with [RhCl(PPh 3 ) 3 ] and mer -[IrH 3 (PPh 3 ) 3 ] in refluxing benzene to afford [RhH(Cl)(Me 2 pymS)(PPh 3 ) 2 ], [Rh(Me 2 pymS) 3 (PPh 3 )], and [IrH 2 (Me 2 pymS)(PPh 3 ) 2 ]. The new complexes have been characterised by infrared and NMR [ 1 H, 31 P{ 1 H}] spectroscopy, and shown to contain monodentate (S-bonded) or chelate (N,S-bonded) Me 2 pymS ligands.

The laminin receptors α3β1 and α6β1 are expressed by endothelial cells, but their direct roles in tumour angiogenesis and especially breast cancer angiogenesis remains unexplored. We show that α6β1-integrin is expressed in 80–90% of blood vessels associated with normal breast or ductal carcinoma in situ. However, the proportion of vessels that express α6β1 drops to less than 30% in invasive ductal carcinoma samples, suggesting that loss of this laminin receptor can enhance invasive carcinoma angiogenic events. Furthermore, the deletion of α6-integrin or α3-integrin in ex vivo angiogenic assays can promote VEGF-mediated microvessel sprouting. Taken together these results implicate these integrins in the negative control of angiogenesis. Since global deletion of the α3-integrin or α6-integrin genes in mice is lethal, we have generated mice where these genes are deleted on endothelial cells only. Our data indicate that mice deficient in individual laminin receptors on endothelial cells in vivo not only support tumour growth but have enhanced tumourigenesis. Moreover, tumour angiogenesis is elevated in these mice, suggesting strongly that laminin receptors are not required for tumour angiogenesis. We also observed that angiogenic responses to hypoxia are enhanced in mice deficient for laminin receptors on endothelial cells and have evidence that, at least in α3-null endothelial cells, VEGF-receptor 2 (FLK1) levels are elevated when compared with controls. We provide the first evidence that α3-integrin and α6-integrin can be differentially expressed in the angiogenic vessels associated with invasive carcinoma of the breast and suggest that these laminin receptors can negatively regulate angiogenesis in vivo and ex vivo.

Platinum metal hydrido and trifluoroacetato complexes react with N,N′-diphenylamidines, PhNC(R)NHPh (R = H, Me, Et, Ph), giving the amidinato derivatives Ru{PhNC(R)NPh}2(CO)(PPh3), MX{PhNC(R)NPh}(CO)(PPh3)2 and IrX2{PhNC(R)NPh}(PPh3)2 (M = Ru, Os; X = H, Cl; X2 = H2, Cl2 or HCl). The reactions of RuH2(PPh3)4 and OsH4(PPh3)3 with amidines are accompanied by an avid alcohol decarbonylation reaction to form the carbonyls MH{PhNC(R)NPh}(CO)(PPh3)2.

Trifluoroacetamide reacted with [RuCl2(PPh3)3]–NEt3 in boiling toluene to afford the binuclear species [Ru2(µ-Cl)(µ-H){µ-NHC(O)CF3}2(PPh3)4]1a(‘head-to-tail’ N,O-amidato bridged isomer). In contrast use of [RuH(Cl)(PPh3)3] as the ruthenium precursor led to formation of 1a as a mixture of ‘head-to-tail’ and ‘head-to-head’ isomers plus a small amount of another product 2a which is tentatively formulated as [Ru2(µ-H){µ-NHC(O)CF3}3(PPh3)4] with one N- and two N,O-bridging amidate ligands. Carbonylation of these products in boiling toluene yielded dicarbonyl species [Ru2(µ-Cl)(µ-H){µ-NHC(O)CF3}2(CO)2(PPh3)2]3a(‘head-to-tail’ and ‘head-to-head’ isomers) plus a trace of [Ru2(µ-H){µ-NHC(O)CF3}3(CO)2(PPh3)2]4a. Under similar conditions trifluoroacetamide reacted with [RuH2(CO)(PPh3)3], [Ru(CO)3(PPh3)2], [OsH2(CO)(PPh3)3] and mer-[IrH3(PPh3)3] to yield the mononuclear products [Ru{NHC(O)CF3}2(CO)(H2O)(PPh3)2]5a, [Ru{NHC(O)CF3}2(CO)2(PPh3)2]6a, [OsH{NHC(O)CF3}(CO)(PPh3)3]7a and [IrH2{NHC(O)CF3}(PPh3)3]8a respectively, all of which contain monodentate N-bonded trifluoroacetamidate ligands. Pentafluoropropionamide and pentafluorobenzamide yielded analogous products 1b, 2b, 3b and 8b, and 1c respectively. The crystal structure of [Ru2(µ-Cl)(µ-H){µ-NHC(O)C2F5}2(PPh3)4]1b has been determined. All other products were characterised by infrared and NMR spectroscopy.

Trifluoroacetamidine, NHC(CF3)–NH2, underwent a condensation reaction in the presence of certain platinum metal hydrides in boiling toluene to liberate ammonia and form complexes containing the N,N′-chelating 1,1,1,5,5,5-hexafluoro-3-azapentane-2,4-diiminate ligand NHC(CF3)NC(CF3)NH. Complexes prepared in this manner were [[graphic omitted]H}H(CO)(PPh3)2, [[graphic omitted]H}Cl(CO)(PPh3)2, [[graphic omitted]H}2(PPh3)2(M = Ru or Os) and [[graphic omitted]H}H2(PPh3)2. Under similar conditions [Ru(O2CCF3)2(CO)(PPh3)2reacted to afford the complex [[graphic omitted]H}(O2CCF3)(CO)(PPh3)2 in which intramolecular hydrogen bonding between the non-co-ordinated oxygen of the monodentate trifluoroacetate ligand and the adjacent NH moiety has been detected. An X-ray crystallographic study performed on [[graphic omitted]H}H(CO)(PPh3)2has confirmed an octahedral ruthenium(II) structure with trans-phosphine ligands and a chelating NHC(CF3)NC(CF3)NH– moiety.

Benzamide reacts with [RuH2(CO)(PPh3)3] and [RuH(Cl)(PPh3)3] or [RuCl2(PPh3)3]–NEt3 in boiling toluene to afford the amidato products [(Ph3P)(OC) [graphic omitted]6H4}{µ-NHC(O)Ph}(µ-H)Ru(CO)(PPh3)2]1a and [Ru2(µ-Cl)(µ-H){µ-NHC(O)Ph}2(PPh3)4]2a respectively as orange or red air-stable crystals. Parallel reactions with o-, m- and p-toluamides yield analogous products 1b–1d and 2b–2d. Carbonylation of [Ru2(µ-Cl)(µ-H){µ-NHC(O)Ph}2(PPh3)4] in boiling toluene affords the dicarbonyl [Ru2(µ-Cl)(µ-H){µ-NHC(O)Ph}2(CO)2(PPh3)2]3. Benzamide also reacts with [OsH2(CO)(PPh3)3] to yield the bis(benzamidato) complex [Os{NHC(O)Ph}2(CO)2(PPh3)2]4. A crystallographic study of 1a established a binuclear structure bridged by hydride, benzamidate(1–) and benzamidate(2–) ligands.

The complexes (MH(O2CCF3) (CO) (PPh3)2] and (M(O2CCF3)2(CO)(PPh3)2] (M = Ru or Os) react with terminal and internal acetylenes to afford oligomerisation and hydrogenation products, respectively, together with vinylic complexes, including the ruthenium species [Ru(C4HPh2)(O2CCF3)(CO) (PPh3)2], which has been shown by x-ray diffraction methods to contain a 1,4-diphenylbut-1-en-3-yn-2-yl ligand.

Ruthenium and osmium hydridonitrosyl complexes, [MH(NO)(PPh3)3], react with perfluorocarboxylic acids RCO2H (R = CF3 or C2F5) to afford the products [Ru(O2CR)3(NO)(PPh3)2] and [OsH(O2CR)2(NO)(PPh3)2] respectively. The reaction intermediates [RuH(O2CR)2(NO)(PPh3)2] and [OsH2(NO)(PPh3)3]+ have been detected in solution by 1H and 31P-{1H} n.m.r.; the latter species has been isolated and characterised as the tetraphenylborate salt. The ruthenium dinitrosyl complex [Ru(NO)2(PPh3)2] reacts with the acids RCO2H in boiling toluene or 2-methoxyethanol to afford the products [Ru(O2CR)3(NO)(PPh3)2]. The corresponding osmium complex [Os(NO)2(PPh3)2] reacts with the same acids in boiling 2-methoxyethanol and boiling toluene to yield the hydrides [OsH(O2CR)2(NO)(PPh3)2] and the novel hydroximate derivatives [[graphic omitted]R}(O2CR)(NO)(PPh3)2] respectively. Possible mechanisms for these reactions are discussed. The X-ray crystal structure of [[graphic omitted]CF3}(O2CCF3)(NO)(PPh3)2]·CH2Cl2 has been determined. The crystals are triclinic, space group P, with a= 12.709(3), b= 22.694(8), c= 9.662(3)A, α= 118.28(3), β= 113.59(3), γ= 59.66(4)°, and Z= 2. The structure has been refined to R(F)= 0.051 and R′(F)= 0.049 for 4 730 observed reflections. The complex contains six-co-ordinated osmium(II) bound to a chelate O,O′-trifluoroacetohydroximate(2–) ligand, a unidentate trifluoroacetate ligand, a linear nitrosyl group, and a pair of mutually cis triphenylphosphine ligands.

The hydrides [MH(O2CCF3)(CO)(PPh3)2] (M = Ru or Os) react with disubstituted acetylenes PhCCPh and PhCCMe to afford vinylic products [M{C(Ph)CHPh}(O2CCF3)(CO)(PPh3)2] and [M{C(Ph)CHMe}(O2CCF3)(CO) (PPh3)2]/[M{C(Me)CHPh}(O2CCF3)(CO)(PPh3)2] respectively. Acidolysis of these products with trifluoroacetic acid in cold ethanol liberates cis-stilbene and cis-PhHCCHMe respectively thus establishing the cis-stereochemistry of the vinylic ligands. The complexes [M(O2CCF3)2(CO)(PPh3)2] formed during the acidolysis step undergo facile alcoholysis followed by β-elimination of aldehyde to regenerate the parent hydrides [MH(O2CCF3)(CO)(PPh3)2] and thereby complete a catalytic cycle for the transfer hydrogenation of acetylenes. The molecular structure of the methanol-adduct intermediate, [Ru(O2CCF3)2(MeOH)(CO)(PPh3)2] has been determined by X-ray methods and shows that the coordinated methanol is involved in H-bonding with the monodentate trifluoroacetate ligand [MEO-H---OC(O)CF3; O...O = 2.54 A]. The hydrides [MH(O2CCF3)(CO) (PPh3)2]react with 1,4-diphenylbutadiyne to afford the complexes [M{C(CCPh)CHPh} (O2CCF3)(CO)(PPh3)2]. The ruthenium product, which has also been obtained by treatment of [RuH(O2CCF3)(CO)(PPh3)2] with phenylacetylene, has been shown by X-ray diffraction methods to contain a 1,4-diphenylbut-1-en-3-yn-2-yl ligand. The osmium complexes [Os(O2CCF3)2(CO)(PPh3)2], [OsH(O2CCF3)(CO)(PPh3)2] and [Os{C(CCPh)CHPh}(O2CCF3)(CO)(PPh3)2] all serve as catalysts for the oligomerisation of phenylacetylene. Acetylene reacts with [Ru(O2CCF3)2(CO)(PPh3)2] in ethanol to afford the vinyl complex [Ru(CHCH2)(O2CCF3)(CO)(PPh3)2].

The chelating diphosphines Ph2P(CH2)nPPh2(n= 1–3) react with binuclear carboxylato complexes [Ru2(O2CR)4Cl](R = Me, Et, or Ph) in cold or refluxing benzene to yield products trans-[Ru(O2CR)2{Ph2P(CH2)nPPh2}2] and cis-[Ru(O2CR)2{Ph2P(CH2)nPPh2}2] respectively, both of which are readily converted to the tetraphenylborate salts [Ru(O2CR){Ph2P(CH2)nPPh2}2]BPh4. Attempts to obtain similar products using samples of [Ru2(O2CR)4Cl](R = CF3 or But), prepared from the corresponding acetate complex by treatment with the appropriate carboxylic acids under vigorous conditions, gave mixtures indicative of incomplete carboxylato exchange. The trans complexes [Ru(O2CR)2(Ph2PCH2PPh2)2] react with NaBH4 and CO to afford cis- and trans-[RuH2(Ph2PCH2PPh2)2] and cis,cis,trans-[ Ru(O2CR)2(CO)2(Ph2PCH2PPh2)2] respectively. The latter species react with NaBH4 to yield cis- and trans-[RuH2(CO)(Ph2PCH2PPh2)2]. Several of these products contain pendant Ph2PCH2PPh2 ligands. The corresponding complexes containing Ph2P(CH2)2PPh2 failed to carbonylate even under vigorous conditions. The relationship between chelate ring size and 31P n.m.r. parameters for some of these complexes is discussed. Confirmation that the cations contained in the tetraphenylborate salts are mononuclear and not, as previously suggested elsewhere, binuclear has been provided by an X-ray diffraction study of one such salt [Ru(O2CMe)(Ph2PCH2PPh2)2]BPh4. The crystals are triclinic, space group P(no. 2), with a= 14.693(5), b= 18.821(4), c= 11.807(3)A, α= 95.39(2), β= 108.03(2), γ= 92.43(2)°, and Z= 2 at 144(2) K. The complex contains tris(chelate)ruthenium(II) cations with bidentate acetate and bis(diphenylphosphino)methane ligands together with tetraphenylborate anions.

The ruthenium(I) triazenido complexes [Ru(ArNNNAr)(C0)3]2 (Ar = p-C6H4Me or p-C6H4Cl) have been prepared by heating RU3(CO)12 with free triazene in benzene under a carbon monoxide atmosphere, and by heating [Ru(O2CMe)(CO)2]n with free triazene and triethylamine in acetonitrile under carbon monoxide. Reactions of the diruthenium(I/I) triazenido complexes with PPh3, P(OME)3 or ArNNNHAr (Ar =p-C6H4Cl) afford axial substitution products of the general form [Ru(ArNNNAr)(CO)2L]2. However, with ArNNNHAr (Ar = p-C6H4Me) cleavage of triazene to generate axial p-toluidine ligands occurs. The structure of the p-toluidine adduct, [Ru(ArNNNAr)(CO)2(NH2Ar)]2 has been determined by X-ray diffraction methods. The compound crystallizes in space group P 1 with a = 11.350(1), b = 20.582(4), c= 10.371(5) A, α = 100.75(4), β = 104.30(3), γ = 84.40(1)°; U = 2303.89 A3 and Z = 2.

The complexes [MCl2(CO)(AsPh3)3] (M = Ru or Os) have been prepared by addtition of EuCl3· 3H2O or Na2OsCl6· 6H2O and aqueous formaldehyde to excess triphenylarsine in boiling 2-methoxyethanol. Similar reaction, modified by addition of triethylamine, afford the corresponding hydrides [MHCl(CO)(AsPh3)3]. In boiling toluene the complexes [MCl2(CO)(AsPh3)3] readily eliminate triphenylarsine to form binuclear complexes [M2Cl4(CO)2(AsPh3)4]. Carbonylation of the complexes [MCl2(CO)(AsPh3)3] and [MHCl(CO)(AsPh3)3] in boiling benzene affords the dicarbonyls [MCl2(CO)2(AsPh32] and [MHCl(CO)2(AsPh3)2] respectively. Reduction of the complexes [MCl2(CO)(AsPh3)3] with sodium borohydride in ethanol yields the corresponding dihydrides [MH2(CO)(AsPh3)3]. The tetrahydride [OsH4(AsPh3)3] is readily prepared from Na2OsCl6· 6H2O, triphenylarsine and sodium borohydride in ethanol, the facial isomer of [IeH3(AsPh3)3] is similarly obtained from Na2IrCl6· 6H2O. By careful adjustment of pH and chloride ion concentration the reaction of Na2IrCl6· 6H2O with triphenylarsine in boiling 2-methoxyethanol can be made to yield [IrH2Cl(AsPh3)3], [IrHCl2(AsPh3)3] or [IrCl3(AsPh3)3]. Attempts to prepare a range of other platinum metal triphenylarsine complexes are described. The new complexes have been characterised by elemental analysis, melting point and spectroscopic data.

The complex “Cu(SO4)(btaH)4·2H2O” (btaH = benzotriazole) deposited as deep blue crystals from aqueous CuSO4·5H2OH2SO4btaH solutions been shown by X-ray diffraction methods to be a monohydrate [Cu(SO4)(H2O)(btaH)3·btaH]. The crystals contain five-coordinate, tetragonal pyramidal Cu(SO4)(H2O)(btaH)3 units and bridging btaH molecules linked together by a three-dimensional array of H-bonding interactions.

p-Tolyl iso cyanate (RNCO) undergoes coordination and fragmentation reactions with [MHX(CO) (PPh3)3] (M = Ru or Os; X = Cl or Br), [MH2(CO)(PPh3)3] and [RuH2(PPh3)4] or [OSH4(PPh3)3] to yield products containing formamido , ureylene [RNC(O)NR] and formamidinato ligands respectively.

The reactions of PriNCNPri with the complexes [RuH(X)(CO)(PPh3)3](X = Cl or Br) in boiling benzene involve insertion of the carbodi-imide moiety into the Ru–H bond and concomitant dehydrogenation of an isopropyl group to yield the derivatives [RuX{CH2C(Me)N CH NCHMe2}(CO)(PPh3)2]. A single-crystal X-ray diffraction study of the chloro-complex (X = Cl) has confirmed the presence of an N-isopropenyl-N′-isopropylformamidinate ligand in which the isopropenyl skeleton is essentially coplanar with, and conjugated to, the formamidinate group. The crystals are monoclinic, space group P21/a, with a= 17.836(2), b= 18.443(3), c= 12.607(1)A, β= 104.59(3)°, and Z= 4. The structure has been solved via the heavy-atom method and refined by least squares using 4 381 observed [I > 1.5σ(l)] diffractometer intensities to a final R of 0.086. The octahedral molecule comprises two trans phosphines [Ru–P 2.383(4) and 2.400(4)A], a chelating formamidinate ligand [Ru–N 2.048(10) and 2.242(10)A], a carbonyl group [Ru–C 1.805(12)A], and a chlorine atom [Ru–Cl 2.434(4)A], the latter being trans to the more strongly bound nitrogen atom. The complex [OsH2(CO)(PPh3)3] reacts with PriNCNPri to afford the intermediate product [OsH(Me2HCN CH NCHMe2)(CO)(PPh3)2] which, on further heating, dehydrogenates to [OsH{CH2C(Me)N CH NCHMe2}(CO)(PPh3)2] in good yield.

The complexes [MHCl(CO)(PPh3)3] (M = Ru or Os) readily undergo substitution at the site trans to the hydride ligand to afford phosphinite-, phosphonite-, or phosphite-containing products [MHCI(CO)(PPh3)2L] [L = P(OR)Ph2, P(OR)2Ph or P(OR)3 respectively; R = Me or Et]. The ruthenium complexes alone undergo further substitution to afford complex cations [RuH(CO)(PPh3)nL4−n]+ [n = 2, L = P(OMe)3; n = 1, L = P(OR)3; n = 0, L = P(OR)2Ph or P(OR)Ph2] which were isolated and characterised as their tetraphenylborate salts. Synthesis of the cationic complexes [IrHL5][BPh4]2 [L = P(OR)3, R = Me or Et] is also reported. Stereochemical assignments based on NMR data are given, and second order 31P and high field 1H NMR patterns are analysed.

The precursors MH 2 (CO)(PPh 3 ) 3 (M = Ru or Os), Ru(CO) 3 (PPh 3 ) 2 /OsH 2 (CO) 2 (PPh 3 ) 2 and IrH(CO)(PPh 3 ) 3 react with 1,3,4-thiadiazole-2,5-dithiol (tddtH 2 ) in boilig toluene to afford the 1,3,4-thiadiazole-2,5-dithiolato (tddtH) complexes M(tddtH) 2 (CO)(PPh 3 ) 2 , M(tddtH) 2 (CO) 2 (PPh 3 ) 2 and IrH(tddtH) 2 (CO)(PPh 3 ) 2 respectively. The molecular structure of the ruthenium complex Ru(tddtH) 2 (CO)(PPh 3 ) 2 has been determined by X-ray diffraction methods, the crystals are triclinic space group P 1 , Z = 2, unit cell dimensions are a = 13.051(3), b = 16.404(7), c = 16.500(5) A, α = 119.60(2), β = 91.46(2), γ = 104.21(3)°, ( V = 2932.0(16) A 3 . The structure contains octahedral ruthenium(II) with mon-dentate (S-coordinated) and bi-dentate (N,S-coordinated) tddtH ligands, a carbonyl group and a trans pair of triphenylphosphine ligands. The complexes M(tddtH) 2 (CO)(PPh 3 ) 2 and the closely related ruthenium 5-methyl-1,3,4-thiadiazole 2-thiolato complex Ru(mtdt) 2 (CO)(PPh 3 ) 2 have been shown by 1 H NMR to display dynamic interchange of mono- and bi-dentate thiolate ligands. Some rhodium(I), palladium(0) and platinum(0) complexes of tddtH 2 are tentatively reformulated.

Nitrato complexes of the platinum group metals have been prepared by treating selected hydridic or zero oxidation state precursors with nitric acid, neat or in organic media. Products obtained in this manner include [M(NO,),(CO)(PPh,),], [.M(NOJ2(CO)2(PPh3),1 (M = Ru or Os), [M’(NO,),(PPh,),], and [M’(NO,),(NO)(PPh,),] (M’ = Rh or Ir). The species [M(N03),(CO)(PPh,)2] undergo carbonylation to yield the dicarbonyls [M(N0,)2(CO)2(PPh3)2] and alcoholysis followed by P-elimination to form the hydrides [MH(NO,)(CO)(PPh,),]. The latter products are readily carbonylated to afford the species [MH(NO,)(CO),(PPh,),]. The new complexes have been characterized and their stereochemistry has been assigned by reference to spectroscopic data. The complex “Rh(N03)(NO)2(0PPh3)2” has been reformulated as [Rh(N03)2(NO)(PPh,)2]. However, one product obtained on treating [RuH,(CO)(PPh,),] with nitric acid has been tentatively identified as a triphenylphosphine oxide derivative [Ru(N0,),(NO)(OPPh3)(PPh,)]. The ability of [RU(NO,)~(CO)(PP~,)~] to catalyze the dehydrogenation of primary and secondary alcohols is noted.

1,3-Diaryltriazenes, ArN = NNHAr (Ar = Ph, p-MeC6H4 and p-MeOC6H4) react with platinum metal halide complexes in the presence of triethylamine to afford products containing mono- or bi-dentate (chelate or bridging) 1,3-diaryltriazenide ligands. Complexes prepared in this manner include derivatives of ruthenium(II), 2(PPh3)2] and (CO)(PPh3)2]; rhodium(I), 2], (C8H12)(PPh3)] and (CO)(PPh3)2]; palladium(II) L2] (X = Cl, L = PPh3, PEt3, AsPh3, PMePh2; X = Br, L = PMePh2; X = I, L = PMe2Ph), and 2(PMe2Ph)2]; and platinum(II(, [PtCl L2] (L = PPh3, PEt3, and PEt2Ph; L = C8H12). The intramolecular N(1)–N(3) exchange process: displayed by the monodentate 1,3-diaryltriazenido derivatives of rhodium(I), palladium(II) and platinum(II) have been studied by dynamic proton NMR spectroscopy, and thermodynamic parameters of activation have been determined. ΔH≠ values were found to lie within the range ca. 32–44 kJ mol−1 for the palladium(II) and platinum(II) complexes, ΔS≠ values are all negative.

The ruthenium(II) and osmium(II) complexes MCl 2 (PPh 3 ) 3 , undergo oxidative substitution reactions with β-diketones under aerobic conditions in warm benzene to afford ruthenium(III) and osmium(III) β-diketonate complexes, MCl 2 (β-diketonate)(PPh 3 ) 2 . Generally these products appear to adopt the less sterically hindered trans -phosphine stereochemistry, but one example, RuCl 2 {CF 3 C(O)CHC(O)CF 3 }(PPh 3 ) 2 , deposits from hot and cold reactions as yellow ( trans -phosphines) and red ( cis -phosphines) isomers, respectively.

Reactions of 4,6-dimethylpyrimidine-2-thiol (Me 2 pymSH) and its oxidation product bis(4,6-dimethylpyrimidine-2-yl)disulphide (Me 2 pymSSpymMe 2 ) with a range of platinum metal complexes are described. The chlorohydrides [MHCl(CO)(PPh 3 ) 3 ] (M=Ru, Os) react with Me 2 pymSH in refluxing toluene to afford [RuCl(Me 2 pymS)(CO)(PPh 3 ) 2 ] and [OsH(Me 2 pymS)(CO)(PPh 3 ) 2 ] (two isomers). A similar reaction in cold benzene affords the substitution product [RuH(Cl)(Me 2 pymSH)(CO)(PPh 3 ) 2 ] (two isomers). Reaction of the precursors [MH 2 (CO)(PPh 3 ) 3 ] (MRu, Os) and [Ru(CO) 3 (PPh 3 ) 2 ] in boiling toluene afford [MH(Me 2 pymS)(CO)(PPh 3 ) 2 ] (two isomers) and [Ru(Me 2 pymS) 2 (CO)(PPh 3 )] (two isomers) respectively whilst the reaction of [Ru(CO) 3 (PPh 3 ) 2 ] with Me 2 pymSSpymMe 2 yields a mixture of [Ru(Me 2 pymS) 2 (CO) 2 (PPh 3 )] and [Ru(Me 2 pymS) 2 (CO)(PPh 3 )]. In the presence of the base (NEt 3 ) the dichlorides [MCl 2 (PPh 3 ) 3 ] (M=Ru, Os) react with Me 2 pymSH to afford the bis-chelates [M(Me 2 pymS) 2 (PPh 3 ) 2 ]. Reactions between Me 2 pymSH and the precursors [IrCl(CO)(PPh 3 ) 2 ] and [IrH(CO)(PPh 3 ) 3 ] at ambient temperature or below afford [IrH(Cl)(Me 2 pymS)(CO)(PPh 3 ) 2 ] and [IrH 2 (Me 2 pymS)(CO)(PPh 3 ) 2 ] respectively, the same ligand reacts with [RhCl(PPh 3 ) 3 ] and mer -[IrH 3 (PPh 3 ) 3 ] in refluxing benzene to afford [RhH(Cl)(Me 2 pymS)(PPh 3 ) 2 ], [Rh(Me 2 pymS) 3 (PPh 3 )], and [IrH 2 (Me 2 pymS)(PPh 3 ) 2 ]. The new complexes have been characterised by infrared and NMR [ 1 H, 31 P{ 1 H}] spectroscopy, and shown to contain monodentate (S-bonded) or chelate (N,S-bonded) Me 2 pymS ligands.