Aliphatic Moieties Research Articles

Insights into the gas-phase structure and internal dynamics of diphenylsilane: A broadband rotational spectroscopy study.

The rotational spectrum of diphenylsilane was investigated using chirped-pulse Fourier transform microwave spectroscopy in the frequency range of 2-8 GHz. The lowest energy structure of diphenylsilane has C2 point group symmetry with the C2 symmetry axis coinciding with the binertial axis of the molecule. Through the assignment of the main isotopologue as well as singly substituted heavy-atom isotopologues, including 13C, 29Si, and 30Si, we were able to obtain a comprehensive gas-phase structure of diphenylsilane. The structure of diphenylsilane was compared with its oxygen analogue, diphenylether, including a discussion of the barrier height to the large-amplitude motion of the phenyl rings. Furthermore, the structural comparison was extended to include a range of C-Si bond lengths and bond angles from other organosilicon molecules where the silicon atom is bonded to aliphatic and/or aromatic moieties.

Hit-to-lead optimization of 4,5-dihydrofuran-3-sulfonyl scaffold against Leishmania amazonensis. Effect of an aliphatic moiety

In line with our objective of designing new antileishmanial compounds for oral use, we report the synthesis and biological evaluation in vitro of original 4,5-dihydrofuran derivatives bearing an amidoxime group. Previous optimization focused on position 3 of the dihydrofuran ring involving aromatic fragments, resulting in the identification of the compound (HIT) 4-(5-benzyl-3-((4-fluorophenyl)sulfonyl)-5-methyl-4,5-dihydrofuran-2-yl)-N′-hydroxybenzimidamide (IC50 = 5.4 ± 1.0 μM, L. amazonensis promastigote, IC50 = 7.9 ± 1.1 μM, L. amazonensis intracellular amastigote). In the present work, position 3 was substituted with an aliphatic moiety. This modification was guided by a ligand-based approach, given the unknown biological target or mechanism of action for this compound. The 4,5-dihydrofuran derivatives were synthesized using microwave-assisted manganese (III) acetate-based oxidative cyclization of linear β-keto-carboxylic and β-keto-sulfone substrates, overcoming synthetic challenges to obtain aliphatic derivatives of 4,5-dihydrofuran-3-carboxamides. Finally, an unexpected and interesting biological activity with the 4,5-dihydrofuran-3-carboxylate (IC50 < 5 μM) against the amastigote form is discussed.

Multimodal Molecular Imaging Reveals a Novel Membrane Component in Sporangia of the Rare Actinomycete Actinoplanes missouriensis.

The bacterium Actinoplanes missouriensis belongs to the genus Actinoplanes, a prolific source of useful natural products. This microbe forms globular structures called sporangia, which contain many dormant spores. Recent studies using transmission electron microscopy have shown that the A. missouriensis sporangium membrane has an unprecedented three-layer structure, but its molecular components remain unclear. Here, we present multimodal (spontaneous Raman scattering, coherent anti-Stokes Raman scattering, second harmonic generation, sum frequency generation, and third-order sum frequency generation) label-free molecular imaging of intact A. missouriensis sporangia. Spontaneous Raman imaging assisted with multivariate curve resolution-alternating least-squares analysis revealed a novel component in the sporangium membrane that exhibits unique Raman bands at 1550 and 1615 cm-1 in addition to those characteristic of lipids. A plausible candidate for this component is an unsaturated carbonyl compound with an aliphatic moiety derived from fatty acid. Furthermore, second harmonic generation imaging revealed that a layer(s) of the sporangium membrane containing this unknown component has an ordered, noncentrosymmetric structure like fibrillar proteins and amylopectin. Our results suggest that the sporangium membrane is a new type of biological membrane, not only in terms of architecture but also in terms of components. We demonstrate that multimodal molecular imaging with Raman scattering as the core technology will provide a promising platform for interrogating the chemical components, whether known or unknown, of diverse biological structures produced by microbes.

Defining the applicable pathway of laccase pre-treatment in the bio-mineral processing of double refractory gold ores based on carbonaceous matter characterization

Enzymes application in mineral processing is a novel alternative to oxidize carbonaceous matter in double refractory gold ores (DRGOs) and reduce Au(CN)2- adsorption during cyanidation. In this work, contrasting flotation concentrates from DRGOs with different Au(CN)2- affinities were sequentially treated to improve Au cyanidation. Sequential pre-treatment comprised sulfide decomposition and carbonaceous matter degradation through laccase-mediator system (LMS). In addition, carbonaceous matter was characterized from various aspects using Raman spectroscopy, 3D-fluorescence spectrometry, preg-robbing test, and gas chromatography-mass spectrometry (GC-MS). The characterization of the original ores showed that Au(CN)2- adsorption densities were positively correlated with the relative intensities of defective carbon to graphitic carbon obtained in Raman spectra. Degradation of carbonaceous matter through LMS was inhibited by the presence of biopolymers formed during extensive bio-oxidation, thus reconsidering the appropriate sulfide decomposition step. When FeCl3 leaching to decompose sulfides proceeded enzymatic treatment, mass spectra of extracted intermediates from carbonaceous matter suggest the presence of alcohols, fatty acids and aliphatic hydrocarbon moieties, mainly on the most polar solvent fractions. This suggests that enzymatic degradation went through the indirect disturbance of the aromatic planes, making the surface more hydrophilic due to the inclusion of oxygen-containing functional groups, thus improving Au extraction. Finally, the current findings provide a general panorama for selecting the appropriate pre-treatments to maximize gold extraction on DRGOs when using LMS.

Redox conditions influence the chemical composition of iron-associated organic carbon in boreal lake sediments: A synchrotron-based NEXAFS study

The global carbon and iron cycles are intimately linked as redox-sensitive iron oxides readily bind organic carbon in a variety of environmental settings, including marine and lacustrine sediments. While these iron-organic carbon complexes sequester vast quantities of organic carbon, the composition of the organic matter within them remains unknown for lacustrine environments. Here we present C K1s and Fe L3,2 edge Near Edge X-ray Absorption Fine Structure (NEXAFS) spectra of surface sediments and authigenic iron complexes from adjacent basins of a pristine boreal lake located in Québec, Canada, with contrasting oxygen exposure regimes. We demonstrate differences in organic carbon speciation in sediments from both basins, as well as co-localization of organic carbon and iron on a sub-micron scale in 100 nm thick samples. Differences in redox cycling across these two basins allow for a direct comparison of the effect of oscillating redox conditions on the composition of organic carbon sequestered by iron. Our results suggest that reactive organic molecules, which may be polysaccharides, were found preferentially associated with iron in the perennially oxic sediments compared to more phenol rich organics in the seasonally anoxic sediments, highlighting the importance of iron oxides in the protection and preservation of labile organic compounds. Traces of aliphatic carbon were observed in sediments from the anoxic basin, alongside carboxyl and aromatic functionalities. This carboxyl-rich aliphatic material could possibly interact with the sediment mineral matrix either through a ligand exchange mechanism between the mineral phases and the carboxyl functionalities, or via non-specific hydrophobic interactions involving the aliphatic moieties. Finally, our work also shows that OC:Fe ratios should be used with caution when inferring a binding mechanism between OC and iron oxides.

Rh‐catalyzed Hydroamination of Allenes: Asymmetric N‐Allylation of Amino Acids and Peptides

AbstractIn the growing field of peptidomimetics, there is a constant need for new synthetic methods to generate new bioactive compounds. Herein, we present an atom‐economic approach for the branched‐selective allylation of aliphatic amine moieties of α‐amino acids and small oligopeptides. This Rh‐catalyzed hydroamination of allenes with a commercially available ligand forms a new stereocenter, often chemoselectively, in a catalyst‐controlled manner, providing high yields and stereoselectivities without the need for an additive. The method is shown to be effective in gram scale without the need for column chromatography for purification, and ready‐to‐use allylated substrates for solid‐phase peptide synthesis can be synthesized in two steps from the products of the catalysis.

Exploration of cytotoxicity of iodoquinazoline derivatives as inhibitors of both VEGFR-2 and EGFRT790M: Molecular docking, ADMET, design, and syntheses.

Novel inhibitors of epidermal growth factor receptor (EGFR)T790M/vascular endothelial growth factor receptor-2 (VEGFR-2) were synthesized based on the iodoquinazoline scaffold linked to different heteroaromatic, aromatic, and/or aliphatic moieties. The novel derivatives were in vitro examined for anticancer activities against A549, HCT116, michigan cancer foundation-7 (MCF-7), and HepG2 cells. Molecular modeling was applied to discover their orientation of binding with both VEGFR-2 and EGFR active sites. Compounds 8d, 8c, 6d, and 6c indicated the highest cytotoxicity with IC50 = 6.00, 6.90, 6.12 and 6.24 µM, 7.05, 7.35, 6.80, and 6.80 µM, 5.75, 7.50, 6.90, and 6.95 µM, and 6.55, 7.88, 7.44, and 7.10 µM against the A549, HepG2, HCT116, and MCF-7 cell lines, correspondingly. The cytotoxicity against normal VERO (normal african green monkey kidney cells) of the extremely active eight compounds 6a-d and 8a-d was evaluated. Our compounds exhibited low toxicity concerning normal VERO cells with IC50 = 45.66-51.83 μM. Furthermore, inhibition assays for both the EGFRT790M and VEGFR-2 enzymes were done for all compounds. Remarkable inhibition of EGFRT790M activity was achieved with compounds 6d, 8d, 6c, and 8c at IC50 = 0.35, 0.42, 0.48, and 0.50 µM correspondingly. Moreover, remarkable inhibition of VEGFR-2 activity was achieved with compounds 8d, 8c, 6d, and 6c at IC50 = 0.92, 0.95, 1.00, and 1.20 µM correspondingly. As planned, derivatives 6d, 8d, 6c, and 8c presented exceptional inhibition of both EGFRT790M/VEGFR-2 activities. Finally, in silico absorption, distribution, metabolism, excretion and toxicity (ADMET) studies were made for the highly active four compounds 6c, 6d, 8c, and 8d in comparison with erlotinib and sorafenib as reference standards.

Structure-Functional Activity of Pyrone Derivatives for Inhibition of Barnacle Settlement and Biofilm Formation.

Naturally occurring 6-pentyl-2H-pyran-2-one and its synthetic analogues greatly inhibit the settlement of Amphibalanus amphitrite cyprids and the growth and biofilm formation of marine bacteria. To optimize the antifouling activities of pyrone derivatives, this study designed pyrone analogues by modifying functional groups, such as the benzyl group, cyclopentane, and halides, substituted on both sides of a pyrone. The antifouling effects of the synthesized pyrone derivatives were subsequently evaluated against five marine biofilm-forming bacteria, Loktanella hongkongensis, Staphylococcus cohnii, S. saprophyticus, Photobacterium angustum, and Alteromonas macleodii, along with barnacle cyprids of Amphibalanus amphitrite. Substituting nonpolar parts-such as the aliphatic, cyclopentyl, or phenyl moieties on C-5 or the furan moieties on C-3-not only increased antibacterial activity and inhibited biofilm formation but also inhibited barnacle cyprid settlement when compared to 6-pentyl-2H-pyran-2-one.

A combined experimental and theoretical study on the mechanism of catalytic oxidation of lignite to carboxylic acids by iron

The oxygen-oxidation of lignite to carboxylic acids (CAs) using environmentally friendly iron catalyst represents an efficient and clean technology for lignite utilization. However, the mechanism remains unclear due to the difficulty in observing the cleavage of chemical bonds and the challenge in capturing transient intermediates and radicals. In this work, the microscopic reaction mechanism of iron-catalytic oxidation of lignite was investigated by combining experimental and theoretical methods. Catalytic oxidation experiments revealed that water-soluble intermediates generated by solid-state lignite decomposition underwent a continuous carbon–carbon bond cleavage oxidation (including oxidative cleavage of aliphatic moieties and oxidative ring-opening of aromatic moieties) to form CAs with aldehyde moieties as the direct precursor. Based on molecular dynamics simulations and density functional theory, a reaction network from lignite to CAs was proposed. The iron catalyst was present in the form of iron-aqua complexes in the liquid phase and iron-phenyl complexes in the solid phase. These iron-aqua/iron-phenyl complexes could reduce the energies of oxidation reactions, promoting the cleavage of bridge bonds, the formation of o-quinones and the oxidation of aromatic moieties, thus accelerating elementary reactions for the formation of CAs. These findings provide a theoretical support for the oxidation of lignite and an in-depth insight into iron-catalytic mechanism.

Green, facile synthesis and evaluation of unsymmetrical carbamide derivatives as antimicrobial and anticancer agents with mechanistic insights

A very practical method for the synthesis of unsymmetrical carbamide derivatives in good to excellent yield was presented, without the need for any catalyst and at room temperature. Using a facile and robust protocol, fifteen unsymmetrical carbamide derivatives (9–23) bearing different aliphatic amine moieties were designed and synthesized by the reaction of secondary aliphatic amines with isocyanate derivatives in the presence of acetonitrile as an appropriate solvent in good to excellent yields. Trusted instruments like IR, mass spectrometry, NMR spectra, and elemental analyses were employed to validate the purity and chemical structures of the synthesized compounds. All the synthesized compounds were tested as antimicrobial agents against some clinically bacterial pathogens such as Salmonella typhimurium, Bacillus subtilis, Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans. Compounds 15, 16, 17, 19 and 22 showed potent antimicrobial activity with promising MIC values compared to the positive controls. Moreover, compounds 15 and 22 provide a potent lipid peroxidation (LPO) of the bacterial cell wall. On the other hand, we investigated the anti-proliferative activity of compounds 9–23 against selected human cancerous cell lines of breast (MCF-7), colon (HCT-116), and lung (A549) relative to healthy noncancerous control skin fibroblast cells (BJ-1). The mechanism of their cytotoxic activity has been also examined by immunoassaying the levels of key anti- and pro-apoptotic protein markers. The results of MTT assay revealed that compounds 10, 13, 21, 22 and 23 possessed highly cytotoxic effects. Out of these, three synthesized compounds 13, 21 and 22 showed cytotoxicity with IC50 values (13, IC50 = 62.4 ± 0.128 and 22, IC50 = 91.6 ± 0.112 µM, respectively, on MCF-7), (13, IC50 = 43.5 ± 0.15 and 21, IC50 = 38.5 ± 0.17 µM, respectively, on HCT-116). Cell cycle and apoptosis/necrosis assays demonstrated that compounds 13 and 22 induced S and G2/M phase cell cycle arrest in MCF-7 cells, while only compound 13 had this effect on HCT-116 cells. Furthermore, compound 13 exhibited the greatest potency in inducing apoptosis in both cell lines compared to compounds 21 and 22. Docking studies indicated that compounds 10, 13, 21 and 23 could potentially inhibit enzymes and exert promising antimicrobial effects, as evidenced by their lower binding energies and various types of interactions observed at the active sites of key enzymes such as Sterol 14-demethylase of C. albicans, Dihydropteroate synthase of S. aureus, LasR of P. aeruginosa, Glucosamine-6-phosphate synthase of K. pneumenia and Gyrase B of B. subtilis. Moreover, 13, 21, and 22 demonstrated minimal binding energy and favorable affinity towards the active pocket of anticancer receptor proteins, including CDK2, EGFR, Erα, Topoisomerase II and VEGFFR. Physicochemical properties, drug-likeness, and ADME (absorption, distribution, metabolism, excretion, and toxicity) parameters of the selected compounds were also computed.

Revisiting and Updating the Interaction between Human Serum Albumin and the Non-Steroidal Anti-Inflammatory Drugs Ketoprofen and Ketorolac.

Ketoprofen (KTF) and ketorolac (KTL) are among the most primarily used non-steroidal anti-inflammatory drugs (NSAIDs) in humans to alleviate moderate pain and to treat inflammation. Their binding affinity with albumin (the main globular protein responsible for the biodistribution of drugs in the bloodstream) was previously determined by spectroscopy without considering some conventional pitfalls. Thus, the present work updates the biophysical characterization of the interactions of HSA:KTF and HSA:KTL by 1H saturation-transfer difference nuclear magnetic resonance (1H STD-NMR), ultraviolet (UV) absorption, circular dichroism (CD), steady-state, and time-resolved fluorescence spectroscopies combined with in silico calculations. The binding of HSA:NSAIDs is spontaneous, endothermic, and entropically driven, leading to a conformational rearrangement of HSA with a slight decrease in the α-helix content (7.1% to 7.6%). The predominance of the static quenching mechanism (ground-state association) was identified. Thus, both Stern-Volmer quenching constant (KSV) and binding constant (Kb) values enabled the determination of the binding affinity. In this sense, the KSV and Kb values were found in the order of 104 M-1 at human body temperature, indicating moderate binding affinity with differences in the range of 0.7- and 3.4-fold between KTF and KTL, which agree with the previously reported experimental pharmacokinetic profile. According to 1H STD-NMR data combined with in silico calculations, the aromatic groups in relation to the aliphatic moiety of the drugs interact preferentially with HSA into subdomain IIIA (site II) and are stabilized by interactions via hydrogen bonding and hydrophobic forces. In general, the data obtained in this study have been revised and updated in comparison to those previously reported by other authors who did not account for inner filter corrections, spectral backgrounds, or the identification of the primary mathematical approach for determining the binding affinity of HSA:KTF and HSA:KTL.

Identification of EA-3167, a Structural Analogue of the BZ Incapacitant, in Objects Delivered from the Zone of a Special Military Operation and Detection of Its Metabolites in Urine during Exposure of Rats

Earlier, we found that two alcohol-containing samples delivered from the zone of special military operation contain a rare psychoactive substance EA-3167, which is a structural analogue of the well-known incapacitant BZ, included in the Schedule 1 of the Chemical Weapons Convention. In addition to EA-3167, additives of methadone, α-pyrrolidinovalerophenone and tetrahydrocannabinol were found in liquids.The aim of the work is to establish the analytical characteristics of EA-3167, as well as its metabolites in rat urine. Research methods. Structural identification of the detected substance by nuclear magnetic resonance, gas and liquid chromatomass spectrometry of delivered objects and rat urine obtained by exposing laboratory animals to the detected substance.The results of the study. Concentrations of EA-3167 in liquids were found to be 910 and 3.9 μg/mL, respectively. It has been established that EA-3167 is subject to intensive metabolism in rats. More than 30 metabolites, representing products of mono- and dihydroxylation of aliphatic moieties of the molecule, ketone formation, and hydrolysis, have been tentatively identified in the urine of laboratory animals. Conclusion. The most convenient markers for confirming poisoning of EA-3167 by gas and liquid chromatography-mass spectrometry were the parent substance, the products of its monohydroxylation and the formation of carbonyl group on the cyclopentyl moiety.

Dehydrogenative synthesis of N-functionalized 2-aminophenols from cyclohexanones and amines: Molecular complexities via one-shot assembly.

Polyfunctionalized arenes are privileged structural motifs in both academic and industrial chemistry. Conventional methods for accessing this class of chemicals usually involve stepwise modification of phenyl rings, often necessitating expensive noble metal catalysts and suffering from low reactivity and selectivity when introducing multiple functionalities. We herein report dehydrogenative synthesis of N-functionalized 2-aminophenols from cyclohexanones and amines. The developed reaction system enables incorporating amino and hydroxyl groups into aromatic rings in a one-shot fashion, which simplifies polyfunctionalized 2-aminophenol synthesis by circumventing issues associated with traditional arene modifications. The wide substrate scope and excellent functional group tolerance are exemplified by late-stage modification of complex natural products and pharmaceuticals that are unattainable by existing methods. This dehydrogenative protocol benefits from using 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO) as oxidant that offers interesting chemo- and regio-selective oxidation processes. More notably, the essential role of in situ generated water is disclosed, which protects aliphatic amine moieties from overoxidation via hydrogen bond-enabled interaction.

Restricting Conformational Space: A New Blueprint for Electrically Switchable Self-Assembled Monolayers.

Tunnel junctions comprising self-assembled monolayers (SAMs) from liquid crystal-inspired molecules show a pronounced hysteretic current-voltage response, due to electric field-driven dipole reorientation in the SAM. This renders these junctions attractive device candidates for emerging technologies such as in-memory and neuromorphic computing. Here, the novel molecular design, device fabrication, and characterization of such resistive switching devices with a largely improved performance, compared to the previously published work are reported. Those former devices suffer from a stochastic switching behavior limiting reliability, as well as from critically small read-out currents. The present progress is based on replacing Al/AlOx with TiN as a new electrode material and as a key point, on redesigning the active molecular material making up the SAM: a previously present, flexible aliphatic moiety has been replaced by a rigid aromatic linker, thereby introducing a molecular "ratchet". This restricts the possible molecular conformations to only two major states of opposite polarity. The above measures have resulted in an increase of the current density by five orders of magnitude as well as in an ON/OFF conductance ratio which is more than ten times higher than the individual scattering ranges of the high and low resistance states.

Depiction of new flavonoids from Nyctanthus arbor-tristis, their antimicrobial activity and drug-likeness prediction

Bioactive compounds derived from medicinal plants, such as alkaloids, tannins and flavonoids, possess significant medicinal properties. These compounds have a broad and versatile impact on human nutrition and physiology, contributing to the treatment and management of various diseases. The isolation, structure elucidation and inhibition studies of two novel flavonoids against specific microorganisms, from the leaves of Nyctanthus arbor-tristis are reported in this study. It has been observed for the first time that the presence of an acyl aliphatic moiety, along with the O- glycoside unit at C-7, and the hydroxyl group at C-5, C-4′ position in apigenin significantly enhanced antimicrobial activity. Moreover, bioactivity was also investigated through ‘Molinspiration’ on various parameters followed by the ‘rule of five’. This study can be used to highlight the need for the potential development of natural therapeutic products with fewer side effects.

Exchangeable disulfide bond containing highly flexible epoxy vitrimers with shape‐memory, self‐healing, and UV shielding attributes

AbstractWith the rise in momentous resource wastage and severe environmental pollution, a viable path for sustainability is through the use of reprocessable and recyclable materials like vitrimers. Herein, we demonstrated the synthesis of dynamic disulfide‐containing epoxy resin by condensing an amide derivative of 2,2′‐dithiodibenzoic acid with epichlorohydrin. The aforementioned epoxy resin was cured utilizing the two bio‐based curing agents poly(amido amine) and cystamine to produce three distinct epoxy vitrimers. The use of reactive diluent reduced the generation of volatile organic compounds during the curing process. The existence of disulfide bond and aliphatic moiety in the epoxy vitrimers established high elongation at break with good tensile strength. Owing to the dynamic bond, the vitrimers exhibited self‐healing properties with a healing efficiency of 71.48% along with good shape memory abilities. Additionally, the disulfide bond dynamic exchange reaction allowed the polymer chain architecture to topologically reorganize, making them reprocessable and degradable. Moreover, these epoxy vitrimers have the ability to shield ultraviolet radiation as well as inhibits oxidation, and have good chemical resistance properties. The investigated epoxy thermoset thus provides a lot of potential for application as a durable thin film material.

Total synthesis of (±)-auranthine confirmed its refined structure.

Auranthine, isolated in 1986 from Penicillium aurantiogriseum, is a fungal benzodiazepine. Through the successful total synthesis of (±)-auranthine, we confirmed the refined structure of natural (-)-auranthine. We established that natural (-)-auranthine is a fused quinazolino benzodiazepine dione 1 featuring an acyclic aliphatic nitrile moiety, thereby disproving the proposed structure 2.

Efficient catalyst regeneration through solvent-based wax extraction for Co/Al2O3 Fischer-Tropsch catalysts

The regeneration of Fischer-Tropsch (FT) catalysts plays a crucial role in sustaining their catalytic activity and longevity in sustainable production processes. This research investigates the effectiveness of various solvents, including n-hexane, n-heptane, toluene, xylene, and the liquid fraction of FT products (LF-FT), for catalyst regeneration and extracting wax from the 15 wt%Co/Al2O3 catalyst. Toluene, with a unique combination of key parameters such as polarity, solubility, boiling point, aromatic structure, and chemical interactions, exhibited the highest wax removal efficiency of 90.6%. However, due to its 41 °C lower boiling point compared to toluene and very similar wax removal efficiency, n-hexane appears as a more energy-efficient and cost-effective option for this process. The regenerated catalysts showed comparable characteristics, including the textural properties (surface area, pore size, and pore volume), crystallinity, and reducibility, to fresh catalysts. The slightly lower reduction temperature in the regenerated catalyst indicates a higher possibility for the formation of cobalt active sites during the catalyst reduction process with hydrogen, leading to an increased potential for higher catalytic activity. The LF-FT, comprising paraffins, iso-paraffins, olefins, napthenes, and aromatics, provided a unique combination of aliphatic and aromatic moieties, enhancing the solubility of both polar and nonpolar components in FT wax and improving the wax removal efficiency to 91.5%. The higher boiling point and operating temperature of the LF-FT also contributed to its better performance. Efficient separation of hydrocarbons from solvents allowed for solvent reusability in subsequent FT wax removal cycles, making it advantageous for large-scale applications.

Design and synthesis of cantharidin derivative DCZ5418 as a TRIP13 inhibitor with anti-multiple myeloma activity in vitro and in vivo

Natural product cantharidin can inhibit multiple myeloma cell growth in vitro, while serious adverse effects limited its clinical application. Therefore, the structural modification of cantharidin is needed. Herein, inspired by the structural similarity of the aliphatic endocyclic moiety in cantharidin and TRIP13 inhibitor DCZ0415, we designed and synthesized DCZ5418 and its nineteen derivatives. The molecular docking study indicated that DCZ5418 had a similar binding mode to TRIP13 protein as DCZ0415 while with a stronger docking score. Moreover, the bioassay studies of the MM-cells viability inhibition, TRIP13 protein binding affinity and enzyme inhibiting activity showed that DCZ5418 had good anti-MM activity in vitro and definite interaction with TRIP13 protein. The acute toxicity test of DCZ5418 showed less toxicity in vivo than cantharidin. Furthermore, DCZ5418 showed good anti-MM effects in vivo with a lower dose administration than DCZ0415 (15 mg/kg vs 25 mg/kg) on the tumor xenograft models. Thus, we obtained a new TRIP13 inhibitor DCZ5418 with improved safety and good activity in vivo, which provides a new example of lead optimization by using the structural fragments of natural products.

Photolysis Products of Fluorinated Pharmaceuticals: A Combined Fluorine Nuclear Magnetic Resonance Spectroscopy and Mass Spectrometry Approach.

The aqueous photolysis of four pharmaceuticals with varying fluorinated functional groups was assessed under neutral, alkaline, advanced oxidation, and advanced reduction conditions with varying light sources. Solar simulator quantum yields were 2.21 × 10-1 mol Ei-1 for enrofloxacin, 9.36 × 10-3 mol Ei-1 for voriconazole, and 1.49 × 10-2 mol Ei-1 for flecainide. Florfenicol direct photolysis was slow, taking 150 h for three degradation half-lives. Bimolecular rate constants between pharmaceuticals and hydroxyl radicals were 109 to 1010 M-1 s-1. Using a combined quantitative fluorine nuclear magnetic resonance spectroscopy (19F-NMR) and mass spectrometry approach, fluorine mass balances and photolysis product structures were elucidated. Enrofloxacin formed a variety of short-lived fluorinated intermediates that retained the aryl F motif. Extended photolysis time led to complete aryl F mineralization to fluoride. The aliphatic F moiety on florfenicol was also mineralized to fluoride, but the resulting product was a known antibiotic (thiamphenicol). For voriconazole, the two aryl Fs contributed more to fluoride production compared with the heteroaromatic F, indicating higher stability of the heteroaromatic F motif. The two aliphatic CF3 moieties in the flecainide structure remained intact under all conditions, further supporting the stability of these moieties found in per- and polyfluoroalkyl substances under a variety of conditions. The advanced treatment conditions generating hydroxyl radicals or hydrated electrons accelerated the degradation, but not the defluorination, of flecainide. The combination of 19F-NMR and mass spectrometry proved powerful in allowing identification of fluorinated products and verifying the functional groups present in the intermediates and products. The results found in the present study will aid in the understanding of which fluorinated functional groups should be incorporated into pharmaceuticals to ensure organofluorine byproducts are not formed in the environment and help determine the water-treatment processes that effectively remove specific pharmaceuticals and more generally fluorinated motifs. Environ Toxicol Chem 2024;43:2285-2296. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.