Synthesis and Characterization of a Series of Uranium(IV) Species: Investigating Coordination With a Redox Innocent Triamine Ligand

Investigation of uranium(IV) complexes chelated by a tridentate amine, H3RITA (H3RITA = (MesNHCH2CH2)2NH, Mes = 2,4,6-trimethylphenyl), has afforded novel new compounds with the potential for small molecule activation. Deprotonation of H3RITA with two equivalents of benzyl potassium affords K2HRITA, which upon reaction with uranium tetrachloride forms (THF)2UCl2(HRITA) (THF = tetrahydrofuran). The labile THF molecules are easily substituted for triphenylphosphine oxide (OPPh3), a much stronger ligand, forming (Ph3PO)UCl2(HRITA). Installation of a cyclopentadienyl ligand, Cp* (Cp* = 1,2,3,4,5-pentamethylcyclopentadienyl), was achieved by the metathesis of (THF)2UCl2(HRITA) with KCp* to form Cp*UCl(HRITA). For Cp*UCl(HRITA), full deprotonation of the RITA ligand was possible by using the strong base, methyllithium. The reaction of methyllithium with Cp*UCl(HRITA) affords Cp*U(RITA)(LiCl(THF)2)—a uranium species containing a weakly bound lithium chloride ligand. Replacement of the lithium chloride with triphenylphosphine oxide forms the neutral species, Cp*U(RITA)(OPPh3), which contains a rare trianionic RITA ligand. All complexes have been characterized by 1H NMR and IR spectroscopies, and where possible, their electronics were probed by electronic absorption spectroscopy. The molecular structures of (THF)2UCl2(HRITA), (Ph3PO)UCl2(HRITA), Cp*UCl(HRITA), and Cp*U(RITA) (LiCl(THF)2) were determined by single X-ray diffraction studies

Use of 15N NMR spectroscopy to probe covalency in a thorium nitride.

Reaction of the thorium metallacycle, [Th{N(R)(SiMe2)CH2}(NR2)2] (R = SiMe3) with 1 equiv. of NaNH2 in THF, in the presence of 18-crown-6, results in formation of the bridged thorium nitride complex, [Na(18-crown-6)(Et2O)][(R2N)3Th(μ-N)(Th(NR2)3] ([Na][1]), which can be isolated in 66% yield after work-up. Complex [Na][1] is the first isolable molecular thorium nitride complex. Mechanistic studies suggest that the first step of the reaction is deprotonation of [Th{N(R)(SiMe2)CH2}(NR2)2] by NaNH2, which results in formation of the thorium bis(metallacycle) complex, [Na(THF) x ][Th{N(R)(SiMe2CH2)}2(NR2)], and NH3. NH3 then reacts with unreacted [Th{N(R)(SiMe2)CH2}(NR2)2], forming [Th(NR2)3(NH2)] (2), which protonates [Na(THF) x ][Th{N(R)(SiMe2CH2)}2(NR2)] to give [Na][1]. Consistent with hypothesis, addition of excess NH3 to a THF solution of [Th{N(R)(SiMe2)CH2}(NR2)2] results in formation of [Th(NR2)3(NH2)] (2), which can be isolated in 51% yield after work-up. Furthermore, reaction of [K(DME)][Th{N(R)(SiMe2CH2)}2(NR2)] with 2, in THF-d 8, results in clean formation of [K][1], according to 1H NMR spectroscopy. The electronic structures of [1]- and 2 were investigated by 15N NMR spectroscopy and DFT calculations. This analysis reveals that the Th-Nnitride bond in [1]- features more covalency and a greater degree of bond multiplicity than the Th-NH2 bond in 2. Similarly, our analysis indicates a greater degree of covalency in [1]- vs. comparable thorium imido and oxo complexes

Human trophoblast function during the implantation process

The implantation process involves complex and synchronized molecular and cellular events between the uterus and the implanting embryo. These events are regulated by paracrine and autocrine factors. Trophoblast invasion and migration through the uterine wall is mediated by molecular and cellular interactions, controlled by the trophoblast and the maternal microenvironment. This review is focused on the molecular constituents of the human trophoblast, their actions and interactions, including interrelations with the uterine endometrium

Ets-2 and p53 mediate cAMP-induced MMP-2 expression, activity and trophoblast invasion

<p>Abstract</p> <p>Background</p> <p>We have previously shown that Matrix metalloproteinase (MMP) -2 is a key-enzyme in early trophoblast invasion and that Protein Kinase A (PKA) increases MMP-2 expression and trophoblast invasion. The aim of this study was to examine MMP -2 regulation by PKA in invasive trophoblasts: JAR choriocarcinoma cell-line and 6-8 w first trimester trophoblasts.</p> <p>Methods</p> <p>The effect of Forskolin (PKA) on MMP-2 expression was assessed by Northern Blot and RT-PCR. Possible transcription factors binding to consensus MMP-2 promoter sequences in response to Forskolin, were detected by EMSA binding assay and their expression assessed by western blot analysis. Antisense transfection of relevant transcription factors was performed and the inhibitory effect assessed on MMP-2 expression (RT-PCR), secretion (zymography) and trophoblast invasiveness (transwell migration assay).</p> <p>Results</p> <p>We found that Forskolin increased MMP-2 mRNA in JAR cells within 24 hours, and induced binding to p53, Ets, C/EBP and AP-2. Transcription factors Ets-2, phospho- p53, C/EBP epsilon, C/EBP lambda and AP-2 alpha bound to their respective binding sequences in response to Forskolin and the expressions of these transcription factors were all elevated in Forskolin- treated cells. Inhibition of Ets-2 and p53 reduced MMP-2 expression, secretion and invasiveness of Forskolin treated cells.</p> <p>Conclusion</p> <p>MMP-2 is regulated by PKA through several binding sites and transcription factors including Ets-2, p53, C/EBP, C/EBP lambda and AP-2 alpha. Ets-2 and p53 mediate cAMP- induced trophoblast invasiveness, through regulation of MMP-2.</p

Expression and importance of matrix metalloproteinase 2 and 9 (MMP-2 and -9) in human trophoblast invasion

BACKGROUND: The aim of this study was to examine the invasiveness of first trimester trophoblasts according to the secretion profile of MMP-2 and -9 at different gestational stages, and to test the similarity between primary trophoblast cell-culture and the JAR choriocarcinoma cell-line. METHODS: First trimester trophoblasts were divided into two groups: 6–8 weeks (early) and 9–12 w (late) of gestation. The two trophoblast groups and JAR cells were cultured in medium, with various concentrations of forskolin and Epidermal Growth Factor (EGF). Proteolytic activity was detected by zymography and invasiveness was assessed by Matrigel invasion assay. Student's T-test was used for statistical analysis. RESULTS: In 6–8 w trophoblast, proMMP-2 was only slightly dominant over proMMP-9 (53.2% vs. 46.8% respectively), whereas in 9–12 w, proMMP-9 was clearly dominant over proMMP-2 (61.7% vs.38.3% respectively). In JAR cells proMMP-2 was strongly dominant (90.2% vs.9.8% respectively). In JAR cells forskolin significantly increased proMMP-2 and -9 secretion (128.5% +/- 12 and 183.2% +/- 27.9 of control, respectively). EGF had a dual effect on JAR cells: at 8 ng/ml both proMMP-2 and -9 were increased (133.5% +/-15 and 223.9% +/- 32.4 of control, respectively) while at 80 ng/ml both proMMP-2 and -9 were decreased (65.1% +/- 18.3 and 66.6% +/- 37 of control, respectively). Forskolin significantly increased both proMMP-2 and -9 secretion in 6–8 w and 9–12 w trophoblasts (125.9% +/- 6.3,128.4% +/- 6.4; 169.7% +/- 20.3, 120.3% +/- 4.5 of control, respectively). EGF also significantly increased both proMMP-2 and -9 secretion in 6–8 w and 9–12 w trophoblasts (141.22% +/- 14.8, 138.8% +/- 10.3; 168.3% +/- 18.2, 117.3 +/- 3.8 of control, respectively). Both forskolin and EGF increased trophoblast cells invasiveness in all groups. The invasive ability of trophoblast cells, induced by forskolin, was reduced by MMP-2 antibody in: JAR cells, 6–8 w and 9–12 w trophoblasts. Likewise trophoblast invasion induced by EGF was reduced by MMP-2 antibody in all groups. However the invasive ability induced by forskolin or EGF was inhibited by MMP-9 antibody only in trophoblasts from 9–12 w. CONCLUSIONS: First trimester trophoblasts express differential gelatinase secretion profile according to the gestational week. In JAR and early trophoblasts (6–8 w) MMP-2 is the main gelatinase and the key enzyme in trophoblast invasion. Thereafter in late first trimester trophoblasts (9–12 w), both MMP-2 and -9 participate in trophoblast invasion

Bone mineral density in patients on home parenteral nutrition: a follow-up study.

Home artificial nutrition