Crystal and molecular structure of bis(8-phenylmenthyl) 2-(2-methyl-5-oxo-3-cyclohexen-1-yl)propandioate, C\u3csub\u3e42\u3c/sub\u3eH\u3csub\u3e54\u3c/sub\u3eO\u3csub\u3e5\u3c/sub\u3e• CH\u3csub\u3e3\u3c/sub\u3eCN

The X-ray crystal structure of the title compound, as crystallized from acetonitrile-water was determined. The relative stereochemistry of the cyclohexenone ring with respect to the 8-phenylmenthyl esters was determined. The title compound crystallizes in the noncentrosymmetric space group P21, with a=8.9850(10) Å, b=15.575(3) Å, c=14.478(2) Å, β=94.61(2)°, and D calc=1.118 g cm−3 for Z=2

Double Carbon−Hydrogen Activation of 2-Vinylpyridine: Synthesis of Tri- and Pentanuclear Clusters Containing the μ-NC\u3csub\u3e5\u3c/sub\u3eH\u3csub\u3e4\u3c/sub\u3eCH═C Ligand

Reactions of 2-vinylpyridine with the triruthenium complexes [Ru3(CO)12] and [Ru3(CO)10(μ-dppm)] leads to a previously unknown double carbon−hydrogen bond activation of the β-carbon of the vinyl group to afford the pentaruthenium and triruthenium complexes [Ru5(CO)14(μ4-C5H4CH═C)(μ-H)2] (1) and [Ru3Cl(CO)5(μ-CO)(μ-dppm)(μ3-NC5H4CH═C)(μ-H)] (2), respectively. Crystal structures reveal two different forms of bridging of the dimetalated 2-vinylpyridyl ligand, capping a square face in 1 and a triangular face in 2

Reactions of Rhenium and Manganese Carbonyl Complexes with 1,8-bis(diphenylphosphino)naphthalene: Ligand Chelation, C–H and C–P bond-cleavage Reactions

Reaction of [Re2(CO)8(MeCN)2] with 1,8-bis(diphenylphosphino)naphthalene (dppn) afforded three mono-rhenium complexes fac-[Re(CO)3(κ1:η1-PPh2C10H6)(PPh2H)] (1), fac-[Re(CO)3{κ1:κ1:η1-(O)PPh2C10H6(O)PPh(C6H4)}] (2) and fac-[ReCl(CO)3(κ2-PPh2C10H6PPh2)] (3). Compounds 1–3 are formed by Re–Re bond cleavage and P–C and C–H bond activation of the dppn ligand. Each of these three complexes have three CO groups arranged in facial fashion. Compound 1 contains a chelating cyclometalated diphenylnaphthylphosphine ligand and a terminally coordinated PPh2H ligand. Compound 2 consists of an orthometalated dppn-dioxide ligand coordinated in a κ1:κ1:η1-fashion via both the oxygen atoms and ortho-carbon atom of one of the phenyl rings. Compound 3 consists of an unchanged chelating dppn ligand and a terminal Cl ligand. Treatment of [Mn2(CO)8(MeCN)2] with a slight excess of dppn in refluxing toluene at 72 °C, gave the previously reported [Mn2(CO)8(μ-PPh2)2] (4), formed by cleavage of C–P bonds, and the new compound fac-[MnCl(CO)3(κ2-PPh2C10H6PPh2)] (5), which has an unaltered chelating dppn and a terminal Cl ligand. In sharp contrast, reaction of [Mn2(CO)8(MeCN)2] with slight excess of dppn at room temperature yielded the dimanganese [Mn2(CO)9{κ1-PPh2(C10H7)}] (6) in which the diphenylnaphthylphosphine ligand, formed by facile cleavage of one of the P–C bonds, is axially coordinated to one Mn atom. Compound 6 was also obtained from the reaction of [Mn2(CO)9(MeCN)] with dppn at room temperature. The XRD structures of complexes 1–3, 5, 6 are reported

X-ray Structure of \u3cem\u3emer\u3c/em\u3e-[Mo(CO)\u3csub\u3e3\u3c/sub\u3e(PPh\u3csub\u3e3\u3c/sub\u3e)(\u3cem\u3eκ\u3c/em\u3e\u3csup\u3e2\u3c/sup\u3e-dppm)]

Treatment of [Mo(CO)3(NCMe)3] with bis(diphenylphosphino)methane (dppm) and triphenylphosphine (PPh3) at 50 °C afforded mer-[Mo(CO)3(PPh3)(κ2-dppm)] (1) in 55% yield which has been characterized by single crystal X-ray diffraction studies and spectroscopic measurements. Compound 1 crystallizes in the triclinic space group P−1 with a = 10.3449(6), b = 11.1570(6), c = 17.8961(10) Å, β = 80.8400(10)°, Z = 2 and V = 1959.8(2) Å3

Reactivity of phenyldi(2-thienyl)phosphine towards Group 7 Metal Carbonyls: Carbon–phosphorus Bond Activation

Addition of phenyldi(2-thienyl)phosphine (PPhTh2) to [Re2(CO)10−n(NCMe)n] (n = 1, 2) affords the substitution products [Re2(CO)10−n(PhPTh2)n] (1, 2) together with small amounts of fac-[ClRe(CO)3(PPhTh2)2] (3) (n = 2). Reaction of [Re2(CO)10] with PPhTh2in refluxing xylene affords a mixture which includes 2, [Re2(CO)7(PPhTh2)(μ-PPhTh)(μ-H)] (4), [Re2(CO)7(PPhTh2)(μ-PPhTh)(μ-η1,κ1(S)-C4H3S)] (5) and mer-[HRe(CO)3(PPhTh2)2] (6). Phosphido-bridged 4 and 5 are formed by the carbon–phosphorus bond cleavage of the coordinated PPhTh2 ligand, the cleaved thienyl group being retained in the latter. Reaction of [Mn2(CO)10] with PPhTh2 in refluxing toluene affords [Mn2(CO)9(PPhTh2)] (7) and the carbon–phosphorus bond cleavage products [Mn2(CO)6(μ-PPhTh)(μ-η1,η5-C4H3S)] (8) and [Mn2(CO)5(PPhTh2)(μ-PPhTh)(μ-η1,η5-C4H3S)] (9). Both 8 and 9 contain a bridging thienyl ligand which is bonded to one manganese atom in a η5-fashion

Strategic & Applied Research & Coordination in Action: Climate Services for Resilient Development (CSRD) in South Asia

A global partnership that is aligned with the Global Framework for Climate Services, Climate Services for Resilient Development (CSRD) works to link climate science, data streams, decision support tools, and training with decision-makers in developing countries. CSRD is led by the United States Government and is supported by the UK Government Department for International Development (DFID), UK Meteorological Office, ESRI, Google, the Inter-American Development Bank, the Asian Development Bank, and the American Red Cross. Led by the International Maize and Wheat Improvement Center (CIMMYT), the CSRD initiative in South Asia works with partners to conduct applied research and facilitate the use of climate information to reduce risk for smallholder farmers. This report details activities of the CSRD project in South Asia during 2018, with emphasis on the second half of 201

Therapeutic potential of cladribine in combination with STAT3 inhibitor against multiple myeloma

<p>Abstract</p> <p>Background</p> <p>Cladribine or 2-chlorodeoxyadenosine (2-CDA) is a well-known purine nucleoside analog with particular activity against lymphoproliferative disorders, such as hairy cell leukemia (HCL). Its benefits in multiple myeloma (MM) remain unclear. Here we report the inhibitory effects of cladribine on MM cell lines (U266, RPMI8226, MM1.S), and its therapeutic potential in combination with a specific inhibitor of the signal transducer and activator of transcription 3 (STAT3).</p> <p>Methods</p> <p>MTS-based proliferation assays were used to determine cell viability in response to cladribine. Cell cycle progression was examined by flow cytometry analysis. Cells undergoing apoptosis were evaluated with Annexin V staining and a specific ELISA to quantitatively measure cytoplasmic histone-associated DNA fragments. Western blot analyses were performed to determine the protein expression levels and activation.</p> <p>Results</p> <p>Cladribine inhibited cell proliferation of MM cells in a dose-dependent manner, although the three MM cell lines exhibited a remarkably different responsiveness to cladribine. The IC50 of cladribine for U266, RPMI8226, or MM1.S cells was approximately 2.43, 0.75, or 0.18 μmol/L, respectively. Treatment with cladribine resulted in a significant G1 arrest in U266 and RPMI8226 cells, but only a minor increase in the G1 phase for MM1.S cells. Apoptosis assays with Annexin V-FITC/PI double staining indicated that cladribine induced apoptosis of U266 cells in a dose-dependent manner. Similar results were obtained with an apoptotic-ELISA showing that cladribine dramatically promoted MM1.S and RPMA8226 cells undergoing apoptosis. On the molecular level, cladribine induced PARP cleavage and activation of caspase-8 and caspase-3. Meanwhile, treatment with cladribine led to a remarkable reduction of the phosphorylated STAT3 (P-STAT3), but had little effect on STAT3 protein levels. The combinations of cladribine and a specific STAT3 inhibitor as compared to either agent alone significantly induced apoptosis in all three MM cell lines.</p> <p>Conclusions</p> <p>Cladribine exhibited inhibitory effects on MM cells <it>in vitro</it>. MM1.S is the only cell line showing significant response to the clinically achievable concentrations of cladribine-induced apoptosis and inactivation of STAT3. Our data suggest that MM patients with the features of MM1.S cells may particularly benefit from cladribine monotherapy, whereas cladribine in combination with STAT3 inhibitor exerts a broader therapeutic potential against MM.</p

LLL-3 inhibits STAT3 activity, suppresses glioblastoma cell growth and prolongs survival in a mouse glioblastoma model

Persistent activation of the signal transducer and activator of transcription 3 (STAT3) signalling has been linked to oncogenesis and the development of chemotherapy resistance in glioblastoma and other cancers. Inhibition of the STAT3 pathway thus represents an attractive therapeutic approach for cancer. In this study, we investigated the inhibitory effects of a small molecule compound known as LLL-3, which is a structural analogue of the earlier reported STAT3 inhibitor, STA-21, on the cell viability of human glioblastoma cells, U87, U373, and U251 expressing constitutively activated STAT3. We also investigated the inhibitory effects of LLL-3 on U87 glioblastoma cell growth in a mouse tumour model as well as the impact it had on the survival time of the treated mice. We observed that LLL-3 inhibited STAT3-dependent transcriptional and DNA binding activities. LLL-3 also inhibited viability of U87, U373, and U251 glioblastoma cells as well as induced apoptosis of these glioblastoma cell lines as evidenced by increased poly (ADP-ribose) polymerase (PARP) and caspase-3 cleavages. Furthermore, the U87 glioblastoma tumour-bearing mice treated with LLL-3 exhibited prolonged survival relative to vehicle-treated mice (28.5 vs 16 days) and had smaller intracranial tumours and no evidence of contralateral invasion. These results suggest that LLL-3 may be a potential therapeutic agent in the treatment of glioblastoma with constitutive STAT3 activation