In the wake of the listing by the Stockholm Convention of PBDEs, an increasing number of “novel” flame retardants (NFRs) are being used in products. The properties that make for desirable flame ...retardants can also lead to negative health effects, long environmental residence times and an affinity for organic matrices. While NFRs are currently in use, little information is available regarding their physical–chemical properties and environmental fate. In this study, 94 halogenated and organophosphate NFRs were evaluated for their persistence and long-range transport potential. Physical–chemical properties (namely liquid sub-cooled vapor pressure Pl and solubility Sl, air–water (KAW), octanol–water (KOW), and octanol-air (KOA) partition coefficients) of the NFRs were predicted using three chemical property estimation tools: EPI Suite, SPARC and Absolv. Physical–chemical properties predicted using these tools were generally within 102–103 for compounds with molecular weight < 800 g/mol. Estimated physical–chemical properties of compounds with >800 g/mol, and/or the presence of a heteroatom and/or a polar functional group could deviate by up to 1012. According to the OECD POV and LRTP Screening Tool, up to 40% of the NFRs have a persistence and/or long range transport potential of medium to high level of concern and up to 60% have persistence and or long range transport potential similar to the PBDEs they are replacing. Long range transport potential could be underestimated by the OECD model since the model under-predicts long range transport potential of some organophosphate compounds.
•Physical–chemical properties, degradation rates of 94 flame retardants estimated.•Most estimates within 102–103, compounds >800 g/mol or polar could differ by 1012.•Using OECD Screening Model, 50% of FRs have high to medium persistence.•About half of FRs have LRTP potential, which is likely an underestimation.
Several groups of flame retardants (FRs) have entered the market in recent years as replacements for polybrominated diphenyl ethers (PBDEs), but little is known about their physical–chemical ...properties or their environmental transport and fate. Here we make best estimates of the physical–chemical properties and undertake evaluative modelling assessments (indoors and outdoors) for 35 so-called ‘novel’ and ‘emerging’ brominated flame retardants (BFRs) and 22 organophosphorus flame retardants (OPFRs). A QSPR (Quantitative Structure-Property Relationship) based technique is used to reduce uncertainty in physical–chemical properties and to aid property selection for modelling, but it is evident that more, high quality property data are required for improving future assessments. Evaluative modelling results show that many of the alternative FRs, mainly alternative BFRs and some of the halogenated OPFRs, behave similarly to the PBDEs both indoors and outdoors. These alternative FRs exhibit high overall persistence (Pov), long-range transport potential (LRTP) and POP-like behaviour and on that basis cannot be regarded as suitable replacements to PBDEs. A group of low molecular weight alternative BFRs and non-halogenated OPFRs show a potentially better environmental performance based on Pov and LRTP metrics. Results must be interpreted with caution though since there are significant uncertainties and limited data to allow for thorough model evaluation. Additional environmental parameters such as toxicity and bioaccumulative potential as well as functionality issues should be considered in an industrial substitution strategy.
•‘Best-estimates’ of physical–chemical properties of alternative FRs are proposed.•The ‘SMURF’ model and the OECD ‘The Tool’ are used to estimate the environmental fate.•Many alternative BFRs and HOPFRs have similar environmental fate to PBDEs.•Among alternative FRs, certain low MW NHOPFRs are the least persistent.•Needs for experimental data for model evaluation are highlighted.
Synthesis methods of 1,2,4-triazole-3-thiones: review Frolova, Yu. S.; Kaplaushenko, A. H.; Ihnatova, T. V. ...
Aktualʹnì pitannâ farmacevtičnoï ì medičnoï nauki ta praktiki,
06/2024, Volume:
17, Issue:
2
Journal Article
Peer reviewed
Open access
1,2,4-Triazole-containing compounds are unique heterocyclic compounds present in an array of pharmaceuticals and biologically important compounds used in drug-discovery studies against cancer cells, ...microbes, and various types of diseases in the human body. The aim of the study was to analyze in detail and combine the available literature materials to study the reactions associated with the formation of different classes of derivatives of 1,2,4-triazole-3-thione and to study their physical-chemical properties. Various innovative methods have been proposed and explored for synthesizing different classes of 1,2,4-triazole compounds, each with distinct applications and potential medicinal benefits. When analyzing the outcomes of studies aimed at obtaining new 1,2,4-triazole-3-thiones, it’s crucial to recognize the multiple stages involved in their synthesis. These stages typically include the esterification of carboxylic acids, hydrazinolysis, the formation of carbothioamides, and thiones through alkaline cyclization. Subsequently, reactions involving the S-function are conducted, leading to the formation of various classes of derivatives of 1,2,4-triazole. The study by a team of scientists introduced a novel method for synthesizing imidazolyl- and imidazole-1,2,4-triazoles, targeting the design of safer analgesic and anti-inflammatory agents. Moreover, researchers have successfully synthesized derivatives of 3-2-(5-thio-4-aryl-4H-1,2,4-triazole-3-yl)ethylquinoxalin-2(1H)-one, N-(3-thio-5-aryl-1,2,4triazole-4-yl)acylamides, 5-alkylthio-4-amino-3-(5,7-dimethyl-1,2,4-triazolo1,5-apyrimidine-2-thiomethyl)-1,2,4-triazole and 3-(5,7-dimethyl-1,2,4-triazolo1,5-apyrimidine-2-thiomethyl)-6-aryl-5,6-dihydrogen-1,2,4-triazole-3,4-b-1,3,4-thiadiazole, 5,5’-(alkyldiyl-bis(sulfandiyl))bis(N-(arylidene)-3-thiophen-2-ylmethyl)-4H-1,2,4-triazole-4-amines, 3-(arylsulfonyl)-4-phenyl-5-(3,4,5-trimethoxyphenyl)-4H-1,2,4-triazole, expanding the scope of 1,2,4-triazole-based, compounds with potential pharmacological activities. Furthermore, the synthesis of molecules containing two 1,2,4-triazole and two benzole rings has gained traction, offering new avenues for drug development. Mannich bases were synthesized from the corresponding thiones through a reaction with N-methylpiperazine or N-phenylpiperazine in dimethylformamide in the presence of formaldehyde. Additionally, the synthesis of salts derived from 1,2,4-triazole highlights its importance in pharmaceutical formulations, with studies focusing on both organic and inorganic salts for potential therapeutic applications. Conclusions. The analysis of the above-mentioned publications indicates that the search for new biologically active compounds among derivatives of 1,2,4-triazole-3-thiones is promising. Many 1,2,4-triazole-3-thiones exhibit a wide spectrum of biological activity with little toxicity.
Meta-analysis of clinical and laboratory studies to compare the performance of bulk-fill and conventional composite resins. It’s possible to conclude that the bulk-fill materials show better or ...similar performance to the conventional materials in clinical trials and laboratory studies, with the only exception being the higher shrinkage for bulk-fill composites with regular viscosity.
Display omitted
Objectives: The objective of this study was to perform a meta-analysis of clinical and laboratory studies to compare the performance of bulk-fill and conventional composite resins in terms of polymerization shrinkage, polymerization stress, cusp deflection, marginal quality, degree of conversion, microhardness, flexural strength, fracture strength and clinical performance. Data: One hundred three articles were included in this study, and the Peto method was used to compare the bulk-fill and conventional composites using the RevMan software. Sources: Searches were performed in the PubMed and Scopus databases. Study selection: Laboratory studies and randomized clinical trials comparing one of the previous detailed outcomes between bulk-fill and control composites were included. Conclusions: The bulk-fill composite resins showed less shrinkage, polymerization stress, cusp deflection and microhardness than conventional composites, while both materials presented a similar marginal quality, flexural strength and fracture strength. Also, bulk-fill materials with regular viscosity showed similar shrinkage. The conversion of bulk-fill materials with flowable consistency were similar to conventional composite resins with a thickness of up to 2mm and greater than conventional composites with a thickness greater than 2mm. Despite these in vitro differences, the clinical performance of bulk-fill and conventional composite resins was similar in randomized clinical trials, with one to ten years of follow up. In conclusion, the bulk-fill materials show better or similar performance to the conventional materials in clinical trials and laboratory studies in terms of volumetric shrinkage, polymerization stress, cusps deflection and marginal quality, with the only exception being the lower level of microhardness observed for bulk-fill composites with thickness up to 2mm.
•Verticle graphene growth from gaseous phase by PECVD.•Verticle orientation of graphene thin films depending on enhancement of plasma.•Fibrous shaped wall growth.•The graphitic structure of graphene ...thin films.
Vertical growth of graphene thin films was achieved on Si (100) substrate employing the sputtering technique. Physical-chemical properties of graphene thin films were examined at annealing temperatures from 500 to 780 °C and flowrate ratios of Ar and C2H2 working gases. The effect of temperature on the growth of graphene thin film, surface morphology, microstructure properties, and chemical state were investigated systematically. The formed graphene thin films were characterized and analyzed using different techniques such as Raman spectroscopy, field emission- and cross-sectional-scanning electron microscopy, transmission electron microscopy, and X-ray photoelectron spectroscopy. The graphene thin films on the Si substrate exhibited the better growth at the 700 °C and 30:15 (Ar:C2H2) flowrate ratio. Results of Raman spectroscopy showed that the graphene thin films have graphitic structure with crystallite size in the range of 10 to 23 nm. Surface morphology exhibited a wall-like structure with a sheet shape. The CS-SEM images indicated columnar growth of films perpendicular to the film plane. Analysis of the chemical states of C 1 s and O 1 s indicated chemical defects in the graphene thin films, evidenced by the presence of lattice oxygen and non-lattice oxygen ions.
Increased attention to thiadiazole and 1,2,4-triazole derivatives is determined by the extensive structural modification capabilities of heterocyclic system derivatives and their high pharmacological ...potential. Synthesis of new molecules containing, along with the 1,2,4-triazole moiety, thiadiazole is a promising trend in the field of biologically active substances.The purpose of this work was to study the reaction of nucleophilic substitution of 5-((5-amino-1,3,4-thiadiazole-2-ylthio)methyl)-1,2,4-triazole-3-thione with haloalkanes and to establish the structure of the obtained compounds. Materials and methods. Thiosemicarbazide was used as the key starting reagent. As a result of the reaction of the starting material with carbon disulfide in dimethylformamide, a thione was obtained which was further reacted with the iso-propyl ester of the chloroethane acid. The resulting ester was used for further transformations using hydrazinolysis reaction, nucleophilic addition, and intramolecular alkaline heterocyclization. The alkylderivatives of the obtained 5-((5-amino-1,3,4-thiadiazole-2-ylthio)methyl)-1,2,4-triazole-3-thione were synthesized by reaction with bromoalkanes, in an alcohol medium with an equimolecular amount of alkali. The structure of the synthesized compounds was confirmed by modern physical-chemical methods of analysis: 1H NMR spectroscopy, IR spectrophotometry, and elemental analysis data. The individuality of substances was established by means of high-performance liquid chromatography. Results. The method of obtaining 5-((5-amino-1,3,4-thiadiazole-2-ylthio)methyl)-1,2,4-triazole-3-thione has been optimized. The optimal conditions for the synthesis S-alkylderivatives of 5-((5-amino-1,3,4-thiadiazole-2-ylthio)methyl)-1,2,4-triazole-3-thione were determined. The structure of the synthesized compounds was established and their physical properties were investigated. Conclusions. A number of S-alkylderivatives of 5-((5-amino-1,3,4-thiadiazole-2-ylthio)methyl)-1,2,4-triazole-3-thione were obtained and their structure was confirmed by modern physical-chemical methods of analysis
Quality control of pharmaceutical and biopharmaceutical products, and verification of their safety and efficacy, depends on reliable measurements of critical quality attributes (CQAs). The task ...becomes particularly challenging for drug products and vaccines containing nanomaterials, where multiple complex CQAs must be identified and monitored. To reduce (i) the risk of measurement bias and (ii) the uncertainty in decision-making during product development, the combination of orthogonal and complementary analytical techniques are generally recommended by regulators. However, despite frequent reference to “orthogonal” and “complementary” in guidance documents, neither term is clearly defined. How does one determine if two analytical methods are orthogonal or complementary to one another? Definitions are needed to design a robust characterization strategy aligned to regulatory needs. Definitions for “orthogonal” and “complementary” are proposed that are compatible with existing metrological terminology and are applicable to complex measurement problems. Orthogonal methods target the quantitative evaluation of the true value of a product attribute to address unknown bias or interference. Complementary measurements include a broader scope of methods that reinforce each other to support a common decision. Examples of the application of these terms are presented, with a focus on measurement of physical properties of nano-enabled drug products, including liposomes and polymeric nanoparticles for cancer treatment, lipid-based nanoparticles (LNPs) and virus-like particles for nucleic acid delivery. The proposed framework represents a first step in advancing the assessment of the orthogonality and complementarity of two measurements and it can potentially serve as the basis for a future international standard. This framework may help product developers to implement more efficient product characterization strategies, accelerate the introduction of novel medicines to the clinic and be applicable to other therapeutics beyond nanomaterial-containing pharmaceuticals.
Display omitted
•Orthogonal or complementary measurements often recommended to reduce bias & uncertainty in nanopharmaceutical measurements•Definitions are lacking, thus the following are proposed and explained using using examples of nano-enabled drug products:•Orthogonal measurements: use different physical principles to measure the same property of the same sample•Orthogonal measurements aim to minimize method-specific biases and interferences of a measurement of a single attribute•Complementary measurements: corroborate each other to support the same decision
Display omitted
•Formic acid pretreatment is universal for depolymerization of biomass, whether woody or herbaceous biomass.•The enzymatic yield of poplar pretreated by formic acid can reach to ...94%•The delignification of poplar and herbaceous biomass by formic acid can reach above 77% at a mild temperature.
Formic acid pretreatment is a promising approach for fractionating biomass, and it has the advantages of efficient recycling and removal of hemicellulose and lignin. Biomass is one of the most plentiful resources on earth, yet its chemical structure differs significantly between woody and herbaceous biomass. The influence of formic acid pretreatment on the fractionation of woody and herbaceous biomasses, as well as changes in physical–chemical properties, was investigated in this study. The results indicated that formic acid is universal in the biorefinery of different biomass, however, herbaceous biomass had greater xylan and lignin removal than woody biomass (especially softwood). Formic acid pretreatment not only considerably improved the enzymatic efficiency of herbaceous biomass, but also had a good effect on the enzymatic efficiency of poplar. This study also found that the correlation between residual xylan content and enzymatic efficiency after pretreatment was much higher than that of lignin content.
Studies in the field of chemistry and pharmacology of derivatives of thiadiazole and 1,2,4-triazole are promising and relevant, which is associated with significant success in creating new drugs ...based on them. The combination of these heterocycles in one molecule makes it possible to increase the probability of detecting substances with a certain type of biological activity among the synthesized compounds.The aim of the work was to optimize the synthesis and study of the properties of S-alkyl derivatives of 5-R-4-phenyl-1,2,4-triazole-3-thione, containing a thiadiazole fragment in their structure, as well as the prediction of possible biological activity to rating the prospects of further studies in vivo and in vitro.Materials and methods. As a key starting reagent, 3-amino-1-phenylthiourea was used. Using the reaction between the starting reagent and carbon disulfide in DMF, thion was obtained, which was further alkylated with isopropyl chloroacetate. The resulting reaction product was then used for subsequent transformations using hydrazinolysis reactions, nucleophilic addition of phenylisothiocyanate and intramolecular alkaline heterocyclization. A number of S-derivatives of the obtained 4-phenyl-5-((5-phenylamino-1,3,4-thiadiazole-2-ylthio)methyl)-1,2,4-triazole-3-thione were synthesized by the interaction with haloalkanes in the presence of an equivalent amount of alkali in alcoholic medium. The structure of the obtained compounds was confirmed by elemental analysis, 1H NMR spectroscopy, and IR-spectrophotometry. The individuality of substances was established by high performance liquid chromatography. For the synthesized substances, an individual calculated screening was performed using the PASS Online® software product.Results. The procedure for preparing 4-phenyl-5-((5-phenylamino-1,3,4-thiadiazole-2-ylthio)methyl)-1,2,4-triazole-3-thione was optimized. The optimal synthesis conditions were determined S-alkylderivatives of 4-phenyl-5-((5-phenylamino-1,3,4-thiadiazole-2-ylthio)methyl)-1,2,4-triazole-3-thiol, the structure was established the obtained substances and their physical properties were studied. With the help of computer-assisted prediction Pass Online®, a promising direction for further studies of the biological activity of the target reaction products was determined.Conclusions. A series of S-alkylderivatives of 4-phenyl-5-((5-phenylamino-1,3,4-thiadiazole-2-ylthio)methyl)-1,2,4-triazole-3-thione were obtained, the structure of these compounds was confirmed by physical-chemical methods of analysis. At the next stages of the study, it would be planned to establish indicators of the antimicrobial activity of the synthesized substances.
PDF
