Lamgriffith9934

We herein report the synthesis and biological and computational evaluation of 12 linear analogues of the cyclic lipopeptide battacin, enabled by Cysteine Lipidation on a Peptide or Amino Acid (CLipPA) technology. Several of the novel "CLipP"ed lipopeptides exhibited low micromolar MICs and MBCs against both Gram-negative and Gram-positive bacteria. The mechanism of action was then simulated with the MIC data using computational methods.Strategies to capitalize on enolate intermediates generated from stereoselective conjugate borylation to α,β-unsaturated carbonyl systems are surprisingly rare despite the ubiquity of Michael acceptors, and the potential to generate valuable scaffolds bearing multiple stereocenters. Herein, we report a mild and stereoselective copper-catalyzed conjugate borylation/Mannich cyclization reaction. This strategy is feasible with a broad range of Michael acceptors, and can be leveraged to generate versatile borylated tetrahydroquinoline scaffolds bearing three contiguous stereocenters. The synthetic potential of these complex heterocycles has been explored through a series of derivatization studies.In nature, a number of enzymes use thiamine diphosphate as a coenzyme to catalyze the pyruvate decarboxylation. The resultant enamine, a so-called "Breslow intermediate," is known to perform single electron transfer to various electron acceptors. Inspired by this enzymatic catalysis, N-heterocyclic carbene (NHC)-catalyzed radical reactions have been developed. This minireview highlights the recent progress and developments in NHC-based radical catalysis. This minireview is categorized according to the reaction types; oxidation type reaction and carbon-carbon bond formation through single electron transfer/radical-radical coupling.We report the selective formation of heterobimetallic PtII/CuI complexes that demonstrate how facile bond activation processes can be achieved by altering the reactivity of common organoplatinum compounds through their interaction with another metal center. The interaction of the Cu center with the Pt center and with a Pt-bound alkyl group increases the stability of PtMe2 towards undesired rollover cyclometalation. The presence of the CuI center also enables facile transmetalation from an electron-deficient tetraarylborate [B(ArF)4]- anion and mild C-H bond cleavage of a terminal alkyne, which was not observed in the absence of an electrophilic Cu center. The DFT study indicates that the Cu center acts as a binding site for the alkyne substrate, while activating its terminal C-H bond.A diiron complex containing a bridging hydride and a protonated terminal thiolate of the form [(μ,κ2-bdtH)(μ-PPh2)(μ-H)Fe2(CO)5]+ has been investigated through 57Fe nuclear resonance vibrational spectroscopy (NRVS) and interpreted using density functional theory (DFT) calculations. We report the Fe-μH-Fe wagging mode, and indications for Fe-μD stretching vibrations in the D-isotopologue, observed by 57Fe-NRVS. Our combined approach demonstrates an asymmetric sharing of the hydride between the two iron sites that yields two nondegenerate Fe-μH/D stretching vibrations. The studied complex provides an important model relevant to biological hydrogen catalysis intermediates. The complex mimics proposals for the binuclear metal sites in [FeFe] and [NiFe] hydrogenases. https://www.selleckchem.com/products/mivebresib-abbv-075.html It is also an appealing prototype for the 'Janus intermediate' of nitrogenase, which has been proposed to contain two bridging Fe-H-Fe hydrides and two protonated sulfurs at the FeMo-cofactor. The significance of observing indirect effects of the bridging hydride, as well as obstacles in its direct observation, is discussed in the context of biological hydrogen intermediates.The first molybdenum-catalyzed allylic sulfonylation of tertiary allylic electrophiles is described. The method employs a readily accessible catalyst (Mo(CO)6/2,2'-bipyridine, both are commercially available) and represents the first example of the use of a group 6 transition metal-catalyst for allylic sulfonylation of substituted tertiary allylic electrophiles to form carbon-sulfur bonds. This atom economic and operationally simple methodology is characterized by its relatively mild conditions, wide substrate scope, and excellent regioselectivity profile, thus unlocking a new platform to forge sulfone moieties, even in the context of late-stage functionalization and providing ample opportunities for further derivatization through traditional Suzuki cross-coupling reactions.Organometallic complexes with novel activation mechanisms are attractive anticancer drug candidates. Here, we show that half-sandwich iodido cyclopentadienyl iridium(iii) azopyridine complexes exhibit potent antiproliferative activity towards cancer cells, in most cases more potent than cisplatin. Despite their inertness towards aquation, these iodido complexes can undergo redox activation by attack of the abundant intracellular tripeptide glutathione (GSH) on the chelated azopyridine ligand to generate paramagnetic intermediates, and hydroxyl radicals, together with thiolate-bridged dinuclear iridium complexes, and liberate reduced hydrazopyridine ligand. DFT calculations provided insight into the mechanism of this activation. GS- attack on the azo bond facilitates the substitution of iodide by GS-, and leads to formation of GSSG and superoxide if O2 is present as an electron-acceptor, in a largely exergonic pathway. Reactions of these iodido complexes with GSH generate Ir-SG complexes, which are catalysts for GSH oxidation. The complexes promoted elevated levels of reactive oxygen species (ROS) in human lung cancer cells. This remarkable ligand-centred activation mechanism coupled to redox reactions adds a new dimension to the design of organoiridium anticancer prodrugs.The hexa-μ2-amido-tetraammine-tetraberyllium compounds [Be4(NH2)6(NH3)4]X2 (X = Cl, Br, I, CN, SCN, N3) have been prepared from beryllium metal and NH4X or [Be(NH3)4]X2 in liquid ammonia at ambient temperature. The obtained compounds feature an adamantyl shaped complex cation, which was examined via X-ray diffraction, IR, Raman and NMR spectroscopy. The speciation in solution was studied via 15N labeling experiments supplemented with quantum chemistry. Hereby, the intermediates [Be2(NH2)(NH3)6]3+ and [Be3(NH2)3(NH3)6]3+ were identified. Reactivity studies provided bis(N-acetimidoylacetamidinato-N,N')-beryllium(ii), when [Be4(NH2)6(NH3)4]2+ was treated with acetonitrile. While the unprecedented octa-nuclear complex cation [Be8O(NH2)12(C5H5N)4]2+ was received from pyridine. This cluster proves that the [Be4O]6+ core can be stabilized without bidentate O-donor ligands.