Aminomethyl tetrahydronaphthalene ketopiperazine MCH-R1 antagonists--Increasing selectivity over hERG

A direct correlation between hERG binding and QTc prolongation was established for a series of aminomethyl tetrahydronaphthalene ketopiperazine MCH-R1 antagonists. Compounds within this class with greater selectivity over hERG were developed. Compound 4h proved to have the best profile, with MCH-R1 Ki = 16 nm and hERG IC50 = 25 microM.     

Relationship between small-scale structural variability and simulated vegetation productivity across a regional moisture gradient in southern Africa

The observed variability in vegetation structure within landscapes was used as the basis for model estimates of the range of annual productivity of landscape patches at four sites along a moisture gradient in southern Africa ranging from 879 to 365 mm mean annual rainfall. Principal components of patch‐scale variability in leaf area, woody biomass and vertical leaf profiles were derived from intensive characterization of the small‐scale spatial structure of woody vegetation at each site. For each site, the mean and extremes of the principal component distribution parameterized an ecophysiology model of vegetation productivity. Vegetation was most heterogeneous at intermediate locations along the rainfall gradient. Variability in vegetation structure led to a range of annual productivity within one site (600 mm) that accounted for 68% of the total range in mean productivity across all sites. Patch‐scale estimates of tree productivity were found to be primarily correlated to annual rainfall (r²=0.66, P=0.001) and not woody leaf area (r²=0.01, P=0.75), while grass productivity was found to be related to values of woody leaf area (r²=0.77, P<0.001) and not annual rainfall (r²=0.11, P=0.29). This result indicates that life‐form interactions have a significant role in controlling vegetation productivity across the rainfall gradient. The findings of this study emphasize the importance of considering heterogeneity rather than mean structure when modeling productivity, particularly when considering dynamic vegetation structure, where differences between landscape patches may not be well represented in the mean structure.     

Dye-sensitized photooxidation of phenanthrene

The dye-sensitized photooxidation of phenanthrene has been studied in a two-phase system employing $\text{n}$-hexane and water. Rose bengal was used as a sensitizer. A number of volatile oxidation products are observed and characterized by GC-MS-COM methods. The data suggest that one oxidation route involves the conversion of phenanthrene to 9,10-epoxy-9,10-dihydrophenanthrene which is related to the potentially carcinogenic arene oxides of more highly condensed polynuclear hydrocarbons. These results may have significance in connection with the enhancement of aberrant effects on biological systems produced by polynuclear hydrocarbons upon exposure to light.     

Combination of high-performance liquid chromatography and thin-layer chromatography separation of five adducted nucleotides isolated from liver resulting from intraperitoneal administration with 7H-dibenzo[c,g]carbazole to mice

7H-Dibenzo[c,g]carbazole, DBC, is a potent environmental liver carcinogen. Liver DNA from mice treated with DBC exhibited seven distinct DBC-DNA adducts as detected by ³²P-postlabeling using multidimensional TLC. To improve quantitation and chemically characterize the adducts, DNA samples were hydrlyzed, ³²P-postlabeled and the adducts were separated from the unadducted normal nucleotides on TLC using a D1 solvent, 0.65 M sodium phosphate (pH 6.8). Adducts were eluted from the TLC plates with 4.0 M pyridinium formate, concentrated, resuspended in 50% aqueous methanol and injected onto the HPLC; five individual adduct peaks were resolved and collected by this method. This approach will prove useful to decrease analysis time and improve chemical characterization of tightly clustered DNA adducts generated in vivo.