Thiocarbonyl Research Articles

Unveiling [3 + 2] cycloaddition reactions of diphenyl diazomethane to thiobenzophenone and cycloaliphatic thioketones in the light of molecular electron density theory

The reactivity, regiochemistry and substituent effects observed in the [3 + 2] cycloaddition (32CA) reactions of diphenyldiazomethane (PDM) with thiobenzophenone and a series of cycloaliphatic thioketones (TKs) have been studied within the molecular electron density theory at the ωB97XD/6-311G(d,p) computational level. The cycloaliphatic TK series shows remarkable substituent effects, changing from a non-polar 32CA reaction to a highly polar one, with the electron density flowing from PDM to the corresponding TK in a reaction classified as a forward electron density flux (FEDF). These 32CA reactions follow a one-step mechanism through earlier asynchronous transition state structures in which the formation of the two new single bonds has not yet begun, and the energetically predicted regiochemistry towards the generation of 1,3,4-thiadiazole is in complete agreement with the experimental outcome.

Potentiating sorafenib efficacy against hepatocellular carcinoma via a carrier-free nanomedicine of artesunate prodrug

Sorafenib is a first-line drug for liver cancer treatment, but its clinical efficacy is still limited by drawbacks such as drug tolerance, toxic effects, and low bioavailability. Therefore, it is urgent to find efficient ways to synergize sorafenib with other agents and increase its bioavailability in order to enhance its clinical efficacy. Herein, we report the successful development of a carrier-free nanoplatform of an artesunate prodrug to potentiate the efficacy of sorafenib against hepatocellular carcinoma. The artesunate prodrug was synthesized by conjugating artesunate and linoleic acid through a thioketone (TK) bond. This prodrug can self-assemble in an aqueous solution via a one-step precipitation method. Furthermore, the inclusion of sorafenib during the self-assembly process results in a carrier-free artesunate/sorafenib mixed nanomedicine (SA@NPs) with a uniform and stable particle size. In addition, SA@NPs possess ROS-responsive drug-releasing ability by breaking up thioketone bonds under high H2O2 levels in tumors. The synergistic anticancer effects of SA@NPs have been demonstrated both in vivo and in vitro. SA@NPs can achieve significantly enhanced synergetic ferroptosis of tumor cells and show potentiated sorafenib efficacy against hepatocellular carcinoma. Moreover, SA@NPs have a tumor inhibition rate of 84.2%, which is 1.63-, 4.22-, and 1.29-fold higher than that in the experimental groups treated with free sorafenib, artesunate, and the simplified combined medication of sorafenib/artesunate, respectively. Overall, this work presents a significant advancement in the clinical chemotherapy of liver cancer and may pave the way for promising developments in the compatibility and clinical combination application of traditional Chinese medicine.

Stimulus-responsive tumor supramolecular nanotherapeutic system based on indocyanine green

Indocyanine green (ICG), a clinical near-infrared fluorescent probe, has the potential to be used as an integrated diagnostic and therapeutic agent for tumors. In this study, ICG-COOH-TK was obtained by connecting ICG molecules through stimulus-responsive thioketone (TK) bond, which can self-assemble into nanoparticles in water. Under 808 nm near-infrared light irradiation, the molecule exhibited excellent photothermal conversion efficiency, as well as better photostability and in vivo circulation stability than free ICG. The nanoparticle can respond to reactive oxygen species (ROS) overexpression in the tumor microenvironment and release ICG upon disassembly, resulting in significantly enhanced fluorescence emission at the tumor. In vitro cell experiments demonstrated excellent biocompatibility and photothermal killing effect on cancer cells, indicating that this molecule can serve as a diagnostic and therapeutic agent for fluorescence-guided tumor photothermal therapy.

Poly (N-Vinyl caprolactam), a thermal responsive support with tunable phase transition temperature for catalyst

Titanium dioxide (TiO2) nanoparticle is one of the most widely used photocatalyst and adsorbent. Post treatment removal of the nanoparticle is an expensive and difficult task. Poly N-vinyl caprolactam (PNVCL) undergo phase transition at molecular weight dependent temperature. Up to now immobilize TiO2 nanoparticle with PNVCL via controlled radical polymerization has not been reported. In this work, surface initiate RAFT polymerization of PNVCL is investigated. Benzyl sulfanyl thio carbonyl sulfanyl propionic acid (BPA) was used as chain transfer agent and covalently bonded to the nanoparticle. The obtained TiO2-PNVCL was tested for photocatalysis and metal ion adsorption. Results indicated that molecular weight distribution of PNVCL was narrowed down to 1.37 in the presence of BPA; LCST of PNVCL was tuned from 36 to 41 °C; RAFT polymerization of PNVCL was successfully initiated from TiO2 surface; the graft percentage was controlled by change feed ratio. TiO2-PNVCL suspension was stable at atmospheric temperture, and precipitated in 10 s upon heating. TiO2-PNVCL showed high adsorption capacity to Mn2+ (16.4 mg/g) and Cr6+ (9.7 mg/g) ions. Photocatalytic activity of TiO2-PNVCL was switchable by changing temperature; the degradation of Rhodamine B was 68.0% at 25 °C and 7.7% at 40 °C in 3 h period.

Thia-Diels-Alder reactions of hetaryl thioketones with non-activated 1,3-dienes

Abstract Dihetaryl thioketones substituted with thiophen-2-yl and seleophen-2-yl rings react as superdienophilic reagents with non-activated 1,3-dienes such as 2,3-dimethylbuta-1,3-diene, cyclopentadiene and mixtures of isomeric hexa-2,4-dienes to produce the expected 2 H -thiopyrans in good to excellent yields. In the latter case, the corresponding cis -3,6-dihydro-3,6-dimethyl-2,2-dihetaryl-2 H -thiopyrans are formed as the sole products in a stereoconvergent thia-Diels-Alder reaction. A step-wise mechanism via delocalized intermediate diradicals is postulated to rationalize the observed reaction course. Treatment of 3,6-dihydro-4,5-dimethyl-2,2-di(thien-2-yl)-2 H -thiopyran with excess m CPBA at room temperature leads to the oxidation of both the C=C bond and the sulfur atom in the six-membered ring.

ChemInform Abstract: The Dimerization of Thiophosgene and Trichlorothioacetyl Chloride S‐Imides — Head‐to‐Head and/or Head‐to‐Tail?

AbstractReview: 31 refs.

The dimerization of thiophosgene and trichlorothioacetyl chloride S-imides – Head-to-head and/or head-to-tail?

GRAPHICAL ABSTRACT

ChemInform Abstract: 1,3‐Dipolar Cycloadditions of Fluorinated Nitrones with Thioketones.

AbstractReadily available fluorinated nitrones (IV) and (XIV) are used in 1,3‐dipolar cycloadditions with thioketones affording 1,4,2 oxathiazolidines in a regioselective manner.

Thermal [2+2]-Cycloadditions of Diphenylketene with Aryl- and Hetaryl-Substituted Thioketones

Thermal [2+2]-Cycloadditions of Diphenylketene with Aryl- and Hetaryl-Substituted Thioketones

Ab Initio, DFT and semi-empirical studies on interactions of phosphoryl, carbonyl, imino and thiocarbonyl ligands with the li+ cation: affinity and associated parameters

+para uma serie de ligantes fosforila, carbonila, imino e tiocarbonila substituidos na posicao para de um anel aromatico foi calculada com os metodos ab initio MP2/6-311+G(d,p), DFT B3LYP/6-311+G(d,p) e semi-empirico PM6. Cada serie de ligante e constituida pelos seguintes grupos substituidos na posicao para: NH 2 , OCH 3 , CH 3 , H, Cl, CN and NO 2 . A entalpia de interacao foi calculada para quantificar a afinidade dos ligantes para o cation Li + . Parâmetros geometricos e eletronicos foram correlacionados com a forca da interacao metal-ligante. A natureza eletronica dos grupos substituintes e o principal parâmetro que modula a intensidade da ligacao metal-ligante. Grupos doadores de eletrons tornam a entalpia de interacao mais exotermica, enquanto grupos aceptores de eletrons tornam a entalpia de interacao menos exotermica. Analise da decomposicao da energia mostra que os grupos substituintes modulam a intensidade da componente eletrostatica da interacao sem afetar a componente covalente. The affinity of the Li + cation for a set of para-substituted phosphoryl, carbonyl, imino and thiocarbonyl ligands was calculated with the ab initio MP2/6-311+G(d,p), DFT B3LYP/6311+G(d,p) and semi-empirical PM6 methods. Each set of ligand is constituted by the following para-substituted groups: NH 2 , OCH 3 , CH 3 , H, Cl, CN and NO 2 . The interaction enthalpy was calculated to quantify the affinity of the ligands for the Li + cation. Geometric and electronic parameters were correlated with the strength of the metal-ligand interaction. The electronic nature of the para-substituted group is the main parameter that modulates the intensity of the metalligand binding energy. Electron donor groups make the interaction enthalpy more exothermic, whereas electron acceptor groups make the interaction enthalpy less exothermic. The energy decomposition analysis shows that the para-substituted groups modulate the intensity of the electrostatic component of the interaction without affecting the covalent component.

Thiolated tRNAs of Trypanosoma brucei Are Imported into Mitochondria and Dethiolated after Import

All mitochondrial tRNAs in Trypanosoma brucei derive from cytosolic tRNAs that are in part imported into mitochondria. Some trypanosomal tRNAs are thiolated in a compartment-specific manner. We have identified three proteins required for the thio modification of cytosolic tRNA(Gln), tRNA(Glu), and tRNA(Lys). RNA interference-mediated ablation of these proteins results in the cytosolic accumulation non-thio-modified tRNAs but does not increase their import. Moreover, in vitro import experiments showed that both thio-modified and non-thio-modified tRNA(Glu) can efficiently be imported into mitochondria. These results indicate that unlike previously suggested the cytosol-specific thio modifications do not function as antideterminants for mitochondrial tRNA import. Consistent with these results we showed by using inducible expression of a tagged tRNA(Glu) that it is mainly the thiolated form that is imported in vivo. Unexpectedly, the imported tRNA becomes dethiolated after import, which explains why the non-thiolated form is enriched in mitochondria. Finally, we have identified two genes required for thiolation of imported tRNA(Trp) whose wobble nucleotide is subject to mitochondrial C to U editing. Interestingly, down-regulation of thiolation resulted in an increase of edited tRNA(Trp) but did not affect growth.

Reaction of 1,2-Di(1-adamantyl)-2-thioxoethanone with Diazomethanes; 1,3- versus 1,5-Dipolar Electrocyclization of a Sterically Crowded Thiocarbonyl S-Methylide

The reaction of 1,2-di(1-adamantyl)-2-thioxoethanone (4c) with diazomethane and 2-diazopropane yielded 2-acylthiiranes 6a and 6b, respectively, and no 1,3-oxathioles of type 7 were formed. The reaction course is explained via [2+3]-cycloaddition, elimination of N2, and 1,3-dipolar electrocyclization of the intermediate acylsubstituted thiocarbonyl ylides of type 1. The failure of the competitive 1,5-dipolar electrocyclization is a result of the sterically unfavorable conformation of 1a.

Kinetic Studies on Nucleophilic Substitution Reactions of O-Aryl Thionobenzoates with Azide, Cyanide, and Hydroxide: Contrasting Reactivity and Mechanism

A kinetic study is reported for nucleophilic substitution reactions of O-Y-substituted phenyl thionobenzoates (1a-h) and O-4-nitrophenyl X-substituted thionobenzoates (2a-f) with N(3)(-) and CN(-) in 80 mol % H(2)O-20 mol % DMSO at 25.0 +/- 0.1 degrees C. The Brønsted-type plot for the reactions of 1a-h with N(3)(-) exhibits a downward curvature, i.e., the slope (beta(lg)) changes from -1.10 to -0.33 as the leaving group basicity decreases, indicating that the reactions proceed through a stepwise mechanism with a change in rate-determining step (RDS). In contrast, the Brønsted-type plot for the corresponding reactions with CN(-) is linear with a beta(lg) value of -0.33. This value is similar to that found previously for the reactions of 1a-h with OH(-) (-0.35). Besides, sigma(o) constants result in much better Hammett correlation than sigma(-) constants. Thus, the reactions with CN(-) and OH(-) have been concluded to proceed through a stepwise mechanism in which departure of the leaving group occurs after RDS. Reactions of 2a-f with N(3)(-) and CN(-) result in nonlinear Hammett plots. However, the Yukawa-Tsuno plots for the same reactions exhibit excellent linearity with r = 0.5 +/- 0.1, indicating that the nonlinear Hammett plots are not due to a change in RDS but are caused by ground state stabilization through resonance interactions between the electron-donating substituent and the thio carbonyl functionality. Calculation of the k(1) values (nucleophile attack as RDS) for the reactions of 1a-h with N(3)(-) indicates that azide ion is more reactive than OH(-) toward the thione esters, although the former is over 11 pK(a) units less basic than the latter. The high polarizability of N(3)(-) has been suggested to be responsible for its great affinity for the polarizable thione esters 1a-h and 2a-f.

Thioaldehyde and Thioketone S,S‐Dioxides and Oxyimides (Sulfenes and Derivatives)

AbstractFor Abstract see ChemInform Abstract in Full Text.

The Interplay of Thio(seleno)amide/Vinylogous Thio(seleno)amide “Resonance” and the Anisotropic Effect of Thiocarbonyl and Selenocarbonyl Functional Groups

Amino-substituted thio(seleno)acrylamides 1-4 were synthesized and their 1H and 13C NMR spectra assigned. Both the NMR data and the results of theoretical calculations at the ab initio level of theory were employed to elucidate the adopted structures of the compounds in terms of E/Z isomerism and s-cis/s-trans configuration. In the case of the asymmetrically N(Me)Ph-substituted compounds, ab initio GIAO-calculated ring current effects of the N-phenyl group were applied to successfully determine the preferred conformer bias. The restricted rotations about the two C-N partial double bonds were studied by DNMR and the barriers to rotation (DeltaG(c)++) determined at the coalescence temperatures, and these were discussed with respect to the structural differences between the compounds. The barriers to rotation were also calculated at the ab initio level of theory where the best results (R(2) = 0.8746) were obtained only with inclusion of the solvent at the SCIPCM-HF/6-31G* level of theory. The calculations also provided means of assessing structural influences which were not available due to inaccessible rotation barriers. By means of natural bond orbital (NBO) analysis of 1-4, the occupation numbers of nitrogen lone pairs and bonding/antibonding pi/pi orbitals were shown to quantitatively describe thio(seleno)amide/vinylogous thio(seleno)amide "resonance". Finally, the thio(seleno)carbonyl anisotropic effect was quantitatively calculated by the GIAO method and visualized by isochemical shielding surfaces (ICSS). Only marginal differences between the two anisotropic effects were calculated and are therefore of questionable utility for previous and future applications with respect to stereochemical assignments.

Oxidation State of Cobalt in the Coordination Compounds with N-(Thio)phosphorylated Acylamidophosphinates in Solutions

Acylamidophosphates and their thio analogs of the general formula RC(X)NHP(Y)R 2 form fairly stable chelates with a series of double-charged metal ions, in particular, with Co(II) ions [1, 2]. The presence of coordination-active (thio)carbonyl and (thio)phosphoryl groups and of a relatively acidic proton in the molecules of N-(thio)phosphorylated (thio)ureas and (thio)amides predetermines the possibility of chelating coordination of these ligands through the sulfur and oxygen donor centers with the formation of a stable six-membered chelate ring [3, 4]. The oxidation state of the central ion, in particular, of the cobalt ion, in such complexes previously seemed doubtless and hence was not evaluated.

Palladium‐Catalyzed Intramolecular O‐Arylation of Enolates: Application to Benzo[b]furan Synthesis.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Palladium-Catalyzed Intramolecular O-Arylation of Enolates: Application to Benzo[b]furan Synthesis

[reaction: see text] A catalyst generated from Pd2(dba)3 and the ligand DPEphos effects intramolecular C-O bond formation between enolates and aryl halides in the conversion of 1-(2-haloaryl)ketones directly into the corresponding benzofurans. Both cyclic and acyclic ketones are efficient substrates. Thio ketones can also be employed allowing the preparation of the corresponding benzothiophenes.

Generation and Trapping of α,β-Unsaturated Thioketones. Synthesis of 5,6-Dihydrothiopyranes

Generation and Trapping of α,β-Unsaturated Thioketones. Synthesis of 5,6-Dihydrothiopyranes

New Adventures with Thioketones and Related Compounds

New Adventures with Thioketones and Related Compounds