Recent Advances in Visible-Light-Mediated Amide Synthesis

Visible-light photoredox catalysis has attracted tremendous interest within the synthetic community. As such, the activation mode potentially provides a more sustainable and efficient platform for the activation of organic molecules, enabling the invention of many controlled radical-involved reactions under mild conditions. In this context, amide synthesis via the strategy of photoredox catalysis has received growing interest due to the ubiquitous presence of this structural motif in numerous natural products, pharmaceuticals and functionalized materials. Employing this strategy, a wide variety of amides can be prepared effectively from halides, arenes and even alkanes under irradiation of visible light. These methods provide a robust alternative to well-established strategies for amide synthesis that involve condensation between a carboxylic acid and amine mediated by a stoichiometric activating agent. In this review, the representative progresses made on the synthesis of amides through visible light-mediated radical reactions are summarized.

Structure of the Potential Virulence Factor from Francisella tularensis Shows Unexpected Presence of the SHS2 Motif and Similarity to Other Bacterial Virulence Factors

Pathogenic bacteria attack their host by secreting virulence factors that in various ways interrupt host defenses and damage their cells. Functions of many virulence factors, even from well-studied pathogens, are still unknown. Francisella tularensis is a class A pathogen and a causative agent of tularemia, a disease that is lethal without proper treatment. Here we report the three-dimensional structure and preliminary analysis of the potential virulence factor identified by the transcriptomic analysis of the F. tularensis disease models that is encoded by the FTT_1539 gene. The structure of the FTT_1539 protein contains two sets of three stranded antiparallel beta sheets, with a helix placed between the first and the second beta strand in each sheet. This structural motif, previously seen in virulence factors from other pathogens, was named the SHS2 motif and identified to play a role in protein-protein interactions and small molecule recognition. Sequence and structure analysis identified FTT_1539 as a member of a large family of secreted proteins from a broad range of pathogenic bacteria, such as Helicobacter pylori and Mycobacterium tuberculosis. While the specific function of the proteins from this class is still unknown, their similarity to the H. pylori Tip-α protein that induces TNF-a and other chemokines through NF-kB activation suggests the existence of a common pathogen-host interference mechanism shared by multiple human pathogens.

Charge Compensation by Iodine Covalent Bonding in Lead Iodide Perovskite Materials

Metal halide perovskite materials (MHPs) are a family of next-generation semiconductors that are enabling low-cost, high-performance solar cells and optoelectronic devices. The most-used halogen in MHPs, iodine, can supplement its octet by covalent bonding resulting in atomic charges intermediate to I− and I0. Here, we examine theoretically stabilized defects of iodine using density functional theory (DFT); defect formation enthalpies and iodine Bader charges which illustrate how MHPs adapt to stoichiometry changes. Experimentally, X-ray photoelectron spectroscopy (XPS) is used to identify perovskite defects and their relative binding energies, and validate the predicted chemical environments of iodine defects. Examining MHP samples with excess iodine compared with near stoichiometric samples, we discern additional spectral intensity in the I 3d5/2 XPS data arising from defects, and support the presence of iodine trimers. I 3d5/2 defect peak areas reveal a ratio of 2:1, matching the number of atoms at the ends and middle of the trimer, whereas their binding energies agree with calculated Bader charges. Results suggest the iodine trimer is the preferred structural motif for incorporation of excess iodine into the perovskite lattice. Understanding these easily formed photoactive defects and how to identify their presence is essential for stabilizing MHPs against photodecomposition.

Thermodynamically Stable Cationic Dimers in Carboxyl-Functionalized Ionic Liquids: The Paradoxical Case of “Anti-Electrostatic” Hydrogen Bonding

We show that carboxyl-functionalized ionic liquids (ILs) form doubly hydrogen-bonded cationic dimers (c+=c+) despite the repulsive forces between ions of like charge and competing hydrogen bonds between cation and anion (c+–a−). This structural motif as known for formic acid, the archetype of double hydrogen bridges, is present in the solid state of the IL 1−(carboxymethyl)pyridinium bis(trifluoromethylsulfonyl)imide [HOOC−CH2−py][NTf2]. By means of quantum chemical calculations, we explored different hydrogen-bonded isomers of neutral (HOOC–(CH2)n–py+)2(NTf2−)2, single-charged (HOOC–(CH2)n–py+)2(NTf2−), and double-charged (HOOC– (CH2)n−py+)2 complexes for demonstrating the paradoxical case of “anti-electrostatic” hydrogen bonding (AEHB) between ions of like charge. For the pure doubly hydrogen-bonded cationic dimers (HOOC– (CH2)n−py+)2, we report robust kinetic stability for n = 1–4. At n = 5, hydrogen bonding and dispersion fully compensate for the repulsive Coulomb forces between the cations, allowing for the quantification of the two equivalent hydrogen bonds and dispersion interaction in the order of 58.5 and 11 kJmol−1, respectively. For n = 6–8, we calculated negative free energies for temperatures below 47, 80, and 114 K, respectively. Quantum cluster equilibrium (QCE) theory predicts the equilibria between cationic monomers and dimers by considering the intermolecular interaction between the species, leading to thermodynamic stability at even higher temperatures. We rationalize the H-bond characteristics of the cationic dimers by the natural bond orbital (NBO) approach, emphasizing the strong correlation between NBO-based and spectroscopic descriptors, such as NMR chemical shifts and vibrational frequencies.

Synthesis, Characterization and Pharmacological Screening of Some Novel 2- substituted and 1(H)-substituted Benzimidazole Derivatives as potent Anti-cancer agents

The most of drugs containing Benzimidazole ring is a prominent structural motif found in numerous therapeutically active compounds. Benzimidazole and its synthetic analogues have been found to exhibit industrial, agricultural and biological application such as antitubercular, anti-inflammatory, analgesic, anticancer, anticoagulant, as well as good antifungal and anti microbial activity. Recent advances in technology considers microwave irradiation energy as the most efficient means of heating reactions for chemical transformations that can be accomplished in a minutes. Microwave irradiation assists organic synthesis (MAOS) not only helps in implementing green chemistry but also led to progress in organic synthesis. We report pharmacological screening of some novel 2 substituted and 1(h)-substituted Benzimidazole derivatives.

Biosynthesis of cyclopropane in natural products

This review discusses the diverse enzymatic pathways in the biosynthesis of cyclopropane, a unique structural motif with important biochemical properties.

Synthesis of oxindoles bearing a stereogenic 3-fluorinated carbon center from 3-fluorooxindoles

3,3-Disubstituted oxindole bearing a stereogenic 3-fluorinated carbon center is a privileged structural motif present in many bioactive molecules. The straightforward functionalization of 3-fluorooxindoles constitutes a powerful method for the synthesis...

The Inversion of Tetrahedral p-Block Element Compounds: General Trends and the Relation to the Second-Order Jahn-Teller Effect

The tetrahedron is the primary structural motif among the p-block elements and determines the architecture of our bio- and geosphere. However, a broad understanding of the configurational inversion of tetrahedral...

Palladium Oxidative Addition Complexes Enabled Synthesis of Amino-Substituted Indolyl-4(3H)-quinazolinones and Their Antitumor Activity Evaluation

The indolyl-4(3H)-quinazolinone core is an important structural motif in functional molecules. However, few methods exist for the direct modification of which limit its potential application. Reported herein is a palladium-mediated...

Photosensitized Nickel Catalysis Enabled Silyl Radical Mediated Direct Activation of Carbamoyl Chlorides to Access (Hetero)aryl Carbamides

The transformation of a readily available molecule to a medicinally relevant functionality is the heart of organic synthesis which literally unfolds new direction in the field of drug discovery and development. Accordingly, synthetic chemistry fraternity is constantly striving to introduce a range of avant-garde techniques to construct an incredibly important fundamental entity like “amide bonds” which connect the amino acids in proteins and exist as a prevalent structural motif in biomolecules. In this context, we want to introduce the concept of cross-electrophile coupling by merging the photoredox and transition metal catalysis to construct carbamides from superabundant (hetero)aryl chlorides or bromides along with commercially feasible carbamoyl chlorides. However, there is barely any report on direct activation of carbamoyl chloride so far. To circumvent the challenge, we employ the intrinsic affinity of silyl radical species towards halogen atom to harness the carbamoyl radical directly from carbamoyl chlorides which is seemingly the first of its kind. The success of this protocol relies on the prior formation of ‘aryl halides to Ni-catalyst’ oxidative addition intermediate that assists in generation of the vital carbamoyl radical. The breadth of application of this technique is significantly demonstrated by the synthesis of a plethora of (hetero)aryl carbamides with diverse functionalities. As stated earlier, we outline the direct utility of this protocol by the late-stage amidation of halide containing drug molecules and pharmacophores.