Tetraethylthiuram Disulphide Research Articles

Kinetic and structural details of urease inactivation by thiuram disulphides

This paper reports on the molecular details of the reactivity of urease, a nickel-dependent enzyme that catalyses the last step of organic nitrogen mineralization, with thiuram disulphides, a class of molecules known to inactivate the enzyme with high efficacy but for which the mechanism of action had not been yet established. IC50 values of tetramethylthiuram disulphide (TMTD or Thiram) and tetraethylthiuram disulphide (TETD or Disulfiram) in the low micromolar range were determined for plant and bacterial ureases. The X-ray crystal structure of Sporosarcina pasteurii urease inactivated by Thiram, determined at 1.68 Å resolution, revealed the presence of a covalent modification of the catalytically essential cysteine residue. This is located on the flexible flap that modulates the size of the active site channel and cavity. Formation of a Cys-S-S-C(S)-N(CH3)2 functionality responsible for enzyme inactivation was observed. Quantum-mechanical calculations carried out to rationalise the large reactivity of the active site cysteine support the view that a conserved histidine residue, adjacent to the cysteine in the active site flap, modulates the charge and electron density along the thiol SH bond by shifting electrons towards the sulphur atom and rendering the thiol proton more reactive. We speculate that this proton could be transferred to the nickel-coordinated urea amide group to yield a molecule of ammonia from the generated Curea-NH3+ functionality during catalysis.

Tetraethylthiuram disulphide alleviates pulmonary fibrosis through modulating transforming growth factor-β signalling

Idiopathic pulmonary fibrosis (IPF) induces significant morbidity and mortality, for which there are limited therapeutic options available. Here, we found that tetraethylthiuram disulphide (disulfiram, DSF), a derivative of thiuram, used in the treatment of alcohol abuse, has an inhibitory effect on bleomycin (BLM)-induced pulmonary fibrosis via the attenuation of the fibroblast-to-myofibroblast transition, migration, and proliferation of fibroblasts. Furthermore, DSF inhibited the activation of primary pulmonary fibroblasts and fibroblast cell line under transforming growth factor-β 1 (TGF-β1) challenge. Mechanistically, the anti-fibrotic effect of DSF on fibroblasts depends on the inhibition of TGF-β signalling. We further determined that DSF interrupts the interaction between SMAD3 and TGF-β receptor Ι (TBR Ι), and identified that DSF directly binds with SMAD3, in which Trp326, Thr330, and Cys332 of SMAD3 are critical binding sites for DSF. Collectively, our results reveal a powerful anti-fibrotic function of DSF in pulmonary fibrosis through the inhibition of TGF-β/SMAD signalling in pulmonary fibroblasts, indicating that DSF is a promising therapeutic candidate for IPF.

Inhibition potency of disulphides and trisulphides on various tumor cell lines growth

Tumor is one of the leading diseases of today. Chemotherapy and radiation therapy healing chances are limited, so some alternative methods are resorted to. Many papers indicated that garlic and organosulphur compounds diallyldisulphide (DADS) and diallyltrisulphide, which are main components of garlic decrease the cancer risk and inhibit the cell proliferation. In this paper inhibition potency of disulphides (DADS and its synthetic analogues) and trisulphides with different alkyl and phenyl substituents on growth of various tumor (Non-Small cell Lung Cancer, Colon cancer, CNS Cancer, Melanoma, Ovarian Cancer, Renal Cancer, Prostate Cancer, Breast Cancer, Leukemia) cell lines was investigated. Concentration of each compound (DADS, diethyl disulphide, dipropyl disulphide, diphenyl disulphide, tetraethylthiuram disulphide (TETUDS), dimetil trisulphide, dipropyl trisulphide and metilpropyl trisulphide (MPTS) was 10 µmol/L. It was found that DADS has an inhibitory effect on the growth of several cancer cell lines, but synthetic analogues TETUDS and MPTS exhibit stronger effect on certain cells lines. MPTS inhibits the growth of even 12 cell lines for more than 10%, especially leukemia cell line SR and NCI-H522 cell line of Non-Small cell Lung Cancer (reduction of growth for 24% and 47%, resp.). Trisulphide analogues exhibit little higher inhibitory effects in comparison to disulphide ones.

Effect of silver nanoparticle on the properties of poly(methyl methacrylate) nanocomposite network made by in situ photoiniferter-mediated photopolymerization

Here we report preparation and characterization of poly(methyl methacrylate)/silver nanoparticles (PMMA/AgNPs) nanocomposite networks prepared via in situ photoiniferter-mediated photopolymerization (in situ PMP) using tetraethylthiuram disulphide (TED) as photoiniferter and 2,2-dimethoxy-2-phenylacetophenone (DMPA) as photoinitiator. Photopolymerization was performed in the presence of allyl methacrylate, as crosslinking agent, and various amount of silver nanoparticles (AgNPs). AgNPs were synthesized via chemical reduction of silver nitrate with t-BuONa-activated sodium hydride in tetrahydrofuran. The degree of monomer conversion (DC%) during polymerization was followed quantitatively via Fourier transform infrared spectroscopy. DC% of nanocomposite networks slightly increased with AgNPs content. Moreover, differential scanning calorimetry results disclosed a decrease in glass transition temperature (T g) of the nanocomposite networks in comparison with the pure polymer network, suggesting the plasticizing effect of AgNPs. Swelling behaviour was also measured in water and ethanol/water (3/1, v/v) solution at 37 ± 1°C after 30 days. The enhanced swelling ratio for nanocomposite networks with increase in the AgNPs content suggested the potential role of AgNPs in photo-crosslinking reactions. The flexural strength and modulus values resulted from three-point bending method revealed an improvement in mechanical properties of the nanocomposites in comparison with pure PMMA networks. The mechanical behaviour observations were rationalized based on the field emission scanning electron microscopy micrographs from the fractured surfaces of the nanocomposite networks. Finally, thermogravimetric analysis showed that while the AgNPs catalyse the degradation in the early stages, they subsequently act as a retardant agent against thermal degradation.

The properties of SBS-modified asphalt binder in the presence of dithiodimorpholine and tetraethyl thiuram disulphide

Sulphur and its compounds are effective to be used as crosslinking agents for polymer-modified asphalt (PMA) binders to solve the separation of styrene–butadiene–styrene (SBS) triblock copolymer and asphalt binders. In this paper, the properties of SBS-modified asphalt binders were investigated after adding two kinds of disulphides, dithiodimorpholine (DTDM) and tetraethyl thiuram disulphide (TETD). It is clear to observe that the addition of DTDM and TETD strongly affects the properties of SBS-modified asphalt binders, such as the softening point, penetration, storage stability as well as the rheological properties. As both of them were added into the PMAs, their high-temperature property and storage stability were highly enhanced at proper content and ratio of DTDM and TETD, especially as the ratio of DTDM and TETD is 2:1 or 1:2. DTDM and TETD may have chemical reactions with SBS and asphalt binder, and network structure was likely to form. The mixtures of DTDM and TETD could be used as a favourable additive of PMA binders.

Effect of dithiodimorpholine and tetraethylthiuram disulphide on ageing properties of SBS-modified asphalts

Effect of additives dithiodimorpholine (denoted as D) and tetraethylthiuram disulphide (denoted as T) on high-temperature storage stabilities and thermal oxidative ageing performance of SBS-modified asphalt were studied. Considering cost and performance, the content and ratio of D:T should be 0.2% and 1:3, respectively, and the result was confirmed by dynamic shear rheological testing of the samples before and after ageing. Mixtures of SBS-modified asphalt with D and T were prepared by physical high-speed shearing. The thin film oven test was used for simulating thermal degradation during short-term ageing. The results show that appropriate content and ratio of additives D and T can improve anti-ageing properties of SBS-modified asphalts; moreover, the advance of high-temperature storage stabilities of the mixture was significant.

Complexes of tetraethylthiuram disulphide with group 12 metals: single-source precursor in metal sulphide nanoparticles’ synthesis

Six new complexes of Zn(II), Cd(II) and Hg(II) with sulphur containing ligand, tetraethylthiuram disulphide in 2:2 and 1:4 ratio have been synthesized. The resulting complexes have been characterized on the basis of molar conductance measurement, elemental analyses, FT-IR, 1H-NMR, and FAB/ESI-mass studies. The complexes were used as a single-source precursor for the synthesis of ZnS/CdS/HgS nanoparticles by their thermal decomposition in the presence of different surfactants. The precursor:surfactant ratio and temperature play an important role in determining the size of the nanoparticles. The size and morphology of nanoparticles have been ascertained by ultra violet–visible spectroscopy, X-ray diffraction measurements and transmission electron microscopy. Schiff bases, complexes and nanoparticles were tested for antibacterial activity and minimum inhibitory concentration values against Escherichia coli. The complexes were found more potent than the corresponding Schiff bases and nanoparticles.

In vitro inhibition of liver aldehyde dehydrogenase by tetraethylthiuram disulphide.

Journal Article IN VITRO INHIBITION OF LIVER ALDEHYDE DEHYDROGENASE BY TETRAETHYLTHIURAM DISULPHIDE Get access W Donald Graham W Donald Graham Food and Drug Laboratories, Department of National Health and Welfare, Ottawa, Canada Search for other works by this author on: Oxford Academic Google Scholar Journal of Pharmacy and Pharmacology, Volume 3, Issue 1, September 1951, Pages 160–168, https://doi.org/10.1111/j.2042-7158.1951.tb13056.x Published: 12 April 2011 Article history Received: 14 November 1950 Published: 12 April 2011

Factors affecting the potentiation of barbiturate action by tetraethylthiuram disulphide.

Factors affecting the potentiation of barbiturate action by tetraethylthiuram disulphide.

Synthesis of controlled polymeric cross-linked coatings via iniferter polymerisation in the presence of tetraethyl thiuram disulphide chain terminator

A “grafting from” approach has been used for controlled deposition of cross-linked polymers by living radical polymerisation. Borosilicate glass was modified with N, N-diethylaminodithiocarbamoylpropyl(trimethoxy)silane, in order to confine the iniferter reactive groups solely at its surface, then placed in solution with monomers and cross-linker. The polymerisation was initiated by UV irradiation. Formation of the cross-linked polymers was studied in terms of time course of the reaction, type of monomers incorporated and influence of oxygen. Grafted surfaces were characterised by AFM, FT-IR, ellipsometry and contact angle measurements. The ability to control the grafted layer improved dramatically when the chain terminator agent, N, N- N′, N′-tetraethyl thiuram disulphide (TED) was added. Upon irradiation TED increases the concentration of passive capping radicals and decreases the possibility of recombination of active macro-radicals, thus prolonging their lifetime. In the absence of TED the thickness of produced coatings was below 10 nm. TED added at different concentrations assisted in the formation of grafted layers of 10–130 nm thickness. Iniferter chemistry in the presence of TED can be used for growing nanometre-scale polymer layers on solid supports. It constitutes a robust general platform for controlled grafting and offer a general solution to address the needs of surface derivatisation in sensors technology.

Dual behavior of thiuram sulphide: Highly selective transport and ion-selective electrode for Ag(I) ions under two different conditions

Performance of tetraethylthiuram disulphide (TETDS) as a carrier of silver ion across a polymeric inclusion membrane has been studied. This compound is also used as an ionophore in coated-wire ion-selective electrode for silver ion determination. Fundamental parameters like ion carrier concentration in the membrane phase and thiosulphate concentration in strip phase were also studied to see their effect on the transport of silver ions. The efficiency of silver transport in the presence of some interfering ions was investigated. The coated-wire electrode gave a Nernstian behavior in the activity range 5 × 10 −6 to 1 × 10 −1 M. The ion-selective electrode exhibits high selectivity towards some alkali, alkaline earth and transition metal ions. The electrode was used as an indicator electrode in titrations of I −, Br − and Cl − with Ag + ion.

From Herbal Roots to Synthetic Medicines: A Historical Perspective

From Herbal Roots to Synthetic Medicines: A Historical Perspective

Cross‐reactivity between thiurams

Retesting with an allergen at a site with previous allergic contact dermatitis has been shown to enhance reactivity. It has been suggested that retesting with a cross-reactive allergen will also induce hyperreactivity. Concurrent sensitization to more than 1 thiuram is common, but whether this is due to concomitant primary sensitization or cross-reactivity is uncertain. The aim of this study was to investigate the use of retesting to distinguish between concomitant sensitization and cross-reactivity in the rubber chemicals tetraethylthiuram disulphide (TETD) and tetramethylthiuram disulphide (TMTD). There was a non-significant trend towards enhanced reactivity for both TETD and TMTD when testing in an area with previous allergic contact dermatitis due to TETD. Cross-reactivity between the 2 chemicals is likely, but a definite conclusion from this pilot study is not possible.

Mechanism of the polymerization ofn-butyl acrylate initiated byN,N-diethyldithiocarbamate derivatives. Part 2. Investigation of the reaction mechanism

The polymerization of n-butyl acrylate (BuAc) initiated with a model compound (butyl-2-(N,N-diethyldithiocarbamyl)propionate, RTC) has been investigated. The living character of this polymerization has been assessed and compared with those of styrene and methyl methacrylate. The small variation of Mn with yield is explained by the faster propagation than for styrene and methyl methacrylate, which leads to slow initiation and extensive transfer to the initiator. Predominant reversible termination (or deactivation) of the growing chains by the dithiocarbamyl radicals gives, however, polymers of functionality near to unity, which are photoinitiated at the same rate as RTC and reinitiate the polymerization of BuAc with a linear growth of the Mn up to 40% yield. This is better than was obtained with methyl methacrylate. Side reactions also take place leading to a decrease of functionality, to the formation of tetraethylthiuram disulphide and of carbon disulphide. Possible mechanisms are proposed for the secondary reactions. © 1998 SCI.

Mechanism of the polymerization of n-butyl acrylate initiated by N,N-diethyldithiocarbamate derivatives. Part 2. Investigation of the reaction mechanism

The polymerization of n-butyl acrylate (BuAc) initiated with a model compound (butyl-2-(N,N-diethyldithiocarbamyl)propionate, RTC) has been investigated. The living character of this polymerization has been assessed and compared with those of styrene and methyl methacrylate. The small variation of Mn with yield is explained by the faster propagation than for styrene and methyl methacrylate, which leads to slow initiation and extensive transfer to the initiator. Predominant reversible termination (or deactivation) of the growing chains by the dithiocarbamyl radicals gives, however, polymers of functionality near to unity, which are photoinitiated at the same rate as RTC and reinitiate the polymerization of BuAc with a linear growth of the Mn up to 40% yield. This is better than was obtained with methyl methacrylate. Side reactions also take place leading to a decrease of functionality, to the formation of tetraethylthiuram disulphide and of carbon disulphide. Possible mechanisms are proposed for the secondary reactions. © 1998 SCI.

Mechanism of the polymerization ofn-butyl acrylate initiated byN,N-diethyldithiocarbamate derivatives. Part 1. Photolysis of butyl-2-(N,N-diethyldithiocarbamyl)propionate and oligomerization of butyl acrylate

The photolysis of n-butyl-(N,N-diethyl dithiocarbamyl)propionate (RTC), an initiator for ‘living’ free radical polymerizations, has been investigated in order to elucidate the mechanism of these polymerizations. The photolysis yields tetraethylthiuram disulphide (TED), and its degradation products, butyl acrylate, butyl propionate and head-to-head dimer of butyl acrylate. These compounds result from reactions following the homolytic bond breaking of the carbon–sulphur bond of RTC, and correspond to termination reactions in the case of a polymerization. However, a functionalized head-to-tail dimer of butyl acrylate is also formed. Photolysis of RTC in the presence of a small amount of butyl acrylate, which mimics a polymerization process, leads mainly to the formation of functionalized oligomers of butyl acrylate. The change of the concentrations of these compounds with reaction time is an argument in favour of a possible reactivation of the functionalized oligomers. © 1998 SCI.

The prevention of nickel contact dermatitis. A review of the use of binding agents and barrier creams.

Chelating agents and other substances can be used to bind nickel or reduce its penetration through the skin, and hence to reduce the symptoms in subjects with nickel sensitivity. Topical usage is mostly described but, in some studies, chelating agents have been given systemically. The most effective ligand for nickel so far described is 5-chloro-7-iodoquinolin-8-ol. Although normally regarded as safe, its usage in some situations may be limited by concerns about its toxicity. Other ligands with demonstrable effect include ethylenediaminetetraacetic acid in various forms, diphenylglyoxime and dimethylglyoxime. Cation exchange resins can effectively bind nickel and work both in vitro and in vivo. Propylene glycol, petrolatum and lanolin reduce the absorption of nickel through the skin. Corticosteroids and cyclosporin work in nickel dermatitis by suppressing the immunological reaction rather than through an effect on nickel. Studies of the oral administration of ligands such as tetraethylthiuram disulphide have given conflicting results but the use of these agents is limited by hepatoxicity in any case. Some compounds offer potential for use in the prophylaxis of nickel dermatitis. Further work is required to develop the existing agents and to look at the use of novel combinations, such as that of a cation exchanger with a ligand.

What is the composition of the thiuram mix?

Oral administration of 63Ni2+ together with thiuram sulphides (tetramethylthiuram disulphide, tetraethylthiuram disulphide, tetrabutylthiuram disulphide, dipentamethylenethiuram monosulphide or dipentamethylenethiuram tetrasulphide) or sodium diethyldithiocarbamate resulted in highly increased levels of 63Ni2+ in several tissues of mice in comparison with animals given 63Ni2+ alone. Administration of these substances to pregnant animals induced increased levels of 63Ni2+ in the fetuses. The uptake of 63Ni2+ in the brains of both adults and fetuses was usually very markedly enhanced by these compounds — dipentamethylenethiuram monosulphide and tetraethylthiuram disulphide being the most efficient compounds in this respect. Determination of the chloroform/water partition coefficients for nickel in the presence of thiuram sulphides or sodium diethyldithiocarbamate showed that these compounds are able to form lipophilic complexes with the metal. A facilitated penetration through the cellular membranes of the lipophilic complexes between nickel and these substances can explain the effects on the fate of the nickel. However, the partition coefficient for nickel in presence of sodium diethyldithiocarbamate was much higher than for the thiuram sulphides, but in spite of that, the effect of sodium diethyldithiocarbamate on the disposition of 63Ni2+ in the mice was not more marked than for most of the thiuram sulphides. It has been shown that tetraethylthiuram disulphide undergoes a reductive fission in the gut to diethyldithiocarbamate, which is considered to be the active form of tetraethylthiuram disulphide. The marked effects on the disposition of the 63Ni2+ induced by the other thiuram sulphides examined in the present study suggest that a similar fission to chelating thiocarbamates will take place. However, the formation of lipophilic complexes with the original thiuram sulphides may contribute to the effects on the disposition of the 63Ni2+.

Effect of Tetraethylthiuramdisulphide and Diethyldithiocarbamate on Nickel Toxicokinetics in Mice

A new experimental pharmacokinetic model using the gamma-emitting isotope 57Ni for studying nickel toxicokinetics was employed in a recent investigation (Nielsen et al. 1993) in order to quantitatively study, for the first time, the effect of tetraethylthiuram disulphide (disulfiram, Antabuse, TTD) and sodium diethyldithiocarbamate (DDC) on whole-body retention and organ distribution of nickel in mice. TTD or its decomposition product DDC given orally by stomach tube shortly after oral administration of a low dose of nickel chloride labelled with 57Ni resulted in an approximately ten times higher whole-body retention of nickel compared to the retention in a control group exposed to nickel only. These chelators increased the whole-body retention of nickel also when given by intraperitoneal injection shortly after oral or intraperitoneal administration of nickel. Oral administration of a single dose of TTD or DDC rapidly after an oral dose of nickel chloride also resulted in extensive changes in the organ distribution of nickel, thus the nickel content in the brain was at least 700 times higher than in a control group given the same dose of nickel only. If DDC was given intraperitoneally after nickel given orally, the relative organ distribution of nickel to most organs was the same as if the chelator was given orally, though the contents of the liver and lungs were lower. That TTD and DDC resulted in a transport of nickel to the brain, is underlined by the fact that after 20 hr, approximately 15% and after 45-50 hr, 30% of the total body burden of Ni was found in the brain.(ABSTRACT TRUNCATED AT 250 WORDS)

The mechanism of the polymerization of n.butyl acrylate initiated with N, N-diethyl dithiocarbamate derivatives

The kinetics of the photo-initiated polymerization of n.butyl acrylate by p-xylylene bis-( N, N-diethyldithiocarbamate) have been investigated in order to check the living character of this polymerization initiated with an “iniferter”. The reaction shows some features of a living system viz. growth of the molecular weight during the reaction under chosen conditions (high [M]/[I] ratios) and preparation of block copolymers. This confirms the existence of a reversible termination reaction between the growing chains and the dithiocarbamyl radicals. However, evidence has been found for the intervention of side reactions (formation of tetraethylthiuram disulphide, and decrease of the functionality of the polymers during the polymerization), indicating that the polymerization is not strictly living.