Uses and limitations of quantitative structure-activity relationships (QSARs) to categorize substances on the Canadian domestic substance list as persistent and/or bioaccumulative,and inherently toxic to non-human organisms

Under sections 73 and 74 of the revised Canadian Environmental Protection Act (CEPA 1999) , Environment Canada and Health Canada must "categorize" and "screen" about 23,000 substances on the Domestic Substances List (DSL) for persistence (P), bioaccumulation (B), and inherently toxic (iT) properties. Since experimental data for P, B and iT are only available for a few DSL substances, a workshop was held to address issues associated with the use of Quantitative Structure-Activity Relationships (QSARs) to categorize these substances. This paper describes the results of an 11-12 November 1999 International Workshop sponsored by Environment Canada to discuss potential uses and limitations of QSARs to categorize DSL substances as either persistent or bioaccumulative and iT to non-human organisms and to recommend future research needed to develop methods for predicting the P, B and iT of difficult-to-model substances.     

Design, synthesis, and structure-activity relationships of 3,4-dihydropyridopyrimidin-2(1H)-one derivatives as a novel class of sodium/calcium exchanger inhibitor

Design, synthesis, and structure-activity relationships for 3,4-dihydropyridopyrimidin-2(1H)-one derivatives, which are aza-3,4-dihydro-2(1H)-quinazolinone derivatives, as the sodium/calcium (Na+/Ca2+) exchanger inhibitors are discussed. These studies based on 3,4-dihydro-2(1H)-quinazolinone derivatives led to the discovery of a structurally novel and potent Na+/Ca2+ exchanger inhibitor, 3,4-dihydropyridopyrimidin-2(1H)-one derivative (26), with an IC30 value of 0.02 microM. Compound 26 directly inhibited the Na+-dependent Ca2+ influx via the Na+/Ca2+ exchanger after Na+-free treatment in cardiomyocytes.     

Selective and mild oxidation of sulfides to sulfoxides or sulfones using H2O2 and Cp′Mo(CO)3Cl as catalysts

Dialkyl, aryl-alkyl, benzylic, and benzothiophenic sulfides are selectively oxidized to sulfoxides or sulfones, with stoichiometric amounts of H₂O₂ (aq) or TBHP, in the presence of complexes Cp′Mo(CO)₃Cl, CpMoO₂Cl and the mesoporous material MCM-41-2 as catalysts. The use of the thianthrene 5-oxide (SSO) probe shows that CpMo(CO)₃Cl/H₂O₂ or TBHP are electrophilic oxidants (Xso ? 15). The same conclusion is drawn from competition experiments with a mixture of p-ClC₆H₄SCH₃ and C₆H₅SOCH₃.     

Synthesis and characterization of [PtIn6](GeO4)2O and its solid solution [PtIn6](GaO4)(2-x)(GeO4)xOx/2 (0 < or = x < or = 2): gradual color change of the solid solution from black (x = 0) to yellow (x = 2) as a consequence of quantum dot effect

A new phase [PtIn6](GeO4)2O, a filled variant of [PtIn6](GaO4)2, and the solid solution [PtIn6](GaO4)(2-x)(GeO4)xOx/2 (0 < or = x < or = 2) were prepared and characterized. Single-crystal structure refinements show that [PtIn6](GeO4)2O is isotypic with the mineral, sulfohalite Na6FCl(SO4)2, and crystallizes in the space group Fmm (Z = 4) with a = 1006.0(1) pm. The building units of [PtIn6](GeO4)2O are isolated [PtIn6]10+ octahedra and (GeO4)4- tetrahedra, and the isolated O2- ions occupy the centers of the In6 octahedra made up of six adjacent PtIn6 octahedra. The lattice parameter of the solid solution [PtIn6](GaO4)(2-x)(GeO4)xOx/2 (0 < or = x < or = 2) varies gradually from a = 1001.3(1) pm at x = 0 to a = 1006.0(1) pm at x = 2, and the color of the solid solution changes gradually from black (x = 0) to red (x = 1) to yellow (x = 2). The cause for the gradual color change was examined by performing density functional theory electronic structure calculations for the end members [PtIn6](GaO4)2 and [PtIn6](GeO4)2O. Our analysis indicates that an oxygen atom at the center of a In6 octahedron cuts the In 5p/In 5p bonding interactions between adjacent [PtIn6]10+ octahedra thereby raising the bottom of the conduction bands, and the resulting quantum dot effect is responsible for the color change.