A Dual Catalytic Approach for the Halogen-Bonding-Mediated Reductive Cleavage of α-Bromodifluoroesters and Amides.

While charge-transfer complexes involving halogen-bonding interactions have emerged as an alternative strategy for the photogeneration of carbon radicals, examples using (fluoro)alkyl bromides are limited. This report describes a dual catalytic approach for radical generation from α-bromodifluoroesters and amides under visible-light irradiation. Mechanistic studies suggest that the reaction proceeds through bromide displacement using a catalytic iodide salt, generating a C-I bond that can be engaged by our halogen-bonding photocatalysis platform.

Parental Attitudes and Hesitancy About COVID-19 Vaccination Versus Routine Childhood Vaccination in a Selected Hospital in the United Arab Emirates: A Cross-Sectional Study.

Background: A complex interplay of social and political influences, cultural and religious beliefs, the availability and interpretation of health and scientific information, individual and population experiences with health systems, and government policies contributes to the anxiety about vaccines and their programs that results in vaccine hesitancy. Vaccine hesitancy is becoming a serious threat to vaccination programs; in 2019, the World Health Organization (WHO) listed it as one of the top ten global health threats. The negative impacts of antivaccination movements are blamed for the major portion of the global resistance to vaccination.

1,4-Dihydropyridine Anions as Potent Single-Electron Photoreductants.

We report the use of simple 1,4-dihydropyridine anions as a general platform for promoting single-electron photoreductions. In the presence of a mild base, 1,4-dihydropyridines were shown to effectively promote the hydrodechlorination and borylation of aryl chlorides and the photodetosylation of N-tosyl aromatic amines under visible light irradiation. Our studies also demonstrate that the C4 substituent can influence the reactivity of these anions, reducing unwanted side reactions like hydrogen atom transfer and back-electron transfer.

Vitamin B -Photocatalyzed Cyclopropanation of Electron-Deficient Alkenes Using Dichloromethane as the Methylene Source.

The cyclopropyl group is of great importance in medicinal chemistry, as it can be leveraged to influence a range of pharmaceutical properties in drug molecules. This report describes a Vitamin B -photocatalyzed approach for the cyclopropanation of electron-deficient alkenes using dichloromethane (CH Cl ) as the methylene source. The reaction proceeds in good to excellent yields under mild conditions, has excellent functional group compatibility, and is highly chemoselective.

Recent Advances in Employing Catalytic Donors and Acceptors in Electron Donor-Acceptor Complex Photochemistry.

Electron donor-acceptor (EDA) complexes provide a means to initiate radical reactions under visible light irradiation using substrates that do not absorb visible light individually. Catalytic approaches to complex formation are vital for advancing this synthetic strategy as it decouples the complexation and photogeneration of radicals from substrate functionalization, a limitation inherent to stoichiometric approaches that restricts structural diversity. This Synopsis highlights recent developments in EDA complex photochemistry in which either the donor or acceptor are employed catalytically.

Radical coupling decreases synthetic burden.

Cross coupling of light-promoted β-keto radicals enables natural product syntheses.

Radical Perfluoroalkylation Enabled by a Catalytically Generated Halogen Bonding Complex and Visible Light Irradiation.

Exploiting charge-transfer complexes in visible light-promoted single-electron redox reactions is a promising route for opening novel synthetic pathways, and catalytic approaches to complex formation are critical for facilitating this chemistry. This report describes the use of a substituted hydroquinone catalyst to promote radical perfluoroalkylation reactions. Mechanistic studies indicate that the reaction is initiated through formation of a visible light-absorbing halogen bonding complex between the hydroquinone catalyst and the perfluoroalkyl halide radical precursor.

Strategic Use of Visible-Light Photoredox Catalysis in Natural Product Synthesis.

Recent progress in the development of photocatalytic reactions promoted by visible light is leading to a renaissance in the use of photochemistry in the construction of structurally elaborate organic molecules. Because of the rich functionality found in natural products, studies in natural product total synthesis provide useful insights into functional group compatibility of these new photocatalytic methods as well as their impact on synthetic strategy. In this review, we examine total syntheses published through the end of 2020 that employ a visible-light photoredox catalytic step.

Lewis Acid Activation of Fragment-Coupling Reactions of Tertiary Carbon Radicals Promoted by Visible-Light Irradiation of EDA Complexes.

The addition of tertiary carbon radicals generated from -(acyloxy)phthalimide esters to cyclic α,β-unsaturated ketones and lactones is markedly enhanced by the addition of substoichiometric amounts of a Ln(OTf). The reaction is accomplished by irradiation with visible light in the absence of a photosensitizer and is suggested to proceed by excitation of a ternary electron donor-acceptor complex between the NHPI ester, Hantzsch ester, and a Ln(OTf).

Chronic Effects of a High Sucrose Diet on Murine Gastrointestinal Nutrient Sensor Gene and Protein Expression Levels and Lipid Metabolism.

The gastrointestinal tract (GIT) plays a key role in regulating nutrient metabolism and appetite responses. This study aimed to identify changes in the GIT that are important in the development of diet related obesity and diabetes. GIT samples were obtained from C57BL/6J male mice chronically fed a control diet or a high sucrose diet (HSD) and analysed for changes in gene, protein and metabolite levels.

In Silico Engineering of Synthetic Binding Proteins from Random Amino Acid Sequences.

Synthetic proteins with high affinity and selectivity for a protein target can be used as research tools, biomarkers, and pharmacological agents, but few methods exist to design such proteins de novo. To this end, the In-Silico Protein Synthesizer (InSiPS) was developed to design synthetic binding proteins (SBPs) that bind pre-determined targets while minimizing off-target interactions. InSiPS is a genetic algorithm that refines a pool of random sequences over hundreds of generations of mutation and selection to produce SBPs with pre-specified binding characteristics.

Forging C(sp)-C(sp) Bonds with Carbon-Centered Radicals in the Synthesis of Complex Molecules.

Radical fragment coupling reactions that unite intricate subunits have become an important class of transformations within the arena of complex molecule synthesis. This Perspective highlights some of the early contributions in this area, as well as more modern applications of radical fragment couplings in the preparation of natural products. Additionally, emphasis is placed on contemporary advances that allow for radical generation under mild conditions as a driving force for the implementation of radical fragment couplings in total synthesis.

Fitness Tradeoffs of Antibiotic Resistance in Extraintestinal Pathogenic Escherichia coli.

Evolutionary trade-offs occur when selection on one trait has detrimental effects on other traits. In pathogenic microbes, it has been hypothesized that antibiotic resistance trades off with fitness in the absence of antibiotic. Although studies of single resistance mutations support this hypothesis, it is unclear whether trade-offs are maintained over time, due to compensatory evolution and broader effects of genetic background.

The photochemical alkylation and reduction of heteroarenes.

The functionalization of heteroarenes has been integral to the structural diversification of medicinally active molecules such as quinolines, pyridines, and phenanthridines. Electron-deficient heteroarenes are electronically compatible to react with relatively nucleophilic free radicals such as hydroxyalkyl. However, the radical functionalization of such heteroarenes has been marked by the use of transition-metal catalyzed processes that require initiators and stoichiometric oxidants.

Designing anti-Zika virus peptides derived from predicted human-Zika virus protein-protein interactions.

The production of anti-Zika virus (ZIKV) therapeutics has become increasingly important as the propagation of the devastating virus continues largely unchecked. Notably, a causal relationship between ZIKV infection and neurodevelopmental abnormalities has been widely reported, yet a specific mechanism underlying impaired neurological development has not been identified. Here, we report on the design of several synthetic competitive inhibitory peptides against key pathogenic ZIKV proteins through the prediction of protein-protein interactions (PPIs).

Photocatalytic Indole Diels-Alder Cycloadditions Mediated by Heterogeneous Platinum-Modified Titanium Dioxide.

Indole alkaloids represent an important class of molecules, with many naturally occurring derivatives possessing significant biological activity. One area that requires further development in the synthesis of indole derivatives is the Diels-Alder reaction. In this work, we expand on our previously developed heterogeneous protocol for the [4+2] cycloaddition of indoles and electron-rich dienes mediated by platinum nanoparticles supported on titanium dioxide semiconductor particles (Pt(0.

Titanium dioxide visible light photocatalysis: surface association enables photocatalysis with visible light irradiation.

Titanium dioxide (TiO) is a widely employed and inexpensive photocatalyst, but its use in organic synthesis has been limited by the short-wavelength ultraviolet irradiation typically used. We have discovered that TiO particles efficiently mediate photocatalytic radical cation Diels-Alder cycloadditions using a simple visible light source, enabled by the formation of a visible light absorbing complex of the substrate on the semiconductor surface.

Evolution of protein-protein interaction networks in yeast.

Interest in the evolution of protein-protein and genetic interaction networks has been rising in recent years, but the lack of large-scale high quality comparative datasets has acted as a barrier. Here, we carried out a comparative analysis of computationally predicted protein-protein interaction (PPI) networks from five closely related yeast species. We used the Protein-protein Interaction Prediction Engine (PIPE), which uses a database of known interactions to make sequence-based PPI predictions, to generate high quality predicted interactomes.

Photodynamic performance of zinc phthalocyanine in HeLa cells: A comparison between DPCC liposomes and BSA as delivery systems.

Comparable intracellular concentrations (≈30pmol/10(6) cells) of bovine serum albumin-ZnPc (BSA) adduct outperformed dipalmitoyl-phosphatidyl-choline (DPPC) liposomes containing ZnPc at photodynamic-killing of human cervical cancer cells (HeLa) after only 15min of irradiation using red light (λ>620nm, 30W/cm(2)). This result could not be simply explained in terms of dye aggregation within the carrier, since in the liposomes the dye was considerably less aggregated than in bovine serum albumin, formulation that was capable to induce cell apoptosis upon red light exposure. Thus, using specific organelle staining, our cumulative data points towards intrinsic differences in intra-cellular localization depending on the cargo vehicle used, being ZnPc:BSA preferentially located in the near vicinity of the nucleus and in the Golgi structures, while the liposomal formulation ZnPc:DPPC was preferentially located in cellular membrane and cytoplasm.

Library of Cationic Organic Dyes for Visible-Light-Driven Photoredox Transformations.

Organic dyes can be excellent catalysts for photoredox chemistry, offering low price, low toxicity, and an exceptional range of available materials. Their use has been limited because in comparison to their transition-metal catalysts the spectroscopic, kinetic, and electrochemical information available is far more limited. To remediate this situation, we have determined the necessary data for 14 readily available dyes with excellent potential as photoredox catalysts.

Understanding the Kinetics and Spectroscopy of Photoredox Catalysis and Transition-Metal-Free Alternatives.

Over the past decade, the field of photoredox catalysis has gained increasing attention in synthetic organic chemistry because of its wide applicability in sustainable free-radical-mediated processes. Numerous examples have shown that under carefully optimized conditions, efficient and highly selective processes can be developed through excitation of a photosensitizer using inexpensive, readily available light sources. However, despite all of these recent advancements, some generalizations and/or misconceptions have become part of the photoredox culture, and often many of these discoveries lack in-depth investigations into the excited-state kinetics and underlying mechanisms.

Visible-Light Actinometry and Intermittent Illumination as Convenient Tools to Study Ru(bpy)3Cl2 Mediated Photoredox Transformations.

Photoredox catalysis provides many green opportunities for radical-mediated synthetic transformations. However, the determination of the underlying mechanisms has been challenging due to lack of quantitative methods that can be easily implemented in synthetic labs, where this research tends to be centered. We report here on the development, characterization and calibration of a novel actinometer based on the photocatalyst tris(2,2'-bipyridyl)ruthenium(II) chloride (Ru(bpy)3Cl2).

Structure-Binding Effects: Comparative Binding of 2-Anilino-6-naphthalenesulfonate by a Series of Alkyl- and Hydroxyalkyl-Substituted β-Cyclodextrins.

Cyclodextrins (CDs) are the most widely used organic hosts for the inclusion of guest molecules. CDs can be readily modified through substitutions of the hydroxyl groups, and these modified CDs can have different host binding properties compared to those of parent CDs. However, only relatively few systematic studies of the effects of chemical substitution on CD binding ability have been reported thus far.

Efficient prediction of human protein-protein interactions at a global scale.

Background: Our knowledge of global protein-protein interaction (PPI) networks in complex organisms such as humans is hindered by technical limitations of current methods.

Results: On the basis of short co-occurring polypeptide regions, we developed a tool called MP-PIPE capable of predicting a global human PPI network within 3 months. With a recall of 23% at a precision of 82.

Phosphatase complex Pph3/Psy2 is involved in regulation of efficient non-homologous end-joining pathway in the yeast Saccharomyces cerevisiae.

One of the main mechanisms for double stranded DNA break (DSB) repair is through the non-homologous end-joining (NHEJ) pathway. Using plasmid and chromosomal repair assays, we showed that deletion mutant strains for interacting proteins Pph3p and Psy2p had reduced efficiencies in NHEJ. We further observed that this activity of Pph3p and Psy2p appeared linked to cell cycle Rad53p and Chk1p checkpoint proteins.