A new twist for Stork-Danheiser products enabled by visible light mediated trans-cyclohexene formation; access to acyclic distal enones

Herein, we investigate the use of visible light to indirectly drive ring opening in unstrained 6- and 7-membered ring systems via reaction with a transiently generated trans-cycloalkene. Identification of conditions that capture visible light energy in the form of ring strain was key to success. Under mildly acidic conditions, cycloalkenols were shown to undergo formally endothermic ring-opening isomerization to give acyclic exo-methylene and distal ketones or aldehydes in high yields. Ultimately, this work demonstrates the ability of cycloalkenes to capture visible light energy and its use to drive both kinetically and thermally unfavorable rearrangements.

In this work, visible light drives a contrathermodynamic isomerization of the classic Stork-Danheiser products through an energy transfer process to yield acyclic distal enone(al) isomers. This is possible because the photochemical energy is transiently captured as ring strain as a trans-, or twisted, cyclohexene.     

Flavonoids with Vicinal Hydroxyl Groups Inhibit Human Calcitonin Amyloid Formation

Human calcitonin (hCT) is a 32-residue peptide hormone that can aggregate into amyloid fibrils and cause cellular toxicity. In this study, we investigated the inhibition effects of a group of polyphenolic molecules on hCT amyloid formation. Our results suggest that the gallate moiety in epigallocatechin-3-gallate (EGCG), a well-recognized amyloid inhibitor, is not critical for its inhibition function in the hCT amyloid formation. Our results demonstrate that flavonoid compounds, such as myricetin, quercetin, and baicalein, that contain vicinal hydroxyl groups on the phenyl ring effectively prevent hCT fibrillization. This structural feature may also be applied to non-flavonoid polyphenolic inhibitors. Moreover, our results indicate a plausible mechanistic role of these vicinal hydroxyl groups which might include the oxidation to form a quinone and the subsequent covalent linkage with amino acid residues such as lysine or histidine in hCT. This may further disrupt the crucial electrostatic and aromatic interactions involved in the process of hCT amyloid fibril formation. The inhibition activity of the polyphenolic compounds against hCT fibril formation may likely be attributed to a combination of factors such as covalent linkage formation, aromatic stacking, and hydrogen bonding interactions.     

Residue‐Specific Dynamics and Local Environmental Changes in Aβ40 Oligomer and Fibril Formation

Elucidating local dynamics of protein aggregation is crucial for understanding the mechanistic details of protein amyloidogenesis. Herein, we studied the residue‐specific dynamics and local environmental changes of Aβ40 along the course of aggregation by using para‐cyanophenylalanine (Phe_CN) as a fluorescent and vibrational probe. Our results show that the Phe_CN residues introduced at various positions all exhibited an immediate decay of fluorescence intensity, indicating a relatively synergistic process in early oligomer formation. The fast decreases in the fluorescence intensities of residues 19 and 20 in the central hydrophobic core region and residue 10 in the N‐terminal region suggest that they play crucial roles in the formation of the oligomeric core. The Phe_CN4 residue exhibits a remarkably slower decrease in fluorescence intensity, implicating its dynamic conformational characteristics in oligomer and fibril formation. Our results also suggest that the N‐terminal residues in fibrils are surrounded by a relatively hydrophobic local environment, as opposed to being solvated.     

Absolute radiance imaging using parametric image amplification

We show that parametric image amplification can be used to achieve a 2D radiance map directly expressed in photons per spatiotemporal mode. Radiance images of incoherent signals with less than one photon per mode (typically 10(-2)) are resolved.     

Off resonance ac mode force spectroscopy and imaging with an atomic force microscope

Using an off resonance ac technique in ultrahigh vacuum we have directly measured the force-gradient interaction characteristics of a gold tip and sample and demonstrated a new atomic force microscope imaging mode with the tip located very close to the surface. The method involves the application of a small sinusoidal oscillating force to the tip via a magnetic field created by a conducting coil which interacts with a magnetic particle glued on the backside of the cantilever. By measuring the change in amplitude during the approach and retraction of the sample we have a continuous and accurate measure of the force gradient. The interaction potential is thus found without the need for complex analysis as is necessary in the case of the commonly used technique of measuring frequency shifts.     

Enantiomeric separation of neutral hydrophobic dihydrofuroflavones by cyclodextrin-modified micellar capillary electrophoresis

The enantiomeric separations of several very hydrophobic dihydrofuroflavones were performed and optimized using cyclodextrin-modified micellar capillary electrophoresis. Overall, the greatest enantiomeric peak-to-peak separations for the greatest number of flavones were obtained with hydroxypropyl-gamma-cyclodextrin. The effects of cyclodextrin and sodium dodecyl sulfate concentration and pH were examined in order to optimize the separation conditions. The ratio of surfactant-to-cyclodextrin concentration affected the chiral discrimination of the system significantly, with increases in the derivatized cyclodextrin concentration generally enhancing resolution. Higher efficiencies were obtained with lower concentrations of surfactant and cyclodextrin, although enantioseparation optimization often required higher concentrations to be used. A highly acidic pH was necessary to effectively suppress the electroosmotic flow when operating in the reversed polarity mode. Experiments utilizing the normal polarity mode and higher pH produced no separations.     

Use of the three-phase model and headspace analysis for the facile determination of all partition/association constants for highly volatile solute–cyclodextrin–water systems

A versatile method for measuring the partition coefficients of volatile analytes with an aqueous pseudophase using headspace gas chromatography is reported. A “three-phase” model accounts for all equilibria present in the system, including the partitioning of the analyte in the gas and aqueous phases to the pseudophase. This method is applicable to a wide variety of volatile analytes and aqueous pseudophases, providing that sufficient pseudophase may be used to reduce the analyte partial pressure. Generally, the method offers good reproducibility and high sensitivity. The associations of five volatile analytes (hydrogen sulfide, methanethiol, dimethyl sulfide, dichloromethane, and ethyl ether) with various cyclodextrins were examined. All analytes were found to partition preferentially to the cyclodextrin pseudophase compared to the aqueous phase. In addition, several analyte–cyclodextrin combinations formed insoluble complexes in solution that enhanced the extraction of the analyte from the gas and aqueous phases. Derivatization of the cyclodextrins generally decreased the extent of analyte–cyclodextrin interaction.