Synthesis Route Research Articles

Design of MnOx/TiO2 Nanostructures for Photocatalytic Removal of 2,4-D Herbicide.

The research and modification of semiconductors through different synthesis routes allow obtaining materials with optimal properties to induce new energy levels and improve charge separation efficiency. In this context, the sol-gel method was used to synthesize TiO2-based materials doped with different percentages of MnOx to evaluate their photocatalytic activity in the degradation of the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) in water under UV irradiation. Characterization results revealed a reduction in crystallite size to 7.2 nm. Adding MnOx enhanced the optical absorption of TiO2, resulting in a shift toward the red end of the spectrum of the forbidden energy band. The photocatalytic activity increased significantly with the percentage of MnOx, reaching a maximum degradation of 70 % in 6 hours with the 3 MnTi material. This increase was attributed to the synthesis method, which facilitated the formation of nanostructured heterojunctions mainly composed of TiO2 and MnO2, reducing the recombination of electron-hole pairs. TEM analysis confirmed these structures. A reaction mechanism for the 3 MnTi material is proposed, considering the mobility of charge carriers and the photooxidation processes of the pollutant.

High-Performance Perovskite Flat Panel X-Ray Imagers via Blade Coating.

Perovskite X-ray detectors are recognized as the most promising candidates for low-dose detectors due to their superior performance. However, it is still full of challenging in the fabrication of flat-panel X-ray imagers (FPXIs), primarily due to the absence of large area thick films that exhibit high uniformity and long-term performance stability. A general synthesis route is urgently needed to grow large-scale halide perovskite thick films directly on a pixeled thin-film transistor (TFT) backplane with high uniformity, closing the gap between the great potential of perovskite X-ray detectors and their entry into the market. In this work, an advanced precursor paste suitable for blade coating is developed to enable high-throughput manufacturing of FPXIs. Highly uniform perovskite films with a thickness of 300-micrometers are directly deposited onto pixeled TFT substrates by the blade-coating method using the above paste, which governs a stable dark current and minimal noise of the X-ray detectors. As a result, (BA)2(MA)9Pb10I31 perovskite X-ray detectors achieved a high sensitivity of 15200 µC Gyair -1 cm-2 and a limit of detection (LoD) of 26.8 nGyair s-1. Moreover, FPXIs with a spatial resolution of 0.95 lp mm-1 (0.475 lp pixel-1) are obtained, which exhibits negligible signal crosstalk and excellent X-ray imaging performance.

Chemoenzymatic Synthesis Planning Guided by Reaction Type Score.

Thanks to the growing interest in computer-aided synthesis planning (CASP), a wide variety of retrosynthesis and retrobiosynthesis tools have been developed in the past decades. However, synthesis planning tools for multistep chemoenzymatic reactions are still rare despite the widespread use of enzymatic reactions in chemical synthesis. Herein, we report a reaction type score (RTscore)-guided chemoenzymatic synthesis planning (RTS-CESP) strategy. Briefly, the RTscore is trained using a text-based convolutional neural network (TextCNN) to distinguish synthesis reactions from decomposition reactions and evaluate synthesis efficiency. Once multiple chemical synthesis routes are generated by a retrosynthesis tool for a target molecule, RTscore is used to rank them and find the step(s) that can be replaced by enzymatic reactions to improve synthesis efficiency. As proof of concept, RTS-CESP was applied to 10 molecules with known chemoenzymatic synthesis routes in the literature and was able to predict all of them with six being the top-ranked routes. Moreover, RTS-CESP was employed for 1000 molecules in the boutique database and was able to predict the chemoenzymatic synthesis routes for 554 molecules, outperforming ASKCOS, a state-of-the-art chemoenzymatic synthesis planning tool. Finally, RTS-CESP was used to design a new chemoenzymatic synthesis route for the FDA-approved drug Alclofenac, which was shorter than the literature-reported route and has been experimentally validated.

A Study on Gas‑sensing Behavior of Reduced Graphene Oxide (rGO) Green Method, Enhansing the Performance of Green-synthesized Reduced Graphene Oxide

This paper presents a comparative study on gas-sensing behavior of reduced graphene oxide (rGO) synthesized by chemical and green synthesis route. GO is synthesized by Hummers method and then reduced employing two reducing agents hydrazine hydrate [represented by (rGO)1] and L-citrulline [represented by (rGO)2]. Synthesized products were then obtained in the form of thin films, and tested for 10 ppm NO2 and CO at operating temperatures of 50, 100, and 150 °C. The green-synthesized reduced graphene oxide (rGO)2 exhibits higher relative response of 254.7% as compared to conventionally synthesized (rGO)1 (93.9%) and GO (22.7%) for 10 ppm NO2 at operating temperature of 150 °C. Furthermore, a switching of conductivity from usual p-type behavior to n-type on exposure of NO2 is observed at all operating temperatures (50, 100, and 150 °C) for GO, (rGO)1, and (rGO)2. The XRD, FTIR, and Raman confirm the oxidation and reduction process. (rGO)2 shows high thermal stability as observed through TGA. FESEM and TEM images show wrinkled sheet structure for GO as well (rGO)1 and (rGO)2. The data observed from the characterization of resultant products have made it possible to explain better reduction of GO through green-reducing agent and enhanced gas-sensing performance of green-synthesized reduced graphene oxide.

Electronic properties of polyaniline–graphene nanocomposites synthesized via solution mixing method

A key advantage of combining the exceptional properties of graphene with conducting polymers, lies in their remarkable property tunability through filler additions into polymer matrices, with synthesis routes playing a crucial role in shaping their characteristics. In this work, we examine the electronic properties of polyaniline and graphene nanocomposites synthesized via a simple solution mixing method, which offers advantages such as ease of use and efficiency. Increasing graphene content enhances nanocomposite conductivity, and a percolation effect is observed. The percolation threshold is high and is consistent with a strong role played by voids in the structure. Temperature-dependent conductivity measurements highlight three distinct conduction regimes: insulating, critical, and metallic. These findings underscore the significant influence of synthesis method and structural disorder on shaping electronic properties, paving the way for engineering multifunctional nanocomposites with exceptional versatility and performance.

Supercritical CO2 in the Development of Highly Efficient Composite Cathodes for Li-S Batteries.

Conventional Li-S battery cathode synthesis routes are time-consuming, energy-intensive, use toxic solvents, and yet fail to effectively confine sulfur into carbon matrices, reducing the cathode efficiency. Supercritical CO₂ (scCO2) presents notable benefits as a "green solvent" due to its affordability, chemical inertness, recyclability, non-flammability, and non-toxicity. It eliminates the need for energy-intensive post-heat treatments, providing a more sustainable and efficient option. CO2 in supercritical state gains unique gas-like and liquid-like properties that enable precise sulfur loading, uniform encapsulation, and improved sulfur-carbon interactions, which enhance conductivity and reaction kinetics. Recent studies show that cathodes prepared using scCO2 exhibit exceptional electrochemical performance, including long-term cycling stability and high coulombic efficiency. The versatility of scCO2 in infiltrating various host architectures also makes it suitable for a wide range of cathode designs. Despite its tremendous potential, this advanced synthesis technology is often overlooked in textbooks, underscoring the need for awareness within the research community. This review highlights the remarkable features of scCO2 and examine up-to-date research progress, focusing on its application in developing high-performance carbon/sulfur composite cathodes. An application-focused audience would benefit from a summary of this review, as they reveal new Li-S cathode synthesis technologies that haven't been widely explored or discussed.

Recent Advancements in the Application of Artificial Intelligence in Drug Molecular Generation and Synthesis Planning

AbstractThe design and synthesis of drug molecules is a pivotal stage in drug development that traditionally requires significant investment in time and finances. However, the integration of artificial intelligence (AI) in drug design accelerates the identification of potential drug candidates, optimizes the drug development process, and contributes to more informed decision-making. The application of AI in molecular generation is changing the way researchers explore the chemical space and design novel compounds. It accelerates the process of drug discovery and materials science, enabling rapid exploration of the vast chemical landscapes for the identification of promising candidates for further experimental validation. The application of AI in predicting reaction products accelerates the synthesis planning process, contributes to the automation of synthetic chemistry tasks, and supports chemists in making informed decisions during drug discovery. This paper reviewed the recent advances in two interrelated areas: the application of AI in molecular generation and synthesis routes. It will provide insights into the innovative ways in which AI is transforming traditional approaches in drug development and predict its future progress in these key fields.

Enhanced Tunability of Photo-Cross-Linkable Silk Sericins from Bombyx mori.

Over the past decade, silk sericin has emerged as a promising material for biomedical applications, especially in tissue engineering, where fine-tuning the physicochemical properties is crucial. However, previous studies, including those on the methacrylation of sericin (yielding SS-MA), showed limited tunability. Here, we developed a photo-cross-linkable sericin-based material modified with 2-aminoethyl methacrylate (AEMA) using two synthesis routes: sequential modification of SS-MA with AEMA (SS-MA-AEMA) and an efficient one-pot synthesis (SS-AEMA). The one-pot synthesis yielded materials containing only methacrylate groups, unlike the sequential modification that yielded a combination of methacrylamides and methacrylates. Our approach resulted in superior physicochemical properties. The resulting materials, including the previously described SS-MA, exhibited a broad range of properties, such as cross-linking kinetics (0.9-64.0 s), swelling behavior (311-3775%), and mechanical properties (10-140 kPa). These properties support applications across various tissues, from dermis to fibrous tissue. The materials also demonstrated fibroblast cytocompatibility with cell viabilities exceeding 96%.

Closed-Loop Chemical Recycling of a Biobased Poly(oxanorbornene-fused γ-butyrolactone).

New polymers, properly designed for end-of-life and efficiently formed from renewable carbon, are key to the transition to a more sustainable circular plastics economy. Ring-opening polymerization (ROP) of bicyclic lactones is a promising method for the production of intrinsically recyclable polyesters, but most lactone monomers lack an efficient synthesis route from biobased starting materials, even though this is essential to sustainably account for material loss during the life cycle. Herein, we present the exceptionally rapid and controlled polymerization of a fully biobased tricyclic oxanorbornene-fused γ-butyrolactone monomer (M1). Polyester P(M1) was formed in low dispersity (D̵ = 1.2-1.3) and controllable molecular weight up to Mn = 76.8 kg mol-1 and exhibits a high glass transition temperature (Tg = 120 °C). The orthogonal olefin and lactone functionalities offer access to a wide range of promising materials, as showcased by postpolymerization modification by hydrogenation of the olefin, which increased polymer thermal stability by over 100 °C. Next to rapid hydrolytic degradation and solvolysis, the poly(oxanorbornene-fused γ-butyrolactone) could be cleanly chemically recycled back to the monomer (CRM), in line with its favorable ceiling temperature (Tc) of 73 °C. The density functional theory (DFT)-computed ΔH° of ring-opening with methanol of γ-butyrolactone-based monomers provided a model to predict Tc, and the DFT-computed and X-ray crystal structure-derived structural parameters of M1, hydrogenated analogue M1-H2, and regioisomer M2 offered insights into the structural descriptors that cause the high polymerizability of M1, which is key to establishing structure-property relations.

Chitosan-capped mesoporous silica nano/microcontainers for waterborne epoxy coating: Implications of size and textural properties modulated by synthesis route

Herein, the dependence of the performance of smart waterborne epoxy coating on the size and textural properties of intercalated nano/microcontainers is critically examined. Two routes were adopted to synthesize nano/microcontainers from similar starting materials resulting in nanocontainers and microcontainers with dissimilar textural properties. The containers were constructed based on mesoporous silica particles (MSPs) loaded with benzotriazole (BTA) and encased with chitosan (CTS) shell to obtain nanocontainers with a slightly crystalline core (C@B@MSP1) and microcontainers with amorphous core (C@B@MSP2), both demonstrating pH-responsiveness. The obtained containers were characterized using SEM, TEM/EDX, XRD, FTIR, TGA, XRD, N2 adsorption/desorption and UV-vis studies. These containers were incorporated into waterborne epoxy coating namely EP/CBS1 and EP/CBS2, respectively. Their performance was investigated in comparison to a reference coating EP/REF and coatings doped with commercial inhibitor zinc phosphate, EP/ZP. The surface morphology and adhesion of coatings were examined using OM, SEM and 3D profilometer. EIS measurements of scribed coating in 3.5 wt% NaCl solution for 48 h demonstrated high active corrosion resistance of EP/CBS1. However, EIS assessment of intact coatings for 30 d shows the dominance of EP/CBS2 with |Z|0.01 Hz value of 6.0×107 Ω cm2 after 30 d of exposure, a performance corroborated by salt spray test carried out for 50 d. Hence, driven by the large size and amorphous core of C@B@MSP2 which allows compatibility with the waterborne epoxy matrix, EP/CBS2 demonstrated a synergy between exceptional barrier properties and adequate active corrosion resistance implying their versatility. Therefore, in addition to inhibitor loading efficiency of containers, their sizes and compatibility of textural properties with the chosen polymer matrix is crucial for better performance as active carriers in waterborne anticorrosive coatings.

Effect of synthesis route of graphene on the hydrogen storage in Mg-Ni-rGO ternary system

The H uptake/release performance of Mg is studied by combining transition metal (Ni) and lightweight C-based (rGO) catalysts. Further, the effect of the synthesis route on the morphology and catalytic ability of rGO is understood by synthesizing it via electrochemical (erGO), chemical (crGO) and thermal (trGO) exfoliation. These rGOs (10 wt%) and 3 atom% of Ni were ball-milled with Mg and subjected to isothermal H uptake at 15 bar and 320 °C. The Mg97-Ni03-erGO nanocomposite shows the lowest incubation period of 2–3 h, whereas it is 8–9 h for Mg97-Ni03-trGO. Moreover, the Mg97-Ni03-erGO nanocomposite shows the lowest onset temperature of H release at 275 °C, which is 300 °C in the case of Mg97-Ni03-trGO. From the spectroscopic analysis, it is inferred that the presence of lower defects in erGO and higher C–C sp2 domains facilitate enhanced Mg–C interaction during the H uptake/release.

Improved InP/ZnSe/ZnSeS/ZnS quantum dots for single-terminal carrier-injection light-emitting devices

The wavelength tunable and environmentally friendly InP quantum dots are considered one of the most powerful alternatives to cadmium-based quantum dots, and the luminescent devices prepared with them also show great potential. There is still room for improvement in the synthesis methods and device applications of InP based quantum dots. In this work, we report one pot synthesis route for InP/ZnSe/ZnSeS/ZnS green QDs based on tris(dimethylamino)phosphine (DMP) phosphorus by using the strategy of multi shell coating and gradient heating to reduce surface defects of quantum dots. The shell structure, dosage, and growth temperature have all been taken into account in order to explore better performance of InP QDs. The synthesized green quantum dots have 86 % PLQY and a full width at half maximum of 36 nm. In addition, the synthesized green InP quantum dots are applied in AC QLED devices. The experimental results show that the luminescence intensity is affected by the driving voltage and frequency, which is similar to the working mode of non-carrier-injected emitting devices. And there is a matching value between the voltage and frequency.

Synthesis and Anti-gastric Cancer Activity by Targeting FGFR1 Pathway of Novel Asymmetric Bis-chalcone Compounds.

Bis-chalcone compounds with symmetrical structures, either isolated from natural products or chemically synthesized, have multiple pharmacological activities. Asymmetric Bis-chalcone compounds have not been reported before, which might be attributed to the synthetic challenges involved, and it remains unknown whether these compounds possess any potential pharmacological activities. The aim of this study is to investigate the synthesis route of asymmetric bis-chalcone compounds and identify potential candidates with efficient anti-tumor activity. The two-step structural optimization of the bis-chalcone compounds was carried out sequentially, guided by the screening of the compounds for their growth inhibitory activity against gastric cancer cells by MTT assay. The QSAR model of compounds was established through random forest (RF) algorithm. The activities of the optimal compound J3 on growth inhibition, apoptosis, and apoptosis-inducing protein expression in gastric cancer cells were investigated sequentially by colony formation assay, flow cytometry, and western blotting. Further, the inhibitory effects of J3 on the FGFR1 signaling pathway were explored by Western Blotting, shRNA, and MTT assays. Finally, the in vivo anti-tumor activity and mechanism of J3 were studied through nude mice xenograft assay, western blotting. 27 asymmetric bis-chalcone compounds, including two types (N and J) were sequentially designed and synthesized. Some N-class compounds have good inhibitory activity on the growth of gastric cancer cells. The vast majority of J-class compounds optimized on the basis of N3 exhibit excellent inhibitory activity on gastric cancer cell growth. We established a QSAR model (R2 = 0.851627) by applying random forest algorithms. The optimal compound J3, which had better activity, concentration-dependently inhibited the formation of gastric cancer cell colonies and led to cell apoptosis by inducing the expression of the pro-apoptotic protein cleaved PARP in a dose-dependent manner. J3 may exert anti-gastric cancer effects by inhibiting the activation of FGFR1/ERK pathway. Moreover, at a dose of 10 mg/kg/day, J3 inhibited tumor growth in nude mice by nearly 70% in vivo with no significant toxic effect on body weight and organs. In summary, this study outlines a viable method for the synthesis of novel asymmetric bischalcone compounds. Furthermore, the compound J3 demonstrates substantial promise as a potential candidate for an anti-tumor drug.

Facile synthesis of Metal-Organic Framework/Chitosan cryogel as a robust Scavenger for Diclofenac sodium

Diclofenac sodium (DS), a commonly detected contaminant in aquatic environments, poses a a significant risk to both the ecological balance and the safety of aquatic products. Therefore, efficient removal of DS from water is ergently needed but remains a major challenge. In this study, an environmentally friendly Fe-based metal–organic framework/chitosan (NH2-MIL-53(Fe)/CS) cryogel was prepared through a Schiff base condensation reaction under mild conditions. Taking advantage of the catalytic role of the MOF in accelerating the reaction between CS and 1,3,5-triformylphloroglucinol, NH2-MIL-53(Fe) powders were incorporated into the polymeric networks within 30 s. Owing to the rich binding sites, the resulting NH2-MIL-53(Fe)/CS cryogel demonstrated remarkable efficacy in eliminating DS from water. The adsorption process reached equilibrium within 120 min with a maximum adsorption capacity of 728.6 mg g−1. A comprehensive mechanistic investigation revealed that the exceptional adsorption capability of the NH2-MIL-53(Fe)/CS cryogel for DS was attributed to the synergistic effect of multiple interactions, including favorable hydrophilicity, electrostatic forces, π-π stacking, hydrogen bonding, and coordination. Thus, this study provides a straightforward and rapid synthesis route for MOF/CS cryogel, offering a promising adsorbent that combines exceptional adsorption performance with ease of separation. The resulting MOF/CS cryogel holds great potential for the treatment of DS-contaminated wastewater.

Enhanced photocatalytic degradation of crystal violet and malachite green oxalate dyes by NiAg2O infused chitosan nanocomposites

The present study investigated the catalysis of Lupeol-loaded chitosan nanoparticles infused with NiAg2O nanoparticles to create a NiAg2O/Lup@CS nanocomposite. Recent advances in nanomaterials with unique architectures and functionalities have successfully treated contaminated soil and industrial wastewaters. Consequently, a lupeol@chitosan nanoparticle loaded with NiAg2O was created, and its catalytic effectiveness in degrading industrial dye pollution was examined. The ionic gelation synthesis route was used to produce the NiAg2O/Lup@CS nanocomposite. After that, the resultant nanocomposite underwent extensive analysis to determine its elemental composition through EDAX, surface bonding, nature, crystallinity using FTIR, FESEM, and XRD, and powdered particle size using HRTEM. Subsequently, the produced nanocomposite's efficacy in photo-catalytically degrading Crystal violet and Malachite green oxalate were evaluated. Moreover, the Crystal violet and Malachite green oxalate degradation kinetics were studied using the Langmuir–Hinshelwood model, which also offered a plausible photocatalytic process. The catalytic mechanism suggested that the addition of Lup@CS nanoparticles would have had the effect of speeding up photocurrent transport by increasing the quantity of electrons and holes produced by the photon's irradiation. This highlights the significance of creating innovative composite photocatalysts. The study also observed the superior photocatalytic activity of NiAg2O/Lup@CS nanocomposite with 86.14 % degradation of Crystal violet and 86.65 % degradation of Malachite green oxalate.

Mini-Review on Renewable Production of Green p-Xylene

The sustainable and renewable production of p-xylene (PX), a crucial component for polyethylene terephthalate (PET), is increasingly important as an alternative to fossil-based processes. This review examines biomass-derived routes for PX synthesis, emphasizing the use of bio-px production pathways to feasible for commercialization. While bio-PX production offers reduced greenhouse gas emissions, challenges remain in cost, catalyst stability, and energy requirements. Recent innovations in catalyst regeneration and hierarchical structures enhance stability and minimize coke formation. Life-cycle assessments confirm bio-PX’s environmental advantages, suggesting that further research into biomass sources and catalyst efficiency will advance bio-based PX production toward commercial viability in a sustainable bioeconomy.

Novel Pyrrolo-Pyrimidine Derivatives Bearing Amide Functionality as Potential Anticancer Agents: Synthesis and Molecular Docking Studies

Current investigation presents the synthesis, molecular docking and anticancer evaluation of novel pyrrolo-pyrimidine derivatives designed to target Janus kinase 1 (JAK1), Janus kinase 2 (JAK2) and cyclin-dependent kinase 4 (CDK4). The synthesis route commenced with 2-amino-4,6-dichloropyrimidine-5-carbaldehyde, proceeding through sequential steps involving intermediate formations and coupling reactions to yield a diverse array of pyrrolo-pyrimidine derivatives. Characterization using spectroscopic techniques (1H NMR, 13C NMR and HRMS) confirmed the chemical structures of the synthesized compounds. Molecular docking studies against JAK1, JAK2 and CDK4 demonstrated substantial binding affinities, remarkably compounds 7k, 7l and 7d, which displayed promising interactions within the active sites of the proteins. Anticancer evaluation against breast cancer (MCF-7), chronic myeloid leukemia (SET-2), colorectal carcinoma (HCT-116) and HEK-293 cell lines revealed diverse cytotoxic profiles. Specifically, compounds 7k and 7f exhibited potent activity against breast cancer (MCF-7), 7k and 7f showed efficacy against chronic myeloid leukemia (SET-2) and compounds 7k and 7l demonstrated effectiveness against colorectal carcinoma (HCT-116). These findings underscore the potential of these pyrrolo-pyrimidine derivatives as selective and effective anticancer agents, prompting further exploration for therapeutic development.

Surfactant‐Free, Simple Hydrothermal Synthesis of Morphologically Porous, Three‐Dimensional SnS2 Nanomaterial as Long term Stable Electrode for Supercapacitor Application

AbstractTin disulfide (SnS2) is a prominent candidate in the class of transition metal dichalcogenides (TMD), whose multiple electrical and electrochemical applications have recently steered much attention to energy storage devices like batteries and supercapacitors. Previous studies on the material came under the efforts to improve its applications by doping, creating composites, and other heterogeneous structures, which are complicated and less economical. Thus, pristine SnS2, utilizing its morphological features in conjunction with a suitable synthesis method, was investigated to improve efficiency and reduce cost without confusing processes or structural iterations. In this work, SnS2 is synthesized in its bare form using the hydrothermal method to investigate its potential supercapacitor application. The synthesis route followed a cost‐efficient and simple protocol, and the material shows a porous morphology favoring electrode–electrolyte interaction desirable for supercapacitors. A comprehensive study on the structural, morphological, and surface features done by XRD, FESEM, EDX, XPS, and nitrogen adsorption–desorption analysis confirmed the formation of SnS2 and interior structure. Supercapacitor analysis by CV, GCD, EIS, and cyclic stability tests reveal an intermittent energy storage mechanism, with a capacitance of 109.6 F g−1 at 1 A g−1 and high cyclic retention of 106% at 5 A g−1 after 7000 cycles.

Microscopic Mechanism for Precise Control of the Sizes of Molybdenum Blue Nanorings.

Molybdenum blue (MB) nanorings with monodispersed, well-defined structures can be feasibly prepared via treatment of molybdate solutions with reducing agents at acidic conditions. However, the hidden constraints that control their ring sizes have been unknown for decades. Herein, the formation of 3.4 and 4.1 nm nanorings, {Mo154} and {Mo176}, is monitored using small-angle X-ray scattering (SAXS) with systematically varied synthetic conditions. Results suggest that {Mo154} forms quickly in solution and then undergoes slow transformation into {Mo176} when reducing agents are used, while {Mo176} can form directly with MoCl5 supplied as reduced MoV. These are attributed to {Mo154} being the kinetic product catalyzed by the template-effect while {Mo176} is the thermodynamic product due to its low ring tension. Our findings unravel one of the long-standing mysteries in MB and point out effective routes for the precise synthesis of nanorings.

Identification and Structural Characterization of Novel Process‐Related Impurities Present in Oseltamivir Phosphate Drug Substance and Its Precursor

ABSTRACTThis article describes the identification, synthesis, and characterization of unknown impurities present in the oseltamivir phosphate drug substance and its precursor. Four unknown impurities were identified in the drug substance using high‐performance liquid chromatography analysis: Relative retention times of 1.05 and 2.50 azide impurities were found in the drug substance's precursor, and their corresponding impurities were found in the drug substance in amine form. Initially, the LC‐MS method was used to screen these impurities by identifying the mass of the impurities. Based on the impurities' mass and the drug substance's synthesis route, possible ways to form impurities were predicted. All these impurities were synthesized as predicted and characterized through infrared spectroscopy, nuclear magnetic resonance, and high‐resolution mass spectrometry techniques. It was found that these impurities are new and the synthesis method for these impurities is novel and has not been documented in the literature. The azido‐impurities found in this study are categorized as genotoxic impurities by Class 3 of the International Council for Harmonisation M7(R2) criteria, and these impurities must be regulated below certain thresholds.