Methylthio Group Research Articles

Heterologous Expression of Type II PKS Gene Cluster Leads to Diversified Angucyclines in Streptomyces albus J1074

Heterologous expression has emerged as an effective strategy in activating Streptomyces cryptic gene clusters or improving yield. Eight compounds were successfully obtained by heterologous expression of the type II PKS gene cluster spi derived from marine Streptomyces sp. HDN155000 in the chassis host Streptomyces albus J1074. The structures with absolute configurations were elucidated using extensive MS and NMR spectroscopic methods, as well as theoretical NMR calculations and electronic circular dichroism (ECD) calculations. Interestingly, compound WS009 Z (2) contains a rare thiomethyl group, angumycinone T (4) has a novel oxo-bridge formed between C12a and C4, and angumycinone X (3) showed cytotoxicity toward K562 and NCI-H446/EP cell lines.

Structural design and characterization of a new type of organic nonlinear optical flavanone crystal

Two new crystals were designed and obtained: the chalcone derivative HMMP (1-(2‑hydroxy-4-methoxyphenyl)-3-(4-(methylthio)phenyl)prop‑2-en-1-one) and the flavanone derivative 7M4MC (7‑methoxy-2-(4-(methylthio)phenyl)chroman-4-one). Yellow bulk 7M4MC single crystal with dimensions of 3 × 2 × 1 mm3 and orange-yellow needle-like HMMP single crystal were grown by solution evaporation. 7M4MC crystal belongs to the P21 space group of the monoclinic structure, which has a non-centrosymmetric structure. HMMP crystal monoclinic, belongs to the P21/m space group with a centrosymmetric structure. In the 7M4MC molecule, the methoxy and methylthio groups act as electron donors (D) and the carbonyl group acts as an electron acceptor (A), forming a d-π-A-π-D structure with an electron gradient. 7M4MC exhibits a high degree of second-harmonic generation intensity (11 × KDP), a broad transmission range (600–1600 nm, >88 %), an elevated optical energy bandgap (Eg = 2.57 eV), high thermal stability (Tm = 105 °C) and excellent dielectric properties (εr ≈ 2.1). This work not only provides two new crystals but also offers a viable molecular design option by changing the degree of intramolecular distortion by altering the backbone structure.

DMSO/SOCl<sub>2</sub>‐Mediated Synthesis of Thiomethylnaphthalenes from Propargyl Alcohols

Herein, we reported the straightforward synthesis of thiomethylnaphthalenes via the reaction of propargyl alcohols with DMSO/SOCl2, which also provided easy access to deuterated thiomethyl and other thioalkyl scaffolds when deuterated dimethyl sulfoxide and dialkyl sulfoxides were used, respectively. In addition, the thiomethyl group can be readily derivatized to the corresponding sulfoxide, sulfone, and sulfoximine of interesting photophysical properties.

Staphylococcal sRNA IsrR downregulates methylthiotransferase MiaB under iron-deficient conditions.

Staphylococcus aureus is a major contributor to bacterial-associated mortality, owing to its exceptional adaptability across diverse environments. Iron is vital to most organisms but can be toxic in excess. To manage its intracellular iron, S. aureus, like many pathogens, employs intricate systems. We have recently identified IsrR as a key regulatory RNA induced during iron starvation. Its role is to reduce the synthesis of non-essential iron-containing proteins under iron-depleted conditions. In this study, we unveil IsrR's regulatory action on MiaB, an enzyme responsible for methylthio group addition to specific sites on transfer RNAs (tRNAs). We use predictive tools and reporter fusion assays to demonstrate IsrR's binding to the Shine-Dalgarno sequence of miaB RNA, thereby impeding its translation. The effectiveness of IsrR hinges on the integrity of a specific C-rich region. As MiaB is non-essential and has iron-sulfur clusters, IsrR induction spares iron by downregulating miaB. This may improve S. aureus fitness and aid in navigating the host's nutritional immune defenses.IMPORTANCEIn many biotopes, including those found within an infected host, bacteria confront the challenge of iron deficiency. They employ various strategies to adapt to this scarcity of nutrients, one of which involves regulating iron-containing proteins through the action of small regulatory RNAs. Our study shows how IsrR, a small RNA from S. aureus, prevents the production of MiaB, a tRNA-modifying enzyme containing iron-sulfur clusters. With this illustration, we propose a new substrate for an iron-sparing small RNA, which, when downregulated, should reduce the need for iron and save it to essential functions.

Metal Ions Trigger the Gelation of Cysteine‐Containing Peptide‐Appended Coordination Cages

AbstractWe report a series of coordination cages that incorporate peptide chains at their vertices, prepared through subcomponent self‐assembly. Three distinct heterochiral tripeptide subcomponents were incorporated, each exhibiting an L−D−L stereoconfiguration. Through this approach, we prepared and characterized three tetrahedral metal‐peptide cages that incorporate thiol and methylthio groups. The gelation of these cages was probed through the binding of additional metal ions, with the metal‐peptide cages acting as junctions, owing to the presence of sulfur atoms on the peripheral peptides. Gels were obtained with cages bearing cysteine at the C‐terminus. Our strategy for developing functional metal‐coordinated supramolecular gels with a modular design may result in the development of materials useful for chemical separations or drug delivery.

Metal Ions Trigger the Gelation of Cysteine-Containing Peptide-Appended Coordination Cages.

We report a series of coordination cages that incorporate peptide chains at their vertices, prepared through subcomponent self-assembly. Three distinct heterochiral tripeptide subcomponents were incorporated, each exhibiting an L-D-L stereoconfiguration. Through this approach, we prepared and characterized three tetrahedral metal-peptide cages that incorporate thiol and methylthio groups. The gelation of these cages was probed through the binding of additional metal ions, with the metal-peptide cages acting as junctions, owing to the presence of sulfur atoms on the peripheral peptides. Gels were obtained with cages bearing cysteine at the C-terminus. Our strategy for developing functional metal-coordinated supramolecular gels with a modular design may result in the development of materials useful for chemical separations or drug delivery.

Columnar Mesomorphism in a Methylthio-Decorated Triindole for Enhanced Charge Transport.

We report a semiconducting triindole-based discotic liquid crystal (TRISMe) functionalized with six p-methylthiophenyl groups at its periphery. While initially a crystalline solid at room temperature, TRISMe transitions to a columnar hexagonal mesophase upon heating and retains this supramolecular organization upon subsequent cooling, despite having only three flexible alkyl chains attached to the core's nitrogens. The incorporation of methylthio groups effectively hinders tight molecular packing, stabilizing the columnar arrangement of this disk-shaped molecule. Single crystal analysis confirmed the high tendency of this compound to organize into a columnar architecture and the role played by the methylthio groups in reinforcing such structure. The mesomorphic behavior of TRISMe provides an opportunity for processing from its molten state. Notably, our research reveals significant differences in charge transport depending on the processing method, whether solution drop-casting or melt-based. TRISMe shows hole mobility values averaging 3 × 10-1 cm2 V-1 s-1 when incorporated in diode-type devices from the isotropic melt and annealed at the mesophase temperature, estimated by SCLC (space-charge-limited current) measurements. However, when integrated into solution-processed organic field-effect transistors (OFETs), crystalline TRISMe exhibits a hole mobility of 3 × 10-4 cm2 V-1 s-1. The observed differences can be attributed to a beneficial supramolecular assembly achieved in the mesophase in spite of its lower order. These results emphasize the material's potential for applications in easy-to-process electronic devices and highlight the potential of methylthio moieties in promoting columnar mesophases.

Pincer Nickel-Catalyzed Olefination of Alcohols with Benzylphosphine Oxides.

N,N,P-Pincer nickel complexes effectively catalyze reaction of alcohols with benzylphosphine oxides to form alkenes in good yields. The protocol suits for a wide scope of substrates and generates only E-configurated alkenes. The method also shows good compatibility of functional groups. Methoxy, methylthio, trifluoromethyl, ketal, fluoro, chloro, bromo, thienyl, and furyl groups are tolerated. The mechanism studies support that the reaction proceeds through catalytic dehydrogenation of alcohols to aldehydes or ketones followed by condensation with benzyldiphenylphosphine oxides in the presence of KOtBu.

Microwave-assisted synthesis, photochemical and electrochemical studies of long-wavelength BODIPY dyes

Novel BODIPY derivatives possessing different styryl substituents were synthesized using different methods of Knoevenagel-type condensation with conventional heating and microwave radiation in two conditions. Microwave-assisted synthesis significantly reduces reaction time while enhancing its efficiency. The introduction of styryl substituents at the 3 and 5 positions of the BODIPY core resulted in a substantial bathochromic shift, which was affected by the substituents within styryl groups. Depending on the solvents, the BODIPY with unsubstituted styryl groups possesses absorption maxima (λAbs) between 616 and 626 nm. While the analogs containing electron-donating methoxy and methylthio groups exhibited bathochromically shifted bands with λAbs values in the 633-654 nm range. Fluorescence studies revealed intensive emission of tested BODIPYs with fluorescence quantum yields at the 0.41-0.83 range. On the other hand, singlet oxygen quantum yields were very low. In the electrochemical studies, the CV and DPV scans showed the presence of three redox processes. The calculated electrochemical gaps were in the range of 1.71-1.87 V.

Design, Synthesis, and Insecticidal Activities of Novel Thioether and Oxide Sulfide-containing Diamide Compounds

Background: With the emerging resistance to mainstream insecticides, it is necessary to develop new insecticides to tackle the problem of pest threat. Diamide insecticides are widely studied because of their broad spectrum of activities, high efficiency, and low toxicity. Most thioether and oxide sulfide-containing compounds have a wide range of biological activities in agricultural chemicals. Objective: The main purpose of the study was to explore novel thioether and oxide sulfide-containing diamide compounds possessing outstanding insecticidal activity. Methods: Based on the “active substructure replacing” method by introducing methylthio groups, 29 sulfide-containing diamide compounds were designed and synthesised. The structures of all synthetic compounds were confirmed by 1H-NMR, 13C-NMR and HRMS. Moreover, the biological activities of all the compounds were tested. Results: The preliminary bioassay indicated that most of the new compounds did not exhibit better activity than the reference insecticide cyproflanilide. However, compounds 18a and 23a showed markedly potent activity against Tetranychus cinnabarinus at 100 mg/L, which was better than cyproflanilide since these compounds possessed 2-methyl-4-cyanophenyl, which might be the reason for their better internal absorption in the plant. Conclusion: The structure-activity relationship showed that some compounds were of potential value to be developed as novel insecticides, but the majority of compounds did not show superior insecticidal activity than cyproflanilide.

Ferroelectric nematogens containing a methylthio group

We report for the first-time a series of methylthio terminated materials which exhibit the ferroelectric nematic phase.

Triazole and methylthio modified covalent organic frameworks for enhancing Hg(II) adsorption from water

The presence of mercury (Hg(II)), a highly toxic pollutant in the aquatic environment, motivates researchers to use an effective method to remove it from water. Herein, we synthesized COF-TAZ and COF-TOE via post-modification with 3-mercapto-1,2,4-triazole and 4-(methylsulfanyl)thiophenol to form triazole group and methylthio group, respectively, and followed by characterization with SEM, FTIR, and XRD, etc. The adsorption behaviors of Hg(II) on two modified COFs were evaluated by adsorption kinetic models using the pseudo-first order, pseudo-second order and intra-particle diffusion models, as well as isotherm models, i.e., Langmuir and Freundlich models. COF-TAZ and COF-TOE manifested maximum experimental uptake capacity of 108.09 mg g−1 and 104.85 mg g−1, respectively. Notably, COF-TAZ exhibited commendable binding selectivity towards Hg(II) and displayed a good recycling ability, with a removal percentage still above 90% after five cycles. Especially, the adsorption mechanisms of COF-TAZ and COF-TOE were clarified by FTIR, XPS and DFT calculations, suggesting that electrostatic interaction and chelation were involved in the adsorption process. This study shows that functionalized COFs have good application prospects in effective removal of heavy metals in water.

Single-Molecule Conductance Behavior of Molecular Bundles.

Controlling the orientation of complex molecules in molecular junctions is crucial to their development into functional devices. To date, this has been achieved through the use of multipodal compounds (i.e., containing more than two anchoring groups), resulting in the formation of tri/tetrapodal compounds. While such compounds have greatly improved orientation control, this comes at the cost of lower surface coverage. In this study, we examine an alternative approach for generating multimodal compounds by binding multiple independent molecular wires together through metal coordination to form a molecular bundle. This was achieved by coordinating iron(II) and cobalt(II) to 5,5'-bis(methylthio)-2,2'-bipyridine (L1) and (methylenebis(4,1-phenylene))bis(1-(5-(methylthio)pyridin-2-yl)methanimine) (L2) to give two monometallic complexes, Fe-1 and Co-1, and two bimetallic helicates, Fe-2 and Co-2. Using XPS, all of the complexes were shown to bind to a gold surface in a fac fashion through three thiomethyl groups. Using single-molecule conductance and DFT calculations, each of the ligands was shown to conduct as an independent wire with no impact from the rest of the complex. These results suggest that this is a useful approach for controlling the geometry of junction formation without altering the conductance behavior of the individual molecular wires.

Substrate-Controlled Regioselective Alkylation of 4-Hydroxycoumarin with Diazo Compounds through TfOH Catalysis

AbstractControl of the regioselectivity of nucleophiles toward alkylating agents is a fundamental problem in heterocyclic chemistry. Substrate-controlled TfOH-catalyzed alkylation of 4-hydroxycoumarin with diazo compounds has been developed to provide rapid access to the C3- or O-alkylated 4-hydroxycoumarins with high efficiency. The regioselectivity can be determined by varying the electronic nature of the diazo substrates, especially those bearing a methylthio group.

Blue Light‐Promoted Synthesis of Thiochromenopyrroledione Derivatives via Titanium Dioxide‐Catalyzed Dual Carbon–Carbon Bond Formation with Thioanisole and Maleimide Derivatives

AbstractUnder anaerobic conditions, thioanisole derivatives bearing a thiomethyl group participated in dual carbon‐carbon bond‐forming reactions with maleimide derivatives in the presence of titanium dioxide. Blue light irradiation facilitated these reactions, producing thiochromenopyrroledione derivatives and nearly equimolar quantities of succinimide derivatives. Specifically, a thiochromenopyrroledione derivative formed from thioanisole and N‐benzylmaleimide was achieved with a 43% yield after 12 hours of blue light exposure (>420 nm), approaching its theoretical maximum yield of 50%. Without titanium dioxide, the reaction remained dormant. Our investigations with five varieties of 4‐substituted thioanisoles and four N‐substituted maleimides as precursors resulted in the synthesis of 20 distinct thiochromenopyrroledione derivatives with moderate to high yields. From observed substituent effects, we postulate that this reaction proceeds through a charge transfer from thioanisole to the conduction band of titanium dioxide during blue light irradiation, initiating the one‐electron oxidation of thioanisole and subsequent generation of α‐thioalkyl radicals via deprotonation.

Tuning the electronic and optical properties of small organic acenedithiophene molecular crystals for photovoltaic applications: First principles calculations.

Periodic density functional theory was employed to investigate the impact of chemical modifications on the properties of π-conjugated acenedithiophene molecular crystals. Here, we highlight the importance of the β-methylthionation effect, the position of the sulfur atoms of the thiacycle group and their size, and the number of central benzene rings in the chemical modification strategy. Our results show that the introduction of the methylthio groups at the β-positions of the thiophene and the additional benzene ring at the center of the BDT crystal structure are a promising strategy to improve the performance of organic semiconductors, as observed experimentally. We found that β-MT-ADT exhibits large charge carrier mobility, which is in good agreement with the experimental results and comparable to that of rubrene. In addition, the electronic and optical properties of these ambipolar materials suggest promising performances with β-MT-ADT > ADT >β-MT-NDT > NDT > BEDT-BDT >β-MT-BDT > BDT. Moreover, functionalization with thiacycle-fused sulfur atoms of different sizes and numbers improve the properties of BDT but is still less efficient than the methylthionation effect. Overall, our findings suggest a promising molecular modification strategy for possibly high performance ambipolar organic semiconducting materials.

The crystal and molecular structure of 1-ferrocenyl-3,3-bis(methylthio)prop-2-en-1-one

Abstract The title compound 1-ferrocenyl-3,3-bis(methylthio)prop-2-en-1-one (1), a key intermediate in the synthesis of ferrocene-containing heterocycles, has been characterized by single-crystal X-ray diffraction. Compound 1 crystallizes in the monoclinic space group P21/c with 8 molecules in the unit cell. Unit cell parameters are 12.8159(10), 10.8121(9), and 20.8411(16) Å for a, b and c, respectively with β = 98.985(4)°. There are two distinct molecules in the asymmetric unit (A and B). Both molecules display a nearly eclipsed conformation with respect to the individual intramolecular cyclopentadienyl units in addition to close intramolecular contacts between the carbonyl O atom and one S atom of the bis-methylthiol functionality. Close intermolecular contacts involving A and B are noted with respect to S⋯H interactions between a thiol-S and the substituted Cp group in addition to C=O∙∙∙HC= interactions with the ene-moiety and a H atom located on one of the thiomethyl groups.

Synthesis of benzothienofuranones and dihydrobenzothienopyranones by palladium iodide-catalyzed carbonylative double cyclization

3-(2-(Methylthio)phenyl)prop-2-yn-1-ols have been successfully converted in one synthetic step into benzo[4,5]thieno[2,3-c]furan-1-ones by a PdI2/KI-catalyzed oxidative carbonylative double cyclization process, performed in MeCN under relative mild conditions (1–10 mol % PdI2, 7 equiv of KI, 80 °C, 60 atm of a 4:1 mixture CO–air). The process takes place through an ordered sequence of steps, involving 5-endo-dig S-cyclization, iodide-promoted demethylation of the ensuing sulfonium salt, CO insertion, a second cyclization (possibly, through the formation of a palladacycle intermediate followed by reductive elimination), and Pd(0) reoxidation by oxygen (from air) used as external benign oxidant. Under similar conditions, 4-(2-(methylthio)phenyl)but-3-yn-1-ols, bearing a butynol moiety ortho to the methylthio group, led to a mixture of double cyclization and dicarbonylation products, however, by slightly tuning the reaction conditions, dihydrobenzo[4,5]thieno[3,2-c]pyran-1-ones could be selectively obtained with no formation of the dicarbonylated byproduct. The structures of four representative products, including two tetracyclic derivatives, have been confirmed by XRD analysis.

Electronic-effect regulated covalent organic frameworks as heterogeneous photoactive catalysts

Crystalline covalent organic frameworks (COFs) materials have good performance in photocatalytic conversions due to their excellent photoelectric properties in recent years. here, two new conjugated pyrene-based covalent organic frameworks (COFs), namely PyDF-COF and PyBMT-COF, were prepared through condensation polymerization of 4,4',4'',4'''-(pyrene-1,3,6,8-tetrayl)tetraaniline and 2,5-difluoroterephthalaldehyde or 2,5-bis(methylthio)terephthalaldehyde, respectively. Highly selective aerobic hydroxylation of arylboronic acids can occur smoothly with high yields and a wide range of substrate universality. Compared with PyDF-COF, PyBMT-COF demonstrates a more efficient ability for this aerobic hydroxylation, indicating electron-donating thiomethyl groups of PyBMT-COF are more favorable to enhance distribution of electron cloud than electron-withdrawing fluorine groups of PyDF-COF, which make the PyBMT-COF more easily afford holes and electrons (h+-e-) separation, more effectively absorb visible light, and own narrower bandgap energy, higher photocurrent response, longer fluorescent lifetime and lower electrochemical impedance.

Macrocyclization and Backbone Rearrangement During RiPP Biosynthesis by a SAM-Dependent Domain-of-Unknown-Function 692.

The domain of unknown function 692 (DUF692) is an emerging family of post-translational modification enzymes involved in the biosynthesis of ribosomally synthesized and post-translationally modified peptide (RiPP) natural products. Members of this family are multinuclear iron-containing enzymes, and only two members have been functionally characterized to date: MbnB and TglH. Here, we used bioinformatics to select another member of the DUF692 family, ChrH, that is encoded in the genomes of the Chryseobacterium genus along with a partner protein ChrI. We structurally characterized the ChrH reaction product and show that the enzyme complex catalyzes an unprecedented chemical transformation that results in the formation of a macrocycle, an imidazolidinedione heterocycle, two thioaminals, and a thiomethyl group. Based on isotopic labeling studies, we propose a mechanism for the four-electron oxidation and methylation of the substrate peptide. This work identifies the first SAM-dependent reaction catalyzed by a DUF692 enzyme complex, further expanding the repertoire of remarkable reactions catalyzed by these enzymes. Based on the three currently characterized DUF692 family members, we suggest the family be called multinuclear non-heme iron dependent oxidative enzymes (MNIOs).