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The efficiency of hemp (Cannabis sativa L.) in remediating sites contaminated with heavy metals has received great attention in recent years. The main advantage of this technology relies on its inherent sustainability with a potential re-utilization of the significant amount of produced biomass which acts as a valuable flow resource. In this study, a combined system consisting of Cannabis sativa L. (hemp) and the blue-green alga Arthrospira platensis (spirulina) was tested to clean up soils contaminated with cadmium, chromium, copper, nickel, lead, and zinc. The application of non-targeted NMR methods combined with ICP-AES quantification provided an efficient strategy for detecting residual heavy metals within plant tissues and soil. Importantly, non-targeted metabolomic analysis helped to reveal the relationships between metabolites distribution in hemp tissues and the sequestered metals. It was demonstrated that hemp accumulates copper, chromium, nickel, and zinc preferentially in the leaves, while lead is distributed mainly in the stems of the plant. Moreover, it was found that, at higher concentrations, spirulina acts as a growth promoter, contributing to an increase in the final generated biomass. Results reported in this work indicate that the hemp/spirulina system represents a suitable tool for remediation of metal contaminated soils by modulating biomass production and metals uptake.

The Champenoise method for the production of sparkling wines consists of an "in bottle" re-fermentation induced by a low number of commercial Saccharomyces cerevisiae strains. However, the limited use of these strains can induce a flattening of the sensorial properties of the produced wine. Indeed, the volatile compounds produced by the yeasts during the fermentative process, play an essential role in the constitution of the Bouchet of sparkling wines prepared using indigenous grape varieties and, in particular, deriving from Apulia (Southern Italy), whose economic significance is constantly increasing . To the best of our knowledge, only two investigations assessed the influence of the autochthonous starter strains on the volatiles profile of sparkling wine. Moreover, no information exists on the oenological potential, for the production of typical sparkling wine, of the indigenous grape cv Maresco. This investigation evaluated the impact of the selected autochthonous yeast strains on the chemical properties of Maresco sparkling wines applying a non-targeted metabolomics approach by the application of HPLC-HRMS and GC-MS techniques. Saccharomyces cerevisiae DV10 (Lallemand, USA) was used as control. The obtained findings indicated that native yeast strains, previously selected, influenced the amount of several fermentative compounds, i.e. polysaccharides, organic acids, phenolic acids, and lipids. In order to reveal any grouping of the wines based on the composition of volatile compounds and chemical data, as well as to identify the main components contained within each group, the data were subjected to principal component analysis (PCA). Also, the correlation matrix on HPLC-HRMS/GC-MS data was performed and permitted to obtain a map, which is a useful tool to monitor the different patterns of aroma release. This contribution supplies information that will support the modulation of the sensorial properties of regional sparkling wines obtained from typical autochthonous grape varieties by using selected autochthonous microbial resources. Acknowledgments: This work was partially supported by the Apulia Region projects: "Innovazione nella tradizione: tecnologie innovative per esaltare le qualità dei vini autoctoni spumante della murgia barese-INVISPUBA" (P.S.R. Puglia 2014/2020 -Misura 16.2).

Nuclear Magnetic Resonance (NMR) is an analytical technique extensively used in almost every chemical laboratory for structural identification. This technique provides statistically equivalent signals in spite of using spectrometer with different hardware features and is successfully used for the traceability and quantification of analytes in food samples. Nevertheless, to date only a few internationally agreed guidelines have been reported on the use of NMR for quantitative analysis. The main goal of the present study is to provide a methodological pipeline to assess the reproducibility of NMR data produced for a given matrix by spectrometers from different manufacturers, with different magnetic field strengths, age and hardware configurations. The results have been analyzed through a sequence of chemometric tests to generate a community-built calibration system which was used to verify the performance of the spectrometers and the reproducibility of the predicted sample concentrations.

Non-targeted NMR-based approach has received great attention as a rapid method for food product authenticity assessment. The availability of a database containing many comparable NMR spectra produced by different spectrometers is crucial to develop functional classifiers able to discriminate rapidly the commodity class of a given food product. Nevertheless, variability in spectrometer features may hamper the production of comparable spectra due to inherent variations in signal resolution. In this paper, we report on the development of a class-discrimination model for grape juice authentication by application of non-targeted NMR spectroscopy. Different approaches for the pre-treatment of data will be described along with details about the model validation. The developed model performed excellently (95.4-100% correct predictions) even when it was tested against 650 spectra produced by 65 spectrometers with different configurations (magnetic field strength, manufacturer, age). This study may boost the use of non-targeted NMR methods for food control.

Spectroscopic non-targeted methods are gaining ever-growing importance in quality control and authenticity assessment of food products because of their strong potential for identification of specific features of the products by data-driven classifiers. One of the factors hampering the diffusion of spectroscopic non-targeted methods and data-driven classifiers is the lack of harmonized guidelines for their development and validation. In particular, to date, neither conditions to directly compare spectra recorded by different spectrometers nor studies demonstrating the statistical equivalence of the spectra are available. Among the spectroscopic analytical techniques suitable for the development of non-targeted methods, nuclear magnetic resonance (NMR) offers the unique opportunity to generate statistically equivalent signals. In this paper, the feasibility of NMR spectroscopy to generate statistically equivalent NMR signals from a number of different spectrometers was demonstrated for complex mixtures (aqueous extracts of wheat and flour) by organizing an inter-laboratory comparison involving 36 NMR spectrometers. Univariate statistics along with multivariate analysis were exploited to establish unbiased criteria for assessing the statistical equivalence of the NMR signals. The aspects affecting the signal equivalence were investigated, and possible solutions to reduce the extent of the human error were proposed and applied with satisfactory results. This study furnishes the scientific community with an appropriate and easy procedure to validate non-targeted NMR methods and provides error values to be used as a reference for future studies.

The difficulty in accessing and safely utilising non-stabilised diazo species has in the past limited the application of this class of compounds. Here we explore further the use of oxadiazolines, non-stabilised diazo precursors which are bench stable, in direct, non-catalytic, aldehyde C-H functionalisation reactions under UV photolysis in flow and free from additives. Commercially available aldehydes are coupled to afford unsymmetrical aryl-alkyl and alkyl-alkyl ketones while mild conditions and lack of transition metal catalysts allow for exceptional functional group tolerance. Examples are given on small scale and in a larger scale continuous production.

The productive use of toxic waste materials derived from industrial processes is one of the main goals of modern chemical research to increase sustainability of the large-scale production. Here we devise a simple and robust strategy for the utilization of trifluoromethane, obtained in large quantities from polytetrafluoroethylene manufacture, and the conversion of this greenhouse gas into valuable fluorinated compounds. The generation of the trifluoromethyl carbanion and its direct and complete consumption through trapping with a number of electrophiles were achieved by a fully contained flow reactor setup. The adoption of modern in-line analytical tools, such as portable Fourier transform infrared and nuclear magnetic resonance devices, allowed the accurate reagent dosing with considerable benefits in terms of controlling the environmental impact during this continuous process. The advantages of the method, with respect to the batch procedure, will be discussed and demonstrated experimentally.

In this work the synthesis, structure–activity relationship (SAR) and biological evaluation of a novel series of triazole-containing 5-lipoxygenase (5-LO) inhibitors are described. The use of structure-guided drug design techniques provided compounds that demonstrated excellent 5-LO inhibition with IC50 of 0.2 and 3.2 μ m in cell-based and cell-free assays, respectively. Optimization of binding and functional potencies resulted in the identification of compound 13d, which showed an enhanced activity compared to the parent bioactive compound caffeic acid 5 and the clinically approved zileuton 3. Compounds 15 and 16 were identified as lead compounds in inhibiting 5-LO products formation in neutrophils. Their interference with other targets on the arachidonic acid pathway was also assessed. Cytotoxicity tests were performed to exclude a relationship between cytotoxicity and the increased activity observed after structure optimization.

By using the Suzuki-Miyaura protocol, a simple straightforward synthesis of functionalized 2-arylaziridines has been developed. By means of this synthetic strategy from readily available ortho-, meta- and para-bromophenylaziridines and aryl- or heteroarylboronic acids, new aziridines could be obtained. The cross-coupling reactions occurred without ring opening of the three membered ring. Preliminary results on the antimicrobial activity of the heterosubstituted biaryl compounds have been also included.

This paper focuses on α-lithiated oxazolinyloxiranes and oxazolinylaziridines, their generation, reactions, and synthetic applications. The ability of the oxazoline ring in providing stabilization to such α-heterosubstituted carbanions either through electronic effects and coordinative action has been stressed as well as the contribution to the configurational stability or instability of such species. IR spectroscopic data, multinuclear NMR investigations, and ab initio calculations planned to get insights on chemical properties and structural features have been carried out. A number of new reactions including alkylations, addition reactions, hydroxyalkylations, cyclopropanations, lactonizations, and rearrangements have been discovered, giving access to a variety of substances including: aziridinolactones, epoxylactones, aryl alkanones, polysubstituted cyclopropanes, cyclopropanefused lactones, dihydro-oxazoloisoquinolines, diversely functionalized oxazolines, and products that can be derived from them by synthetic elaboration.

Microreactor-mediated organocatalysed Michael reactions have been developed. By using a soluble proline-derived catalyst, Michael-type reactions, leading to γ-nitroketones, have been optimized in homogeneous and continuous-flow conditions. As proof of principle, an integrated microfluidic system able to perform domino processes useful in the preparation of bicyclo[4.4.0]decanes with six contiguous stereogenic centres has been set up.

Flow chemistry: A flow-microreactor-mediated synthesis of 1,2,3,4-tetrahydroisoquinolines (THIQs) is reported (see scheme). Starting from a laterally lithiated aziridine, a tetrahydroisoquinoline lithiated at C4 was generated by thermally induced isomerization. Because the reaction temperature is a crucial parameter, the exquisite thermal control possible in a flow-microreactor system allowed for fast, efficient, and highly reproducible synthesis of functionalized aziridines or THIQs.

A new, single-mode bench-top resonator was evaluated for the microwave-assisted flow generation of primary ketenes by thermal decomposition of α-diazoketones at high temperature. A number of amides and β-lactams were obtained by ketene generation in situ and reaction with amines and imines, respectively, in good to excellent yields. The preferential formation of trans-configured β-lactams was observed during the [2+2] Staudinger cycloaddition of a range of ketenes with different imines under controlled reaction conditions. Some insights into the mechanism of this reaction at high temperature are reported, and a new web-based molecular viewer, which takes advantage from Augmented Reality (AR) technology, is also described for a faster interpretation of computed data., The authors are also thankful to the EPSRC (Award Nos. EP/K009494/1, EP/K039520/1 and EP/M004120/1) for financial support.

An enantioselective preparation of O-acetylcyanohydrins has been accomplished by a three-step telescoped continuous process. The modular components enabled an accurate control of two sequential biotransformations, safe handling of an in situ generated hazardous gas, and in-line stabilization of products. This method proved to be advantageous over the batch protocols in terms of reaction time (40 min vs 345 min) and ease of operation, opening up access to reactions which have often been neglected due to safety concerns.

Alpha,alpha-disubstituted aziridines can be produced in good yields by selective lithiation of N-tert-butylsulfonyl-2-phenylaziridine (n-BuLi/TMEDA, Et(2)O) at the benzylic position and subsequent trapping with a range of electrophiles. Repetition of the lithiation/electrophilic trapping sequence provides a stereocontrolled route to trisubstituted aziridines. Using (R)-N-tert-butylsulfonyl-2-phenylaziridine, the alpha,alpha-disubstituted aziridines can be produced as single enantiomers (er >98:2), indicating that the intermediate organolithium is configurationally stable. Efficient aziridine ring-opening reactions leading to 1,2-diamines and 1,4-diamines are also reported.

The reductive cleavage of C-O bond of chiral alkyl aryl ethers (I) and (III) proceeds with a full retention of the configuration leading to alcohols (II) and (IV).

A novel integrated web-based system which can compute, visualise and store systematised key parameters of a reaction has been developed from open-source components. As a proof of concept, it has been used to rationalise and predict the regioselectivity of lithiation reactions as well as relative reactivity of substrates. Excellent agreement between the in silico analysis and experimental data was obtained.

The ortho lithiation-trapping sequence of phenylaziridines is described. This methodology, which counts on the ability of the aziridino group to act as a directed metalation group (DMG), provides an easy access to functionalized arylaziridines as well as to phthalans and phthalides. The importance of the aziridine N-substituent in this DoM reaction is stressed as well. [reaction: see text]

We have investigated the regio- and stereochemistry of the reductive dealkoxylation of alkyl aryl ethers. Chiral non-racemic secondary alcohols were converted into the corresponding m-terphenyl or 2-biphenyl ethers either via inversion of configuration under Mitsunobu reaction conditions or with retention of configuration under SNAr conditions. The successive cleavage of the aromatic C O bond occurred in the presence of a stoichiometric amount of Na metal in dry tetrahydrofuran at rt with retention of configuration, thus highlighting that the overall inversion or retention of configuration for the whole two-step procedure is dictated by the stereochemistry of the first synthetic step.

The method provides a new straightforward approach to cis- and trans-2,5-disubstituted piperazines.

BH(3) complexes of N-alkyl-2-phenylaziridines have been synthesized and their structure and stereochemistry proved with DFT calculations and NMR experiments. It has been demonstrated that the Lewis acid complexation is able to promote a regioselective β-lithiation in 2-phenylaziridino-borane complexes. The lithiated intermediates were configurationally stable, allowing an enantioselective preparation of cis-2,3-disubstituted aziridines.

A highly stereo- and regiose- lective functionalisation of chiral non- racemic aziridines is reported. By start- ing from a parent enantioenriched azir- idine and finely tuning the reaction conditions, it is possible to address the regio- and stereoselectivity of the lith- iation/electrophile trapping sequence, thereby allowing the preparation of highly enantioenriched functionalised aziridines. From chiral N-alkyl trans- 2,3-diphenylaziridines (S,S)- 1a ,b ,t wo differently configured chiral aziridinyl- lithiums could be generated (trans- 1a ,b-Li in toluene and cis- 1a ,b-Li in THF), thus disclosing a solvent-depen- dent reactivity that is useful for the synthesis of chiral tri-substituted aziri- dines with different stereochemistry. In contrast, chiral aziridine (S,S)- 1c showed a temperature-dependent reac- tivity to give chiral ortho-lithiated aziri- dine 1c -ortho-Li at 788C and a-lithi- ated aziridine 1c -a-Li at 08C. Both lithiated intermediates react with elec- trophiles to give enantioenriched ortho- and a-functionalised aziridines. The reaction of all the lithiated aziri- dines with carbonyl compounds fur- nished useful chiral hydroxyalkylated derivatives, the stereochemistry of which was ascertained by X-ray and NMR spectroscopic analysis. The use- fulness of chiral non-racemic function- alised aziridines has been demonstrat- ed by reductive ring-opening reactions furnishing chiral amines that bear qua- ternary stereogenic centres and chiral 1,2-, 1,3- and 1,5-aminoalcohols. It is remarkable that the solvent-dependent reactivity observed with (S,S)- 1a ,b per- mits the preparation of both the enan- tiomers of amines (11 and ent-11) and 1,2-aminoalcohols (13 and ent-13) start- ing from the same parent aziridine. In- terestingly, for the first time, a configu- rationally stable chiral a-lithiated aziri- dine ( 1c -a-Li) has been generated at 08C. In addition, ortho-hydroxyalkylat- ed aziridines have been easily convert- ed into chiral aminoalkyl phthalans, which are useful building blocks in me- dicinal chemistry.

Alpha,alpha-disubstituted aziridines can be produced in good yields by selective lithiation of N-tert-butylsulfonyl-2-phenylaziridine (n-BuLi/TMEDA, Et(2)O) at the benzylic position and subsequent trapping with a range of electrophiles. Repetition of the lithiation/electrophilic trapping sequence provides a stereocontrolled route to trisubstituted aziridines. Using (R)-N-tert-butylsulfonyl-2-phenylaziridine, the alpha,alpha-disubstituted aziridines can be produced as single enantiomers (er >98:2), indicating that the intermediate organolithium is configurationally stable. Efficient aziridine ring-opening reactions leading to 1,2-diamines and 1,4-diamines are also reported.

The lithiation reaction of o-tolylaziridine 1 has been investigated by using the aziridine ring capability to act as a directing metalation group. Trapped with electrophiles, the resulting o-aziridinyl benzyllithium 1-Li elves access to several functionalized aziridines 2a-j. The hydroxyalkylated derivatives 2d-j were converted into important scaffolds such as isochromans 3a-d. A stereoselective preparation of isochromans (R)-3b, (1R,3S)-3d, and (1R,3R)-3d has been developed starting froth enantioenriched o-tolylaziridine.

The lithiation reaction of monophenyl- and diphenylaziridines has been investigated in detail in an effort to understand why the former undergo exclusively or mainly ortho-lithiation while the latter are lithiated exclusively at the alpha-position. Evidence is reported that ruled out the possibility that the alpha-lithiation, observed for the diphenylaziridines, is the result of an ortho- to alpha-translocation phenomenon, thus substantiating a direct alpha-deprotonation process. The role of the aziridine nitrogen lone-pair has been considered: dynamics at the aziridine nitrogen as well as complex-induced proximity effects seem to be responsible for the observed regioselectivity in both monophenyl and diphenylaziridines. It turns out that, by tuning the reaction conditions for the lithiation of trans-1-alkyl-2-methyl-3-phenylaziridines, it is possible to generate with high regioselectivity alpha- and/or ortho-lithiated aziridines, which can be stereoselectively functionalized by electrophilic trapping. A regioselective ortho-functionalization of diphenylaziridines is made possible by halogen- or tin-lithium exchange and by deprotonation of bis-deuterated aziridines.

The a-lithiation-trapping sequence of trans-N-alkyl-2,3-diphenylaziridines (s-BuLi or s-BuLi/TMEDA), taking place with a stereochemistry which dramatically depends on the solvent coordinating ability (inversion of configuration in THF and retention in toluene), has been carefully investigated. 1 H, 13 C, and 7 Li multinuclear NMR investigations at low temperature suggest that two differently configured lithiated aziridines (monomeric cis-1-Li in THF and dimeric trans-1-Li in toluene) are involved.

[structure: see text]. The lithiation reaction of cis- and trans-N-alkyl-2,3-diphenylaziridines has been investigated. While cis-diphenylaziridines do not undergo any lithiation upon treatment with organolithiums, the lithiation reaction of the trans counterparts is completely alpha-regioselective and the stereochemical course of the lithiation-trapping sequence is solvent dependent: inversion of configuration in coordinating solvents (THF or toluene/crown ether) and retention in hexane, ether, or toluene. The preparation of stereodefined functionalized N-alkyl-2,3-diphenylaziridines is described.

The ortho lithiation−trapping sequence of phenylaziridines is described. This methodology, which counts on the ability of the aziridino group to act as a directed metalation group (DMG), provides an easy access to functionalized arylaziridines as well as to phthalans and phthalides. The importance of the aziridine N-substituent in this DoM reaction is stressed as well.

The preparation of N-substituted oxazolinylaziridines and their deprotonation to afford the corresponding aziridinyllithiums is described. The chemical and configurational stability of the lithiated species depends on the N-substituent on the aziridine ring. The trapping with carbonyl compounds of (R*,S*) configurated oxazolinylaziridines is an interesting route for the preparation of functionalised α,β-aziridino-γ-lactones.

Herein we report a new straightforward synthesis of cis and trans 2,5-disubstituted N,N-dialkylpiperazines, even in enantioenriched form, by reacting non-activated N-alkyl arylaziridines in the presence of a catalytic amount of a Lewis acid. A stereochemical and NMR investigation revealed useful mechanistic insights for this process.