The Constitutional Isomerism of One-Component Ionizable Amphiphilic Janus Dendrimers Orchestrates the Total and Targeted Activities of mRNA Delivery.

Constitutional isomerism has been previously demonstrated by one of our laboratories to represent a powerful design strategy for the elaboration of complex functional self-organizations. Here we report the design, synthesis, and characterization of 14 positional, skeletal, and functional constitutional isomeric one-component, multifunctional, sequence-defined, amphiphilic ionizable Janus dendrimers (IAJDs). Their coassembly by simple injection with luciferase mRNA (Luc-mRNA) to form dendrimersome nanoparticles (DNPs) was studied. Subsequently, the resulting DNPs were employed to investigate, with screening experiments, the delivery of Luc-mRNA in vivo. Constitutional isomerism was shown to produce changes of up to two orders of magnitude of the total-body luciferase activity and targeted luciferase activity to the spleen and liver, of up to three orders of magnitude difference in targeted luciferase activity to the lungs and up to six orders of magnitude to lymph nodes. These results indicate that constitutional isomerism may represent not only a simple but also an important synthetic strategy that most probably may impact the activity of all components of synthetic vectors used in RNA-based nanomedicine, including in mRNA vaccines and therapeutics.

Dinuclear Zn-Catalytic System as Brønsted Base and Lewis Acid for Enantioselectivity in Same Chiral Environment.

Zinc (Zn) is a crucial element with remarkable significance in organic transformations. The profusion of harmless zinc salts in the Earth's outer layer qualifies zinc as a noteworthy contender for inexpensive and eco-friendly reagents and catalysts. Recently, widely recognized uses of organo-Zn compounds in the field of organic synthesis have undergone extensive expansion toward asymmetric transformations. The ProPhenol ligand, a member of the chiral nitrogenous-crown family, exhibits the spontaneous formation of a dual-metal complex when reacted with alkyl metal (R-M) reagents, e.g., ZnEt2. The afforded Zn complex possesses two active sites, one Lewis acid and the other Brønsted base, thereby facilitating the activation of nucleophiles and electrophiles simultaneously within the same chiral pocket. In this comprehensive analysis, we provide a thorough account of the advancement and synthetic potential of these diverse catalysts in organic synthesis, while emphasizing the reactivity and selectivities, i.e., dr and ee due to the design/structure of the ligands employed.

On-DNA hydroalkylation of N-vinyl heterocycles via photoinduced EDA-complex activation.

The emergence of DNA-encoded library (DEL) technology has provided a considerable advantage to the pharmaceutical industry in the pursuit of discovering novel therapeutic candidates for their drug development initiatives. This combinatorial technique not only offers a more economical, spatially efficient, and time-saving alternative to the existing ligand discovery methods, but also enables the exploration of additional chemical space by utilizing novel DNA-compatible synthetic transformations to leverage multifunctional building blocks from readily available substructures. In this report, a decarboxylative-based hydroalkylation of DNA-conjugated N-vinyl heterocycles enabled by single-electron transfer (SET) and subsequent hydrogen atom transfer through electron-donor/electron-acceptor (EDA) complex activation is detailed. The simplicity and robustness of this method permits inclusion of a broad array of alkyl radical precursors and DNA-tethered nitrogenous heterocyles to generate medicinally relevant substituted heterocycles with pendant functional groups. Moreover, a successful telescoped route provides the opportunity to access a broad range of intricate structural scaffolds by employing basic carboxylic acid feedstocks.

Facile Synthesis of Functionalized Phenoxy Quinolines: Antibacterial Activities against ESBL Producing Escherichia coli and MRSA, Docking Studies, and Structural Features Determination through Computational Approach.

The synthesis of new 6-Bromoquinolin-4-ol derivatives (3a-3h) by Chan-Lam coupling utilizing different types of solvents (protic, aprotic, and mixed solvents) and bases was studied in the present manuscript. Furthermore, their potential against ESBL producing Escherichia coli (ESBL E. coli) and methicillin-resistant Staphylococcusaureus (MRSA) were investigated. Commercially available 6-bromoquinolin-4-ol (3a) was reacted with different types of aryl boronic acids along with Cu(OAc)2 via Chan-Lam coupling methodology utilizing the protic and aprotic and mixed solvents. The molecules (3a-3h) exhibited very good yields with methanol, moderate yields with DMF, and low yields with ethanol solvents, while the mixed solvent CH3OH/H2O (8:1) gave more excellent results as compared to the other solvents. The in vitro antiseptic values against ESBL E. coli and MRSA were calculated at five different deliberations (10, 20, 30, 40, 50 mg/well) by agar well diffusion method. The molecule 3e depicted highest antibacterial activity while compounds 3b and 3d showed low antibacterial activity. Additionally, MIC and MBC standards were calculated against the established bacteria by broth dilution method. Furthermore, a molecular docking investigation of the derivatives (3a-3h) were performed. Compound (3e) was highly active and depicted the least binding energy of -5.4. Moreover, to investigate the essential structural and physical properties, the density functional theory (DFT) findings of the synthesized molecules were accomplished by using the basic set PBE0-D3BJ/def2-TZVP/SMD water level of the theory. The synthesized compounds showed an energy gap from 4.93 to 5.07 eV.

Palladium(0) Catalyzed Synthesis of (E)-4-Bromo-N-((3-bromothiophen-2-yl)methylene)-2-methylaniline Derivatives via Suzuki Cross-Coupling Reaction: An Exploration of Their Non-Linear Optical Properties, Reactivity and Structural Features.

A series of (E)-4-bromo-N-((3-bromothiophen-2-yl)methylene)-2-methylaniline analogs synthesized in considerable yields through Suzuki cross-coupling reactions. Various electron donating and withdrawing functional moieties were successfully incorporated under the employed reaction conditions. Reaction of 4-bromo-2-methylaniline (1) with 3-bromothiophene-2-carbaldehyde (2b) in the existence of glacial acetic acid, provided (E)-4-bromo-N-((3-bromothiophen-2-yl)methylene)-2-methylaniline (3b) in excellent yield (94%). Suzuki coupling of 3b with different boronic acids in the presence of Pd(PPh3)4/K3PO4 at 90 °C led to the synthesis of the monosubstituted and bisubstituted products 5a-5d and 6a-6d in moderate yields (33-40% and 31-46%, respectively). Density functional theory (DFT) investigations were performed on different synthesized analogues 5a-5d, 6a-6d to determine their structural characteristics. The calculations provide insight into the frontier molecular orbitals (FMOs) of the imine-based analogues and their molecular electrostatic potential (MESP). Reactivity descriptors like ionization energy (I), electron affinity (A), chemical hardness (ƞ) and index of nucleophilicity have been calculated for the first time for the synthesized molecules.

How Authoritarian Leadership Affects Employee's Helping Behavior? The Mediating Role of Rumination and Moderating Role of Psychological Ownership.

Interpersonal helping behaviors, i.e., voluntarily assisting colleagues for their workplace related problems, have received immense amount of scholarly attention due to their significant impacts on organizational effectiveness. Among several other factors, authoritarian leadership style could influence helping behavior within organizations. Furthermore, this relationship could be mediated by workplace stressor such as rumination, known as a critical psychological health component leading to depressive symptoms, hopelessness and pessimism. In the meantime, less research attention has devoted to probe the crucial role of psychological ownership, which can buffer the adverse effects of authoritarian leadership upon rumination. Building on conservation of resources theory, this study investigates the adverse impacts of authoritarian leadership on employees' helping behaviors through mediating role of rumination, and also examines the moderating effect of psychological ownership between the relationship of authoritarian leadership and rumination. The data were collected from 264 employees in education and banking sectors and the results show: (i) authoritarian leadership has adverse impacts on helping behavior, (ii) rumination mediates the relationship between authoritarian leadership and employees' helping behaviors, and (iii) psychological ownership moderates the positive relationship between authoritarian leadership and rumination. This study concludes that authoritarian leadership has adverse impacts upon helping behavior, which needs to be controlled/minimized. The findings are of great significance for managers, employees, and organizations in terms of policy implications. The limitations and future research directions are also discussed.