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The synthesis of a series of 2- and 8-substituted 4-amino-7-chloroquinolines is presented. Starting from 4,7-dichloroquinolines, the chloro in the 4-position can be effectively substituted using amino alcohols to yield novel analogues of the antimalarial (hydroxy)chloroquine. Both short-chain (2-aminoethanol) and long-chain (5-[N-ethyl-N-(2-hydroxyethyl)amino]-2-aminopentane) coupling partners can be used. While ketone and nitro functionalities were found to be incompatible with the coupling conditions, electron-donating amino and dimethylamino substituents were tolerated. In addition to characterization in solution using multinuclear NMR spectroscopy and high-resolution mass spectrometry, single-crystal X-ray structures are presented of two 4,7-dichloroquinolines as well as three of the N-alkylated products including a unique species in which a pyrrole heterocycle formed at the 2-position of the quinoline subunit and a rare example of a 4-aza-1,10-phenanthroline. Key words: chloroquine analogues, quinoline synthesis, X-ray crystallography, Introduction Quinoline (benzo[b]pyridine) is a prominent pharmacophore, appearing in numerous biologically active synthetic molecules and natural products including prominent antimalarials such as the cinchona alkaloid quinine and the clinically critical [...]

Carmofur, a 5-fluorouracil (5-FU) derivative, was initially developed as an antineoplastic agent to treat colorectal cancer. Through drug repurposing efforts, it has been identified as a potent covalent inhibitor of the main protease of SARS-CoV-2 ([M.sup.pro]), making it a promising therapeutic agent against COVID-19. However, previous synthetic procedures suffer from low yields or long reaction times. In this study, benchtop [.sup.19]F nuclear magnetic resonance (NMR) spectroscopy enables the realtime quantitative monitoring and characterization of the synthesis of carmofur by providing kinetic insight. Furthermore, its proton lock capabilities no longer require the use of deuterated solvents and have enabled convenient and rapidly scalable synthesis of our compound. Here, we present the application of benchtop [.sup.19]F NMR as an efficient method for optimizing the synthesis of carmofur and its future application in the synthesis of related 5-FU analogs. Key words: carmofur, benchtop nuclear magnetic resonance spectroscopy, [.sup.19]F NMR, reaction monitoring, reaction optimization, Introduction Fluorinated bioactive small molecules have a remarkable role in modern medicinal chemistry, as the incorporation of fluorine into drug candidates enhances their bioavailability, metabolic stability, and binding affinity to [...]

Orb-weaving spiders produce up to seven silk types, each with distinct biological roles, protein compositions, and mechanics. Pyriform (or piriform) silk is composed of pyriform spidroin 1 (PySp1) and is the fibrillar component of attachment discs that attach webs to substrates and to each other. Here, we characterize the 234-residue repeat unit (the 'Py unit') from the core repetitive domain of Argiope argentata PySp1. Solution-state nuclear magnetic resonance (NMR) spectroscopy-based backbone chemical shift and dynamics analysis demonstrate a structured core flanked by disordered tails, structuring that is maintained in a tandem protein of two connected Py units, indicative of structural modularity of the Py unit in the context of the repetitive domain. Notably, AlphaFold2 predicts the Py unit structure with low confidence, echoing low confidence and poor agreement to the NMR-derived structure for the Argiope trifasciata aciniform spidroin (AcSp1) repeat unit. Rational truncation, validated through NMR spectroscopy, provided a 144-residue construct retaining the Py unit core fold, enabling near-complete backbone and side chain [.sup.1]H, [.sup.13]C, and [.sup.15]N resonance assignment. A six [alpha]-helix globular core is inferred, flanked by regions of intrinsic disorder that would link helical bundles in tandem repeat proteins in a beads-on-a-string architecture. Key words: recombinant silk, attachment silk, chemical shift assignment, backbone structure and dynamics, beads-on-a-string, Introduction Spider silks are renowned for their strength and toughness (Lewis 2006; Yarger et al. 2018; Blamires 2022), exhibit tunability in these properties (Teule et al. 2012; Simmons et al. [...]

ansa-Ferrocenes with pyrazahole bridges are chemically robust entities and therefore suitable building blocks for the synthesis of rigid-rod polymers that combine redox-active Fe(II) centers and beltene-like [pi] faces. The specific monomers we developed bear OEt groups at both tetracoordinated boron atoms (for solubility reasons) and ethynyl substituents at the 4-positions of the two pyrazole rings. Polymerization was accomplished by a condensation reaction with 1,4-diiodobenzene using a Sonogashira-Hagihara-type protocol. As a result, oligomers with a number-average molecular weight of [M.sub.n] = 7.6 kDa and dispersity of D= 1.55 were obtained, suggesting an average chain length of about 14 repeating units based on gel permeation chromatography analysis in THF relative to narrow polystyrene standards. The molecular weight determination was complemented by MALDI-TOF mass spectrometry and (heteronuclear) NMR spectroscopy to verify the intact pyrazabole monomer repeat units and the nature of the end groups. The oligomers were further characterized by UV-vis spectroscopy and cyclic voltammetry which demonstrated the successful synthesis of a new class of redox-active materials. Key words: boron, ferrocene, organometallic polymer, pyrazabole Les ansa-ferrocènes avec ponts pyrazabole sont des entités chimiquement robustes et peuvent donc servir d'unités de base pour la synthèse de polymères à tiges rigides qui comportent à la fois des atomes centraux de Fe(II) présentant une activité rédox et des faces [pi] de type beltène. Les monomères précis que nous avons mis au point portent des groupes OEt sur les deux atomes de bore tétracoordonnés (pour des raisons de solubilité) et des substituants éthynyles en position 4 des deux cycles pyrazole. Nous avons réalisé la polymérisation par condensation avec le 1,4-diiodobenzène en utilisant une méthode de type Sonogashira-Hagihara. Nous avons ainsi obtenu des oligomères dont le poids moléculaire moyen [M.sub.n] est de 7,6 kDa et l'indice de dispersité D, de 1,55, et dont la longueur moyenne des chaînes est d'environ 14 unités répétitives d'après la comparaison par chromatographie sur gel perméable (GPC) dans le THF à des étalons de polystyrène à intervalles étroits de longueur de chaîne. Nous avons déterminé le poids moléculaire par spectrométrie de masse MALDI-TOF et confirmé la présence des unités répétitives intactes du monomère pyrazabole ainsi que la nature des groupes terminaux par spectroscopic RMN (hétéroonucléaire). Les oligomères ont été caractérisés par spectroscopic UV-visible et voltampérométrie cyclique, ce qui a permis de confirmer la synthèse d'une nouvelle classe de matériaux présentant une activité rédox. [Traduit par la Rédaction] Mots-clés : bore, ferrocéne, polymère organométallique, pyrazabole, Introduction Organometallic macromolecules are a class of materials that often possess useful optical, electronic, and magnetic properties. (1) Ferrocene is a particularly valuable building block in this context as it [...]

Lignin is quickly emerging as a biomass-derived source for the production of some crucial organic chemistry building blocks, typically obtained from unsustainable and non-renewable petroleum feedstocks. As a complex polymer, lignin characterization is often challenging due to its random structure and multitudes of different repeating substructures. Over the last 20 years, advances in our understanding and processing of lignin, as well as important work on its characterization using (31) P NMR, have led to numerous publications highlighting the many potential uses of this material. With the emergence of high-resolution benchtop NMR instruments, these types of analyses can now be accessed by many laboratories and industries that have historically not been able to take advantage of NMR due to cost or size constraints. Herein, we demonstrate that bench-top NMR is a viable technique for the (31) P NMR analysis of lignin and compare our results to those obtained on a traditional high-field instrument. Key words: lignin, wood chemistry, benchtop nuclear magnetic resonance, biomass, (31) P NMR La lignine est en voie de rapidement devenir une nouvelle source derivee de la biomasse pour la production de certains synthons essentiels en chimie organique qui sont habituellement obtenus a partir de matieres premieres petrolieres non renouvelables et non durables. La lignine etant un polymere complexe, sa caracterisation est souvent difcile, en raison de sa structure aleatoire et de la presence d'une multitude de repetitions de differentes sous-structures. Au cours des 20 dernieres annees, les avancees dans notre comprehension de la lignine et dans les procedes de traitement de cette matiere, ainsi que les importants travaux sur sa caracterisation a l'aide de la RMN du (31) P, ont mene a de nombreuses publications mettant en evidence les nombreuses possibilites d'application de ce materiau. Avec l'emergence des modeles de spectrometres RMN de paillasse a haute resolution, ces types d'analyses sont desormais accessibles a de nombreux laboratoires et etablissements industriels qui n'avaient jamais pu auparavant beneficier de la RMN en raison de contraintes de cout ou d'espace. Dans le cadre des presents travaux, nous demontrons que la RMN de paillasse est une technique convenable pour l'analyse de la lignine par RMN du (31) P et nous comparons nos resultats a ceux obtenus sur un instrument classique a haut champ. [Traduit par la Redaction] Mots-cles : lignine, chimie du bois, resonance magnetique nucleaire de paillasse, biomasse, RMN du (31) P, Introduction The need for the development and widespread incorporation of renewable resources into society has been clear for decades, as climate change, energy security, and dwindling petroleum feedstocks make it [...]

Detailed syntheses are reported for the previously reported homoleptic 1-norbornyl complexes [M([norb).sub.4]] {M = Ti (1), Zr (3), Hf (4), and Mn (5)}. These compounds were characterized by combustion elemental analysis, NMR spectroscopy single crystal X-ray diffraction (for 1 and 3), and SQUID magnetometry (for 5). The reaction by-product [{([norb).sub.3][Ti}.sub.2]([micro]-0)] (2) was also spectroscopically and structurally characterized. To assess the potential viability of 1 and 3-5 as precursors for thin film deposition by CVD or ALD, their volatility and thermal stability were evaluated by sublimation, thermogravimetric analysis, and in the case of 4, bulk thermolysis. Key words: homoleptic 1-norbornyl complexes, titanium, zirconium, hafnium, manganese Nous presentons des protocoles detailles pour la synthese des complexes homoleptiques de 1 norbornyle publies anterieurement [M([norb).sub.4]] {M = Ti (1), Zr (3), Hf (4) et Mn (5)}. Nous avons caracterise ces composes par analyse elementaire par combustion, spectroscopie de resonance magnetique nucleaire (RMN), diffraction des rayons X sur monocristal (dans le cas des complexes 1 et 3) et magnetometrie a interferometre quantique supraconducteur (SQUID pour Superconducting Quantum Interference Device) (dans le cas du complexe 5). Le sous-produit de la reaction [{([norb).sub.3][Ti}.sub.2]([micro]-0)] (2) a egalement ete caracterise par analyse spectroscopique et structurale. Ann d'evaluer si les complexes 1 et 3 a 5 pourraient etre des precurseurs viables pour le depot chimique en phase vapeur (CVD pour Chemical Vapor Deposition) de couches minces, ou le depot de couches atomiques (ALD pour Atomic Layer Deposition), nous avons mesure leur volatilite et leur stabilite thermique par sublimation et par analyse thermogravimetrique, et dans le cas du complexe 4, par thermolyse de l'echantillon. [Traduit par la Redaction] Mots-cles : complexes homoleptiques de 1-norbornyle, titane, zirconium, hafnium, manganese, Introduction Homoleptic alkyl complexes, with or without additional neutral Lewis base coordination, are of interest as starting materials for the synthesis of new alkyl derivatives (via alkane elimination), (1) as [...]

Nonalcoholic steatohepatitis (NASH), a chronic liver disease without an approved therapy, is associated with lipotoxicity and insulin resistance and is a major cause of cirrhosis and hepatocellular carcinoma. Aramchol, a partial inhibitor of hepatic stearoyl-CoA desaturase (SCD1) improved steatohepatitis and fibrosis in rodents and reduced steatosis in an early clinical trial. ARREST, a 52-week, double-blind, placebo-controlled, phase 2b trial randomized 247 patients with NASH (n = 101, n = 98 and n = 48 in the Aramchol 400 mg, 600 mg and placebo arms, respectively; NCT02279524). The primary end point was a decrease in hepatic triglycerides by magnetic resonance spectroscopy at 52 weeks with a dose of 600 mg of Aramchol. Key secondary end points included liver histology and alanine aminotransferase (ALT). Aramchol 600 mg produced a placebo-corrected decrease in liver triglycerides without meeting the prespecified significance (-3.1, 95% confidence interval (CI) -6.4 to 0.2, P = 0.066), precluding further formal statistical analysis. NASH resolution without worsening fibrosis was achieved in 16.7% (13 out of 78) of Aramchol 600 mg versus 5% (2 out of 40) of the placebo arm (odds ratio (OR) = 4.74, 95% CI = 0.99 to 22.7) and fibrosis improvement by [greater than or equal to]1 stage without worsening NASH in 29.5% versus 17.5% (OR = 1.88, 95% CI = 0.7 to 5.0), respectively. The placebo-corrected decrease in ALT for 600 mg was -29.1 IU l.sup.-1 (95% CI = -41.6 to -16.5). Early termination due to adverse events (AEs) was In a phase 2b study, inhibition of hepatic stearoyl-CoA desaturase in patients with nonalcoholic steatohepatitis was safe and tolerated; although reductions in liver fat were not significant, changes in liver enzymes and histology were observed., Author(s): V. Ratziu [sup.1] , L. de Guevara [sup.2] , R. Safadi [sup.3] , F. Poordad [sup.4] , F. Fuster [sup.5] , J. Flores-Figueroa [sup.6] , M. Arrese [sup.7] , [...]

Diglycidyl ether Schiff base monomers were prepared from vanillin and various diamines. FT-IR, [sup.1]H NMR, [sup.13]C NMR, and mass spectroscopy were used to determine their structure. Cured thermoset epoxies made with them were compared to commercial epoxy in terms of mechanical properties. Tensile strengths ranged from 35.1 to 60.4 MPa, Young's modulus from 3.9 to 6.9 GPa, similar to the commercial product. The glass transition ranged from 80 to 117[degrees]C, the phase transition [T.sub.[alpha]] from 80 to 121[degrees]C and the storage modulus from 2 to 3.5 GPa. Thermogravimetric analysis showed that the vanillin-based epoxies were less heat resistant but had higher residual mass (20-30% wt/wt). Hydrolysis, hydrophobicity and degradation were also monitored to evaluate their potential for coating applications. KEYWORDS biosourced, bisphenol A, epoxy, thermoset, vanillin, 1 | INTRODUCTION Thermoset plastics are used widely in coating and composite applications, due to their high strength modulus and resistance to heat and chemical hydrolysis. [1-5] They are characterized [...]

Phases of matter are usually identified through spontaneous symmetry breaking, especially regarding unconventional superconductivity and the interactions from which it originates. In that context, the superconducting state of the quasi-two-dimensional and strongly correlated perovskite Sr.sub.2RuO.sub.4 is considered to be the only solid-state analogue to the superfluid .sup.3He-A phase.sup.1,2, with an odd-parity order parameter that is unidirectional in spin space for all electron momenta and breaks time-reversal symmetry. This characterization was recently called into question by a search for an expected 'split' transition in a Sr.sub.2RuO.sub.4 crystal under in-plane uniaxial pressure, which failed to find any such evidence; instead, a dramatic rise and a peak in a single-transition temperature were observed.sup.3,4. Here we use nuclear magnetic resonance (NMR) spectroscopy of oxygen-17, which is directly sensitive to the order parameter via hyperfine coupling to the electronic spin degrees of freedom, to probe the nature of superconductivity in Sr.sub.2RuO.sub.4 and its evolution under strain. A reduction of the Knight shift is observed for all strain values and at temperatures below the critical temperature, consistent with a drop in spin polarization in the superconducting state. In unstrained samples, our results contradict a body of previous NMR work reporting no change in the Knight shift.sup.5 and the most prevalent theoretical interpretation of the order parameter as a chiral p-wave state. Sr.sub.2RuO.sub.4 is an extremely clean layered perovskite and its superconductivity emerges from a strongly correlated Fermi liquid, and our work imposes tight constraints on the order parameter symmetry of this archetypal system. .sup.17O nuclear magnetic resonance measurements on Sr.sub.2RuO.sub.4 reveal a drop of the Knight shift in the superconducting state, contradicting previous work and imposing tight constraints on the order parameter symmetry of the system., Author(s): A. Pustogow [sup.1] , Yongkang Luo [sup.1] [sup.2] , A. Chronister [sup.1] , Y.-S. Su [sup.1] , D. A. Sokolov [sup.3] , F. Jerzembeck [sup.3] , A. P. Mackenzie [...]

Nuclear magnetic resonance (NMR) spectroscopy is a powerful technique for analysing the structure and function of molecules, and for performing three-dimensional imaging of their spin densities. At the heart of NMR spectrometers is the detection of electromagnetic radiation, in the form of a free induction decay signal.sup.1, generated by nuclei precessing around an applied magnetic field. Whereas conventional NMR requires signals from 10.sup.12 or more nuclei, recent advances in sensitive magnetometry.sup.2,3 have dramatically lowered the required number of nuclei to a level where a few or even individual nuclear spins can be detected.sup.4-6. It is unclear whether continuous detection of the free induction decay can still be applied at the single-spin level, or whether quantum back-action (the effect that a detector has on the measurement itself) modifies or suppresses the NMR response. Here we report the tracking of single nuclear spin precession using periodic weak measurements.sup.7-9. Our experimental system consists of nuclear spins in diamond that are weakly interacting with the electronic spin of a nearby nitrogen vacancy centre, acting as an optically readable meter qubit. We observe and minimize two important effects of quantum back-action: measurement-induced decoherence.sup.10 and frequency synchronization with the sampling clock.sup.11,12. We use periodic weak measurements to demonstrate sensitive, high-resolution NMR spectroscopy of multiple nuclear spins with a priori unknown frequencies. Our method may provide a useful route to single-molecule NMR.sup.13,14 at atomic resolution. Periodic weak measurements of just a few carbon-13 nuclear spins in diamond demonstrate sensitive, high-resolution nuclear magnetic resonance spectroscopy at the molecular level., Author(s): K. S. Cujia [sup.1] , J. M. Boss [sup.1] , K. Herb [sup.1] , J. Zopes [sup.1] , C. L. Degen [sup.1] Author Affiliations: (1) Department of Physics, ETH [...]

We consider methods for the mathematical preprocessing of signals in the spectrometric analysis of multicomponent mixtures using chemometric algorithms aimed at adjusting the baseline, experimental noise, and random shift of spectral bands. Practical examples of using simple mathematical operations (scaling, centering, derivatization) are given. The effectiveness of algorithms is illustrated by a wide range of spectroscopic signals (electronic absorption, IR, and NMR spectra) combined with chemometric methods of principal component analysis and independent component analysis. Keywords: spectrometry, chemometrics, data preprocessing, spectral artifacts, The preprocessing of spectra is an integral part of any chemometric analysis, aimed at eliminating unwanted variations in the experimental data. It is known that the selection of a method [...]

Abstract In this work, the application of hyperbranched polyglycerol as a performance additive for water-based printing inks is demonstrated. The hyperbranched polyglycerol, (BPG), was synthesized through anionic ring-opening polymerization from [...]

Animal models suggest that acetylcarnitine production is essential for maintaining metabolic flexibility and insulin sensitivity. Because current methods to detect acetylcarnitine involve biopsy of the tissue of interest, noninvasive alternatives to measure acetylcarnitine concentrations could facilitate our understanding of its physiological relevance in humans. Here, we investigated the use of long-echo time (TE) proton magnetic resonance spectroscopy (¹H-MRS) to measure skeletal muscle acetylcarnitine concentrations on a clinical 3T scanner. We applied long-TE 1H-MRS to measure acetylcarnitine in endurance-trained athletes, lean and obese sedentary subjects, and type 2 diabetes mellitus (T2DM) patients to cover a wide spectrum in insulin sensitivity. A long-TE ¹H-MRS protocol was implemented for successful detection of skeletal muscle acetylcarnitine in these individuals. There were pronounced differences in insulin sensitivity, as measured by hyperinsulinemic-euglycemic clamp, and skeletal muscle mitochondrial function, as measured by phosphorus-MRS ([sup.31]P-MRS), across groups. Insulin sensitivity and mitochondrial function were highest in trained athletes and lowest in T2DM patients. Skeletal muscle acetylcarnitine concentration showed a reciprocal distribution, with mean acetylcarnitine concentration correlating with mean insulin sensitivity in each group. These results demonstrate that measuring acetylcarnitine concentrations with ¹H-MRS is feasible on clinical MR scanners and support the hypothesis that T2DM patients are characterized by a decreased formation of acetylcarnitine, possibly underlying decreased insulin sensitivity., Introduction The use of proton magnetic resonance spectroscopy ('H-MRS) in human skeletal muscle has been instrumental in establishing the importance of ectopic fat accumulation in the development of type 2 [...]

Despite the central role of the liver in the regulation of glucose and lipid metabolism, there are currently no methods to directly assess hepatic oxidative metabolism in humans in vivo. [...]

In this study, we monitored glycolysis in mouse lymphoma and lung tumors by measuring the conversion of hyperpolarized [U-[sup.2.sup.]H], [U-[sup.13.sup.]C]]glucose to lactate using [sup.13.sup.]C] magnetic resonance spectroscopy and spectroscopic imaging. [...]