Thio Groups Research Articles

Synthesis, and molecular docking of thiourea derivatives as antibacterial agents targeting enzymes involved in biosynthesis of bacterial cell wall

Background: New antibacterials are needed due to the increasing resistance of bacteria to existing antibiotics. Thiourea derivative compounds (benzoylthiourea and 1,3-dibenzoylthiourea) contain aromatic groups, thio groups (C=S), and amide groups (H2N-C=O), which are commonly found in the class of antibacterial drugs. Molecular docking can be used to predict their antibacterial activity. Objective: This study aimed to synthesise thiourea derivatives and predict their antibacterial activity by in silico method. Methods: Synthesis was performed using nucleophilic substitution reactions. The synthesised compounds were identified using UV-Vis, FT-IR, and 1H-NMR. Molecular docking was conducted using the MOE program ver 2022.02. Results: Benzoylthiourea (BTU) and 1,3-dibenzoylthiourea (DBTU) compounds were obtained with yields of 36.55% and 12.68%, respectively. The melting point 171-173°C for BTU and 202-204°C for DBTU. Molecular docking results showed higher binding affinity of DBTU against PBP2a (docking score < -5.75 kcal/mol) and FaBH (docking score <-4.7935 kcal/mol) compared to the corresponding native ligands, while the two compounds had lower affinity for the muramyl ligase. Conclusion: BTU and DBTU can be synthesised by nucleophilic substitution reactions. DBTU is predicted to exhibit antibacterial activity against Methicilin Resistant Staphylococcus aureus (MRSA) and Mycobacterium tuberculosis.

Synthesis of N,N-spiro-bridged bis(cyclotriphosphazene) derivatives bearing aryl thio groups and their comparison with alkoxy and amino derivatives

In this study, bis (1a, b) and tetrakis (2a, b) cyclotriphosphazenes containing aryl thio groups were reacted with n-butyl amine. Deprotonation reactions of the obtained mono amino bis phenylthio (3a, b) and bis naphthylthio (4a, b) cyclotriphosphazenes were carried out in the presence of NaH base. New N,N-spiro bridged biscyclotriphosphazenes containing bis geminal phenylthio (5a-I and 5a-II) and naphthythio (5b-I and 5b-II) groups were created. Characterization of the newly synthesized compounds was performed by MALDI-TOF, 31P and 1H NMR spectroscopy, and single-crystal X-Ray crystallography (5a-I and 5b-I). Photophysical properties of compounds 1a, b, 2a, b, 5a-I, and 5b-I were determined using UV/vis and fluorescence spectroscopies. At the same time, the structures of N,N-spiro bridged biscyclophosphazenes were comprehensively evaluated with the structures of previously synthesized biscyclophosphazenes containing different functional groups.

Peroxodisulfate-assisted synthesis of 2-thiocyanato glycals and their transformation to C-2-thio acrylo/aryl nitrile-substituted glycals.

An efficient regioselective method to attach thiocyanato groups at the β-position of enol double bonds in sugar enol ethers using KSCN and potassium persulfate has been developed. The highly regioselective addition of the resulting sugar thiocyanate to electron rich species like terminal alkynes and benzynes under Pd catalysis generated C-2-thio acrylo/aryl nitrile glycals via simultaneous introduction of thio and cyano groups into carbon-carbon triple bonds.

Theoretical and conceptual framework to design D-π-A type organic dyes for application dye-sensitized solar cells

The optimized structures and absorption spectra of five D-A-type organic dyes (M1, M2, M3, M4, and M5) were investigated using Density Functional Theory (DFT) and Time-Dependent Density Functional Theory (TD-DFT). These dyes contain the same electron acceptors and -spacers but distinct 3,6- and 2,7-carbazole electron-donating groups. The results showed coplanar geometries for the dyes, which implied strong conjugation. When intramolecular charge transfer was investigated, it was discovered that 3,6-carbazole had a better capacity to give electrons than 2,7-carbazole. These dyes' projected orbital energy levels indicate that excited dyes might successfully decrease by electrolyte while oxidized dyes could successfully inject electrons into semiconductor conduction bands. The study investigated the suitability of different dyes for use in dye-sensitized solar cells (DSSCs) and found that the M2 dye, which contains a thio group as the terminal electron donor, exhibited the most promising optoelectronic properties. In particular, M2 had a narrow energy gap, superior optical qualities, optimal FMO energy levels, the lowest total value, and greater GInject and GReg values compared to the other dyes tested. These factors contributed to M2's superior photosensitizing performance, suggesting that using M2 in DSSCs may lead to higher optoelectronic characteristics and total energy conversion efficiency compared to using other dyes.

Synthesis and Determination of Cerium(IV)-Reducing Antioxidant Capacity (CERAC) Assay of Some New Anthraquinones

Novel anthraquinone-based cyclic antioxidants containing amino, thio and oxo groups were synthesized and their antioxidant capacity was determined by using the cerium(IV)-reducing antioxidant capacity (CERAC) assay. 1H, 13C NMR, FTIR-spectroscopy and ESI (Electrospray Ionization) mass spectrometry were used for the characterization of anthraquinone derivatives exhibiting CERAC antioxidant capacity. This study is of great importance, because the antioxidant capacity of anthraquinone compounds was analyzed for the first time by the CERAC method and CERAC-Trolox equivalent antioxidant capacity (TEAC) values were higher than that for Trolox. It should also be noted that, since all synthesized anthraquinone derivatives have the potential to find applications in terms of their biological properties due to their sulfur and nitrogen content, they will make an important contribution to the literature.

Modular Synthesis of ortho‐Thiolated Aryl Esters Enabled with Thiocarbonate through Catellani Strategy

AbstractHerein, we report a palladium/norbornene/copper co‐catalyzed single‐step approach that merges selective ortho C−H bond esterification with ipso thiolation for construction of synthetically versatile 2‐arylthio aryl esters under exceptionally mild conditions. Importantly, this process proceeded in a highly efficient manner, allowing alkoxycarbonyl and thio groups to be installed into one aryl iodides simultaneously by harnessing thiocarbonate as bifunctional reagent. The method has been demonstrated to accommodate good functionalities and features broad substrate scope.

How far the chemistry of self-assembled monolayers on gold surfaces affects their work function?

Self-assembled monolayers composed of various long-chain aliphatic molecules and different tail functional groups have been synthesized on the Au(111) surface and characterized by Kelvin probe force microscopy and ultraviolet photoelectron spectroscopy. Carboxy, amino, thio and methyl terminal groups have been considered in the design of self-assembled monolayers with different aliphatic chain lengths (from C6 to C16). Work function measurements by Kelvin probe force microscopy have been carried out under a controlled and room atmosphere. Remarkably, a reduction of the relative humidity from 40% to 3% has induced a work function shift of up to 0.3 eV. As expected, the changes of the chain length of the aliphatic moiety and of the tail group have a significant impact on the tuning of the measured work function (3.90 eV for dodecanethiol versus 4.57 eV for mercaptohexadecylamine). Surprisingly, the change of the net dipole moment of the tail group (sign and amplitude) does not dominate the work function variations. In contrast, the change of the chain length and the possibility of the tail group to form a complex hydrogen bond network between molecules lead to significant modulations of the work function. In order to interpret these original findings, density functional theory models of equivalent self-assembled monolayers adsorbed on the Au(111) surface have been developed at an unprecedented level of description with large supercells including simultaneously 27 co-adsorbed molecules and weak van der Waals interactions between them. Such large systems have allowed the theoretical modeling of complex hydrogen bond networks between molecules when possible (carboxy tail group). The comparison between computed and measured work functions shows a striking agreement, thus allowing the disentanglement of the previously mentioned competing effects. This consistency between experiment and theory will help in designing the electronic properties of self-assembled monolayers in the context of molecular electronics and organic transistors.

Photoredox-Promoted Selective Synthesis of C-5 Thiolated 2-Aminothiazoles from Terminal Alkynes.

A mild photoredox approach enabling the first one-step synthesis of thiolated 2-aminothiazoles has been reported. Notably, the incorporation of thio group on electron-rich heteroarenes such as aminothiazoles via conventional nucleophilic aromatic substitution (SNAr) presents a significant challenge owing to polarity mismatch. Herein, we present a remarkable site-selective installation of thio group at the C-5 position of the electron-rich aminothiazole skeleton and successfully used them for the postfunctionalization of drugs and natural products.

Theoretical vibrational spectroscopy (FT-IR), PED and DFT calculations of chromones and thiochromones

Chromones are heterocyclic compounds having a benzoannelated γ-pyrone ring and recognized as privileged structures and useful templates for the design of novel compounds. For the first time, this protocol presents a combined experimental and theoretical studies aiming at the vibrational properties and density functional theory (DFT) calculations of chromone and thiochromone analogs. The calculated HOMO and LUMO energies illustrate that charge transfers within the molecule. The effects on these energy gaps due to the substitution of different functional groups were investigated. The molecular geometries calculated using DFT was compared with available experimental data. The FT-IR spectra of the title compounds were recorded in the region 4000-400 cm−1. The vibrational spectra calculated at the B3LYP/6-31G(d,p) level were compared with the experimental spectral data, and thus each vibrational frequency was assigned on the basis of potential energy distribution (PED). The comparative experimental and theoretical 1H and 13C-NMR analysis of representative compounds 1d and 2d was also carried out to evaluate the effect of corresponding oxo and thio groups on the chemical shift values. The structural and spectral results obtained from DFT are in good agreement with the experimental data.

Surface modification and characterization of waste derived carbon particles to reinforce photo-cured shape memory composites.

Carbon fillers have been a source of inspiration to accommodate a range of surface chemistries for different applications. In this study different surface chemistries have been compared for shape memory effect on polymeric composites. Sugar industry waste (fly ash) has been utilized to prepare carbon particles named FCB. Surface modification of FCB has been done in two steps, oxidation and thiolation, respectively. In the first step, different reagents have been used to anchor the surface of FCB with oxygenated functionalities. In the second step, oxygenated FCB has been treated with a thiolating agent to covalently link thio groups on its surface. Polymeric composites have been photo cured with both types of particles, separately. A thermal actuation study has been carried out to check the shape recovery behavior of the composites. A quick shape recovery has been observed for thiolated FCB composites, due to thio linkages in the polymeric network. Samples have been characterized by scanning electron microscopy (SEM), attenuated total reflectance (ATR), dynamic light scattering (DLS), thermal gravimetric analysis (TGA), pH, conductivity, acid content particle dispersion, and composite gel content.

Flow dearomatization of electron-poor 3-fluoromethylthioindoles by 1,3-dipolar cycloaddition

Indoles substituted by electron-depleted thio groups at positions 1 and 3 react as C2 = C3 dipolarophiles with an electron-rich azomethine ylide dipole under flow conditions. The dearomatizing (3 + 2) cycloadditions readily occur to afford the corresponding fluorinated 3D-pyrrolidinoindolines bearing a tetrasusbtituted carbon centre at the ring junction.

Photoinduced selective hydrophosphinylation of allylic compounds with diphenylphosphine oxide leading to γ-functionalized P-ligand precursors

A series of bifunctional phosphine compounds promising as γ-functionalized phosphine ligand precursors are conveniently synthesized by the radical addition of diphenylphosphine oxide (Ph2P(O)H) to allylic compounds under photoirradiation. The photoinduced addition proceeds regioselectively in an anti-Markovnikov manner, and phosphines having hydroxy, alkoxy, aryloxy, acyloxy, and thio groups at the γ-position can be prepared by simple operation. Interestingly, novel continuous addition of Ph2P(O)H to two molecules of allylic ethers and related compounds is also observed, although their yields are moderate. The substituent and steric effects of the allylic substituents on the radical addition are discussed in detail.

An electrochemiluminescence sensor of magnetic glycosyl-imprinted microspheres based on multi-probe signal amplification for CD44v6 determination

A CD44v6 detection method was developed by using glycosyl-imprinted technique and enhanced with multi-probe signal amplification. Oligomeric hyaluronic acid was used as the template molecule, which was prepared by the cleavage of polyhyaluronic acid using hyaluronidase. Mercaptophenylboronic acid was self-assembled on the surface of core-shell [email protected]3O4 magnetic microspheres through the covalent interaction between its thio group and Au. Then oligomeric hyaluronic acid (<10 kDa) was linked on [email protected]3O4 via the formation of a cyclic ester between boronic acid and the ortho-dihydroxy group of oligomeric hyaluronic acid. By using oligomeric hyaluronic acid as a template and p-aminophenylboronic acid (p-APBA) as the functional monomer, boronate affinity glycosyl-imprinted polymer films were prepared on [email protected]3O4 by chemical polymerization. The magnetic glycosyl-imprinted polymer microspheres (MGIP) were attached on the surface of the magnetron-controlled glassy carbon electrode (MGCE) as the recognition component rebinding for the template, and CD44v6 was specifically recognized by the binding of the imprinted cavities to the oligomeric hyaluronic acid. The boronic acid functionalized tris-(2,2’-bipyridyl) ruthenium (II) (Ru(bpy)3-BO3) was used as a molecular probe to label the adsorbed oligomeric hyaluronic acid of CD44v6. With the aid of the multiply captured Ru(bpy)32+ probes on CD44v6 and the high luminescence efficiency of Ru(bpy)32+, the electrochemiluminescence response of the sensor exhibits a high sensitivity for CD44v6 determination with a detection limit of 0.08 ng/L. The method was applied in the assay of CD44v6 in serum samples.

Inhibition of Amyloid Fibrillation of HEWL by 4-Methylcoumarin and 4-Methylthiocoumarin Derivatives.

Several human diseases like Parkinson's, Alzheimer's disease, and systemic amyloidosis are associated with the misfolding and aggregation of protein molecules. The present study demonstrated the comparison of 4-methyl coumarin and 4-methylthiocoumarin derivative for their anti-amyloidogenic and disaggregation activities. The hen egg-white lysozyme is used as a model system to study protein aggregation and disaggregation under in vitro conditions. Techniques used in the study were Thioflavin T fluorescence assay, intrinsic fluorescence assay, circular dichroism, transmission electron microscopy, and molecular dynamics. Fifteen compounds were screened for their anti-amyloidogenic and disaggregation potential. Six compounds significantly inhibited the fibril formation, whereas ten compounds showed disaggregation property of pre-formed fibrils. Under in vitro conditions, the compound C3 and C7 showed significant inhibition of fibril formation in a concentration-dependent manner as compared to control. C3 and C7 demonstrated 93% and 76% inhibition of fibril formation, respectively. Furthermore, C3 and C7 exhibited 83% and 76% disaggregation activity, respectively, of pre-formed HEWL fibrils at their highest concentration. These anti-amyloidogenic and disaggregation potential of C3 and C7 were validated by intrinsic fluorescence, CD, molecular dynamics, and TEM study. 4-methylthiocoumarins derivatives have shown better anti-amyloidogenic activity as compared to 4-methylcoumarin derivatives for both amyloid formation as well as disaggregation of preformed amyloid fibrils. Structurally, the derivatives of 4-methylthiocoumarins (C3 and C7) contain thio group on 2nd position that might be responsible for anti-amyloidogenic activity as compared to 4- methylcoumarin derivatives (C2 and C4). C3 and C7 are novel 4-methylthiocoumarin derivatives that can be used as a lead for alleviation and symptoms associated with protein aggregation disorders.

Adsorption of heavy metals by l-cysteine intercalated layered double hydroxide: Kinetic, isothermal and mechanistic studies

To understand the interaction mechanisms between heavy metals and functional groups modified nanomaterials, the l-cysteine (Cys) intercalated MgAl-layered double hydroxide (MgAl-Cys-LDH) was designed by a facile co-precipitation method and used to remove Cu(II), Pb(II) and Cd(II) in water solutions. The XRD, FTIR, SEM, TEM, EDS and XPS characterization analyses proved the carboxyl, thio and amido groups were successfully introduced into MgAl-LDH. The possible mechanisms were analyzed by the XPS and XRD spectra and involved the precipitation of metal hydroxides or sulfides, surface complexation with abundant surface groups, and the isomorphic substitution of Mg(II). The adsorption kinetics and isotherms data of Cu(II), Pb(II) and Cd(II) on MgAl-Cys-LDH were well described by the pseudo-second-order kinetic equation and the Langmuir model. The influence factors such as initial solution pH of heavy metals, dosage of MgAl-Cys-LDH, adsorption time and various types of water were investigated, and the results suggested that MgAl-Cys-LDH had potential applications in real wastewater treatment containing heavy metals.

Influence of Perinatal Polychlorinated Biphenyl or Thiouracil on Dopamine Function

Objective: Dopamine function is sensitive to toxin exposure. The environmental toxin polychlorinated biphenyl (PCB) alters dopamine physiology in several, harmful ways. Intermediary signals include thyroid hormones as PCB exposure alters thyroid function leading to changes in dopamine neurochemistry. To compare PCB and thyroid alterations directly, we exposed rats perinatally to either PCB (25 ppm) or thiouracil (THIO; 0.625%) from gestational day 1 to separation from the dam at postnatal day (PND) 25 and examined a set of tests sensitive to dopamine function. Methods: We measured behaviors including prepulse inhibition (PPI) of the acoustic startle response (ASR) in adulthood (60-90 PND) and ultrasonic vocalizations (USVs) during pup and adult periods. Dopamine levels in striatum were estimated using tyrosine hydroxylase immunohistochemistry and thyroid hormone levels were assayed in adulthood. Results: Animals exposed to thiouracil had significantly elevated startle response and impaired PPI relative to controls and PCB exposed animals. This group also had significant reductions in both USV emission during PPI and tyrosine hydroxylase staining within striatum. Conversely, PCB exposure during the perinatal period did not lead to alterations in gating or dopamine levels in adulthood. Similar to previous studies using perinatal exposure to PCB or THIO, thyroid hormone levels were unchanged (THIO group) relative to controls or actually increased (PCB group) by adulthood. Conclusion: The findings support an important role for thyroid function in dopamine-dependent behaviors. Results suggest PCB exposure leads to different outcomes in comparison to direct thyroid manipulations suggesting PCB exposure has distinct mechanisms of developmental hormone dysfunction and potential compensatory changes in response to endocrine disruption.

Interface properties and electronic structures of aromatic molecules with anhydride and thio-functional groups on Ag (111) and Au (111) substrates**Project supported by the National Natural Science Foundation of China (Grant Nos. 51471185 and 51325204), the National Key Research and Development Program of China (Grant No. 2016YFJC020013), and the National Supercomputing Center in Tianjin.

First-principles calculations for several aromatic molecules with anhydride and thio groups on Ag (111) and Au (111) reveal that the self-assembly structures and the interface properties are mainly determined by the functional groups of aromatic molecules. Detailed investigations of the electronic structures show that the electrons in molecular backbone are redistributed and charge transfer occurs through the bond between the metal and the functional groups after these molecules have been deposited on a metal substrate. The interaction between Ag (111) (or Au (111)) and aromatic molecules with anhydride functional groups strengthens the π bonds in the molecular backbone, while that between Ag (111) (or Au (111)) and aromatic molecules with sulfur weakens the π bonds. However, the intrinsic electronic structures of the molecules are mostly conserved. The large-sized aromatic backbone has less influence on the nature of electronic structures than the small-sized one, either at the interface or at the molecules. These results are useful to build the good metal–molecule contact in molecule-based devices.

Extremely Rapid and Specific Metabolic Labelling of RNA In Vivo with 4-Thiouracil (Ers4tU).

The nucleotide analogue, 4-thiouracil (4tU), is readily taken up by cells and incorporated into RNA as it is transcribed in vivo, allowing isolation of the RNA produced during a brief period of labelling. This is done by attaching a biotin moiety to the incorporated thio group and affinity purifying, using streptavidin coated beads. Achieving a good yield of pure, newly synthesized RNA that is free of pre-existing RNA makes shorter labelling times possible and permits increased temporal resolution in kinetic studies. This is a protocol for very specific, high yield purification of newly synthesized RNA. The protocol presented here describes how RNA is extracted from the yeast Saccharomyces cerevisiae. However, the protocol for purification of thiolated RNA from total RNA should be effective using RNA from any organism once it has been extracted from the cells. The purified RNA is suitable for analysis by many widely used techniques, such as reverse transcriptase-qPCR, RNA-seq and SLAM-seq. The specificity, sensitivity and flexibility of this technique allow unparalleled insights into RNA metabolism.

Some new NH-, NH,S-, S,S- and NH,NH- substituted 1,4-naphtho(benzo)quinones

The synthesis of new NH- and NH,S- substituted 1,4-naphthoquinones and NH-, NH,NH- and S,S- substituted 1,4-benzoquinones have been achieved (4, 5, 7, 10a, 10 b, 10c, 11c, 14, 15, 18). Among them, compounds 4, 5, 7 and 10a, 10 b, 10c include the monoamino-1,4-naphthoquinone moiety and (2,5-bis)amino-1,4-benzoquinone moiety, respectively. Compound 18 has two different thio groups (-S-C6H3-(CH3)2 and -S-CH2-CO-OCH3) in the 2,6-position on the 1,4-benzoquinone skeleton. Compounds 14 and 15 have mono- and bis- NH-substituted-1,4-benzoquinone structures, including a methyl group on the benzoquinone moiety. Structural elucidation of new synthesized compounds was carried out by using elemental analysis and 1H NMR, 13C NMR, FTIR spectrocopies and mass spectrometry (ESI-MS) techniques.

Palladium-Catalyzed C(sp2)−H Olefination/Annulation Cascades of Aryl Carboxamides Assisted by N,S-Bidentate Auxiliary

A palladium(II)-catalyzed olefination/annulation of aryl carboxamides, assisted by an N, S-bidentate auxiliary, with methyl acrylate is described. Various carboxamides with a number of functional groups were compatible with this reaction to afford, regioselectively and in moderate yield, (E)-3-methyleneisoindolin-1-one derivatives bearing an alkyl(aryl)thio group.