Biomimetic S-Adenosylmethionine Regeneration Starting from Multiple Byproducts Enables Biocatalytic Alkylation with Radical SAM Enzymes.

S-Adenosylmethionine (SAM) is an enzyme cofactor involved in methylation, aminopropyl transfer, and radical reactions. This versatility renders SAM-dependent enzymes of great interest in biocatalysis. The usage of SAM analogues adds to this diversity. However, high cost and instability of the cofactor impedes the investigation and usage of these enzymes. While SAM regeneration protocols from the methyltransferase (MT) byproduct S-adenosylhomocysteine are available, aminopropyl transferases and radical SAM enzymes are not covered. Here, we report a set of efficient one-pot systems to supply or regenerate SAM and SAM analogues for all three enzyme classes. The systems' flexibility is showcased by the transfer of an ethyl group with a cobalamin-dependent radical SAM MT using S-adenosylethionine as a cofactor. This shows the potential of SAM (analogue) supply and regeneration for the application of diverse chemistry, as well as for mechanistic studies using cofactor analogues.

The community perception of human-water connections is indirectly influenced by the landscape context: A case study in the lower reaches of the Yellow river.

Humans and water are closely connected in large river basins and form social-ecological systems (SESs). However, cross-scale effect in SESs make it difficult to identify the key forces driving human-water connections at the community scale when ignoring the landscape context. Focusing on the incongruous human-water relationships in the lower reaches of the Yellow River, we built local resident perception-based networks linking the agricultural subsystem, environmental subsystem, and cultural subsystem by distributing farmer household questionnaires and extracted 13 indicators from 7 kinds of network metrics to indicate human-water connections. We applied analysis of variance (ANOVA), random forest (RF) and multilevel linear model (MLM) methods to identify the driving forces of perception-based human-water connections among 20 factors at both the community and landscape scales. The results showed that the perception-based network indicators were mainly directly influenced by community-level driving factors, especially the accessibility of information, such as the frequency of going out, the frequency of accessing the Yellow River channel, and the information source for the national policy on the Yellow River. The influences of community-level driving factors on network indicators were affected by landscape-level driving factors, e.g., the nighttime light, population density, gross domestic product and proportion of artificial land, thus indicating indirect influences from the landscape context. These analyses and findings can enrich the methods by which social, ecological and hydrological elements are structurally linked in sociohydrologic research and highlight the cross-scale effect of the landscape context on human-water systems at the community level.

Synthetic Reagents for Enzyme-Catalyzed Methylation.

Late-stage methylation is a key technology in the development of pharmaceutical compounds. Methyltransferase biocatalysis may provide powerful options to insert methyl groups into complex molecules with high regio- and chemoselectivity. The challenge of a large-scale application of methyltransferases is their dependence on S-adenosylmethionine (SAM) as a stoichiometric, and thus exceedingly expensive co-substrate. As a solution to this problem, we and others have explored the use of methyl halides as reagents for the in situ regeneration of SAM. However, the need to handle volatile electrophiles, such as methyl iodide (MeI), may also hamper applications at scale. As a more practical solution, we have now developed an enzyme-catalyzed process for the regeneration of SAM with methyl toluene sulfonate. Herein, we describe enzymes from the thiopurine methyltransferase family that accept sulfate- and sulfonate-based methyl donors to convert S-adenosylhomocysteine into SAM with efficiencies that rival MeI-based reactions.

Selenoimidazolium Salts as Supramolecular Reagents for Protein Alkylation.

Se-benzyl selenoimidazolium salts are characterized by remarkable alkyl-transfer potential under physiological conditions. Structure-activity relationship studies show that selective monoalkylation of primary amines depends on supramolecular interactions between the selenoimidazole leaving group and the target nucleophile. We demonstrate that these reagents can be used for site-selective and nearly quantitative modification of the model protein lysozyme on Lys13, bypassing the higher intrinsic reactivities of Lys1 and Lys33. These observations introduce selenoimidazolium salts as novel class of electrophiles for selective N-alkylation of native proteins.

Acetonitrile Activation: An Effective Two-Carbon Unit for Cyclization.

A novel activation of acetonitrile for the construction of cyclobutenones by [2+2] cyclization was developed. Acetonitrile is utilized for the first time as two-carbon (C2) cyclization building block. The present protocol successfully inhibits the competitive cycloaddition with the C≡N bond of acetonitrile, but enables the in situ formation of an unsaturated carbon-carbon bond and the subsequent cycloaddition as a C2 unit. This chemistry features simple reaction conditions, high chemoselectivities, wide substrate scope, and offers a new and practical approach to cyclobutenones and cyclobuteneimines.

Oxygenation of Simple Olefins through Selective Allylic C-C Bond Cleavage: A Direct Approach to Cinnamyl Aldehydes.

A novel metal-free allylic C-C σ-bond cleavage of simple olefins to give valuable cinnamyl aldehydes is reported. 1,2-Aryl or alkyl migration through allylic C-C bond cleavage occurs in this transformation, which is assisted by an alkyl azide reagent. This method enables O-atom incorporation into simple unfunctionalized olefins to construct cinnamyl aldehydes. The reaction features simple hydrocarbon substrates, metal-free conditions, and high regio- and stereoselectivity.

Rh-Catalyzed Direct Amination of Unactivated C(sp(3) )-H bond with Anthranils Under Mild Conditions.

C-N Bond formation is of great significance due to the ubiquity of nitrogen-containing compounds. Here, a mild and efficient Rh(III) -catalyzed C(sp(3) )-H aryl amination reaction is reported. Anthranil is employed as the nitrogen source with 100 % atom efficiency. This C-H amination reaction exhibits broad substrate scope without using any external oxidants. Mechanistic studies including rhodacycle intermediates, H-D exchange, kinetic isotope effect (KIE) experiments, and in situ IR are presented.

Temporal variation and grade categorization of methane emission from LNG fueling stations.

Natural gas is increasingly seen as the fossil fuel of choice for China as it transitions to renewable sources. The significant development of China's LNG vehicle application and fueling stations and the urgency of climate changes make it particularly important to quantify methane emission from LNG stations, where the data are extremely rare. We carried out a pilot study on direct measurement and quantitative analysis of methane emission from five LNG fueling stations located in Shandong, China following the standard stationary EPA OTM 33A method. The measured methane emission of these five stations vary from 0.01 to 8.76 kg/h. The loss rates vary from 0.004 to 0.257%. We demonstrated that the emission from LNG stations consist of continuous and intermittent contents. The intermittent emission shows a strong temporal variation. If a station is only monitored for 20 min, it may either under-estimate or over-estimate the total emission. Both the distribution of emission events and total emission rates among different stations are highly skewed. We found that these LNG fueling station emission can be categorized into 3 grades, as low, medium and high, corresponding to emission rates below 0.1 kg/h; between 0.1 and 1 kg/h and above 1 kg/h, which can be characterized by the measured average methane concentration enhancement.

Intramolecular Csp3-H/C-C bond amination of alkyl azides for the selective synthesis of cyclic imines and tertiary amines.

The intramolecular Csp3-H and/or C-C bond amination is very important in modern organic synthesis due to its efficiency in the construction of diversified N-heterocycles. Herein, we report a novel intramolecular cyclization of alkyl azides for the synthesis of cyclic imines and tertiary amines through selective Csp3-H and/or C-C bond cleavage. Two C-N single bonds or a C[double bond, length as m-dash]N double bond are efficiently constructed in these transformations. The carbocation mechanism differs from the reported metal nitrene intermediates and therefore enables metal-free and new transformation.

Nitromethane as a nitrogen donor in Schmidt-type formation of amides and nitriles.

The Schmidt reaction has been an efficient and widely used synthetic approach to amides and nitriles since its discovery in 1923. However, its application often entails the use of volatile, potentially explosive, and highly toxic azide reagents. Here, we report a sequence whereby triflic anhydride and formic and acetic acids activate the bulk chemical nitromethane to serve as a nitrogen donor in place of azides in Schmidt-like reactions. This protocol further expands the substrate scope to alkynes and simple alkyl benzenes for the preparation of amides and nitriles.

Silver-catalyzed remote Csp3-H functionalization of aliphatic alcohols.

Aliphatic alcohols are common and bulk chemicals in organic synthesis. The site-selective functionalization of non-activated aliphatic alcohols is attractive but challenging. Herein, we report a silver-catalyzed δ-selective Csp3-H bond functionalization of abundant and inexpensive aliphatic alcohols. Valuable oximonitrile substituted alcohols are easily obtained by using well-designed sulphonyl reagents under simple and mild conditions. This protocol realizes the challenging δ-selective C-C bond formation of simple alkanols.