Alternative Method For Synthesis Research Articles

Microwave Irradiated, Sodium Aluminate Supported and Zinc Catalyzed Suzuki-Miyaura Cross-Coupling Reaction on Fused Tricyclic Oxa-Aza-Quinolone: A Green Protocol

Alternative synthesis methods are need of the hour to provide easy protocol for synthesizing biologically active heterocyclic compounds. In this connection, this paper describes the development of a concise, convergent protocol for diversely substituted Suzuki–Miyaura cross-coupling reactions of heteroaryl bromides and boronic acids under microwave irradiation using Sodium aluminate (NaAlO2) as a solid support as well as base. According to my knowledge, this is the first report of the strategy that involves the use of zinc as a catalyst on fused tricyclic di-halo quinolones in a solvent-free condition using simple microwave irradiation. Earlier research from the same laboratory established a solid support assisted Suzuki–Miyaura cross-coupling reaction for forming C–C bonds under the influence of microwave irradiation. Therefore, sodium aluminate (NaAlO2) was attempted as a base and solid support instead of traditional mineral bases. Moreover, zinc was used as a catalyst replacing palladium. The new method is unique and effective due to its energy economy, procedural simplicity, and general applicability. Moreover, the use of Sodium aluminate (NaAlO2) is expected to extend this green-protocol and atom-friendly chemistry for the synthesis of varied heterocyclic compounds of interest.

Revisiting the Synthesis of Gibbsite, a Precursor for Li/Al LDH Synthesis and Its Use as a Support for Porphyrin Immobilization

In this work, some of the synthesis methods already reported for aluminum(III) hydroxide polymorphs with layered structure like gibbsite are revisited. Gibbsite was synthesized with high purity and yield by a simple route developed from modifications of a heating method proposed in the literature, making it possible to prepare gibbsite in regular glassware, avoiding the use of hydrothermal reactor and oven, as described in the literature. The proposed synthesis was conducted with a heating system under reflux conditions in a glass heating flask, using an oil bath, without the need for more sophisticated equipment. This is an accessible alternative method for crystalline gibbsite synthesis, with yield (76 wt.%). The obtained gibbsite was used as a precursor for the synthesis of a lithium/aluminum layered double hydroxide (LDH) from the intercalation method of Al(OH)3 in aqueous solution of lithium chloride. Gibbsite and the obtained LDH Li/Al were used for the immobilization of an anionic porphyrin with a loading on the order of 10-5 mol g-1 of solid, thus being alternative solid supports for catalytic species such as porphyrins.

Oxidation of Cyclohexane/Cyclohexanone Mixture with Oxygen as Alternative Method of Adipic Acid Synthesis

Herein, an alternative method for adipic acid (AA) synthesis of industrial importance has been reported. The proposed novel method involves the one-step, solvent-free oxidation of a cyclohexane/cyclohexanone (CH/CH=O) mixture, with a cheap oxidizing agent such as O2 or air under mild conditions in the presence of N-hydroxyphtalimide (NHPI) and transition metals as catalysts. It has been showed that CH/CH=O mixture under applied mild conditions oxidized faster than CH and CH=O separately. This was due to the greater oxidizability of CH=O compared to CH. The peroxyl radicals formed by CH=O oxidation initiated the oxidation of the less reactive CH. Additionally, CH=O increased the polarity of the reaction mixture, promoting the solubility of NHPI. The influence of type and amount of catalyst, cyclohexane to cyclohexanone ratio, temperature, time, type of oxidizing agent on the composition of CH/CH=O oxidation products have been reported.

Plastic and Waste Tire Pyrolysis Focused on Hydrogen Production—A Review

In this review, we compare hydrogen production from waste by pyrolysis and bioprocesses. In contrast, the pyrolysis feed was limited to plastic and tire waste unlikely to be utilized by biological decomposition methods. Recent risks of pyrolysis, such as pollutant emissions during the heat decomposition of polymers, and high energy demands were described and compared to thresholds of bioprocesses such as dark fermentation. Many pyrolysis reactors have been adapted for plastic pyrolysis after successful investigation experiences involving waste tires. Pyrolysis can transform these wastes into other petroleum products for reuse or for energy carriers, such as hydrogen. Plastic and tire pyrolysis is part of an alternative synthesis method for smart polymers, including semi-conductive polymers. Pyrolysis is less expensive than gasification and requires a lower energy demand, with lower emissions of hazardous pollutants. Short-time utilization of these wastes, without the emission of metals into the environment, can be solved using pyrolysis. Plastic wastes after pyrolysis produce up to 20 times more hydrogen than dark fermentation from 1 kg of waste. The research summarizes recent achievements in plastic and tire waste pyrolysis development.

TiO2-C nanocomposite synthesized via facile surfactant-assisted method as a part of less energy-consuming LED-based photocatalytic system for environmental applications

A novel facile method was used to incorporate carbon into the titania structure. An alternative synthesis method of carbon-doped TiO2 has been proposed by using a widely used and cheap surfactant. During the process, cetyltrimethylammonium bromide plays a dual role, as a morphology modifier and as a carbon source. The presented approach allows obtained TiO2-C nanostructures to be anatase nanocrystals with carbon being deposited either on the surface or between the TiO2 nanoparticles. The innovative nature of the research subject is related to the design of cheap LED solutions and facile synthesis of TiO2-C for use in novel energy-saving photocatalytic systems. Photocatalytic studies showed promising activity in the oxidation of 4-chlorophenol. Furthermore, it was indicated that LED-based photocatalytic systems allow a significant reduction in energy consumption compared to conventional photocatalytic sets. In addition, the high thermal efficiency of LED systems was confirmed with a thermal imaging camera. Hence, the presented novel LED photocatalytic systems can be an important part of a broad strategy for the protection of the environment.

A magnetic sludge carbon combined persulfate-based ISCO system for leachate-contaminated groundwater remediation

Activation of persulfate by a green magnetic Steel Converter Slag-Sludge Carbon composite (SCS@SC) and subsequent remediation of actual leachate wastewater was studied in an intermittent reactor and column system to assess the potential of the persulfate-based in situ chemical oxidation (SR-ISCO) system for combined oxidative-reductive removal of organic contaminants from groundwater. In the batch experiment, an iron leaching concentration of 6942 mg/L, was higher than 223.2 and 124.4 times that of steel converter slag (31.14 mg/L) and sole sludge carbon (55.80 mg/L). In the column experiments, the total organic carbon (TOC) removal was maintained at 41.7 %, the loading rate reached 48.86 % with 15 g SCS@SC and 0.15 M persulfate after 400 min. The persulfate consumption, sulfuric acid generation, free radical generation, and iron ions flow out under acidic conditions, which are consistent with TOC removal. The mechanism of persulfate activation and organic matter removal was discussed and proposed by electron paramagnetic resonance (EPR) and energy dispersive spectroscopy (EDS), X-ray diffraction (XRD), transmission electron microscopy (TEM), and gas chromatography-mass Spectrometry (GC–MS) to characterize the chemistry of solid and aqueous phases. A mechanism for contaminant removal was presented, which involves free radicals of persulfate activation by zero-valent iron (Fe0) and iron carbide (Fe3C) and precipitation removal by iron oxides. According to the findings, a viable alternative method for the inexpensive synthesis of catalysts from solid wastes such as sludge and steel converter slag was developed.

Removing roadblocks and opening new opportunities for MXenes

The 2D carbides and nitrides, known as MXenes, are among the most recent, and quickly expanding, material families. The field is experiencing very fast growth with the number of papers on MXenes roughly doubling every year since their discovery in 2011. Great progress in synthesis and control of MXene properties has since been achieved. Synthesis of numerous theoretically predicted MXenes, including ordered solid solutions and high-entropy structures, led to the exploration of numerous applications. MXenes are not only promising candidates for energy storage and related electrochemical applications, such as electrocatalysis, but also applications in optoelectronics, plasmonics, electromagnetic interference shielding, medicine, sensing, catalysis and water desalination. We particularly focus on key material manufacturing and stability issues. We describe the scalable synthesis of MXenes by selective etching in aqueous acidic solutions; alternative synthesis methods, particularly fluorine-free synthesis; delamination without the use of organic intercalants; and improving the environmentally stability and shelf life of MXenes in colloidal suspensions. Finally, we discuss the current understanding of electronic transport in MXene films, which is of critical importance for many MXene applications.

Heating using microwave technique: An approach towards green chemistry

Green chemistry focuses on minimizing waste, minimizing use of chemicals/reagents, reducing pollution and preservation of human health and environment. Using conventional methods of synthesis are creating the said problems in present scenario. To solve these problems new alternate methods must be developed. Many alternatives have been already developed but many more have to do. Use of microwave radiations are one the alternative in which these radiations are used for heating purpose instead of conventional heating methods which uses solvents in large amount and requires much time. Lot of benefits are there in heating using microwave radiations over conventional methods of heating but have limitations too. Not for every reaction/synthesis, but microwaves can be only used for the reactant having specific properties. Single mode and multi-mode microwave ovens are usually used for achieving this purpose. Heating by microwave radiations not only saves time i.e. it converts hours to minutes because it accelerates the reaction, increases the yield, reduces the energy requirement and the most important thing is no or minimum pollution/waste. Health hazards are also been noticed in using these radiations both external and internal. This short communication was aimed to find out the necessity of alternative methods of synthesis that fulfils the concept of green chemistry which will fulfill the need of healthy life and environment.

Elucidation and modulation of active sites in holey graphene electrocatalysts for H2O2 production

AbstractSelective electrochemical oxygen reduction (ORR) toward a two‐electron (2e−) pathway is an eco‐friendly alternative method for H2O2 synthesis to replace the energy‐intensive anthraquinone oxidation process. Carbon‐based electrocatalysts (CBEs) show great potential for practical H2O2 synthesis. However, their complex structures make it challenging to determine the nature of active sites and to precisely control them. Herein, we show that precise modulation of the chemistry and structures of holey graphene with edge sites enriched by oxygen‐containing functional groups can facilitate 2e− ORR. These combined functionalities could improve ORR performance under various pH conditions, for example, resulting in an average of 95% H2O2 selectivity, ~97% Faraday efficiency, high productivity of 2360 mol kgcat−1 h−1 in alkaline media. Density functional theory calculations on the oxygen functional groups at the edge sites revealed the most active site for 2e− ORR is a synergy between ether (COC) and carbonyl (CO) functional groups with nearly zero overpotential.image

Highly efficient biosynthesis of spermidine from L-homoserine and putrescine using an engineered Escherichia coli with NADPH self-sufficient system.

Spermidine is an important polyamine that can be used for the synthesis of various bioactive compounds in the food and pharmaceutical fields. In this study, a novel efficient whole-cell biocatalytic method with an NADPH self-sufficient cycle for spermidine biosynthesis was designed and constructed by co-expressing homoserine dehydrogenase (HSD), carboxyspermidine dehydrogenase (CASDH), and carboxyspermidine decarboxylase (CASDC). First, the enzyme-substrate coupled cofactor regeneration system from co-expression of NADP+-dependent ScHSD and NADPH-dependent AfCASDH exactly provides an efficient method for cofactor cycling. Second, we identified and characterized a putative CASDC with high decarboxylase activity from Butyrivibrio crossotus DSM 2876; it showed an optimum temperature of 35°C and an optimum pH of 7.0, which make it better suited for the designed synthetic route. Subsequently, the protein expression level of each enzyme was optimized through the variation of the gene copy number, and a whole-cell catalyst with high catalytic efficiency was constructed successfully. Finally, a yield of 28.6mM of spermidine was produced in a 1-L scale of E. coli whole-cell catalytic system with a 95.3% molar conversion rate after optimization of temperature, the ratio of catalyst-to-substrate, and the amount of NADP+, and a productivity of 0.17g·L-1·h-1 was achieved. In summary, this novel pathway of constructing a whole-cell catalytic system from L-homoserine and putrescine could provide a green alternative method for the efficient synthesis of spermidine. KEY POINTS: • A novel pathway for spermidine biosynthesis was developed in Escherichia coli. • The enzyme-substrate coupled system provides an NADPH self-sufficient cycle. • Spermidine with 28.6mM was obtained using an optimized whole-cell system.

Trinuclear Magnesium Imidazolate Borohydride Complex.

A new type of hybrid compound, combining properties of MOFs and borohydrides, was synthesized solvothermally using Mg(BH4)2 and imidazole as precursors. Material in the form of acetonitrile solvate with formula [Mg3{(Im)BH2(Im)}6(ImH)6]·CH3CN crystallizes in the space group R3̅, having the unit cell parameters a = 15.1942(2) Å and c = 28.3157(3) Å as determined by single crystal X-ray diffraction. The structure was further investigated by solid-state NMR and DFT quantum chemical calculations. The main feature of the structure, reported here for the first time, is a linear trinuclear complex, where octahedrally nitrogen-coordinated Mg2+ ions are bridged with {(Im)BH2(Im)}− units, forming inside voids of 4.6 Å in diameter between the magnesium ions. Polar intermolecular interactions hold the molecules in a dense rhombohedral stacking, where a disordered acetonitrile molecule plays a cohesive role. The compound is stable in air and upon heating to about 160 °C. Using an alternative synthesis method from an imidazole melt, an imidazole solvate with the formula [Mg3{(Im)BH2(Im)}6(ImH)6]·ImH and a very similar crystal structure to acetonitrile solvate was prepared. It is stable up to 220 °C. Upon further heating, it transformed into a layered structure with the formula Mg(Im3BH)2, space group P3̅1c, and unit cell parameters a = 8.7338(9) Å and c = 17.621(2) Å determined by synchrotron powder diffraction. Besides its structural novelty, two types of potentially reactive hydrogens, bonded to boron and nitrogen in the same molecule, make the material highly interesting for future investigations in the fields of energy storage applications.

Liquid-phase oxidation of betulin over supported Ag NPs catalysts: Kinetic regularities, catalyst deactivation and reactivation

Betulin, being a pentacyclic triterpene alcohol and an extractive from birch bark, along with its oxo-derivatives, has a broad range of physiological properties of interest for synthesis of pharmaceuticals. Instead of oxidizing betulin with strong and toxic oxidizing agents the present study shows a possibility of using liquid-phase oxidation of betulin with air over supported Ag NPs catalysts as an alternative method for synthesis of its oxo-derivatives. Based on catalytic studies, high resolution transmission electron microscopy, X-ray photoelectron spectroscopy and ultraviolet-visible diffuse reflectance spectroscopy, the evolution of the surface of nanosilver catalysts during the catalysis was demonstrated, as well as under the impact of reactant gas composition. The kinetic regularities and causes of deactivation of supported Ag NPs catalysts were revealed. An approach to the regeneration of silver catalysts was proposed. Kinetic analysis with numerical data fitting was performed resulting in an adequate description of the concentration dependencies.

One-step fluorine-free synthesis of delaminated, OH-terminated Ti3C2: High photocatalytic NOx storage selectivity enabled by coupling TiO2 and Ti3C2-OH

Difficulties associated with MXene fabrication typified by an environmentally hazardous fluorine-based etching process followed by delamination and fluorine reduction steps create obstacles against the expansion of this outstanding material and its application in air purification. Herein, we demonstrate a one-step hydrothermal process that involves alkali (NaOH)-assisted aluminum etching in the presence of a delaminating agent (hydrazine) for synthesis of delaminated, OH-terminated MXene (Ti3C2-OH). The process does not require the use of fluorine-containing compounds and produces Ti3C2-OH sheets without the need for post-synthesis treatment. Ti3C2-OH shows a strong synergistic effect as a co-catalyst when coupled with TiO2 during photocatalytic oxidation of NOx. Excellent NOx storage selectivity (91 %) and a positive DeNOx index (+ 0.30) were achieved at NO conversion of 54 %. The photocatalytic activity of the hybrid shows high sensitivity to the surface chemistry of the co-catalyst as Ti3C2-OH outperforms delaminated, F-terminated Ti3C2 (fabricated via the traditional process), which shows low NOx storage selectivity (65 %) and a negative DeNOx index (−0.05) at NO conversion of 47 %. We envision that these findings will benefit ongoing efforts aimed at developing effective alternative methods for MXene synthesis and provide a pathway for rational design of efficient NOx abatement photocatalysts.

Green Synthesis via Eucalyptus globulus L. Extract of Ag-TiO2 Catalyst: Antimicrobial Activity Evaluation toward Water Disinfection Process.

The problem of water pollution by persistent substances and microorganisms requires solutions that materials such as silver-modified titanium dioxide can provide due to their excellent photocatalytic and antimicrobial properties. However, the synthesis methods conventionally used to obtain these materials involve toxic chemical reagents such as sodium borohydride (NaBH4). The search for alternative synthesis methods that use environmentally friendly substances, such as the biosynthesis method, was evaluated. Silver-titanium dioxide (Ag-TiO2) was synthesized by a Eucalyptus globulus L. extract as a reductive agent through sol-gel and microwave-assisted sol-gel processes. Four different solvents were tested to extract secondary metabolites to determine their roles in reducing silver nanoparticles. Titanium dioxide nanoparticles with sizes from 11 to 14 nm were obtained in the anatase phase, and no narrowing of the bandgap was observed (3.1–3.2 eV) for the Ag-TiO2 materials compared with the pure TiO2. Interestingly, the bacterial inhibition values were close to 100%, suggesting an effective antimicrobial mechanism related to the properties of silver. Finally, by the physicochemical characterization of the materials and their antimicrobial properties, it was possible to obtain a suitable biosynthesized Ag-TiO2 material as a green option for water disinfection that may be compared to the conventional methods.

Synthesis and Characterization of Silver Doped Zinc Oxide Nanoparticle from Beetle Leaf Extract- Evaluation of Antimicrobial Activity Against Human Pathogenic Bacteria and Fungi

Abstract: Plants or natural resources have been found to be a good alternative method for nanoparticles synthesis. In this study, silver doped zinc oxide nanoparticles (AgZno4NPs) synthesized from Piper betle leaves extract were investigated for their antibacterial and antifungal activity. ZnO nanoparticles were prepared from the reduction of Zinc oxide and NaBH4 was used as reducing agent, later doped with silver nitrate. Silver doped zinc nanoparticles were mixed thoroughly and subjected for characterization studies. Prepared nanoparticles were characterized by Visual inspection, Ultraviolet-visible spectroscopy (UV), Fourier transform infrared Spectroscopy (FT-IR), Transmission Electron Microscopy (TEM) techniques. Antimicrobial activities of the synthesized silver nanoparticles were tested against Staphylococcus aureus ATCC 25923, Salmonella typhi ATCC 14028, Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853. UV–Vis spectrum of reaction mixture showed strong absorption peak with centering at 400 nm. The FT-IR results imply that Ag-Zn NPs were successfully synthesized and capped with bio-compounds present in P. betle and particle size ranging from <100nm. The result revealed that AgZn-Extract NPs showed 12.78±0.64 mm zone of inhibition against S. typhi, whereas streptomycin (positive control) showed maximum 15.15±0.40 mm zone of inhibition for S.mutans. Again, maximum zone of inhibition found for S. mutans. The results obtained by this study can’t be directly extrapolated to human; so further studies should be undertaken to established the strong antimicrobial activity of Ag-Extract NPs for drug development program

Ultrasmall Nanodiamonds: Perspectives and Questions.

Nanodiamonds are at the heart of a plethora of emerging applications in areas ranging from nanocomposites and tribology to nanomedicine and quantum sensing. The development of alternative synthesis methods, a better understanding, and the availability of ultrasmall nanodiamonds of less than 3 nm size with a precisely engineered composition, including the particle surface and atomic defects in the diamond crystal lattice, would mark a leap forward for many existing and future applications. Yet today, we are unable to accurately control nanodiamond composition at the atomic scale, nor can we reliably create and isolate particles in this size range. In this perspective, we discuss recent advances, challenges, and opportunities in the synthesis, characterization, and application of ultrasmall nanodiamonds. We particularly focus on the advantages of bottom-up synthesis of these particles and critically assess the physicochemical properties of ultrasmall nanodiamonds, which significantly differ from those of larger particles and bulk diamond.

Highly Stereoselective, Organocatalytic Mannich-type Addition of Glyoxylate Cyanohydrin: A Versatile Building Block for the Asymmetric Synthesis of β-Amino-α-ketoacids

β-Amino-α-ketoacids are important unnatural amino acids that exhibit unique bioactivity and reactivity derived from the highly electrophilic carbonyl group at the α-position. Despite the broad utility of the motif, reliable synthetic methods for β-amino-α-ketoacids have been limited to the oxidative homologation of α-amino acids based on a chiral-pool approach. In this article, we report an alternative practical method for the asymmetric synthesis of β-amino-α-ketoacid equivalents based on a highly stereoselective organocatalyzed Mannich-type addition using glyoxylate cyanohydrin. The optimal aminothiourea catalyst provides a wide variety of adducts from N-Boc imines in excellent yield and stereoselectivity (up to 100% yield, 99% ee, 94:1 dr), and the reaction can be applied to the direct use of α-amido sulfones as imine precursors, which significantly expands the substrate scope. The experimental structure–activity relationships and computational studies indicated that steric repulsion with the substituent on the amine moiety and the attractive interaction with the bis(trifluoromethyl)phenyl group might contribute to the high diastereoselectivity and that the thiourea scaffold provides a narrower catalytic pocket compared to benzothiadiazine due to the difference in the length of the intramolecular hydrogen bonding, which results in excellent enantioselectivity. The asymmetric adducts can be readily converted into β-amino-α-ketoacids that maintain their optical purity, and these can be used for the decarboxylative formation of amides without purification by column chromatography. Peptide-α-ketoacids were also prepared via intramolecular acyl migration as a key step and applied to decarboxylative peptide coupling with dipeptides that bear various unprotected functional groups and to [2 + 2 + 2] sequential peptide coupling. Furthermore, the efficient synthesis of peptide-α-ketoamides with retention of the stereo-information was achieved by using the cyanohydrin motif at the highly reactive α-carbonyl group, and the synthesis of an α-ketoamide-containing medicine, Telaprevir, was accomplished without any epimerization.

Oxidation of 1,2-cyclohexanediol as a step for adipic acid synthesis

Adipic acid is the most important of the commercially available aliphatic dicarboxylic acids. It is obtained industrially from cyclohexanone and/or cyclohexanol by oxidation with nitric acid(V). One of the by-products of the process is nitrous oxide, which is difficult to utilize. In this paper we propose an alternative method of adipic acid synthesis. In the first stage, cyclohexene is oxidized with hydrogen peroxide to epoxide, which hydrolyses to 1,2-cyclohexanediol that in the second stage is then oxidized with oxygen. From an environmental point of view, this two-stage method can offer a significant and attractive reduction of N2O production compared to the industrial methods. We apply a simple catalytic system composed of transition metal compounds and HNO3 or organic nitrites, to the second stage of adipic acid synthesis synthesis, namely 1,2-cyclohexenediol oxidation using oxygen.

A systematic review of inequalities in the uptake of, adherence to, and effectiveness of behavioral weight management interventions in adults.

SummaryThe extent to which behavioral weight management interventions affect health inequalities is uncertain, as is whether trials of these interventions directly consider inequalities. We conducted a systematic review, synthesizing evidence on how different aspects of inequality impact uptake, adherence, and effectiveness in trials of behavioral weight management interventions. We included (cluster‐) randomized controlled trials of primary care‐applicable behavioral weight management interventions in adults with overweight or obesity published prior to March 2020. Data about trial uptake, intervention adherence, attrition, and weight change by PROGRESS‐Plus criteria (place of residence, race/ethnicity, occupation, gender, religion, education, socioeconomic status, social capital, plus other discriminating factors) were extracted. Data were synthesized narratively and summarized in harvest plots. We identified 91 behavioral weight loss interventions and 12 behavioral weight loss maintenance interventions. Fifty‐six of the 103 trials considered inequalities in relation to at least one of intervention or trial uptake (n = 15), intervention adherence (n = 15), trial attrition (n = 32), or weight outcome (n = 34). Most trials found no inequalities gradient. If a gradient was observed for trial uptake, intervention adherence, and trial attrition, those considered “more advantaged” did best. Alternative methods of data synthesis that enable data to be pooled and increase statistical power may enhance understanding of inequalities in behavioral weight management interventions.

Challenges of modelling approaches for network meta-analysis of time-to-event outcomes in the presence of non-proportional hazards to aid decision making: Application to a melanoma network.

BackgroundSynthesis of clinical effectiveness from multiple trials is a well-established component of decision-making. Time-to-event outcomes are often synthesised using the Cox proportional hazards model assuming a constant hazard ratio over time. However, with an increasing proportion of trials reporting treatment effects where hazard ratios vary over time and with differing lengths of follow-up across trials, alternative synthesis methods are needed.ObjectivesTo compare and contrast five modelling approaches for synthesis of time-to-event outcomes and provide guidance on key considerations for choosing between the modelling approaches.MethodsThe Cox proportional hazards model and five other methods of estimating treatment effects from time-to-event outcomes, which relax the proportional hazards assumption, were applied to a network of melanoma trials reporting overall survival: restricted mean survival time, generalised gamma, piecewise exponential, fractional polynomial and Royston-Parmar models.ResultsAll models fitted the melanoma network acceptably well. However, there were important differences in extrapolations of the survival curve and interpretability of the modelling constraints demonstrating the potential for different conclusions from different modelling approaches.ConclusionThe restricted mean survival time, generalised gamma, piecewise exponential, fractional polynomial and Royston-Parmar models can accommodate non-proportional hazards and differing lengths of trial follow-up within a network meta-analysis of time-to-event outcomes. We recommend that model choice is informed using available and relevant prior knowledge, model transparency, graphically comparing survival curves alongside observed data to aid consideration of the reliability of the survival estimates, and consideration of how the treatment effect estimates can be incorporated within a decision model.