Thioamide Group Research Articles

Methanobactins: Structures, Biosynthesis, and Microbial Diversity.

Methanobactins (Mbns) are ribosomally synthesized and posttranslationally modified peptide natural products released by methanotrophic bacteria under conditions of copper scarcity. Mbns bind Cu(I) with high affinity via nitrogen-containing heterocycles and thioamide groups installed on a precursor peptide, MbnA, by a core biosynthetic enzyme complex, MbnBC. Additional stabilizing modifications are enacted by other, less universal biosynthetic enzymes. Copper-loaded Mbn is imported into the cell by TonB-dependent transporters called MbnTs, and copper is mobilized by an unknown mechanism. The machinery to biosynthesize and transport Mbn is encoded in operons that are also found in the genomes of nonmethanotrophic bacteria. In this review, we provide an update on the state of the Mbn field, highlighting recent discoveries regarding Mbn structure, biosynthesis, and handling as well as the emerging roles of Mbns in the environment and their potential use as therapeutics.

Solution-processable polymers of intrinsic microporosity for selective silver removal from aqueous solution and subsequent disinfection by silver-laden coatings

Silver ions (Ag+) in waterways pose a growing threat to the environment and living organisms. Achieving an effective and green process for Ag+ removal requires an adsorbent with excellent specificity for silver ions and easy recoverability after fouling or blocking. However, this remains a major challenge. To address this concern, we developed a high-performance adsorbent by grafting polymers of intrinsic microporosity (PIM) with thioamide groups. This thioamide-modified PIM (TPIM-1) adsorbent exhibited an exceptional adsorption capacity of 656 mg g−1 and high selectivity (distribution coefficient of 833.3 mL g−1, selectivity coefficient of 346 over Cd2+) for aqueous Ag+ removal. TPIM-1 also features good solubility in selected solvents, allowing regeneration through a dissolution separation precipitation (DSP) procedure once fouling or blocking occurs. Over 80 % of the adsorption capacity was recovered after nine continuous regeneration cycles, showcasing potential cost-effective reusability. Density Functional Theory (DFT) results reveal that the grafted thioamide groups play a critical role in selective Ag+ adsorption, with a binding energy of 54 kcal mol−1. In addition, the Ag+-loaded PIM-coated glass surface showed excellent antibacterial ability, inhibiting the growth of Bacillus subtilis and E. coli. This study provides a viable strategy for the development of a low-carbon footprint silver removing adsorbent from wastewater.

An Aryl-ether-linked Covalent Organic Framework Modified with Thioamide Groups for Selective Extraction of Palladium from Strong Acid Solutions.

Efficient adsorption of palladium ions from acid nuclear waste solution is crucial for ensuring the safety of vitrification process for radioactive waste. However, the limited stability and selectivity of most current adsorbents hinder their practical applications under strong acid and intense radiation conditions. Herein, to address these limitations, we designed and synthesized an aryl-ether-linked covalent organic framework (COF-316-DM) grafted dimethylthiocarbamoyl groups on the pore walls. This unique structure endows COF-316-DM with high stability and exceptional palladium capture capacity. The robust polyarylether linkage enables COF-316-DM to withstand irradiation doses of 200 or 400 kGy of β/γ ray. Furthermore, COF-316-DM demonstrates fast adsorption kinetics, high adsorption capacity (147 mg g-1 ), and excellent reusability in 4 M nitric acid. Moreover, COF-316-DM exhibits remarkable selectivity for palladium ions in the presence of 17 interference ions, simulating high level liquid waste scenario. The superior adsorption performance can be attributed to the strong binding affinity between the thioamide groups and Pd2+ ions, as confirmed by the comprehensive analysis of FT-IR and XPS spectra. Our findings highlight the potential of COFs with robust linkers and tailored functional groups for efficient and selective capture of metal ions, even in harsh environmental conditions.

Cyanothioacetamides as a synthetic platform for the synthesis of aminopyrazole derivatives.

It was shown that the reaction of 2-cyanothioacetamides with hydrazine involves both cyano- and thioamide groups, and 3,5-diaminopyrazoles are formed. In the reaction of 2-cyano-3-(dimethylamino)-N,N-dimethylprop-2-enethioamides with hydrazine and its derivatives, the interaction proceeds with the participation of cyano- and enamine groups, not affecting the thiocarbamoyl group, and leads to the formation of 4-thiocarbamoylpyrazoles. A synthesis method has been developed and a series of 1-substituted-4-thiocarbamoyl pyrazoles has been thus synthesized. The structure of the reaction products was studied using NMR spectroscopy and mass spectrometry and confirmed by X-ray diffraction analysis.

Copper(I)-Catalyzed Conjugate Addition/Enantioselective Protonation with Selenols and α-Substituted α,β-Unsaturated Thioamides.

Herein, a copper(I)-catalyzed asymmetric conjugate addition/protonation with selenols and α-substituted α,β-unsaturated thioamides is disclosed, which affords a series of chiral selenides in high to excellent enantioselectivity. As for both selenols and α-substituted α,β-unsaturated thioamides, the reaction enjoys broad substrate scopes. The present catalytic system is also successfully applied to asymmetric selenation of β-substituted α,β-unsaturated thioamides. A [Cu-(R,RP )-TANIAPHOS]-SePh species is characterized by its 77 Se NMR spectra, which gives a chemical shift at δ 462 ppm. Moreover, a {[Cu-(R)-TOL-BINAP]-SePh}2 species is characterized by X-ray analysis, which confirms the formation of Cu-Se bond in the reaction. Finally, the transformations of the thioamide group to amine and thioester are demonstrated to be straightforward.

Copper(I)‐Catalyzed Conjugate Addition/Enantioselective Protonation with Selenols and α‐Substituted α,β‐Unsaturated Thioamides

AbstractHerein, a copper(I)‐catalyzed asymmetric conjugate addition/protonation with selenols and α‐substituted α,β‐unsaturated thioamides is disclosed, which affords a series of chiral selenides in high to excellent enantioselectivity. As for both selenols and α‐substituted α,β‐unsaturated thioamides, the reaction enjoys broad substrate scopes. The present catalytic system is also successfully applied to asymmetric selenation of β‐substituted α,β‐unsaturated thioamides. A [Cu‐(R,RP)‐TANIAPHOS]‐SePh species is characterized by its 77Se NMR spectra, which gives a chemical shift at δ 462 ppm. Moreover, a {[Cu‐(R)‐TOL‐BINAP]‐SePh}2 species is characterized by X‐ray analysis, which confirms the formation of Cu−Se bond in the reaction. Finally, the transformations of the thioamide group to amine and thioester are demonstrated to be straightforward.

New dithiocarbamate-based polymer (DTCP) as an additive to improve microporous polysulfone membrane efficiency in lead and dye removal

For fabricating a membrane with hydrophilic and complexing agent groups, a new dithiocarbamate-based polymer (DTCP) containing dithiocarbamate, thioamide, and ethereal oxygen groups was synthesized and blended in polysulfone (PSF) matrix with 1, 2, 5, and 10 wt% proportion. The membranes were produced by the nonsolvent induced phase separation method. For DTCP characterization, NMR, FTIR, TGA and GPC techniques were used. SEM images show that no morphological change can be seen even in 10 wt% blended membranes. AFM surface images show that the roughness of 5 and 10 wt% membranes extremely increased. The performance of the DTCP/PSF membranes were investigated in the separation of lead ions and Reactive Yellow 39 dye from the contaminated water. The outcomes indicated that by increasing the amount of DTCP up to 10 wt%, the pure water flux, bovine serum albumin flux, and the lead removal increased very efficiently compared to the bare one. Blending of more than 1 wt% DTCP, cause to removal of 99.6% lead ions. The water contact angle decreased by the adding of DTCP, caused to increase fouling resistance. The results of this research shows that the synthesized DTCP can be used as a good additive for improving membrane permeability, anti-fouling and especially heavy metal removal efficiency.

Synthesis and molecular modeling studies of 1-benzyl-2-indolinones as selective AChEinhibitors.

Background: Possible bioisosteres can be developed by replacing the 1-indanone ring (one of three pharmacophore groups) of donepezil with an indoline ring. As H2S donors, thioamide, thiocarbamate and thiourea groups are also critically important. Materials & methods: The 1-benzyl-2-indolinones 6a-n were designed using molecular modeling and synthesized, and their acetylcholinesterase and butyrylcholinesterase inhibitory effects were then investigated. Results: The compounds 6h (inhibition constant [Ki] =0.22μM; selectivity index [SI] =26.22), 6i (Ki=0.24μM; SI=25.83), 6k (Ki=0.22μM; SI=28.31) and 6n (Ki=0.21μM; SI=27.14) were approximately twofold more effective against and >12-fold more selective for acetylcholinesterasecompared with donepezil (Ki=0.41μM; SI=2.12). Analysis of molecular dynamics simulations with compounds 6k and 6n indicated that the preferred binding might be at allosteric binding pocket 4 of the enzyme. Conclusion: Benzyl substitution at the 1-position of the indole ring significantly increased potency and selectivity.

Impact of the Hydrogen-Bonding Functional Group on Hydrogelation of Amphiphilic Naphthalene-diimide Derivatives and Nonspecific Protein Adsorption.

This manuscript reports the effect of hydrogen-bonding functionality on the supramolecular assembly of naphthalene-diimide (NDI)-derived amphiphilic building blocks in water. All the molecules contain a central NDI chromophore, functionalized with a hydrophilic oligo-oxyethylene (OE) wedge in one arm and a phenyl group on the opposite arm. They differ by a single H-bonding functionality, which links the NDI chromophore and the phenyl moiety. The H-bonding functionalities are amide, thioamide, urea, and urethane in NDI-A, NDI-TA, NDI-U, and NDI-UT, respectively. All of these molecules exhibit π-stacking in water, as evident from their distinct UV/vis absorption spectra when compared to that of the monomeric dye in THF. However, among these four, only NDI-A and NDI-TA show hydrogelation, while the other two precipitate out of the medium. The NDI-A hydrogel also exhibits transient stability and leads to a crystalline precipitate within ∼5 h. Only NDI-TA produces stable transparent hydrogel with the entangled fibrillar morphology that is typical for gelators. Both NDI-A and NDI-TA showed a thermoresponsive property with a lower critical solution temperature of about 41-42 °C. Powder XRD studies show a parallel orientation for NDI-A and an antiparallel orientation for NDI-TA. Computational studies support this experimental observation and indicate that the NDI-A assembly is highly stabilized by strong H-bonding among the amide groups and π-stacking interaction in the parallel orientation. On the other hand, due to weak H-bonding among the thioamide groups, the binding energy of the parallelly oriented NDI-TA was significantly lower and the optimized structure was disordered. Instead, its antiparallel orientation was more stable, with criss-cross aligned H-bonding interactions and π-π interactions between adjacent aromatic rings. The NDI-TA hydrogel with less ordered OE chains on the surface showed prominent adsorption of serum protein BSA. In sharp contrast, NDI-A did not exhibit any notable interaction with BSA, as evident from the ITC studies.

Synthesis, characterization, and biological activity of Cu(II), Ni(II), and Zn(II) complexes of a tridentate heterocyclic Schiff base ligand derived from thiosemicarbazide and 2-benzoylpyridine

Ni(II), Cu(II), and Zn(II) complexes of the tridentate heterocyclic ligand, 2-(phenyl(pyridin-2-yl)methylene)hydrazine-1-carbothioamide (HL) have been synthesized and characterized by various spectroscopic techniques and elemental analyses. Infrared spectroscopy shows that the ligand coordinates to the metal ions through the azomethine and pyridine nitrogen atoms as well as the sulfur atom of the thioamide group to form a tridentate chelate system. In vitro screening of metal complexes against four bacterial strains (Staphylococcus aureus (ATCC 43300), Klebsiella pneumoniae (ATCC 700603), Methicillin resistant staphylococcus aureus (ATCC 33591), Shigella flexneri (NR 518)) and four fungal strains (Candida albicans (NR 29444), Candida albicans (NR 29445), Candida albicans (NR 29451), Candida krusei (HM 1122)) indicate that the Cu(II) complex showed good antibacterial activity on Methicillin resistant staphylococcus aureus (ATCC 33591) while the Zn(II) complex showed moderate activity against some of the bacterial and fungi strains. Antioxidant studies reveal that the complexes are more potent than the ligand to eliminate free radicals, with the Ni(II) complex showing the best free radical scavenger.

Effective flow modifiers for high-filled poly(phenylene sulfide) composites based on chemical structure similarity

Polyphenylene sulfide (PPS) is one of the representative engineering plastics used for various applications in the automobile industry. In actual applications, fiber-reinforced polymers (FRPs) are used to ensure the enhanced performance of engineering plastics. However, during processing, high-filled polymer composites suffer from high viscosity and poor dispersion. In this study, we propose a method for reducing the melt viscosity of PPS composites. We synthesized a novel flow modifier using multicomponent polymerization (MCP) to achieve effective processability and superior compatibility with PPS. The prepared flow modifier, polyhexylbenzothioamide (PHBTA), exhibits enhanced compatibility with PPS due to similarities in the chemical structure (i.e. a thioamide group). Polyhexyl phenylacetamide (PHPA) is used as a reference demonstrating a poor compatibility with PPS. Furthermore, PPS/glass fiber (GF) composites containing PHBTA exhibit enhanced rheological properties, mechanical properties, GF dispersion, and an increase in the length of GFs in the fracture state. To better understand the mechanical properties of PPS/GF40/PHBTA composites, we predict their tensile moduli using the Mori-Tanaka theory and the Halpin-Tsai equation, and the predictions agree well with the experiment results. This study aims to improve flowability in PPS/GF40 composites, thereby ensuring the effective and low cost processing of polymers for practical applications. Moreover, this approach provides further insight into the rheological and mechanical properties of FRP composites.

Synthesis, crystal structure and Hirshfeld surface analysis of (1H-benzimidazol-2-yl)(morpholin-4-yl)methane-thione.

The title compound, C12H13N3OS, was synthesized via the Willgerodt-Kindler method. The benzimidozole moiety is essentially planar (r.m.s. deviation = 0.0084 Å). The thio-amide group is inclined by 54.80 (14)° to the benzimidazole ring system. The morpholine ring is disordered over two sets of sites [ratio 0.841 (11):0.159 (11)], with chair conformations for both components. In the crystal, mol-ecules are linked into N-H⋯N hydrogen-bonded chains running parallel to the c axis. Hirshfeld surface analysis was used to qu-antify the inter-molecular inter-actions.

Dynamics of Formation of Binuclear Metal Complexes: A New Cu(I) Compound with N‐(2‐thiophenecarbonyl)‐N’‐(3‐Cl, 4‐F‐phenyl)thiourea as Ligand

AbstractHerein we report the synthesis and characterization of a new copper(I) complex with triphenylphosphine (PPh3) and N‐(2‐thiophenecarbonyl)‐N’‐(3‐Cl, 4‐F‐phenyl)thiourea (HL), as ligands. The complex was characterized by vibrational (FTIR and FT‐Raman) and multinuclear (1H, 13C {1H}, 31P{1H}) NMR spectroscopies. The crystalline structure of the complex was determined by single‐crystal X‐ray diffraction, confirming that a neutral binuclear compound, identified as [Cu(PPh3)(L‐κ2‐N,μ‐S)]2, was obtained. The anionic thiourea ligand coordinates to the metal through the sulfur and nitrogen atoms in an unusual bidentate κ2‐N,μ‐S coordination mode. The complex is a dimer sited on a crystallographic center of symmetry. Each Cu2(μ‐S)2 cation bridges trough the sulfur atoms of two symmetry related thiourea moieties and is also coordinated to the nitrogen atom of the thiourea ligand and the phosphorus atom from PPh3 co‐ligand, forming a slightly distorted tetrahedral geometry. An intramolecular N−H⋅⋅⋅O=C hydrogen bond is observed in the anionic ligand, forming a six‐membered ring that stabilizes the N−H thioamide group. Hirshfeld surface analysis shows that the molecules are connected by weak intermolecular contacts C⋅⋅⋅C, H⋅⋅⋅C and H⋅⋅⋅H which add to the stability of the crystalline packing. The in vitro cytotoxicity study of the complex indicates that it is more active against human lung carcinoma cells (A549), when compared to the free ligand.

Theoretical unraveling the complexation and separation of uranyl–ligand complexes towards chiral R/S‐profenofos

AbstractThe identification and separation of chiral pesticides R/S‐profenofos are of great significance due to different biological toxicity of chiral isomers. In the study, we designed two novel ligands: (2,2′:6′,2″‐terpyridin)‐6‐yl(5‐methoxy‐1H‐pyrazol‐1‐yl) methanethione (TMMT) and (2,2′:6′,2″‐terpyridin)‐6‐yl(5‐methoxy‐1H‐pyrazol‐1‐yl) methanone (TMMO), and taking them as ligands coordinated with uranyl, two novel complexes [Uranyl‐TMMT]2+ and [Uranyl‐TMMO]2+ as receptors were successfully constructed. The complexation and enantioselectivity of two receptors towards R/S‐profenofos as guests were systematically unraveled based on the density functional theory (DFT) method. The results showed that the receptor [Uranyl‐TMMT]2+ containing thioamide group has stronger electron donating ability than the receptor [Uranyl‐TMMO]2+ containing amide group. All analyses including Mayer bond order (MBO), quantum theory of atoms in molecules (QTAIM), localized orbital locator (LOL) function, molecular orbital, and infrared spectrum illustrated that the UX (X = S, O) bonds play a larger role than the UN bonds in the selective complexation of receptors towards guests; the US bond in [Uranyl‐TMMT]2+ is more covalent than the UO bond in [Uranyl‐TMMO]2+. The thermodynamic calculations showed that the separation factors of [Uranyl‐TMMT]2+ towards R/S‐PFFs were between 8356 and 1219 in different solvents, and the separation factors of [Uranyl‐TMMO]2+ towards R/S‐PFFs were at range of 4951–710. The separation factors exhibited that two receptors have stronger coordination and complexation ability to S‐PFF than to R‐PFF, while [Uranyl‐TMMT]2+ exhibited significantly greater recognition ability and enantioselectivity for guests R/S‐PFFs molecules than the receptor [Uranyl‐TMMO]2+.

Density functional theory and molecular dynamics simulation of the corrosive particle diffusion in pyrimidine and its derivatives films

The search and discovery of corrosion inhibitors to mitigate sweet corrosion in the oil and gas industry has been carried out mainly using tedious and costly experimental approaches. In this study, theoretical approach using density functional theory (DFT) and molecular dynamics (MD) simulation were utilized to investigate the adsorption and diffusion properties of pyrimidine and six (6) of its derivatives on carbon steel corrosion in simulated CO2-containing environment. The DFT calculations revealed that the electrons can easily flow from the HOMO orbitals of all the pyrimidine molecules to the empty substrate orbitals until reaching the equilibrium state as the values of EHOMO (-7.63 to −5.55 eV) are much higher than the Fermi level energy of Fe (-13.16 eV). Besides, the binding energy of molecules on the Fe (110) surface obtained using MD simulation was found to be in the range of 60.67 to 99.28 kcal/mol, indicating the pyrimidine molecules can strongly interact with the iron atoms of the metal surface. In the sweet medium, the diffusion coefficient (D) of HCO3– was in the range of 0.81 to 1.41 m2 s−1, which is about three times less than the diffusion coefficient of HCO3– in water. Self-diffusion coefficient (D'), and fractional free volume (FFV) were used to further investigate the diffusion mechanism of the pyrimidine molecules in CO2 corrosive medium. Pyrimidine containing carboxylic acid and thioamide groups gave the best result as CO2 corrosion inhibitor theoretically. The DFT and MD results provided useful insights and a theoretical basis for the screening and design of new sweet corrosion inhibitors for carbon steel.

Analiza farmakoterapijskog pristupa kod pacijenata obolelih od hipertireoze

Introduction: Hyperthyroidism represents a condition that occurs due to increased synthesis of thyroid hormones (T3, T4). In 90% of all cases it is caused by: Graves' disease, toxic multinodular goiter and toxic adenoma. Therapy of hyperthyroidism includes medication, radioiodine treatment and surgery. The most prescribed antithyroid drugs belong to the thioamide group (thiamazole and propylthiouracil). Aim: The aim of this study was to analyze the preoperative pharmacotherapeutic approach with the use of 3 drugs from the thioamide group (PTU® (propylthiouracil), Thyrozol® (thiamazole) and Tiastat® (thiamazole) in relation to the demographic and clinical characteristics of patients with hyperthyroidism. Material and methods: The study was conducted as a retrospective study among 62 patients aged 18 to 84 years, who reported to the Center for Endocrine Surgery KCS for the operative treatment of hyperthyroidism in period 2014-2019. Results: Diagnosis of Graves' disease was detected in 35.48% of patients, where 32.26% had toxic multinodular goiter, and 32.26% toxic adenoma. The most patients were prescribed Tiastat® (45.16%), 29.03% of them were prescribed PTU®, and 25.8% of them Thyrozol®. The most of patients suffering from Graves' disease were treated with Tiastat®, those suffering from toxic adenoma with PTU® and toxic multinodular goiter with Tiastat®. The most commonly used doses were 100 mg/day for PTU®, 20 mg/day for Tiastat® and 20 and 30 mg/ day for Thyrozol®. Total thyroidectomy is most commonly performed in patients treated with Tiastat® and hemithyroidectomy in those treated with PTU®. It was observed that there was a statistically significant difference (p < 0.05) in the use of individual drugs regarding to diagnosis, total daily dose of drug, body mass index and type of surgical procedure. Conclusion: The most of patients were prescribed Tiastat®. Pharmacotherapeutic approach in paients with hyperthyroidism is in accordance with the national guidelines.

Impact of dithiocarbamate-based polymeric additives on the performance of polyethersulfone membrane for the treatment of arsenic contaminated waters

Two types of aliphatic and aromatic dithiocarbamate (DTC) polymers, having the thioamide groups were synthesized and used as hydrophilic agents as well as arsenic adsorbents in fabrication and modification of polyethersulfone (PES) membranes for the separation of arsenic from the contaminated water. The synthesized DTCs were characterized by nuclear magnetic resonance (NMR) and Fourier transform infrared spectroscopy (FTIR), and their arsenic adsorption test demonstrated arsenic removal of 85.5% and 91.4% for the aromatic and aliphatic DTC polymers respectively. The results indicated that by increasing the concentration of DTCs, both membrane flux and rate of arsenic removal increased compared to the bare one. The water flux reached a maximum value at 0.5 wt% DTCs and further increase lead to decreased flux. The aliphatic DTC behaved better than the aromatic one: the membrane with aromatic DTC showed better arsenic rejection than the aliphatic one, corresponding well to the adsorption results. The water contact angle was reduced by the addition of DTCs, indicating increased hydrophilicity. The fouling resistance increased by the addition of DTCs which was demonstrated by increased flux recovery ratio (FRR) after BSA fouling. The real arsenic polluted groundwater treatment for a long-time showed that tailored-made DTC polymers are excellent candidates for arsenic removal and improvement for the fouling resistance of PES membranes.

Synthesis of Some Novel Nanosized Chelates of Anchoring Bisazo Dye 5-[5-(4,6-Dioxo-2-thioxo-hexahydro-pyrimidin-5-ylazo)-naphthalen-1-ylazo]-2-mercapto-1H-pyrimidine-4,6-dione and Their Applications as Antioxidant and Antitumor Agents.

A novel bisazo 5-[5-(4,6-dioxo-2-thioxo-hexahydro-pyrimidin-5-ylazo)-naphthalen-1-ylazo]-2-mercapto-1H-pyrimidine-4,6-dione (H4L) ligand has been synthesized from diazotization coupling between naphthalene-1,5-diamine and 2-thiobarbituric acid. Mn(II), Co(II), Ni(II), Cu(II), Zn(II), and Fe(III) chelates were prepared. All prepared compounds were characterized by different techniques. The azo groups did not participate in chelation according to the infrared spectra, whereas the thioamide group did participate. The azo dye ligand coordinated with all metallic ions in a neutral–keto–thiol structure and behaved as a bi- and tridentate moiety. Zinc, manganese, and iron chelates had an octahedral structure, while nickel and cobalt chelates had a tetrahedral structure, but the copper chelate had a square pyramidal geometry. The thermal behavior of all prepared compounds was investigated and thermokinetic parameters were also discussed. X-ray diffraction (XRD) data reflected that Fe(III) and Zn(II) complexes were crystalline while the Cu(II) complex was amorphous. Calcination of the Fe(III) complex at 600 °C yielded a nanosized Fe2O3 crystalline phase, elucidated by XRD and transmission electron microscope. The novel azo dye and some of its chelates were tested against HepG-2. The Fe2O3 nanooxide showed remarkable activity against the HepG-2 cell line rather than its precursor Fe(III) complex. Co(II) had a higher antioxidant activity than the other investigated complexes. In both activities, the Cu(II) complex did not show any activity. Molecular modeling and some theoretical studies were validated, and the experimental results were interpreted.

Characterization of a Copper-Chelating Natural Product from the Methanotroph Methylosinus sp. LW3

Methanobactins (Mbns) are ribosomally produced, post-translationally modified peptidic natural products that bind copper with high affinity. Methanotrophic bacteria use Mbns to acquire copper needed for enzymatic methane oxidation. Despite the presence of Mbn operons in a range of methanotroph and other bacterial genomes, few Mbns have been isolated and structurally characterized. Here we report the isolation of a novel Mbn from the methanotroph Methylosinus (Ms.) sp. LW3. Mass spectrometric and nuclear magnetic resonance spectroscopic data indicate that this Mbn, the largest characterized to date, consists of a 13-amino acid backbone modified to include pyrazinedione/oxazolone rings and neighboring thioamide groups derived from cysteine residues. The pyrazinedione ring is more stable to acid hydrolysis than the oxazolone ring and likely protects the Mbn from degradation. The structure corresponds exactly to that predicted on the basis of the Ms. sp. LW3 Mbn operon content, providing support for the proposed role of an uncharacterized biosynthetic enzyme, MbnF, and expanding the diversity of known Mbns.

Reactivity of (Z)-4-Aryliden-5(4H)-thiazolones: [2 + 2]-Photocycloaddition, Ring-Opening Reactions, and Influence of the Lewis Acid BF3.

The irradiation of (Z)-2-phenyl-4-aryliden-5(4H)-thiazolones 2 with blue light (465 nm) in CH2Cl2 solution promotes [2 + 2]-photocycloaddition of the exocyclic C=C bonds and the formation of the dispirocyclobutanes 3. This reaction takes place with high stereoselectivity, given that the ε-isomer (1,3 head-to-tail syn coupling) is formed in more than 90% yield in most of the cases. However, irradiation of 5(4H)-thiazolones 2 with blue light (456 nm) in dry MeOH in the presence of BF3·OEt2 leads to the monospirocyclobutanes 4 with full stereoselectivity, also affording the ε-isomer. A ring-opening reaction of only one of the thiazolone rings appears to have taken place in 4 upon methanolysis, leading to the corresponding ester and thioamide groups. The treatment of free 4-aryliden-5(4H)-thiazolones 2 with a base in alcohol (NaOR/ROH) also produces a ring-opening reaction of the heterocycle by methanolysis, although, under these reaction conditions, further intramolecular S-attack at the exocyclic C(H)=C bond and cyclization is observed, forming the dihydrothiazoles 5 or 6 as mixtures of cis (RS/SR)- and trans (RR/SS)-isomers with high diastereomeric excess. trans-(RR/SS)-Dihydrothiazoles 6 can be isolated as pure diastereoisomers by column chromatography. Surprisingly, dihydrothiazoles 5 can also be obtained by the treatment of 4-aryliden-5(4H)-thiazolones 2 with BF3·OEt2 in methanol in the absence of a base.