Silver-Catalyzed, N-Formylation of Amines Using Glycol Ethers.

A silver-catalyzed protocol was found to afford the N-formylation of amines in moderate-to-good yields. Ethylene glycol-derived, oligomeric ethers were found to function as the formylating agent, with 1,4-dioxane affording the best results. This reaction does not require the use of stoichiometric activating reagents, and avoids the use of explosive reagents or toxic gases, such as CO, as the C1 synthon. Mechanistic studies indicate a single-electron transfer-based pathway. This work highlights the ability of silver to participate in unexpected reaction pathways.

Ab interno canaloplasty (ABiC)-12-month results of a new minimally invasive glaucoma surgery (MIGS).

PURPOSE: The aim of this study is to assess whether the ab interno canaloplasty is a reasonable minimally invasive method to lower significantly the IOP level and number of antiglaucomatous medication over a certain period of time in adult primary open angle glaucoma (POAG). METHODS: In this retrospective cohort outcome study, 36 eyes of 28 POAG patients (mean age 74.8 ± 9.3 years) with an IOP above target pressure were included. Ab interno canaloplasty (ABiC) was performed in all subjects (MEyeTech GmbH, Alsdorf, Germany) as sole procedure in pseudophakic eyes (n = 20) or in combination with cataract surgery in phakic eyes (n = 16). The intraocular pressure (IOP) and the number of glaucoma medication were assessed preoperatively, day 1, week 6, month 3, month 6, and month 12. RESULTS: IOP decreased from 19.8 ± 4.1 to 13.8 ± 3 mmHg at 12 months follow-up (n = 21, p < 0.001). The IOP reduction showed significant results at all time points (1 day p < 0.001; 6 weeks p < 0.001; 3 months p < 0.001; 6 months p = 0.001; 12 months p < 0.001). Glaucoma therapy was stabilized at 2.1 ± 1.6 number of medications after 12 months postoperatively. There was no significant difference in the number of medication at 12 months follow-up (p = 1.0). No major perioperative complications can be reported. CONCLUSION: The ABiC effectively lowers the IOP in POAG in the short term follow-up of 12 months. A reduction of glaucoma therapy cannot be achieved and should be discussed with the patients prior to surgery.

Contralateral eye comparison study in MICS & MIGS: Trabectome® vs. iStent inject®.

PURPOSE: To compare the safety and efficacy profile after combined micro-incision cataract surgery (MICS) and micro-invasive glaucoma surgery (MIGS) with the ab interno trabeculectomy (Trabectome®) in one eye versus two iStent® inject devices in the contralateral eye in patients with open-angle glaucoma (OAG) and cataract. METHODS: This retrospective, intraindividual eye comparison study included 27 patients (54 eyes) who were treated with combined MICS and ab interno trabeculectomy (group I, Trabectome®) in one eye and two iStent® inject devices (group II, GTS 400) in the fellow eye. Primary outcome measures included intraocular pressure (IOP) and glaucoma medication after 6 weeks, 3, 6, and 12 months follow-up. Secondary outcome measures were number of postoperative interventions, complications, and best-corrected visual acuity (BCVA). RESULTS: Mean preoperative IOP decreased from 22.3 ± 3.7 mmHg in group I and 21.3 ± 4.1 mmHg in group II to 15.6 ± 3.6 mmHg for Trabectome (p < 0.001) and 14.0 ± 2.3 mmHg for iStent inject (p < 0.001) at 12 months after surgery without a significant difference between the two groups (p > 0.05). No vision-threatening complications such as choroidal effusion, choroidal hemorrhage, or infection occurred. In each group trabeculectomy had to be performed in two eyes due to insufficient IOP lowering effect. CONCLUSIONS: Ab interno trabeculectomy and iStent® inject were both effective in lowering IOP with a favourable and comparable safety profile in an intraindividual comparative study over a 12-months follow-up in OAG. However, longer follow-up of these patients will be necessary to determine long-term outcomes and to evaluate significant differences.

"Click" and Olefin Metathesis Chemistry in Water at Room Temperature Enabled by Biodegradable Micelles.

The two laboratory reactions focus on teaching several concepts associated with green chemistry. Each uses a commercial, nontoxic, and biodegradable surfactant, TPGS-750-M, to promote organic reactions within the lipophilic cores of nanoscale micelles in water. These experiments are based on work by K. Barry Sharpless (an azide-alkyne "click" reaction) and Robert Grubbs (an olefin cross-metathesis reaction); both are suitable for an undergraduate organic laboratory. The copper-catalyzed azide-alkyne [3+2] cycloaddition of benzyl azide and 4-tolylacetylene is very rapid: the triazole product is readily isolated by filtration and is characterized by thin-layer chromatography and melting point analysis. The ruthenium-catalyzed olefin cross-metathesis reaction of benzyl acrylate with 1-hexene is readily monitored by thin-layer chromatography and gas chromatography. The metathesis experiment comparatively evaluates the efficacy of a TPGS-750-M/water medium relative to a traditional reaction performed in dichloromethane (a common solvent used for olefin metathesis).

Characterization and dynamics of substituted ruthenacyclobutanes relevant to the olefin cross-metathesis reaction.

The reaction of the phosphonium alkylidene [(H(2)IMes)RuCl(2)=CHP(Cy)(3))](+) BF(4)(-) with propene, 1-butene, and 1-hexene at -45 °C affords various substituted, metathesis-active ruthenacycles. These metallacycles were found to equilibrate over extended reaction times in response to decreases in ethylene concentrations, which favored increased populations of α-monosubstituted and α,α'-disubstituted (both cis and trans) ruthenacycles. On an NMR time scale, rapid chemical exchange was found to preferentially occur between the ß-hydrogens of the cis and trans stereoisomers prior to olefin exchange. Exchange on an NMR time scale was also observed between the α- and ß-methylene groups of the monosubstituted ruthenacycle (H(2)IMes)Cl(2)Ru(CHRCH(2)CH(2)) (R = CH(3), CH(2)CH(3), (CH(2))(3)CH(3)). EXSY NMR experiments at -87 °C were used to determine the activation energies for both of these exchange processes. In addition, new methods have been developed for the direct preparation of metathesis-active ruthenacyclobutanes via the protonolysis of dichloro(1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene)(benzylidene) bis(pyridine)ruthenium(II) and its 3-bromopyridine analogue. Using either trifluoroacetic acid or silica-bound toluenesulfonic acid as the proton source, the ethylene-derived ruthenacyclobutane (H(2)IMes)Cl(2)Ru(CH(2)CH(2)CH(2)) was observed in up to 98% yield via NMR at -40 °C. On the basis of these studies, mechanisms accounting for the positional and stereochemical exchange within ruthenacyclobutanes are proposed, as well as the implications of these dynamics toward olefin metathesis catalyst and reaction design are described.

Auricular stimulation vs. expressive writing for exam anxiety in medical students - A randomized crossover investigation.

OBJECTIVE: Auricular stimulation (AS) is a promising method in the treatment of situational anxiety. Expressive writing (EW) is an established psychological method, which reduces test anxiety and improves exam results. The aim of this crossover trial was to compare AS with EW, and with the no intervention (NI) condition, for treatment of exam anxiety. METHODS: Healthy medical students underwent 3 comparable anatomy exams with an interval of one month, either performing EW, receiving AS or NI prior to the exam; the order of interventions was randomized. AS was applied using indwelling fixed needles bilaterally at the areas innervated mostly by the auricular branch of the vagal nerve on the day before the exam. Anxiety level, measured using State-Trait-Anxiety Inventory (STAI) before and after the interventions and immediately before exam, was the primary outcome. Quality of night sleep, blood pressure, heart rate and activity of salivary alpha-amylase (sAA) were analyzed across 3 conditions. RESULTS: All 37 included participants completed the study. Anxiety level (STAI) decreased immediately after AS in comparison with baseline (P = 0.02) and remained lower in comparison with that after EW and NI (P<0.01) on the day of exam. After EW and NI anxiety increased on the day of exam in comparison with baseline (P<0.01). Quality of sleep improved after AS in comparison with both control conditions (P<0.01). The activity of sAA decreased after EW and after AS (P<0.05) but not after NI condition. CONCLUSION: Auricular stimulation, but not expressive writing, reduced exam anxiety and improved quality of sleep in medical students. These changes might be due to reduced activity of the sympathetic nervous system.

iStent inject as a reasonable alternative procedure following failed trabeculectomy?

PURPOSE:: The aim of this study is to assess the intraocular pressure lowering effect and the performance of the glaucoma therapy of the iStent inject in glaucoma patients with uncontrolled intraocular pressure after failed trabeculectomy. METHODS:: In this retrospective study, iStent inject implantation (Glaukos Corporation, Laguna Hills, CA, USA) was performed in 22 eyes of 21 subjects suffering from glaucoma (n = 18 primary open angle glaucoma, n = 3 pseudoexfoliation glaucoma, and n = 1 for secondary glaucoma) with an intraocular pressure above target pressure after failed trabeculectomy (mean = 9.6 ± 8.1 years; range: 1-35 years). The intraocular pressure and the number of antiglaucomatous medication were assessed preoperatively, 1 day, 6 weeks, 3 months, 6 months, and 1 year after surgery and compared to preoperative findings (SPSS v23.0; Shapiro-Wilk test, Wilcoxon test, Friedman test). RESULTS:: The results showed a significant intraocular pressure decrease from 22.5 ± 4.6 to 15.5 ± 3.4 mmHg after 1 year follow-up (p = 0.012). The glaucoma therapy was 2.6 ± 1.2 preoperatively and reduced to 2.25 ± 1.5 number of medications after 1 year (p > 0.05). There was no significant difference in the number of medication during the whole follow-up period (1 year, p = 0.012). No significant intra- or postoperative complications were reported. CONCLUSION:: Minimal invasive glaucoma surgery (iStent inject) can offer an effective intraocular pressure reduction in advanced adult primary and secondary open angle glaucoma after failed trabeculectomy in a follow-up period of 1 year. Glaucoma therapy, however, needs to be maintained to achieve an individual target pressure and to prevent glaucoma progression. In addition, a failure rate of 27.3% makes it necessary to select carefully patients for this treatment option.

Decomposition of ruthenium olefin metathesis catalysts.

The decomposition of a series of ruthenium metathesis catalysts has been examined using methylidene species as model complexes. All of the phosphine-containing methylidene complexes decomposed to generate methylphosphonium salts, and their decomposition routes followed first-order kinetics. The formation of these salts in high conversion, coupled with the observed kinetic behavior for this reaction, suggests that the major decomposition pathway involves nucleophilic attack of a dissociated phosphine on the methylidene carbon. This mechanism also is consistent with decomposition observed in the presence of ethylene as a model olefin substrate. The decomposition of phosphine-free catalyst (H2IMes)(Cl)2Ru=CH(2-C6H4-O-i-Pr) (H2IMes = 1,3-dimesityl-4,5-dihydroimidazol-2-ylidene) with ethylene was found to generate unidentified ruthenium hydride species. The novel ruthenium complex (H2IMes)(pyridine)3(Cl)2Ru, which was generated during the synthetic attempts to prepare the highly unstable pyridine-based methylidene complex (H2IMes)(pyridine)2(Cl)2Ru=CH2, is also reported.

Ruthenium metallacycles derived from 14-electron complexes. New insights into olefin metathesis intermediates.

Ruthenium(IV) metallacycles derived from both ethylene and propene are reported. The propene-derived metallacycles represent the first observed examples of substituted ruthenacyclobutanes and offer new insight into the preferred stereochemical orientation about metathesis intermediates. In addition, a metallacycle possessing an unsymmetrical N-heterocyclic carbene (NHC) ligand was prepared and investigated to ascertain the dynamics of the NHC relative to the metallacycle ring. Metallacycles investigated were found to possess exchange cross-peaks between the alpha- and beta-positions in the 2D NMR, indicating a dynamic structure. The implications of these results to the mechanism of ruthenium-catalyzed olefin metathesis are discussed.

Asymmetric catalytic Mannich reactions catalyzed by urea derivatives: enantioselective synthesis of beta-aryl-beta-amino acids.

Highly enantioselective addition reactions between silyl ketene acetals and N-Boc aldimines are catalyzed by the thiourea-based catalyst 1c. Extraordinary scope is observed in this methodology with regard to the imine substrate, with aryl and heteroaromatic derivatives generally affording nearly quantitative yields of beta-amino ester product in up to 98% enantioselectivity.