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Ultrafast electronic and ligand dissociation dynamics proceeds on different time scales in the gas phase and solution phase owing to solvent-induced stabilization of charge-transfer states.

An organocatalyzed, formal (3+3) cycloaddition reaction is described for the practical synthesis of substituted pyridines. Starting from readily available enamines and enal/ynal/enone substrates, the protocol affords tri- or tetrasubstituted pyridine scaffolds bearing various functional groups. This method was demonstrated on a 50 g scale, enabling the synthesis of 2-isopropyl-4-methylpyridin-3-amine, a raw material used for the manufacture of sotorasib. Mechanistic analysis using two-dimensional nuclear magnetic resonance (NMR) spectrometry revealed the transformation proceeds through the reversible formation of a stable reaction off-cycle species that precedes pyridine formation.

Orthogonal coordination of gold and zinc yields mono- and bimetallic complexes, which are investigated concerning their photophysics.

A novel protocol for the synthesis of a Janus periodic mesoporous organosilica material (JPMO) is presented here. In this strategy, the surface of the hollow silica material was selectively functionalized with two different bridged organic-inorganic hybrid groups. It was found that the resulting bifunctional material is able to form a stable Pickering emulsion. This new type of PMO material may serve for widespread applications in various fields related to material science and catalysis.

The central Appalachian shale barrens, a globally unique habitat type restricted to the eastern United States, presents an insular and physiologically stressful environment with sparse vegetation and extreme ground surface and air temperatures. Despite the high levels of plant species endemism within these systems, information on invertebrate communities and habitat preferences is extremely limited.Through this study, we aimed to better understand a shale barren arthropod community, microhabitat selection, and the influence of habitat characteristics and climatic factors. We employed pitfall traps to sample epigeic arthropods during the 2016 growing season in a shale barren habitat.Arthropod community composition was driven by overstory trees, mediated through accumulated leaf litter and availability of shaded microhabitats. Ambient air temperature also influenced the surface activity of various taxa with spiders decreasing at higher temperatures and ants, crickets, flies, and harvestmen all increasing in relative abundance.Habitat integrity of the central Appalachian shale barrens is threatened by forest succession and mesophication, encroaching invasive plant species, and rising ambient air temperatures, all of which can alter the extent of overstory vegetation and availability of shaded microhabitats. These biotic and physical pressures will subsequently affect epigeic arthropod community composition, depending on adaptive capacity of individual taxa.To the authors’ knowledge, these findings constitute only the second published work on arthropod communities and the first to focus on epigeic taxa in this globally rare habitat type. Continued conservation of these unique, insular habitats and their adapted inhabitants requires a multifaceted approach that considers current and future conditions., Globally rare central Appalachian shale barrens exhibit high levels of plant endemism, yet extremely little is known about the wildlife communities therein. We uncovered the importance of overstory trees, mediated by shaded microhabitats and accumulated leaf litter, in predicting epigeic arthropod community composition. Given these results, current and future conservation threats to these unique habitats may differentially affect various invertebrate taxa, depending on adaptive capacity and resiliency to environmental change.

A simple and efficient protocol allows the oxidation of the cyclopentadiene derivative 5H-dibenzo[e,h]-dibenzo[3,4 : 6,7]cyclohept[1,2-a]azulene (CpCH) provide according ketone CpCO. Comparable to the situation found for CpCH, the bending of the four annulated six-membered rings defines the C2 symmetric molecular structure of CpCO. The cyclopentadienone CpCO readily reacts with [Ru3(CO)12] and [Fe3(CO)12] to generate tricarbonyl complexes of the type [(η4-CpCO)M(CO)3]. In contrast to [(η4-CpCO)Ru(CO)3], the tricarbonyliron(0) complex is sensitive to oxygen and moisture. Refluxing [(η4-CpCO)Ru(CO)3] in isopropanol makes the hydrido-bridged complex [((η4-CpCO)2H)Ru2(CO)4H] accessible, an analogue to Shvo's catalyst. Both ruthenium complexes and their ligand CpCO were characterized spectroscopically and by single crystal x-ray diffraction. The activity of [(η4-CpCO)Ru(CO)3] was investigated for a series of transfer hydrogenation reactions.

Nucleophilic substitution of [(η5‐cyclopentadienyl)(η6‐chlorobenzene)iron(II)] hexafluorophosphate with sodium imidazolate resulted in the formation of [(η5‐cyclopentadienyl)(η6‐phenyl)iron(II)]imidazole hexafluorophosphate. The corresponding dicationic imidazolium salt, which was obtained by treating this imidazole precursor with methyl iodide, underwent cyclometallation with bis[dichlorido(η5‐1,2,3,4,5‐pentamethylcyclopentadienyl]iridium(III) in the presence of triethyl amine. The resulting bimetallic iridium(III) complex is the first example of an NHC complex bearing a cationic and cyclometallated [(η5‐cyclopentadienyl)(η6‐phenyl)iron(II)]+ substituent. As its iron(II) precursors, the bimetallic iridium(III) complex was fully characterized by means of spectroscopy, elemental analysis and single crystal X‐ray diffraction. In addition, it was investigated in a catalytic study, wherein it showed high activity in transfer hydrogenation compared to its neutral analogue having a simple phenyl instead of a cationic [(η5‐cyclopentadienyl)(η6‐phenyl)iron(II)]+ unit at the NHC ligand., Iron power: A cyclometalated Fe(II) and Ir(III) complex based on the cationic (η5‐cyclopentadienyl)(η6‐phenyl)iron(II)]imidazole skeleton is reported. Compared to its neutral analogue without the [CpFe]+ fragment, it is surprisingly active in the transfer hydrogenation of ketones. Mechanistic investigation on the reaction paths performed by DFT calculations provided a better understanding of the reaction mechanism, possible intermediates and the active species.

Vaginitis is a common condition that affects women of reproductive age. Early and accurate diagnosis and identification of the causative agents (ie, fungi, protozoa, bacterial species, etc.) help to avoid incorrect treatment and subsequent visits that add costs and therapies, which increase overall health care utilization. A prior study by Kong et al presented a cost analysis demonstrating that women who received a nucleic acid amplification test (NAAT) on the day of their vaginitis diagnosis had significantly lower 12-month follow-up costs than women who received a direct probe (DP) test or women who received clinical evaluation without the use of a molecular test. This prior analysis included pregnant women, which may have influenced the findings. The objective of this analysis is to determine whether the exclusion of pregnant women from the study cohort impacts the previously observed NAAT cost-savings results. The current analysis adds evidence that nonpregnant women diagnosed with NAAT at their initial visit have significantly lower 12-month overall health care costs than women evaluated through DP or other clinical methods. This is an update to an article titled "Diagnostic Testing of Vaginitis: Improving the Value of Care," which was published on August 16, 2021 and is available at https://doi.org/10.1089/pop.2021.0143.

Janus materials are anisotropic nano- and microarchitectures with two different faces consisting of distinguishable or opposite physicochemical properties. In parallel with the discovery of new methods for the fabrication of these materials, decisive progress has been made in their application, for example, in biological science, catalysis, pharmaceuticals, and, more recently, in battery technology. This Minireview systematically covers recent and significant achievements in the application of task-specific Janus nanomaterials as heterogeneous catalysts in various types of chemical reactions, including reduction, oxidative desulfurization and dye degradation, asymmetric catalysis, biomass transformation, cascade reactions, oxidation, transition-metal-catalyzed cross-coupling reactions, electro- and photocatalytic reactions, as well as gas-phase reactions. Finally, an outlook on possible future applications is given.

The synthesis and characterization of a series of novel cationic multimetallic transition-metal complexes based on the cationic phosphine ligand (η6-diphenylphosphinobenzene)(η5-cyclopentadienyl)ir...

Formaldehyde reacts with solvents that contain hydroxyl groups (R–OH) in oligomerization reactions to oxymethylene oligomers (R–(OCH2)n–OH). The chemical equilibria of these reactions have been studied in the literature for water, for the mono-alcohols methanol, ethanol, and 1-butanol, as well as for the diols ethylene glycol and 1,4-butynediol. In the present work, the collective data were analyzed. It was found that the prolongation of the oxymethylene chains by the addition of formaldehyde can be described very well with a generalized chemical equilibrium constant Kx,n≥2R–OH, which is independent of the substructure (R) of the solvent. This holds for the oligomerization reactions leading to R–(OCH2)n–OH with n ≥ 2. The chemical equilibrium constant Kx,1R–OH of the reaction of formaldehyde with the solvent R–OH depends on the solvent, but simple trends are observed. The hypotheses of the existence of a generalized chemical equilibrium constant Kx,n≥2R–OH was tested for the reactions of formaldehyde with ethanol and 1-propanol, for which neither Kx,1R–OH nor Kx,nR–OH was previously available. The corresponding equilibria were studied by 13C NMR spectroscopy and the equilibrium constants were determined. A novel method was developed and used in these studies to obtain data on Kx,1R–OH by NMR spectroscopy, which is difficult because of the low amount of molecular formaldehyde. It was found that the generalized equilibrium constant is even valid for the acid-catalyzed formation of poly(oxymethylene) dimethyl ethers (OME).

Cyclopentadienide derivatives possessing intrinsic helical chirality have only rarely been published in the past. The ligand CpCH, which is well-accessible from inexpensive dibenzosuberenone, is pa...

A Bronsted acidic, ionic liquid containing, heteropolyanion functionalized polysiloxane network was formed by self-condensation of dodecatungstophosphoric acid and a zwitterionic organosilane precursor containing both imidazolinium and sulfonate groups. The resulting hybrid material POS-HPA-IL was investigated as a catalyst for the selective esterification of dicarboxylic acids.

Two pentadentate N3,P2 ligands coordinate zinc(ii) by their N3 pocket. Four free phosphine donors allow the coordination of four AuCl moieties leading to a pentanuclear ZnAu4 complex. In contrast, the attempt to use the phosphines for chelating coordination of two Rh(CO)Cl units results in a well-organized rearrangement that ends up with the formation of a metallomacrocycle in high yields.

Ultrafast electronic dynamics and UV absorption of [RuII(bipyridine)2(nicotinamide)2]2+ isolated in an ion trap reveal by transient photodissociation short time constants and spectra comparable to transient absorption in solution. Ligand dissociation dynamics are elucidated.

The speciation in CO2-loaded aqueous solutions of 16 different derivates of triacetoneamine (EvAs) was investigated in a comprehensive NMR-spectroscopic study. About 350 experiments were carried out for CO2-loadings up to 3 moles CO2 per mole amine, temperatures between 20 °C and 100 °C, and a mass fraction of EvA in the unloaded solvent of 0.1 g/g. The observed CO2-containing species were primary and secondary carbamates, alkylcarbonate, (bi)carbonate, and molecular CO2. Some EvAs can form zwitterions with a ring structure, which have an important influence on the speciation. From the comprehensive set of data, relationships between the chemical structure of the EvAs and the observed speciation in aqueous solution were established. These results were related to application properties of the EvAs that were taken from previous work. Based on the findings, some general guidelines for the design of new amines were derived and applied for proposing new amines for CO2-absorption.

A heterogeneous Janus-type palladium interphase catalyst was obtained by selective surface modification of a hollow mesoporous silica material. The catalyst comprises hydrophobic octyl groups on one side of the silica nanosheets and single-site bis-imidazoline dichlorido palladium(II) complexes on the other. The structure of this composite material has been analyzed by means of elemental analysis, atomic absorption spectroscopy, BET surface analysis, TGA, SEM and solid-state CP-MAS 13C and 29Si NMR spectroscopy. The catalyst showed extraordinary activity for the aqueous-phase oxidation of styrene to acetophenone using 30% hydrogen peroxide as the oxidant. An 88% yield of acetophenone could be achieved after 60 min.

We herein describe a rational design of a heterogeneous catalyst composed of a dinuclear cuprate anion being immobilized electrostatically on one surface of Janus-type nanosheets while the other surface is decorated with highly hydrophobic octyl groups. The catalyst was found to be well dispersible in the organic phase of a biphasic aqueous/organic mixture. It was characterized by means of elemental analysis, atomic absorption spectroscopy, mass spectrometry, N2 absorption-desorption analysis, thermogravimetric analysis, scanning electron microscopy (SEM), and solid-state 13C and 29Si cross-polarization magic-angle spinning nuclear magnetic resonance spectroscopy. The Janus nature of the catalyst was investigated by employing a selective surface labeling method and by means of SEM. The catalyst shows higher activity compared to a non-Janus analogue in a biphasic synthesis. It was successfully used for the azide-alkyne cycloaddition and the Chan-Lam C-N coupling reaction. In addition, new and simple ways have been established for the production of a coumarin-triazole derivative and for the synthesis of the biologically active compound Monastrol via a solvent-free Biginelli reaction. The role of the dinuclear copper centers is discussed mechanistically.

The development of a factory process to manufacture the novel cardiac myosin activator omecamtiv mecarbil (1) is described. Omecamtiv mecarbil is prepared via the convergent synthesis and coupling ...

Oleic acid (OA) and formic acid (FA) react to formoxystearic acid (FSA), in the presence of acidic catalysts.This reaction is of interest as OA can be obtained from renewable resources and FSA is a potential precursor for biopolymers.We have recently studied the liquid−liquid equilibrium (LLE) in the uncatalyzed nonreacting system OA + FA + FSA. Thiswork is extended here to the reactive system, in which a reactive liquid−liquid equilibrium (RLLE) exists. The reactionequilibrium is studied by quantitative NMR spectroscopy at temperatures between 333 and 353 K in homogeneous OA-richmixtures. This information is combined with that on the LLE to determine the RLLE. The physicochemical equilibria aremodeled in a thermodynamically consistent way using the associating lattice cluster theory (ALCT). Furthermore, data on thechemical equilibrium of the formation of the OA-isomer elaidic acid (EA) is supplied. Also the decomposition of FA and theformation of estolides (EL), which are oligomers of OA and EA, was observed and quantified.

Two different phenothiazines carrying quaternary ammonium groups in the side chain have been synthesized and fully characterized. These compounds were immobilized by ion exchange on the surface of a periodic mesoporous organosilica (PMO) and a neat silica SBA-15 material bearing sulphonate groups covalently bound to the pore surface. The resulting porous and electrochromophoric materials were studied by means of solid state CP-MAS NMR, IR, UV/Vis and fluorescence spectroscopy, nitrogen adsorption/desorption measurements and cyclic voltammetry. Independent of the nature of the support, the colour of these materials changes to pink by irradiation with light, indicating the formation of phenothiazine radical cations. These species, which turned out to be highly stable even in the presence of atmospheric oxygen, were characterized by EPR spectroscopy.

A concept for the quantification of cooperative effects in transition-metal complexes is presented. It is demonstrated for a series of novel N,N- (mononuclear) and C,N-coordinated homo- and heterometallic binuclear complexes based on the (2-dimethylamino)-4-(2-pyrimidinyl)pyrimidine ligand, which are accessible by applying roll-over cyclometallation. These iridium-, platinum-, and palladium-containing compounds are investigated with respect to their absorption and fluorescence spectra. The cooperative effects in the electronic absorptions, i. e., the energetic shifts between mononuclear and dinuclear complexes, and free ligands are analyzed on the basis of the lowest energy π-π* transitions and compared to calculated data, obtained from TD-DFT calculations. Furthermore the corresponding fluorescence spectra are presented and analyzed with respect to the concept of cooperativity.

Since the first reports of periodic mesoporous organosilicas (PMOs) in 1999, this class of materials has attracted more and more attention. In general, such ordered templated mesoporous organosilicas are synthesized via the hydrolysis and co-condensation of bifunctional organosiloxane precursors, also referred to as bridged silsesquioxanes, in the presence of a structure directing agent (SDA) in either an acidic or alkaline environment. The uniqueness of PMO materials that combine the advantages of numerous organic functionalities with the outstanding characteristics of porous inorganic frameworks makes them a powerful toolbox for unlimited applications in multiple fields. Here, we will give a comprehensive review in this field by emphasizing the recent advances that have been achieved concerning their synthesis, morphology, functionalities, and applications mainly after 2014. In the final section, we pay a special attention to research that deals with the design, synthesis and application of a new family of PMOs denoted as hollow spherical and hollow/yolk shell periodic mesoporous organosilicas which display additional benefits as compared with traditional PMOs.

The last decade of small-molecule process development has witnessed a trend of increasing molecular complexity for clinical candidates. The continued advance of novel catalytic methods and subsequent translation to efficient and scalable processes has enabled process chemists to overcome the challenges associated with increasing complexity. This Account highlights several examples from the process chemistry laboratories at Amgen.1 Introduction2 The Evolution of Molecular Complexity3 Catalysis as a Lever to Build Complexity4 Ru(II)-Catalyzed Dynamic Kinetic Resolution Enabling the Manufacture of AMG 2325 Application of Enzymatic Desymmetrization toward Scale-Up of the MCL-1 Inhibitor AMG 1766 Synthesis of Fucostatin 1: Catalytic Asymmetric Transfer Hydrogenation7 Manganese-Catalyzed Asymmetric Epoxidation To Prepare a Carfilzomib Intermediate8 Asymmetric Reduction Strategies: Novel Apelin Receptor Agonists and AMG 9869 Conclusions

An improved API step for the formation of an aminopyrimidine-based kinase inhibitor is described. The presence of a reactive acrylamide functional group presented a considerable challenge during scale-up, resulting in side-product formation and low in-process yields for the final SNAr reaction. Impurity identification guided process development efforts, enabling rapid scale-up of a safe and phase-appropriate process to deliver the API to support toxicology studies.

A concerted approach of synthesis and gas phase experiments characterizes the relative cyclometallation barriers of a series of cationic h5-Cp* iridium(III) compounds. The common feature of the investigated compounds is a bidentate N,N’-donor ligand possessing a pyridine site functionalized with a 5-butylpyrimidin-2-yl ring in the 2-position. In addition, the pyridine ring was functionalized with electron-donating or -withdrawing groups. The compounds were characterized by means of NMR and IR spectroscopy and elemental analysis. For the measurements of the relative barriers of the cyclometallation, collision-induced dissociation (CID) experiments were carried out, which revealed a clear dependence of the relative barriers from the nature and the position of the substituents at the pyridine ring could be worked out.

In this work we report the synthesis of a periodic mesoporous organosilica (PMO) derived from 1,4-bis(triethoxysilyl)benzene (BTEB) and its functionalization with propane sulphonic acid groups via the post synthetic grafting method according to modified procedures from the literature. The material contains an acid loading of approx. 0.50 mmol/g. Being applied in various catalytic reactions, it shows moderate to little activity in condensation reactions. In THP-protection of alcohols the material is highly efficient and superior to known silica supported sulphonic acid catalysts. The activity in the corresponding deprotection reaction is comparable to typical catalysts used in this field. In addition, the acidic PMO is recyclable without any loss of activity over three catalytic runs. The mesoporous material was thoroughly characterized by solid-state CP-MAS NMR to follow the functionalization process, powder XRD to show the 2D hexagonal structure that remains pristine through all modifications and BET measurements that show a high surface area between 1185 m 2 /g and 681 m 2 /g and a stable pore diameter of around 50 A.

This study elucidates structures, activation barriers, and the gas-phase reactivity of cationic ruthenium transfer hydrogenation catalysts of the structural type [(η6-cym)RuX(pympyr)]+. In these complexes, the central ruthenium(+II) ion is coordinated to an η6-bound p-cymene (η6-cym), a bidentate 2-R-4-(2-pyridinyl)pyrimidine ligand (pympyr) with R = NH2 or N(CH3)2, and an anion X = I–, Br–, Cl–, or CF3SO3–. We present infrared multiple-photon dissociation (IR-MPD) spectra of precursors (before HCl loss) and of activated complexes (after HCl loss), which elucidates C–H activation as the key step in the activation mechanism. A resonant two-color IR-MPD scheme serves to record several otherwise “dark” bands and enhances the validity of spectral assignments. We show that collision-induced dissociation (CID)-derived activation energies of the [(η6-cym)RuX(pympyr)]+ (R = N(CH3)2) complexes depend crucially on the anion X. The obtained activation energies for the HX loss correlate well with quantum chemical act...

CpCH is a chiral cyclopentadienide-type ligand consisting of a CpH core with two annulated dibenzocycloheptatriene wings. Due to the presence of the seven-membered rings, the wings are bent making CpCH a novel, intrinsically chiral CpH derivative. Starting from ClTi(OiPr)3 and (CpC)-, obtained by deprotonation of CpCH with BuLi, the titanium (IV) half-sandwich complex (CpC)Ti(OiPr)3 was obtained. Further treatment of (CpC)Ti(OiPr)3 with an excess of Me3SiI gave the iodo derivative (CpC)Ti(OiPr)I2 in good yields. Both complexes could structurally be characterized by means of single crystal X-ray crystallography. Direct conversion of (CpC)- with TiCl4 resulted in oxidation of the anionic ligand and thus formation of the C C bridged dimer (CpC)2.