Crystallization and Interconversions of Vapor-Sensitive, Luminescent Polymorphs of [(C₆H₁₁NC)₂Au^I](AsF₆) and [(C₆H₁₁NC)₂Au^I](PF₆)

The remarkable, vapor-induced transformation of the yellow polymorphs of [(C₆H₁₁NC)₂Au^I]­(AsF₆) and [(C₆H₁₁NC)₂Au^I]­(PF₆) into the colorless forms are reported along with related studies of the crystallization of these polymorphs. Although the interconversion of these polymorphs is produced by vapor exposure, <i>molecules of the vapor are not incorporated into the crystals</i>. Thus, our observations may have broad implications regarding the formation and persistence of other crystal polymorphs where issues of stability and reproducibility of formation exist. Crystallographic studies show that the colorless polymorphs, which display blue luminescence, are isostructural and consist of linear chains of gold­(I) cations that self-associate through aurophilic interactions. Significantly, the yellow polymorph of [(C₆H₁₁NC)₂Au^I]­(AsF₆) is not isostructural with the yellow polymorph of [(C₆H₁₁NC)₂Au^I]­(PF₆). Both yellow polymorphs exhibit green emission and have the gold cations arranged into somewhat bent chains with significantly closer Au···Au separations than are seen in the colorless counterparts. Luminescence differences in these polymorphs clearly enhance the ability to detect and monitor their phase stability

Unfolded Protein Response in Cancer: IRE1α Inhibition by Selective Kinase Ligands Does Not Impair Tumor Cell Viability

The kinase/endonuclease inositol requiring enzyme 1 (IRE1α), one of the sensors of unfolded protein accumulation in the endoplasmic reticulum that triggers the unfolded protein response (UPR), has been investigated as an anticancer target. We identified potent allosteric inhibitors of IRE1α endonuclease activity that bound to the kinase site on the enzyme. Structure–activity relationship (SAR) studies led to <b>16</b> and <b>18</b>, which were selective in kinase screens and were potent against recombinant IRE1α endonuclease as well as cellular IRE1α. The first X-ray crystal structure of a kinase inhibitor (<b>16</b>) bound to hIRE1α was obtained. Screening of native tumor cell lines (>300) against selective IRE1α inhibitors failed to demonstrate any effect on cellular viability. These results suggest that IRE1α activity is not essential for viability in most tumor cell lines, in vitro, and that interfering with the survival functions of the UPR may not be an effective strategy to block tumorigenesis

Proceedings of the 4th World Conference on Research Integrity

CITATION: O’Brien, S. P., et al. 2016. Proceedings of the 4th World Conference on Research Integrity. Research Integrity and Peer Review, 1:9, doi:10.1186/s41073-016-0012-9.The original publication is available at https://researchintegrityjournal.biomedcentral.comThese Proceedings contain the abstracts of the presentations given at the 4th World Conference in concurrent sessions, partner symposia, and poster sessions. Also included are summaries of the discussions in three focus tracks, which allowed delegates to consider and work on questions about the roles of funders, institutions, and countries in improving research systems and strengthening research integrity. Videos of the plenary presentations are available at the conference website (www.wcri2015.org).https://researchintegrityjournal.biomedcentral.com/articles/10.1186/s41073-016-0012-