Deckerjiang1512

Therefore, RL provides a good framework to tailored design approaches for different discovery phases.Reaction of [Ru(PPh3)3HCl] with LiCH2TMS, MgMe2, and ZnMe2 proceeds with chloride abstraction and alkane elimination to form the bis-cyclometalated derivatives [Ru(PPh3)(C6H4PPh2)2H][M'] where [M'] = [Li(THF)2]+ (1), [MgMe(THF)2]+ (3), and [ZnMe]+ (4), respectively. In the presence of 12-crown-4, the reaction with LiCH2TMS yields [Ru(PPh3)(C6H4PPh2)2H][Li(12-crown-4)2] (2). These four complexes demonstrate increasing interaction between M' and the hydride ligand in the [Ru(PPh3)(C6H4PPh2)2H]- anion following the trend 2 (no interaction) less then 1 less then 3 less then 4 both in the solid-state and solution. SRI011381 Zn species 4 is present as three isomers in solution including square-pyramidal [Ru(PPh3)2(C6H4PPh2)(ZnMe)] (5), that is formed via C-H reductive elimination and features unsaturated Ru and Zn centers and an axial Z-type [ZnMe]+ ligand. A [ZnMe]+ adduct of 5, [Ru(PPh3)2(C6H4PPh2)(ZnMe)2][BArF4] (6) can be trapped and structurally characterized. 4 reacts with H2 at -40 °C to form [Ru(PPh3)3(H)3(ZnMe)], 8-Zn, and contrasts the analogous reactions of 1, 2, and 3 that all require heating to 60 °C. This marked difference in reactivity reflects the ability of Zn to promote a rate-limiting C-H reductive elimination step, and calculations attribute this to a significant stabilization of 5 via Ru → Zn donation. 4 therefore acts as a latent source of 5 and this operational "dual unsaturation" highlights the ability of Zn to promote reductive elimination in these heterobimetallic systems. Calculations also highlight the ability of the heterobimetallic systems to stabilize developing protic character of the transferring hydrogen in the rate-limiting C-H reductive elimination transition states.Out of the 14 lanthanide (Ln) ions, molecular complexes of Ln(IV) were known only for cerium and more recently terbium. Here we demonstrate that the +IV oxidation state is also accessible for the large praseodymium (Pr) cation. The oxidation of the tetrakis(triphenysiloxide) Pr(III) ate complex, [KPr(OSiPh3)4(THF)3], 1-PrPh, with [N(C6H4Br)3][SbCl6], affords the Pr(IV) complex [Pr(OSiPh3)4(MeCN)2], 2-PrPh, which is stable once isolated. The solid state structure, UV-visible spectroscopy, magnetometry, and cyclic voltammetry data along with the DFT computations of the 2-PrPh complex unambiguously confirm the presence of Pr(IV).To identify Janus kinase (JAK) inhibitors that selectively target gastrointestinal tissues with limited systemic exposures, a class of imidazopyrrolopyridines with a range of physical properties was prepared and evaluated. We identified compounds with low intrinsic permeability and determined a correlation between permeability and physicochemical properties, clogP and tPSA, for a subset of compounds. This low intrinsic permeability translated into compounds displaying high colonic exposure and low systemic exposure after oral dosing at 25 mg/kg in mouse. In a mouse PK/PD model, oral dosing of lead compound 2 demonstrated dose-dependent inhibition of pSTAT phosphorylation in colonic explants post-oral dose but low systemic exposure and no measurable systemic pharmacodynamic activity. We thus demonstrate the utility of JAK inhibitors with low intrinsic permeability as a feasible approach to develop gut-restricted, pharmacologically active molecules with a potential advantage over systemically available compounds that are limited by systemic on-target adverse events.C-C reductive elimination from [PdL2(C6F5)2] to form polyfluorinated biaryls has been a challenge for over 50 years. Thus, palladium-catalyzed homocoupling of arylboronates (ArF-Bpin) containing two ortho-fluorine substituents is very difficult, as the reaction typically stops at the [PdL2(ArF)2] stage after two transmetalation steps. The transmetalated complexes cis-[Pd(MeCN)2(C6F5)2] (3a), cis-[Pd(MeCN)2(2,4,6-C6F3H2)2] (3b), and cis-[Pd(MeCN)2(2,6-C6F2H3)2] (3e) have been isolated from the reaction of ArF-Bpin with Pd(OAc)2 in acetonitrile solvent, with no homocoupling observed. However, catalytic homocoupling proceeds smoothly in a "weakly coordinating" arene solvent as long as no ancillary ligands or coordinating solvents are present. DFT computations reveal that the active catalyst formed by arene solvent coordination leads to an overall reduced barrier for the reductive elimination step compared to the formation of stable [PdL2(ArF)2] complexes in the presence of a donor ligand or solvent L.Terpenes constitute one of the most structurally varied classes of natural products. A wide range of these structures are produced in nature by type I terpene cyclase enzymes from one single substrate. However, such reactivity has proven difficult to reproduce in solution with man-made systems. Herein we report the shortest synthesis of the tricyclic sesquiterpene presilphiperfolan-1β-ol to date, utilizing the supramolecular resorcinarene capsule as catalyst for the key step. This synthetic approach also allows access to unnatural derivatives of the natural product, which would not be accessible through the biosynthetic machinery. Additionally, this study provides useful insight into the biosynthesis of the presilphiperfolanol natural products, including the first experimental evidence consistent with the proposed biosynthetic connection between caryophyllene and the presilphiperfolanols.Design and implementation of synthetic biological circuits highly depends on well-characterized, robust promoters with predictable input-output responses. While great progress has been made with heterotrophic model organisms such as Escherichia coli, the available variety of tunable promoter parts for phototrophic cyanobacteria is still limited. Commonly used synthetic and semisynthetic promoters show weak dynamic ranges or no regulation at all in cyanobacterial models. Well-controlled alternatives such as native metal-responsive promoters, however, pose the problems of inducer toxicity and lacking orthogonality. Here, we present the comparative assessment of dose-response functions of four different inducible promoter systems in the model cyanobacterium Synechocystis sp. PCC 6803. Using the novel bimodular reporter plasmid pSHDY, dose-response dynamics of the re-established vanillate-inducible promoter PvanCC was compared to the previously described rhamnose-inducible Prha, the anhydrotetracycline-inducible PL03, and the Co2+-inducible PcoaT.