AppliedChem, Volume 4, Issue 1 (March 2024) – 8 articles

Since the initial 2018 recall of angiotensin receptor blockers due to unacceptable levels of mutagenic N-nitrosodimethylamine (NDMA) impurity, numerous drug products delivering diverse active pharmaceutical ingredients (APIs) have been recalled. Regulators and the industry are working together to understand and address this widescale problem. Conventional analysis of NDMA utilizes liquid or gas chromatography-based procedures that can involve complicated sample preparation and slow sample analysis. Selected ion flow tube mass spectrometry (SIFT-MS) analyses NDMA directly in the gas phase using soft chemical ionization, with an LOQ of 2 ng g⁻¹. Through the novel application of the multiple headspace extraction (MHE) technique, NDMA was quantified directly and rapidly from the drug product without dissolution, at levels well below the regulatory acceptable intake of 96 ng day⁻¹. A comparative analysis of recalled metformin using MHE-SIFT-MS and a conventional liquid chromatography–mass spectrometry/mass spectrometry (LC-MS/MS) method showed good agreement. Use of the novel MHE-SIFT-MS approach may enable a wider screening of drug products to be conducted, since it provides around a three-fold increase in daily sample throughput. Full article

Nickel nanoparticles have wide-ranging applications in diverse fields, including electronics, catalysis, and biomedicine. The unique properties of these nanoparticles depend on their physical and chemical attributes. Consequently, there is a growing interest in understanding the performance relationships through a nuanced comprehension of their controlled synthesis. This review explores the advancements related to precisely defined nickel nanoparticles, with a specific focus on unraveling the connections between performance and their physical/chemical characteristics. The emphasis is on elucidating how manipulating synthetic parameters, such as precursor concentration, reductant agent properties, temperature, time, and the presence of stabilizing agents, can provide additional avenues for refining the performance in terms of size and morphology. Through the analysis of each variable, we illustrate the methodology for synthesizing well-controlled nickel nanoparticles, showcasing the ability to exert precision over their composition, size, and surface morphology. Full article

The multifaceted health benefits of curcumin (Curcuma longa), attributed to its antioxidant, antitumor, and anti-inflammatory activities, have drawn significant scientific attention. Curcumin shows promise as a potential modulator of macrophage polarization, offering a natural strategy for managing inflammation and promoting tissue repair. However, a limiting factor for this beneficial molecule is its limited bioavailability due to its low solubility in water. This study aimed to quantify the effect of curcumin gold nanoparticle (CurAuNP)-mediated ultrasound irradiation on THP-1-derived macrophages as potential therapeutic targets. The photoreduction method was applied to synthesize the gold nanoparticles with curcumin as a ligand (CurAu). The effect of adding polyethylene glycol in the synthesis process was studied (CurAuPEG). CurAuNP characterization included UV/Vis, Zeta potential, transmission electron microscopy, and FTIR. The amount of singlet oxygen released by curcumin and CurAuNPs was quantified by observing 1.3-diphenylisobenzofuran quenching upon ultrasound irradiation (1 MHz and 1 W/cm²). The results indicated that ultrasound therapy for 4 min with CurAuNPs significantly enhanced singlet oxygen generation and reduced macrophage viability compared to curcumin alone. The increased sonoluminescence and curcumin delivery facilitated by CurAuNPs led to greater curcumin activation. Consequently, CurAuNPs could offer promising therapeutic options for modulating macrophage polarization in pro-inflammatory and anti-inflammatory stages. Full article

This work evaluated the green extraction of oleoresin from pink pepper fruits (OR_PPF) using ultrasound-assisted extraction (UAE) and ethanol as a solvent. The effects of temperature, ultrasound power intensity, sample to solvent ratio and time on the global extraction yield (Y_GE) and phenolic compounds yield (Y_PC) were evaluated. The oleoresin samples were characterized and its antimicrobial activity determined, and the obtained results were compared to conventional extraction in Soxhlet. From the results it was found that the application of the highest levels of the independent variables favored the extraction process. The maximum values of Y_GE and Y_PC were 28.60 wt% and 6.37 mg GAE per g fruit, respectively, obtained at 60 °C, 100% of ultrasound power (165 W), 1:20 g mL⁻¹ (sample:solvent) and 45 min. Under maximized conditions, the OR_PPF obtained by UAE showed a content of phenolic compounds and antioxidant activity inferior to soxhlet–ethanol extraction. However, the time and solvent consumption were reduced. Oleic and linoleic acids predominated in the fatty acid composition of OR_PPF, in addition to sesquiterpenes and gallic and syringic acids. The OR_PPF presented weak antibacterial activity, with minimum inhibitory concentration ranging from 31.25 to 125 mg mL⁻¹. Full article

The hydroxyalkyl amination of agarose gels was studied as an approach to improve adsorption of polyphenols and pharmaceuticals from water. Three commercially available agarose gels, Zetarose FlashFlow4, ZetaCell-CL6B and Sepharose 4B were chemically modified using tris-(hydroxymethyl)aminomethane, TRIS, and ethanolamine, EA. The adsorbed amounts of bisphenol A and diclofenac were significantly higher on TRIS- and EA-derivatives compared with the parent gels. Regarding bisphenol A adsorption on TRIS-ZetaCell-CL6B, a maximal adsorption capacity, Q max of 16 μmol/mL gel and an equilibrium dissociation constant K_L of 2.7 × 10⁻⁴ mol/L were observed. Filtration of diclofenac-contaminated water through TRIS-Zetarose FlashFlow 4 resulted in a 10-fold reduction of the pollutant concentration within 64 column volumes of the effluent. The moderate binding affinity of polyphenols to TRIS- and EA-adsorbents facilitates efficient polyphenol desorption and column regeneration. The effects of TRIS- and EA-substituents in agarose gels, can be harnessed for the development of environmental adsorbents, as well as for the preparative separation of polyphenols and pharmaceuticals. We consider the physical shapes and textures of the prospective adsorbents with a particular focus on spongy macroporous cryogels. These innovative materials hold promise for future applications in liquid and air filtration. Full article

Rhodium-catalyzed reactions of 3-ethynyl-2-pentamethyldisilanylthiophene derivatives (1a–1c) have been reported. At 110 °C, compounds 1a–1c reacted in the presence of a rhodium complex catalyst, yielding thiophene-fused siloles (2a–2c) through intramolecular trans-bis-silylation. To understand the production of 2a from 1a, the mechanism was investigated using density functional theory (DFT) calculations. Full article

The yellow-flowering plant Cladanthus arabicus (L.) Cass., commonly called Arabian Cladanthus or palm springs daisy, is typical of the West Mediterranean region and is particularly abundant in Morocco. The plant is used in traditional Moroccan medicine for the treatment of diabetes and other ailments. Over the past 20 years, this abundant wild plant has been neglected from a phytochemical viewpoint. For the first time, the present review provides a survey of the pharmacological properties reported from extracts of C. arabicus and from essential oils derived from the aerial parts, mainly antimicrobial, antioxidant, and anti-inflammatory properties. The main bioactive natural products are discussed, with a focus on two rare sesquiterpenes of major interest, which are abundant in the stems and leaves: the 6,12-guaianolide cladantholide and the germacranolide sintenin. These sesquiterpene lactones and their analogues are presented to highlight their properties, extraction or total synthesis, and their therapeutic benefits. They both represent convenient biosourced precursors for the synthesis of derivatives. Sintenin may be used as a starting material for the design of hemi-synthetic germacradienolide-type costunolide or parthenolide derivatives. The 6,12-guaianolide scaffold of cladantholide offers opportunities to design novel arglabin derivatives. The therapeutic potential of the neglected and under-utilized plant Cladanthus arabicus and its original phytochemicals shall be explored further. Full article

When two or more surfactants are mixed, the critical micelle concentration and solubilization capability are changed, and a careful selection of the combination promotes the micelle formation and enhances the solubilizing capability. Thus, understanding the mechanism behind the phenomena is essential for controlling the physical properties of the mixed micelle. The interaction parameters β and B that describe the formation of mixed micelles and their partitioning of solutes, respectively, were proposed by Treiner four decades ago. In this work, data on the formation and partitioning in binary surfactant systems were collected. Although the data on the parameters β and B for polar solutes and theoretical development are still insufficient, the directions of research to acquire an in-depth understanding of the formation and partitioning of the mixed micelle are proposed. Full article