Chemistry
Adsorption and Reaction of Cyclohexanone (C6H10O) on Pt(111)
Adsorption of oxygen-containing cyclic hydrocarbons on transition-metal single-crystal surfaces is of considerable interest to practical heterogeneous catalytic reactions including hydrogenation/dehydrogenation, as well as hydrodeoxygenation reactions. We have investigated adsorption and reaction of cyclohexanone (C6H10O) on Pt(111) by using TPD, HREELS, AES, and LEED. The Pt(111) surface was very reactive towards chemisorbed cyclohexanone; adsorption in the monolayer was completely irreversible. We concluded that C6H10O had a barrier to decomposition below 11 kcal/mol; C6H10O decomposed to yield CO, H2O, H2 and CH4. At least some C-O bond breaking occurred during decomposition to form H2O and leave some amount of carbon on the surface after TPD. HREELS data showed that some cyclohexanone decomposition occurred below 90 K; all cyclohexanone decomposition in the monolayer occurred by 200 K. Studies of the chemistry of C6H10O on the (2×2) and (√3x√3)R30˚-Sn/Pt(111) surface alloys have been carried out and offer additional information about the adsorption and reaction of this molecule on alloyed surfaces.
Loss of Endogenous Oncoprotein18/Stathmin in Mouse Embryo Fibroblasts Induces Changes in Tubulin Isoform Expression with Minimal Changes to Microtubule Dynamics
Op18/Stathmin is a ubiquitous microtubule (MT) destabilizing protein linked to cancer and cell health: Op18 is over-expressed in leukemias and its expression level correlates with breast cancer stage progression. We are using MEFs (mouse embryonic fibroblasts) WT (+/+), heterozygous (+/-), or knockout (-/-) for the Op18 gene to further characterize Op18s roles in MT polymerization and dynamics. MT polymer level and nucleation rate increased with loss of Op18. In contrast, loss of one or both copies of the Op18 gene results in surprisingly modest changes to MT dynamics. For example MT dynamicity, a measure of total tubulin addition and loss from MT ends, and catastrophe frequency were similar in all three lines. Since MT dynamics depend on tubulin (Tb) isotype composition (Panda et al., 1994), we used quantitative reverse transcription-PCR to measure differences in mRNA levels for each Tb isotype. The alpha-Tb I mRNA level did not change across genotypes, but protein level nearly doubled in the (-/-) line compared to WT. Cells (-/-) for Op18 also under-express mRNA for Tbs II (20% less) and IV (36% less) and over-express Tb III (78% more) compared to WT. This change in Tb isotype expression is consistent with that observed in taxol-resistant breast cancer cells (Shalli et al., 2005). Other differentially regulated mRNAs include increases in alpha-Tb VII and VIII, and Tb VII. We conclude that cells respond to loss of Op18 by changing the ratio of tubulin isoforms, allowing cells to maintain dynamic MT turnover. We hypothesize that it is changes to MT polymer content and specific Tb isoform expression, rather than changes to MT dynamics, that are responsible for Op18s role in cancer and cell survival. Thanks to Jutta Marzillier, Lehigh Genomics Facility, and G. Shyumyatsky, Rutgers University (mice).
Funded by NIH.
Blocking Heparin-Induced MKP-1 Synthesis or Activity Intereferes with Heparin-Induced Decreases in ERK Activity
We have previously identified increases in MKP-1 synthesis in response to heparin treatment of vascular smooth muscle cells (VSMC). The MKP-1 increases correspond to decreased ERK activity in heparin-treated VSMC and were mimicked by treating the cells with antibodies that block heparin binding to cells. Here we report that while treatment of VSMC with heparin prior to activation with PMA resulted in an approximately 30% decrease in ERK activity at 15 min, the presence of vanadate (a tyrosine phosphatase inhibitor) blocked the heparin effect (p<0.05) with resulting ERK activity values that were statistically the same as those of cells not heparin treated. Vanadate treatments longer than 30 min. caused loss of cell viability. Previous reports indicated that doxorubicin treatments blocked the synthesis of MKP-1. We therefore evaluated the ability of doxorubicin to block heparin-induced MKP-1 synthesis in VSMC and found that doxorubicin treatment decreased the MKP-1 synthesis to below control levels in a dose dependent manner whether induced by heparin treatment or heparin-receptor antibody treatment. Heparin and antibody treatments resulted in between 30% and 50% decreases in serum induced ERK activity over a 30 minute time frame. The doxorubicin treated cells also retained ERK activity compared to heparin or antibody treated cells without doxorubicin. Again, the heparin-treated (and antibody-treated) cells levels of active ERK were significantly (P<0.05) different from serum activated cell active ERK levels. Together these data support a role for MKP-1 in heparin induced decreases in VSMC ERK activity. These studies were supported by PHS award HL54269.
Solvation Controlled Luminescence of Sm(II) Complexes
Changes in solvation of samarium diiodide (SmI2) can significantly alter the interaction between a ligand and metal. Addition of the appropriate crown ether to SmI2 in acetonitrile not only stabilizes the ground state complex but also generates a highly luminescent complex. The advantage of direct excitation of lanthanide(II) complexes includes elimination of different deactivation pathways as well as the multi-step syntheses involved in preparing antenna ligands necessary for producing luminescent lanthanide(III) complexes. We demonstrate how controlling the coordination sphere of SmI2 through changes in solvation induces remarkable changes both in the ground and excited states. By providing a chelating ligand for SmI2 in a solvent incapable of displacing it significantly enhances the luminescent properties of Sm(II) by: 1.) encapsulating the metal through a strong metal-ligand interaction and 2) decreasing the frequency of solvent collision. This study led to the discovery of the longest reported excited-state lifetime for a Sm(II) complex in solution.