Reductive Elimination Leading to C-C Bond Formation in Gold(III) Complexes: A Mechanistic and Computational Study

The factors affecting the rates of reductive C-C cross-coupling reactions in gold(III) aryls were studied using complexes that allow easy access to a series of electronically modified aryl ligands, as well as to gold methyl and vinyl complexes, using the pincer compounds (C^N^C)AuR (R = C6F5, CH=CMe2, Me and p-C6H4X, where X = OMe, F, H, But, Cl, CF3, or NO2) as starting materials (C^N^C = 2,6-(4′-ButC6H3)2pyridine dianion). Protodeauration followed by addition of 1 equiv. SMe2 leads to the quantitative generation of the thioether complexes [(C^N-CH)AuR(SMe2)]+. Upon addition of a second SMe2 pyridine is displaced, which triggers reductive aryl-R elimination. The rates for these cross-couplings increase in the sequence k(vinyl) > k(aryl) >> k(C6F5) > k(Me). Vinyl-aryl coupling is particularly fast, 1.15 × 10–3 L mol–1 s–1 at 221 K, while both C6F5 and Me couplings encountered higher barriers for the C-C bond forming step. Using P(p-tol)3 in place of SMe2 greatly accelerates C–C couplings. Computational modelling shows that in the C^N bonded compounds displacement of N by a donor L is required before the aryl ligands can adopt a conformation suitable for C-C bond formation, so that elimination takes place from a four-coordinate intermediate. C-C bond formation is rate limiting. In the non-chelating case, reductive C(sp2)-C(sp2) elimination from three-coordinate cations [(Ar1)(Ar2)AuL]+ is almost barrierless, particularly if L = phosphine

ATM-based multi-party conferencing system

Conference Record / IEEE Global Telecommunications Conference1592-596CRIE

Analysis of actual healthcare costs of early versus interval cholecystectomy in acute cholecystitis

10.1002/jhbp.196Journal of Hepato-Biliary-Pancreatic Sciences223237-24

Recurrence-free survival results from a pilot study of adjuvant gefitinib in resected hepatocellular carcinoma (HCC)

404 Background: Epidermal growth factor receptor (EGFR) pathway activation or over-expression plays an important role both in cirrhosis and hepatocellular carcinogenesis. We hypothesized that gefitinib (G), an oral tyrosine kinase inhibitor of EGFR, should reduce recurrence rate and/or prolong recurrence free survival when given in adjuvant setting. Methods: We designed a multicenter pilot study with a plan to enroll 40 HCC patients with complete resection and or with positive resection margin or residual disease < 0.5 cm (microscopic disease). Treatment consisted of G 250 mg orally daily for 6 months starting within 6 weeks of surgery. Follow-up included serum alpha-fetoprotein levels and imaging studies every 3 months for the first 2 years, every 6 months for years 3-5 and yearly thereafter. Main endpoints were recurrence-free survival, toxicity and correlative genetic studies. All statistical analyses were carried out on an intention-to-treat basis. The end point of recurrence free survival will be presented here. Results: 65 patients consented to the study, 40 were eligible and 25 were screen failures due to: diagnosis other than HCC (6 patients); poor post-operative recovery (9 patients); unresectable disease (3 patients); withdrawal of consent (2 patients); 1 patient had 2 cancers, and 4 developed metastatic disease.39 patients had R0 resection, whereas 1 patient had R1 resection. 4 female, 36 male. All patients completed 6 months of adjuvant G. Toxicities were mild; mainly grade 1 and 2 skin toxicity, diarrhea and pruritis. Median age - 63 years, median Child score-6, median TNM stage - II, median size - 4.9cm. 20 patients had liver cirrhosis. With a median duration of follow up of 4.1 years, the median recurrence free survival was 24 months. (95% CI 20-48). Conclusions: A median recurrence free survival of 24 months in patients with resected hepatocellular carcinoma treated with 6 months of adjuvant gefitinib compares favorably to historical data. Toxicity of gefitinib was mild and easily manageable. We await results of correlative genetic studies to identify potential prognostic and predictive biomarkers before considering embarking on a larger study. Clinical trial information: NCT00282100

Oral vs Intravenous Antibiotics for Patients With Klebsiella pneumoniae Liver Abscess: A Randomized, Controlled Noninferiority Study

10.1093/cid/ciz881CLINICAL INFECTIOUS DISEASES714952-95