Explore the toxicological mechanism of 6PPD-Q on human health through a novel perspective: The interaction between lactate dehydrogenase and 6PPD-Q.

N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine-quinone (6PPD-Q), an oxidative derivative of tire anti-degradant, has been linked to mortality in coho salmon (Oncorhynchus kisutch) and has exhibited potential human toxicity. Hence, exploring how 6PPD-Q interacts with biomacromolecules like enzymes is indispensable to assess its human toxicity and elucidate its mechanism of action. This investigation aims to explore the impact of 6PPD-Q on lactate dehydrogenase (LDH) through various methods.

TMSN Initiated Electrochemical Mono-Dealkylation of Tertiary Amides.

-Dealkylation of amides is a general process in living organisms and organic synthetic chemistry, but an efficient chemical approach for this transformation has not been explored. Herein, we report an electrochemical method for the monodealkylation of a wide range of tertiary amides, including benzamides, alkyl amides, lactams, and sulfonamides. The reaction proceeds smoothly under mild conditions using TMSN as the initiator and is not limited to deethylation or demethylation.

Electrooxidative Ni-Catalyzed Decarboxylation of Arylacetic Acids Towards the Synthesis of Carbonyls under Air Conditions.

After systematic realization of decarboxylative functionalization of carboxylic acids under heating conditions in our group, we herein reported an electrochemical method for Ni-catalyzed decarboxylative oxygenation of arylacetic acids under open air conditions. The protocol provided corresponding carbonyls including aldehydes and ketones in moderate to satisfactory yields with good functional group tolerance, furthermore, the practicability and advantage of the method was highlighted through Ni-catalyzed oxidative decarboxylation of carboxylic acid-containing drugs and preformation of scalable transformation. Mechanistic studies demonstrated that the possible involvement of free radical intermediate in the conversion.

Visible-light-induced C(sp)-C(sp) bond formation radical/radical cross-coupling.

Radical/radical cross-coupling remains challenging due to diffusion control issues. Herein, we report a visible-light-induced radical/radical cross-coupling reaction of quaternary ammonium salts and Hantzschs C-N and C-C bond cleavage. The current synthetic approach furnishes 1,2-diphenylethanes in moderate to good yields and provides a method for the construction of the C(sp)-C(sp) bond.

Bromide ion promoted practical synthesis of phosphinothioates of sulfinic acid derivatives and H-phosphine oxides.

A feasible method for the synthesis of phosphinothioates from sulfinic acid derivatives and phosphine oxides is described. This reaction can be carried out in an open flask at room temperature and in an aqueous medium. The scope of the sulfinic acid derivatives is extensive, with a wide range of sulfinate esters, sulfinic acids, and sodium sulfinates compatible with these conditions, with good to excellent yields of phosphinothioates.

An Electrochemical Method for Deborylative Hydroxylation of Arylboronic Acids under Metal-free Conditions.

An electrochemical method for the synthesis of (poly)phenols via deborylative hydroxylation of arylborons has been well established under metal-free conditions, whose practicability and advantage has been highlighted by the preparation of drug molecules and preformation of scalable transformation. Mechanistic studies have demonstrated that superoxide anion radical was involved in the conversion followed by the reaction with arylboronic acid substrate.

Nickel-Catalyzed 1,1-Dihydrophosphinylation of Nitriles with Phosphine Oxides.

Treatment of phosphine oxides with nitriles usually furnishes 1,2-dihydrophosphinylation products. Herein, we developed a nickel-catalyzed 1,1-dihydrophosphinylation of nitriles with phosphine oxides to access primary amines. This reaction proceeded smoothly under very mild conditions.

Selective C-C bond cleavage of amides fused to 8-aminoquinoline controlled by a catalyst and an oxidant.

Herein, copper-catalyzed direct C-C bond cleavage of amides fused to 8-aminoquinoline as a directing group to form urea in the presence of amines and dioxygen is reported. Compared to the previous C-H aminations of amides via C-H activation, this reaction presents a catalyst and oxidant controlled C-C bond cleavage strategy that enables amidation through a radical process. CuBr/AgCO/O shows the best catalytic result at 150 °C.

Conversions of aryl carboxylic acids into aryl nitriles using multiple types of Cu-mediated decarboxylative cyanation under aerobic conditions.

Here, we used malononitrile or AMBN as a cyanating agent to develop efficient and practical protocols for Cu-mediated decarboxylative cyanations, under aerobic conditions, of aryl carboxylic acids bearing nitro and methoxyl substituents at the ortho position as well as of heteroaromatic carboxylic acids. These protocols involved economical methods to synthesize value-added aryl nitriles from simple and inexpensive raw materials. Further diversification of the 2-nitrobenzonitrile product was performed to highlight the practicality of the protocols.

Pd-Catalyzed Decarboxylative Ortho-Halogenation of Aryl Carboxylic Acids with Sodium Halide NaX Using Carboxyl as a Traceless Directing Group.

A highly regioselective Pd-catalyzed carboxyl directed decarboxylative ortho-C-H halogenation of cheap o-nitrobenzoic acids with NaX (X = I, Br) under aerobic conditions has been established. The utility of the method has been demonstrated by the gram-scale reaction and derivatization of the product. Experimental results have confirmed Pd and Bi played critical roles in the transformation and indicated the transformation might proceed via 2-halo-6-nitrobenzoic acid derivative intermediate.

Inexpensive NaX (X = I, Br, Cl) as a halogen donor in the practical Ag/Cu-mediated decarboxylative halogenation of aryl carboxylic acids under aerobic conditions.

Versatile and practical Ag/Cu-mediated decarboxylative halogenation between readily available aryl carboxylic acids and abundant NaX (X = I, Br, Cl) has been achieved under aerobic conditions in moderate to good yields. The halodecarboxylation is shown to be an effective strategy for S-containing heteroaromatic carboxylic acid and benzoic acids with nitro, chloro and methoxyl substituents at the ortho position. A gram-scale reaction and a three-step procedure to synthesize iniparib have been performed to evaluate the practicality of this protocol.

Decarboxylative Halogenation and Cyanation of Electron-Deficient Aryl Carboxylic Acids via Cu Mediator as Well as Electron-Rich Ones through Pd Catalyst under Aerobic Conditions.

Simple strategies for decarboxylative functionalizations of electron-deficient benzoic acids via using Cu(I) as promoter and electron-rich ones by employing Pd(II) as catalyst under aerobic conditions have been established, which lead to smooth synthesis of aryl halides (-I, Br, and Cl) through the decarboxylative functionalization of benzoic acids with readily available halogen sources CuX (X = I, Br, Cl), and easy preparation of benzonitriles from decarboxylative cyanation of aryl carboxylic acids with nontoxic and low-cost K4Fe(CN)6 under an oxygen atmosphere for the first time.

Cu(II)-mediated phenol oxygenation: chemical evidence implicates a unique role of the enzyme active site in promoting the chemically difficult tyrosine monooxygenation in TPQ cofactor biogenesis of copper amine oxidases.

Cu(II)-mediated autoxidations of 4-tert-butylphenol under various conditions was studied, the data confirmed imidazole is the best ligand to promote phenol oxygenation. The same reaction of 2,4-di-tert-butylphenol proceeded much more quickly to lead nearly exclusively to oxidative coupling rather than oxygenation under high pressure O2. These results suggested that Cu(II)-catalyzed phenol autoxidation by activating O2 and phenol in terms of a phenoxy radical (ArO)-Cu(II)-superoxide ternary complex, whereas selectivity between oxygenation and coupling depends mainly on the electronic structure of ArO.

Pd-catalyzed decarboxylative arylation of silyl enol ester sp3 β-C-H bond under aerobic conditions.

Pd-catalyzed aerobic oxidative coupling of various benzoic acids with silyl enol esters proceeds via a combination of decarboxylation with sp(3) β-C-H bond activation to give Heck-type products. Mechanistic studies reveal this coupling involves in situ generation of olefin from aerobic oxidation of silyl enolate, followed by decarboxylative Heck coupling.

Pd-catalyzed dearboxylative Heck coupling with dioxygen as the terminal oxidant.

Pd-catalyzed decarboxylative Heck coupling of aromatic carboxylic acids with various olefins is developed using O(2) as the terminal oxidant. Enhancement of O(2) pressure leads to improving reaction turnover in this transformation and allows significantly reducing catalyst loading for efficient conversion of electron-rich benzoic acids. A Pd catalyst supported by a carbene ligand enables using electron-deficient benzoic acids as coupling partners.