Substrate Reaction Research Articles

Aberrant BCAT1 expression augments MTOR activity and accelerates disease progression in chronic lymphocytic leukemia.

We performed gene expression profiling of mRNA/cDNA isolated from N = 117 flow sorted CLL. We detected aberrant expression of the metabolic enzyme branched chain amino acid transferase (BCAT1) in CLL with del17p/TP53mut. Through extensive validation, we confirmed the highly preferential expression of BCAT1 in CLL with del17p/TP53mut (66%) or trisomy 12 (77%). BCAT1 was not expressed in B cells isolated from normal human lymph nodes. The products of the bidirectional BCAT1 reaction, including leucine, acetyl-CoA, and alpha-ketoglutarate are known activators of MTOR. We measured an ~two-fold higher MTOR activity via normalized p-S6K levels in primary CLL with BCAT1 high versus absent expression before and after sIgM crosslinking. Through steady state metabolomics and heavy isotope metabolic tracing in primary CLL cells, we demonstrate that CLL cells are avid consumers of branched chain amino acids (BCAAs) and that BCAT1 in CLL engages in bidirectional substrate reactions. Of additional interest, CLL with aberrant BCAT1 expression were less sensitive to Venetoclax-induced apoptosis. Biologically, three CLL-derived cell lines with disruption of BCAT1 had substantially reduced growth ex vivo. Clinically, the expression of any detectable BCAT1 protein in CLL independently associated with shorter median survival (125 months versus 296 months; p < 0.0001), even after exclusion of del17p/TP53mut cases.

Ru-Catalyzed Redox-Neutral Coupling of N-Chlorobenzamides with Unsymmetrical Alkynes in Water.

In water, Ru-catalyzed annulation of N-chlorobenzamides with unsymmetrical internal alkynes bearing aryl, hydroxy, ester, and sulfonyl functionalities has been accomplished to afford isoquinolone scaffolds under external oxidant-free conditions at room temperature. Use of water as reaction medium, redox-neutral conditions, regioselectivity, and substrate scope are important practical features.

An easy and sensitive assay for acetohydroxyacid synthases based on the simultaneous detection of substrates and products in a single step.

Acetohydroxyacid synthase (AHAS, EC 2.2.1.6) catalyzes the first step in the synthesis of the branched-chain amino acids valine, leucine, and isoleucine, pathways being present in plants and microorganisms, but not in animals. Thus, AHAS is an important target for numerous herbicides and, more recently, for the development of antimicrobial agents. The need to develop new and optimized herbicides and pharmaceuticals requires a detailed understanding of the biochemistry of AHAS. AHAS transfers an activated two-carbon moiety derived from pyruvate to either pyruvate or 2-oxobutyrate as acceptor substrates, forming 2-acetolactate or 2-acetohydroxy-2-butyrate, respectively. Various methods have been described in the literature to biochemically characterize AHAS with respect to substrate preferences, substrate specificity, or kinetic parameters. However, the simultaneous detection and quantification of substrates and unstable products of the AHAS-catalyzed reaction have always been a challenge. Using AHAS isoform II from Escherichia coli, we have developed a sensitive assay for AHAS-catalyzed reactions that uses derivatization with ethyl chloroformate to stabilize and volatilize all reactants in the aqueous solution and detect them by gas chromatography coupled to flame ionization detection or mass spectrometry. This assay allows us to characterize the product formation in reactions in single and dual substrate reactions and the substrate specificity of AHAS, and to reinterpret previous biochemical observations. This assay is not limited to the AHAS-catalyzed reactions, but should be applicable to studies of many metabolic pathways.

Synthesis and evaluation of new mono- and binuclear salen complexes for the Cα-alkylation reaction of amino acid substrates as chiral phase transfer catalysts

In this study, we present a series of Zn(II) mono- and Cu(II) binuclear salen complexes synthesized and assessed for their effectiveness in the Cα-alkylation reaction. Through systematic experimentation, it was observed that the introduction of a methoxy group at position 3 of the phenyl group in the salicylidene ligand led to a notable enhancement in asymmetric yield, while an allyl group reduced yield. Computational DFT calculations supported the involvement of the binuclear complex in the transition state of the reaction, elucidating the underlying mechanisms governing the observed catalytic behavior. A newly synthesized binuclear complex exhibited significantly higher catalytic activity compared to its mononuclear counterpart which could potentially be explained by increased intramolecular rigidity. This comprehensive investigation not only advances our understanding of structure-activity relationships in chiral salen complexes but also provides valuable insights for the rational design and optimization of catalysts for the asymmetric Cα-alkylation reaction.

Cage-Shaped Borate Catalysts Bearing Precisely Controlled Lewis Acidity and Their Application in Glycosylations.

Cage-shaped borates, whose Lewis acidity can be precisely modulated by the structural attributes of the triphenolic ligands, were employed as catalysts for glycosylation. Each cage-shaped borate displayed distinctive reactivity; thus, screening of the borate catalysts enabled controllable activation of glycosyl fluorides under mild conditions. Practical glycosylation was achieved by fine-tuning the Lewis acidity tailored to the substrate reactivity, thereby providing a versatile method applicable to the synthesis of complex glycans.

Mitochondrial Maintenance in Skeletal Muscle.

Skeletal muscle is one of the tissues with the highest range of variability in metabolic rate, which, to a large extent, is critically dependent on tightly controlled and fine-tuned mitochondrial activity. Besides energy production, other mitochondrial processes, including calcium buffering, generation of heat, redox and reactive oxygen species homeostasis, intermediate metabolism, substrate biosynthesis, and anaplerosis, are essential for proper muscle contractility and performance. It is thus not surprising that adequate mitochondrial function is ensured by a plethora of mechanisms, aimed at balancing mitochondrial biogenesis, proteostasis, dynamics, and degradation. The fine-tuning of such maintenance mechanisms ranges from proper folding or degradation of individual proteins to the elimination of whole organelles, and in extremis, apoptosis of cells. In this review, the present knowledge on these processes in the context of skeletal muscle biology is summarized. Moreover, existing gaps in knowledge are highlighted, alluding to potential future studies and therapeutic implications.

Lying or Standing of Thiophene on a Surface Determines the Reaction Difference.

Adsorption configurations of molecules on a surface play an important role in the on-surface reaction. In the on-surface synthesis reaction, most of the molecules prefer the lying adsorption configuration to maximize the interaction between the molecule and substrate. In this work, we report an on-surface study of 2,3,4,5-tetrabromothiophene by scanning tunneling microscopy, density functional theory, and X-ray photoelectron spectroscopy. Due to different interactions between thiophene and metal surfaces, lying or standing configurations of 2,3,4,5-tetrabromothiophene can be selected by the choice of metal substrates. Moreover, a catalytic role of the metal substrate in the molecular reaction with lying and standing adsorption configurations is demonstrated at the molecular level. This work broadens the understanding of thiophene's configurations in surface reactions and the product diversity driven by adsorption configurations. It also offers a guiding framework for synthesizing multifunctional materials by thiophene derivatives.

Quantitative Reactivity Models for Oxidative Addition to L2Pd(0): Additional Substrate Classes, Solvents, and Mechanistic Insights.

Quantitative molecular structure-reactivity models are useful for generating predictions to guide synthesis design, and in formulating and testing mechanistic hypotheses. We report an expanded multivariate linear regression (MLR) model for the rate of (hetero)aryl (pseudo)halide oxidative addition to L2Pd(0), here exemplified by Pd(PCy3)2. This builds on a prior model from our group, with additional substrate classes (aryl chlorides and iodides) and reaction solvents (THF, toluene, THF/DMF mixture). Overall solvent effects across the entire substrate set are minimal under these conditions, enabling a unified MLR model without introduction of new molecular descriptors beyond the original five. Examining the mechanistic origin of the two molecular electrostatic potential (ESP) descriptors led to generation of a simpler, four descriptor model that is suitable for aryl halides, but not for 2-halopyridines. Using this model we identified a mechanistic outlier, 2-pyridyl triflate, which undergoes a nucleophilic displacement oxidative addition that does not involve the adjacent nitrogen atom. Finally, we discuss the relationship between C-X bond strength and oxidative addition rates, and compare the intrinsic bond strength index (IBSI) to bond dissociation enthalpy (BDE) as a bond strength descriptor.

Transition Metal-Catalyzed C(sp3)-C(sp3) Coupling to Construct All-Carbon Quaternary Carbon Centers

Transition metal-catalyzed C(sp³)-C(sp³) coupling reactions represent a powerful strategy for constructing all-carbon quaternary centers. However, these reactions remain challenging due to significant steric hindrance effects and the propensity for side reactions such as elimination and isomerization. This review provides a comprehensive summary of the progress made over the past few decades in the construction of all-carbon quaternary centers, with a focus on coupling reactions involving tertiary C(sp³) and primary/secondary C(sp³) centers (as the cross coupling of two tertiary C(sp³) centers remains unsuccessful). The discussion is organized around reaction conditions, substrate scope, and reaction mechanisms, and a brief overview of transformations based on these coupling reactions is also presented.

An improved gold(I) catalytic system for the preparation of coumarins via intramolecular cyclization.

A catalytic system comprising a gold(I) complex with an N-heterocyclic carbene (NHC) ligand in an ionic liquid as solvent exhibits higher catalytic efficiency compared to state of the art systems in the title reaction, which enables using down to 0.01 mol% gold. A commercial gold(I) catalyst such as IPrAuNTf2 can be employed for this purpose. In the case of less reactive substrates bearing electron-withdrawing substituents at the phenol moiety, a tailor made NHC-gold(I) precatalyst exhibits improved reactivity and can be advantageously employed compared to the commercial one.

Synthesis of Hetaryl Substituted Pyrazolo[3,4-b]Quinolinone Systems by Multicomponent Cyclocondensation Reaction

In this study, the synthesis of pyrazolo[3,4-b]quinolinone compounds was carried out via one-pot three-component reactions. These reactions proceed as domino processes, making them easier to occur than the conventional multistep organic reactions. By employing this method, new organic molecules can be synthesized in a single step, using minimal time and number of trials. In the first phase of this two-step study, heteroaromatic carbaldehydes (quinoline-8-carboxaldehyde and quinoline-4-carboxaldehyde) were prepared to be used as substrates in subsequent reactions by oxidation of 8-methylquinoline and 4-methylquinoline with selenium dioxide, a mild oxidant. In the second step, heteroaromatic carbaldehyde reacted with aminopyrazole and dimedone in anhydrous ethanol by one-pot multicomponent condensation method to synthesize six new compounds with heteryl-substituted pyrazolo[3,4-b]quinolinone ring system. The crude products were obtained in excellent yields and further purified by crystallization. The structures of the compounds, which were found to be completely pure as a result of chromatographic studies, were elucidated by spectroscopic methods and elemental analysis.

Fabrication of thick Cr masks for reactive ion substrate etching by electron beam lithography and lift-off techniques

Fabrication of tall Cr nanostructures of different shapes by lithography and lift-off processes is demonstrated. By varying resist thickness, metal layer thickness, and diameter of holes in the resist mask, it is demonstrated that metal structures with shapes ranging from sharp-tipped conical over flat-top cones to nearly cylindrical can be fabricated. A comparison of resist layer dissolution in acetone, covered by Ag and Cr films, reveals that Cr films grow with an open structure of particles that allow rapid solvent diffusion through Cr layers that are several hundred nanometers thick. On the other hand, the 2D growth of Ag on the resist forms a barrier against acetone diffusion. The open structure of Cr enables the lift-off process to fabricate several-μm-high nanostructures using a single resist layer. As an example, high-aspect-ratio Si structures are demonstrated by reactive ion etching using thick Cr layers as a mask, fabricating nanopillars with 3 μm height at room temperature.

Application of a Film Model to Mass Transfer and Chemical Reaction at a Plasma-Liquid Interface

Abstract Plasma electrodes provide novel ways of conducting electrochemical processes in liquids, in particular because of the ability to generate unique reactive radical species. However, the radicals injected into the liquid and their ensuing reactions are often confined to a narrow region near the interface of the plasma and the liquid. Thus, mass transfer has been found to play an important role in the observed kinetics and a modeling framework that includes both transport and kinetics is required to interpret experimental data. Here, we apply the idea of a film model for interphase mass transfer to plasma-liquid electrochemical processes, whereby transport is described by a stagnant film that is inherently linked to the concentration boundary layer and the mass transfer coefficient. Equations that govern the transport and reaction of radicals and substrates within the film are solved assuming a quasi-steady state approximation. The model is applied to specific case studies from the literature to estimate important parameters that cannot easily be measured in experiments, such as the mass transfer coefficient. Our study shows that a film model can elucidate the effect of mass transfer on observed conversion rates and allow the intrinsic kinetics to be unraveled.

Chiral Polar Bifunctional Polyimide Enantiomers for Asymmetric Photo- and Piezo-catalysis.

Chiral catalysts for asymmetric catalysis represent a crucial research focus in chemistry and materials science. However, a few cases about chiral-dependent photocatalysts primarily focus on plasmonic noble metals. Particularly, developing chiral nano-catalysts that can be driven by mechanical energy remains in the blank stage. Herein, organic polymer-based enantiomers, chiral polar polyimide (PI) microspheric nano-assembly are synthesized as novel bifunctional catalysts for asymmetric photocatalysis and piezocatalysis. The PI catalyst enantiomers present enantioselectivity towards left- and right-circularly polarized light, demonstrating chiral-dependent H2O2 photoproduction. Interestingly, enantioselectivity of the catalyst reverses under irradiation of different bands, presenting tunability in the interaction between chiral catalysts and circularly polarized light. For the first time, enantioselective piezocatalytic behavior is demonstrated by the chiral polar PI catalysts. They show remarkable chiral preference for asymmetric Diels-Alder reaction and enantioselective conversion of tyrosine substrates under ultrasonic vibration. The findings provide a new perspective into exploring metal-free chiral catalysts and their asymmetric catalysis applications across multiple energy forms.

Chiral Polar Bifunctional Polyimide Enantiomers for Asymmetric Photo‐ and Piezo‐catalysis

Chiral catalysts for asymmetric catalysis represent a crucial research focus in chemistry and materials science. However, a few cases about chiral‐dependent photocatalysts primarily focus on plasmonic noble metals. Particularly, developing chiral nano‐catalysts that can be driven by mechanical energy remains in the blank stage. Herein, organic polymer‐based enantiomers, chiral polar polyimide (PI) microspheric nano‐assembly are synthesized as novel bifunctional catalysts for asymmetric photocatalysis and piezocatalysis. The PI catalyst enantiomers present enantioselectivity towards left‐ and right‐circularly polarized light, demonstrating chiral‐dependent H2O2 photoproduction. Interestingly, enantioselectivity of the catalyst reverses under irradiation of different bands, presenting tunability in the interaction between chiral catalysts and circularly polarized light. For the first time, enantioselective piezocatalytic behavior is demonstrated by the chiral polar PI catalysts. They show remarkable chiral preference for asymmetric Diels‐Alder reaction and enantioselective conversion of tyrosine substrates under ultrasonic vibration. The findings provide a new perspective into exploring metal‐free chiral catalysts and their asymmetric catalysis applications across multiple energy forms.

CdWO4 Sub‐1 nm Nanowires for Visible‐light CO2 Photoreduction

Quantum size effect usually causes energy level splitting and band broadening as material size decreases. However, this may change again by the surface adsorbents, doping and defects, which rarely attracts much attention. Herein, CdWO4 sub‐1 nm nanowires (SNWs) with oleylamine adsorption, PO43‐‐doping and oxygen defects are synthesized by combining Cd(CH3COO)2, H3PW12O40 (PW12) and oleylamine (abbreviated as PO43‐‐CdWO4‐X SNWs). Compared with bulk CdWO4, they exhibit unexpected absorption spectra (extended from 292 nm to 453 nm) and bandgap (reduced from 4.25 eV to 2.74 eV), thus bringing remarkable visible‐light CO2 photoreduction activity. Under 410 nm LED light irradiation, PO43‐‐CdWO4‐40 SNWs exhibit the highest photocatalytic performance with a CO2‐to‐CO generation rate of 1685 µmol g‐1 h‐1. Density functional theory (DFT) calculations demonstrate the adsorbed oleylamine raises the valence band and enhances the adsorption of reaction substrate and intermediates, thus decreasing their reduction energy barriers. Furthermore, PO43‐‐doping and oxygen defects will generate defect energy band below the conduction band of PO43‐‐CdWO4‐40 SNWs, resulting in remarkable visible light absorption and superior photocatalytic CO2 reduction performance. This work highlights the significant impacts of surface adsorbents, doping and defects on the physicochemical and catalytic properties of sub‐nano materials.

CdWO4 Sub-1 nm Nanowires for Visible-light CO2Photoreduction.

Quantum size effect usually causes energy level splitting and band broadening as material size decreases. However, this may change again by the surface adsorbents, doping and defects, which rarely attracts much attention. Herein, CdWO4 sub-1 nm nanowires (SNWs) with oleylamine adsorption, PO43--doping and oxygen defects are synthesized by combining Cd(CH3COO)2, H3PW12O40 (PW12) and oleylamine (abbreviated as PO43--CdWO4-X SNWs). Compared with bulk CdWO4, they exhibit unexpected absorption spectra (extended from 292 nm to 453 nm) and bandgap (reduced from 4.25 eV to 2.74 eV), thus bringing remarkable visible-light CO2 photoreduction activity. Under 410 nm LED light irradiation, PO43--CdWO4-40 SNWs exhibit the highest photocatalytic performance with a CO2-to-CO generation rate of 1685 µmol g-1 h-1. Density functional theory (DFT) calculations demonstrate the adsorbed oleylamine raises the valence band and enhances the adsorption of reaction substrate and intermediates, thus decreasing their reduction energy barriers. Furthermore, PO43--doping and oxygen defects will generate defect energy band below the conduction band of PO43--CdWO4-40 SNWs, resulting in remarkable visible light absorption and superior photocatalytic CO2 reduction performance. This work highlights the significant impacts of surface adsorbents, doping and defects on the physicochemical and catalytic properties of sub-nano materials.

Controlling Chemoselectivity in Ruthenium(II)-Induced Cyclization of Aniline-Functionalized Alkynes.

The cyclization of heteroatom-functionalized alkynes induced by d6-transition-metal centers has traditionally been associated with the vinylidene pathway. However, recent evidence suggests that d6-transition-metal centers can also activate alkynes through non-vinylidene pathways. In this study, we conducted a comprehensive experimental and theoretical investigation into the reactions between the Ru(II) complex [Ru([9]aneS3)(bpy)(OH2)]2+ and 2-alkynylanilines. Our study revealed that the selectivity between the vinylidene and non-vinylidene pathways can be tuned by reaction temperature, substrate, and solvent polarity. This strategic control allows for the preferential formation of either C2- or C3-metalated indole zwitterion complexes. Additionally, we identified a rare decyclization mechanism that enables the conversion of C2-metalated indoles to C3-metalated indoles, underscoring the significance of product stability in these pathways. Overall, this work demonstrates practical approaches to control the preference between vinylidene and non-vinylidene pathways, which is crucial for the design of new catalysts and metalated heterocyclic complexes.

Lignin-based monophenolic model compounds in L-tyrosine derivative synthesis via tyrosine phenol lyase

Tyrosine phenol lyase (TPL) synthesises L-tyrosine derivatives from monophenols, pyruvate and ammonia. Production of such high-value aromatic chemicals from biomass-derived raw materials is of great interest. In this study, six monophenols (guaiacol, phenol, o-cresol, m-cresol, catechol and syringol) were chosen based on the structure of lignin and were studied as substrates in the enzymatic reaction. Single monophenol reactions (SMR) and binary monophenol reactions (BMR) with guaiacol were carried out. TPL-M379V was found to be selective towards guaiacol (84.5 % conv.). The highest single activity was measured towards phenol (93.9 % conv.). However, the enzyme preferred guaiacol over phenol in the BMRs. Syringol was found to be inert in the reaction, whereas catechol had an inhibitory effect on the enzymatic reaction, in addition to causing degradation of all the substrates in the medium. Doubling the guaiacol concentration in the SMR did not significantly increase the production of 3-O-methyldopa (conv. 45.9 %). However, in the binary reaction systems the total monophenol conversions were higher with guaiacol and phenol (total 62.4 %) or o-cresol (total 57.1 %). This indicates possible substrate/product specific inhibition. The study provides new data on activity, selectivity and inhibitory effects of monophenols in the synthetic reaction catalysed by TPL-M379V, especially in mixed-substrate reactions.

Alkali‐Mediated/Catalyzed Transition‐Metal‐Free Tandem Reaction Triggered by the Borrowing Hydrogen and Aerobic Dehydrogenation Processes of Alcohols

AbstractThe transformation of alcohols to important classes of compounds is a central topic in chemistry because they are abundant, renewable, and attractive building blocks. The alkali‐mediated/catalyzed borrowing hydrogen and aerobic dehydrogenation processes of alcohols open a new and sustainable access for the alcohol conversion under transition‐metal‐free conditions. In this review, we summarize the recent alkali‐mediated/catalyzed sequential reactions involving the borrowing hydrogen and aerobic dehydrogenation processes of alcohols. Furthermore, this review not only introduces the tentative pathways of these transformations, but also discusses the role of alkali, solvent effects, and substrate reactivity on these reactions.