Recent advances in the contribution of glucosinolates degradation products to cruciferous foods odor: factors that influence degradation pathways and odor attributes.

As one of the most important vegetables and oils consumed globally, cruciferous foods are appreciated for their high nutritional value. However, there is no comprehensive knowledge to sufficiently unravel the "flavor mystery" of cruciferous foods. The present review provides a comprehensive literature on the recent advances regarding the contribution of glucosinolates (GSL) degradation products to cruciferous foods odor, which focuses on key GSL degradation products contributing to distinct odor of cruciferous foods (Brassica oleracea, Brassica rapa, Brassica napus, Brassica juncea, Raphanus sativus), and key factors affecting GSL degradation pathways (i.e., enzyme-induced degradation, thermal-induced degradation, chemical-induced degradation, microwave-induced degradation) during different processing and cooking. A total of 93 volatile GSL degradation products (i.e., 36 nitriles, 33 isothiocyanates, 3 thiocyanates, 5 epithionitriles, and 16 sulfides) and 29 GSL (i.e., 20 aliphatic, 5 aromatic, and 4 indolic) were found in generalized cruciferous foods. Remarkably, cruciferous foods have a distinctive pungent, spicy, pickled, sulfur, and vegetable odor. In general, isothiocyanates are mostly present in enzyme-induced degradation of GSL and are therefore often enriched in fresh-cut or low-temperature, short-time cooked cruciferous foods. In contrast, nitriles are mainly derived from thermal-induced degradation of GSL, and are thus often enriched in high-temperature, long-time cooked cruciferous foods.

Processing and cooking can cause degradation of glucosinolates and formation of volatiles.Structure­odor relationship of glucosinolates degradation products is discussed.Nitriles, isothiocyanates, and sulfides play an important role in cruciferous foods odor.Both enzyme- and thermal-induced degradation of glucosinolates is strongly pH-dependent.

Recent Advances in Catalytic Systems for the Reduction of Aromatic and Aliphatic Nitrile Compounds to Amines.

Amines are important and valuable compounds widely used in the chemical industry to produce various products such as dyes, detergents, solvents, additives, pharmaceutical products, and anti-foam agents. A property that distinguishes primary amines from other compounds is their straightforward functionalization. Therefore, the synthesis of different amine compounds has been considered by many researchers in recent years. Usually, primary amines are produced via amination of alcohols, reductive amination, and reduction of nitro and amide compounds. Furthermore, a useful and atom-economical method for producing primary amines is reducing nitrile compounds using catalytic systems. Traditionally, nitriles are reduced using metal hydrides such as LiAlH4 or NaBH4. These methods have important restrictions in terms of selectivity and waste generation. Hence, the heterogeneous and homogeneous catalysts were investigated for the hydrogenation of nitriles to diverse amines. This review describes the performance of different catalytic systems for reducing nitrile compounds to their corresponding amines.

Immobilization of aldoxime dehydratases on metal affinity resins and use of the immobilized catalysts for the synthesis of nitriles important in fragrance industry.

Nitriles have a wide range of uses as building blocks, solvents, and alternative fuels, but also as intermediates and components of flavors and fragrances. The enzymatic synthesis of nitriles by aldoxime dehydratase (Oxd) is an emerging process with significant advantages over conventional approaches. Here we focus on the immobilization of His-tagged Oxds on metal affinity resins, an approach that has not been used previously for these enzymes. The potential of the immobilized Oxd was demonstrated for the synthesis of phenylacetonitrile (PAN) and E-cinnamonitrile, compounds applicable in the fragrance industry. A comparison of Talon and Ni-NTA resins showed that Ni-NTA with its higher binding capacity was more suitable for the immobilization of Oxd. Immobilized Oxds were prepared from purified enzymes (OxdFv from Fusarium vanettenii and OxdBr1 from Bradyrhizobium sp.) or the corresponding cell-free extracts. The immobilization of cell-free extracts reduced time and cost of the catalyst production. The immobilized OxdBr1 was superior in terms of recyclability (22 cycles) in the synthesis of PAN from 15 mM E/Z-phenylacetaldoxime at pH 7.0 and 30 °C (100% conversion, 61% isolated yield after product purification). The volumetric and catalyst productivity was 10.5 g/L/h and 48.3 g/g of immobilized protein, respectively.

Identification and evolution of non-traditional nitrilase from Spirosoma linguale DSM 74 with high hydration activity.

Hydration, a secondary activity mediated by nitrilase, is a promising new pathway for amide production. However, low hydration activity of nitrilase or trade-off between hydration and catalytic activity hinders its application in the production of amides. Here, natural C-terminal-truncated wild-type nitrilase, mined from a public database, obtained a high-hydration activity nitrilase as a novel evolutionary starting point for further protein engineering. The nitrilase Nit-74 from Spirosoma linguale DSM 74 was successfully obtained and exhibited the highest hydration activity level, performing 50.7 % nicotinamide formation and 87.6 % conversion to 2 mM substrate 3-cyanopyridine. Steric hindrance of the catalytic activity center and the N-terminus of the catalytic cysteine residue helped us identify three key residues: I166, W168, and T191. Saturation mutations resulted in three single mutants that further improved the hydration activity of N-heterocyclic nitriles. Among them, the mutant T191S performed 72.7 % nicotinamide formation, which was much higher than the previously reported highest level of 18.7 %. Additionally, mutants I166N and W168Y exhibited a 97.5 % 2-picolinamide ratio and 97.7 % isonicotinamide ratio without any loss of catalytic activity, which did not indicate a trade-off effect. Our results expand the screening and evolution library of promiscuous nitrilases with high hydration activity for amide formation.

Heteroditopic NHC Ligand Supported Manganese(I) Complexes: Synthesis, Characterization, and Activity as Non-bifunctional Phosphine-Free Catalyst for the α-Alkylation of Nitriles.

In the present work, several manganese(I) complexes of chelating heteroditopic ligands Mn1-3, featuring ImNHC (imidazol-2-ylidene) connected to a 1,2,3-triazole-N or tzNHC (1,2,3-triazol-5-ylidene) donors via a methylene spacer, with possible modifications at the triazole backbone have been synthesized and completely characterized. Notably, the CO stretching frequencies, electrochemical analysis, and frontier orbital analysis certainly suggest that the chelating ImNHC-tzNHC ligands have stronger donation capabilities than the related ImNHC-Ntz ligand in the synthesized complexes. Moreover, these well-defined phosphine-free Mn(I)-NHC complexes have been found to be effective non-bifunctional catalysts for the α-alkylation of nitriles using alcohols and importantly, the catalyst Mn1 containing ImNHC connected to a weaker triazole-N donor displayed higher activity compared to Mn2/Mn3 containing an unsymmetrical bis-carbene donors (ImNHC and tzNHC). A wide range of aryl nitriles were coupled with diverse (hetero)aromatic as well as aliphatic alcohols to get the corresponding products in good to excellent yields (32 examples, up to 95 % yield). The detailed mechanistic studies including deuterium labelling experiments reveal that the reaction follows a Borrowing Hydrogen pathway.

Introducing a protic ionic liquid from aminoethyl piperazine and triflic acid immobilized on pectin as a reusable nanocatalyst for the selective Schmidt synthesis of nitriles.

Preparation of reusable protic ionic liquid, triflic acid-immobilized aminoethyl piperazine-modified pectin (Pec-AEP-TfOH), with excellent activity and selectivity in modified Schmidt synthesis of nitriles from aldehydes and Si(CH3)3N3 has been described. The structure of the catalyst was characterized using FT-IR, XRD, FE-SEM, EDX-mapping, and TGA-DTA. The reaction demonstrated a broad substrate scope for a variety of benzaldehyde derivatives with electron withdrawing/donating substituents and heterocyclic aldehydes with yields between 85 and 96 % at room temperature. Also, the Pec-AEP-TfOH showed an excellent selectivity for the nitriles in which no formanilide was obtained. Furthermore, the Pec-AEP-TfOH revealed a remarkable chemoselectivity for aldehydes in the presence of acids or ketones. It is worth noting that TfOH as a precious superacid was immobilized for the first time in the selective Schmidt synthesis of nitriles to improve the eco-friendliness and economic efficiency of the process. Furthermore, the catalyst was cost-effective, metal-free, safe, scalable, and reusable (5 times) and its heterogeneity was confirmed by hot-filtration test.

Electrohydrogenation of Nitriles with Amines by Cobalt Catalysis.

Catalytic hydrogenation of nitriles represents an efficient and sustainable one-step synthesis of valuable bulk and fine chemicals. We report herein a molecular cobalt electrocatalyst for selective hydrogenative coupling of nitriles with amines using protons as the hydrogen source. The key to success for this reductive reaction is the use of an electrocatalytic approach for efficient cobalt-hydride generation through a sequence of cathodic reduction and protonation. As only electrons (e- ) and protons (H+ ) as the redox equivalent and hydrogen source, this general electrohydrogenation protocol is showcased by highly selective and straightforward synthesis of various functionalized and structurally diverse amines, as well as deuterium isotope labeling applications. Mechanistic studies reveal that the electrogenerated cobalt-hydride transfer to nitrile process is the rate-determining step.

A Catalytic Method to Activate Nitromethane by the Cooperation of Homo- and Heterogeneous Catalysis.

The achievement of directly activating and utilizing bulk small molecules has remained a longstanding objective in the field of chemical synthesis. The present work reports a catalytic activation method for bulk chemical nitromethane (MeNO2 ). This method combines homogeneous Lewis acid with recyclable heterogeneous Brønsted acid catalysis, featuring practicality, sustainability, and low cost, thus solving the inherent drawbacks of previous Nef processes where stoichiometric reductants or activators were required. By combining the advantages of both homo- and heterogeneous catalysts, this chemistry may not only offer new opportunities for the further development of MeNO2 as a nitrogen source for organic synthesis, but also promote the catalysis design in synthetic chemistry.

Electric Field Enhanced Ammoxidation of Aldehydes Using Supported Fe Clusters Under Ambient Oxygen Pressure.

Heterogeneous catalytic ammoxidation provides an eco-friendly route for the cyanide-free synthesis of nitrile compounds, which are important precursors for synthetic chemistry and pharmaceutical applications. However, in general such a process requires high pressures of molecular oxygen at elevated temperatures to accelerate the oxygen reduction and imine dehydrogenation steps, which is highly risky in practical applications. Here, we report an electric field enhanced ammoxidation system using a supported Fe clusters catalyst (Fe/NC), which enables efficient synthesis of nitriles from the corresponding aldehydes under ambient air pressure at room temperature (RT). A synergistic effect between the external electric field and the Fe/NC catalyst promotes the ammonia activation and the dehydrogenation of the generated imine intermediates and avoids the unwanted backwards reaction to aldehydes. This electric field enhanced ammoxidation system presents high efficiency and selectivity for the conversion of a series of aldehydes under mild conditions with high durability, rendering it an attractive process for the green synthesis of nitriles with fragile functional groups.

Grignard Reagent-Catalyzed Hydroboration of Esters, Nitriles, and Imines.

The reduction in esters, nitriles, and imines requires harsh conditions (highly reactive reagents, high temperatures, and pressures) or complex metal-ligand catalytic systems. Catalysts comprising earth-abundant and less toxic elements are desirable from the perspective of green chemistry. In this study, we developed a green hydroboration protocol for the reduction in esters, nitriles, and imines at room temperature (25 °C) using pinacolborane as the reducing agent and a commercially available Grignard reagent as the catalyst. Screening of various alkyl magnesium halides revealed MeMgCl as the optimal catalyst for the reduction. The hydroboration and subsequent hydrolysis of various esters yielded corresponding alcohols over a short reaction time (~0.5 h). The hydroboration of nitriles and imines produced various primary and secondary amines in excellent yields. Chemoselective reduction and density functional theory calculations are also performed. The proposed green hydroboration protocol eliminates the requirements for complex ligand systems and elevated temperatures, providing an effective method for the reduction in esters, nitriles, and imines at room temperature.

Halogen Bonding Involving Isomeric Isocyanide/Nitrile Groups.

2,3,5,6-Tetramethyl-1,4-diisocyanobenzene (1), 1,4-diisocyanobenzene (2), and 1,4-dicyanobenzene (3) were co-crystallized with 1,3,5-triiodotrifluorobenzene (1,3,5-FIB) to give three cocrystals, 1·1,3,5-FIB, 2·2(1,3,5-FIB), and 3·2(1,3,5-FIB), which were studied by X-ray diffraction. A common feature of the three structures is the presence of I···Cisocyanide or I···Nnitrile halogen bonds (HaBs), which occurs between an iodine σ-hole and the isocyanide C-(or the nitrile N-) atom. The diisocyanide and dinitrile cocrystals 2·2(1,3,5-FIB) and 3·2(1,3,5-FIB) are isostructural, thus providing a basis for accurate comparison of the two types of noncovalent linkages of C≡N/N≡C groups in the composition of structurally similar entities and in one crystal environment. The bonding situation was studied by a set of theoretical methods. Diisocyanides are more nucleophilic than the dinitrile and they exhibit stronger binding to 1,3,5-FIB. In all structures, the HaBs are mostly determined by the electrostatic interactions, but the dispersion and induction components also provide a noticeable contribution and make the HaBs attractive. Charge transfer has a small contribution (<5%) to the HaB and it is higher for the diisocyanide than for the dinitrile systems. At the same time, diisocyanide and dinitrile structures exhibit typical electron-donor and π-acceptor properties in relation to the HaB donor.

Enzymatic properties of a non-classical aldoxime dehydratase capable of producing alkyl and arylalkyl nitriles.

Nitriles are of significant interest in the flavor and fragrance industries with potential application in cosmetics due to their higher stability than analogous aldehydes. However, the traditional methods to prepare nitriles need toxic reagents and hash conditions. This work aimed to develop a chemoenzymatic strategy to synthesize nitriles from natural aldehydes with aldoxime as the intermediate. A non-classical aldoxime dehydratase (Oxd) was discovered from the fungus Aspergillus ibericus (OxdAsp) to catalyze the dehydration of aldoximes to corresponding nitriles under mild conditions. The amino acid sequence of OxdAsp exhibits an approximately 20% identity with bacterial Oxds. OxdAsp contains a heme prosthetic group bound with the axial H287 in the catalytic pocket. The structure models of OxdAsp with substrates suggest that its catalytic triad is Y138-R141-E192, which is different from the classically bacterial Oxds of His-Arg-Ser/Thr. The catalytic mechanism of OxdAsp was proposed based on the mutagenesis of key residues. The hydroxyl group of the substrate is fixed by E192 to increase its basicity. Y138 acts as a general acid-based catalyst, and its phenolic proton is polarized by the adjacent R141. The protonated Y138 would donate a proton to the hydroxyl group of the substrate and eliminate a water molecule from aldoxime to produce nitrile. The recombinant OxdAsp can efficiently dehydrate citronellal oxime and cinnamaldoxime to citronellyl nitrile and cinnamonitrile in aqueous media, which are applied as fragrance ingredients in the food and cosmetic fields. KEY POINTS: • A novel aldoxime dehydratase from the Aspergillus genus was first characterized as a heme-binding protein. • The catalytic mechanism was predicted based on the molecular interactions of the catalytic pocket with the substrate. • A chemoenzymatic strategy was developed to synthesize nitriles from natural aldehydes with aldoxime as the intermediate.

Tuning Benzylic C-H Functionalization of (Thio)xanthenes with Electrochemistry.

Here, we report a tunable electrochemical benzylic C-H functionalization of (thio)xanthenes with terminal alkynes and nitriles in the absence of any catalyst or external chemical oxidant. The benzylic C-H functionalization can be well controlled by varying the electrochemical conditions, affording the specific coupling products via C-C and C-N bond formation.

Metal Catalysis Acting on Nitriles in Early Earth Hydrothermal Systems.

Hydrothermal systems are areas in which heated fluids and organic molecules rush through basaltic material rich in metals and minerals. By studying malononitrile and acetonitrile, we examine the effects of metal and mineral nanoparticles on nitrile compounds in anoxic, hydrothermal conditions representing a prebiotic environment of early Earth. Polymerization, reduction, cyclization, and a phenomenon colloquially known as 'chemical gardening' (structure building via reprecipitation of metal compounds or complexing with organics) are all potential outcomes with the addition of metals and minerals. Reduction occurs with the addition of rhodium (Rh) or iron (II) sulfide (FeS), with positive identification of ethanol and ethylamine forming from acetonitrile reduction. We find that polymerization and insoluble product formation were associated with oxide minerals, metallic nickel (Ni), and metallic cobalt (Co) acting as catalysts. Oxide minerals strongly promoted polymerization into insoluble, tar-like products of nitriles. FeS, iron-nickel alloy (FeNi), and rhodium are unique cases that appear to act as reagents by actively participating in chemical gardening without returning to their initial state. Further, FeS tentatively had a phase change into the mineral parabutlerite. This research aims to identify metals and metal minerals that could best serve nitrile catalysis and reactions on early Earth.

An update on the discovery and development of reversible covalent inhibitors.

Small molecule drugs that covalently bind irreversibly to their target proteins have several advantages over conventional reversible inhibitors. They include increased duration of action, less-frequent drug dosing, reduced pharmacokinetic sensitivity, and the potential to target intractable shallow binding sites. Despite these advantages, the key challenges of irreversible covalent drugs are their potential for off-target toxicities and immunogenicity risks. Incorporating reversibility into covalent drugs would lead to less off-target toxicity by forming reversible adducts with off-target proteins and thus reducing the risk of idiosyncratic toxicities caused by the permanent modification of proteins, which leads to higher levels of potential haptens. Herein, we systematically review electrophilic warheads employed during the development of reversible covalent drugs. We hope the structural insights of electrophilic warheads would provide helpful information to medicinal chemists and aid in designing covalent drugs with better on-target selectivity and improved safety.

Organic Acid to Nitrile: A Chemoenzymatic Three-Step Route.

Various widely applied compounds contain cyano-groups, and this functional group serves as a chemical handle for a whole range of different reactions. We report a cyanide free chemoenzymatic cascade for nitrile synthesis. The reaction pathway starts with a reduction of carboxylic acid to aldehyde by carboxylate reductase enzymes (CARs) applied as living cell biocatalysts. The second - chemical - step includes in situ oxime formation with hydroxylamine. The final direct step from oxime to nitrile is catalyzed by aldoxime dehydratases (Oxds). With compatible combinations of a CAR and an Oxd, applied in one-pot two-step reactions, several aliphatic and aryl-aliphatic target nitriles were obtained in more than 80% conversion. Phenylacetonitrile, for example, was prepared in 78% isolated yield. This chemoenzymatic route does not require cyanide salts, toxic metals, or undesired oxidants in contrast to entirely chemical procedures.

Functional metagenomics uncovers nitrile-hydrolysing enzymes in a coal metagenome.

Introduction: Nitriles are the most toxic compounds that can lead to serious human illness through inhalation and consumption due to environmental pollution. Nitrilases can highly degrade nitriles isolated from the natural ecosystem. In the current study, we focused on the discovery of novel nitrilases from a coal metagenome using in silico mining. Methods: Coal metagenomic DNA was isolated and sequenced on the Illumina platform. Quality reads were assembled using MEGAHIT, and statistics were checked using QUAST. Annotation was performed using the automated tool SqueezeMeta. The annotated amino acid sequences were mined for nitrilase from the unclassified organism. Sequence alignment and phylogenetic analyses were carried out using ClustalW and MEGA11. Conserved regions of the amino acid sequences were identified using InterProScan and NCBI-CDD servers. The physicochemical properties of the amino acids were measured using ExPASy's ProtParam. Furthermore, NetSurfP was used for 2D structure prediction, while AlphaFold2 in Chimera X 1.4 was used for 3D structure prediction. To check the solvation of the predicted protein, a dynamic simulation was conducted on the WebGRO server. Ligands were extracted from the Protein Data Bank (PDB) for molecular docking upon active site prediction using the CASTp server. Results and discussion: In silico mining of annotated metagenomic data revealed nitrilase from unclassified Alphaproteobacteria. By using the artificial intelligence program AlphaFold2, the 3D structure was predicted with a per-residue confidence statistic score of about 95.8%, and the stability of the predicted model was verified with molecular dynamics for a 100-ns simulation. Molecular docking analysis determined the binding affinity of a novel nitrilase with nitriles. The binding scores produced by the novel nitrilase were approximately similar to those of the other prokaryotic nitrilase crystal structures, with a deviation of ±0.5.

Hydration Reactions Catalyzed by Transition Metal-NHC (NHC = N-Heterocyclic Carbene) Complexes.

The catalytic addition of water to unsaturated C-C or C-N π bonds represent one of the most important and environmentally sustainable methods to form C-O bonds for the production of synthetic intermediates, medicinal agents and natural products. The traditional acid-catalyzed hydration of unsaturated compounds typically requires strong acids or toxic mercury salts, which limits practical applications and presents safety and environmental concerns. Today, transition-metal-catalyzed hydration supported by NHC (NHC = N-heterocyclic carbene) ligands has attracted major attention. By rational design of ligands, choice of metals and counterions as well as mechanistic studies and the development of heterogeneous systems, major progress has been achieved for a broad range of hydration processes. In particular, the combination of NHC ligands with gold shows excellent reactivity compared with other catalytic systems; however, other systems based on silver, ruthenium, osmium, platinum, rhodium and nickel have also been discovered. Ancillary NHC ligands provide stabilization of transition metals and ensure high catalytic activity in hydration owing to their unique electronic and steric properties. NHC-Au(I) complexes are particularly favored for hydration of unsaturated hydrocarbons due to soft and carbophilic properties of gold. In this review, we present a comprehensive overview of hydration reactions catalyzed by transition metal-NHC complexes and their applications in catalytic hydration of different classes of π-substrates with a focus on the role of NHC ligands, types of metals and counterions.

Straightforward Creation of Possibly Prebiotic Complex Mixtures of Thiol-Rich Peptides.

At the origin of life, extremely diverse mixtures of oligomers and polymers could be obtained from relatively simple molecular bricks. Here, we present an example of the polymerization of two amidonitriles derived from cysteine, Cys-Ala-CN and Cys-Met-CN. The thiol function in a molecule adds onto the nitrile group of another one, allowing efficient condensation reactions and making available an extensive range of polymers containing amide bonds and/or five-membered heterocycles, namely thiazolines. Macrocycles were also identified, the biggest one containing sixteen residues (cyclo(Cys-Met)8). MALDI-TOF mass spectrometry was used to identify all the present species. What these examples show is that complex mixtures are likely to have formed on the primitive Earth and that, ultimately, the selection that must have followed may have been an even more crucial step towards life than the synthesis of the pre-biological species themselves.

Crystal structures of 4-(2/3-meth-oxy-phen-oxy)phthalo-nitrile.

The syntheses and crystal structures are reported of 4-phen-oxy-substituted phthalo-nitriles with meth-oxy groups in the ortho- and meta-positions of the terminal benzene rings, respectively, namely, 4-(2-meth-oxy-phen-oxy)phthalo-nitrile and 4-(3-meth-oxy-phen-oxy)phthalo-nitrile, both C15H10N2O2. The https://journals.iucr.org/e/issues/2023/03/00/mol-ecular structure was determined using the single-crystal X-ray diffraction method. It is shown that short contacts play a more decisive role in the mol-ecular packing compared to van der Waals inter-actions.