Benchtop nuclear magnetic resonance performance evaluation according to ASTM E691-22 on a population of instruments: Molar substitution determination in hydroxypropyl betadex as a case study for use in quality control environments.

The inclusion of quantitative nuclear magnetic resonance (qNMR) spectroscopy in industry has historically been stifled by a lack of accessibility, caused in-part by the large costs of traditional high-field spectrometers, the maintenance required for these, and the expertise necessary to manage and use them. In recent years, the emergence of benchtop NMR technology, an accessible, affordable, and automatable alternative, has led to a more feasible incorporation of NMR into quality control spaces, an area traditionally reserved for other techniques such as gas chromatography and liquid chromatography, which are routinely combined with detection techniques such as mass spectrometry. While these techniques are commonly used in analyzer-type applications using gold standard methods of analysis, wherein an instrument is dedicated to performing specific assays, this remains uncommon for NMR. Herein, we perform a full method verification using benchtop qNMR on a population of benchtop NMR instruments according to the ASTM designation E691-22, a standard used to determine the precision of a test method. To our knowledge, this is the first published example of this type of study for benchtop NMR spectroscopy. For this work, a total of five analysts performed assays on 23 different benchtop NMR instruments for the analysis of hydroxypropyl betadex according to the USP-NF method, and the results are compared using a variety of statistical methods. The results of this work demonstrate that benchtop NMR technology is effective and robust under repeatability and reproducibility conditions and is a powerful tool for these types of routine quality control analyses.

Determination of copolymer compositions in polyhydroxyalkanoates using 1H benchtop nuclear magnetic resonance spectroscopy.

Continuous research into polyhydroxyalkanoates (PHAs), biodegradable polymers which can be produced by, and harvested from, various bacteria has led to more cost-effective ways of isolating and commercializing them. As bio-based polymers, PHAs can be transformed into compostable bioplastics and utilized for a variety of applications. Often isolated as copolymers, the monomeric ratio compositions of these products greatly affect both the properties and consequently, possible end uses of these products. As such, methods of reliably characterizing these ratios are important for quality control and product development purposes. Herein, we discuss how 1H benchtop nuclear magnetic resonance (NMR) instruments can be used for the determination of monomeric ratio compositions in PHAs and compare results obtained at three different NMR field strengths: 1.40 T (60 MHz), 2.35 T (100 MHz), and 9.4 T (400 MHz).

Quantitative analysis of cannabinoids using benchtop NMR instruments.

The quantification of cannabinoids is an essential part of cannabis profiling and testing, whether for medical or recreational use. As regulatory bodies continue to increase testing requirements for these products, it is crucial that alternative and effective analytical methods be developed. Herein, we describe the use of benchtop NMR instruments for the quantification of Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in a variety of cannabis concentrates and compare the values to those obtained using HPLC, the most common approach for the quantification of cannabinoids. Based on the discrepancies observed in test values from different laboratories using only HPLC, the value of orthogonal testing methods has been identified and is increasingly desired.

Transition-Metal-Free Formation of C-E Bonds (E = C, N, O, S) and Formation of C-M Bonds (M = Mn, Mo) from N-Heterocyclic Carbene Mediated Fluoroalkene C-F Bond Activation.

Herein, a recently reported polyfluoroalkenyl imidazolium salt is shown to react with nitrogen-, oxygen- and sulfur-based nucleophiles at the C ß position in a stereoselective and regioselective fashion, without the use of a transition metal. In contrast, reactivity with 1-methylimidazole demonstrates net substitution at C α . This product reacts quantitatively with water, affording clean transformation of a difluoromethylene group to give an α,ß-unsaturated trifluoromethyl ketone. Further reactivity studies demonstrate that the difluoromethyl fragment of an N-heterocyclic fluoroalkene is capable of direct C-C bond formation with NaCp through loss of sodium fluoride and double C-F bond activation (Cp = cyclopentadienide). TD-DFT calculations of this product indicate that both the HOMO and LUMO are of mixed π/π* character and are delocalized over the N-heterocyclic and Cp fragments, giving rise to a very intense absorption feature in the UV-vis spectrum. Additionally, two carbonylmetalate-substituted fluorovinyl imidazolium complexes featuring Mn and Mo were isolated and fully characterized.

Selective Activation of Fluoroalkenes with N-Heterocyclic Carbenes: Synthesis of N-Heterocyclic Fluoroalkenes and Polyfluoroalkenyl Imidazolium Salts.

Selective reactions between nucleophilic N,N'-diaryl-heterocyclic carbenes (NHCs) and electrophilic fluorinated alkenes afford NHC fluoroalkenes in high yields. These stable compounds undergo efficient and selective fluoride abstraction with Lewis acids to give polyfluoroalkenyl imidazolium salts. These salts react at Cß with pyrrolidine to give ammonium fluoride-substituted salts, which give rise to conjugated imidazolium-enamine salts through loss of HF. Alternatively, reaction with 4-(dimethylamino)-pyridine provides a Cα-pyridinium-substituted NHC fluoroalkene. These compounds were studied using multinuclear NMR spectroscopy, mass spectrometry, and X-ray crystallography. Insight into their electronic structure and reactivity was gained through the use of DFT calculations.

Perfluoroalkyl Cobalt(III) Fluoride and Bis(perfluoroalkyl) Complexes: Catalytic Fluorination and Selective Difluorocarbene Formation.

Four perfluoroalkyl cobalt(III) fluoride complexes have been synthesized and characterized by elemental analysis, multinuclear NMR spectroscopy, X-ray crystallography, and powder X-ray diffraction. The remarkable cobalt fluoride (19)F NMR chemical shifts (-716 to -759 ppm) were studied computationally, and the contributing paramagnetic and diamagnetic factors were extracted. Additionally, the complexes were shown to be active in the catalytic fluorination of p-toluoyl chloride. Furthermore, two examples of cobalt(III) bis(perfluoroalkyl)complexes were synthesized and their reactivity studied. Interestingly, abstraction of a fluoride ion from these complexes led to selective formation of cobalt difluorocarbene complexes derived from the trifluoromethyl ligand. These electrophilic difluorocarbenes were shown to undergo insertion into the remaining perfluoroalkyl fragment, demonstrating the elongation of a perfluoroalkyl chain arising from a difluorocarbene insertion on a cobalt metal center. The reactions of both the fluoride and bis(perfluoroalkyl) complexes provide insight into the potential catalytic applications of these model systems to form small fluorinated molecules as well as fluoropolymers.

Alkaline-earth metal carboxylates characterized by 43Ca and 87Sr solid-state NMR: impact of metal-amine bonding.

A series of calcium and strontium complexes featuring aryl carboxylate ligands has been prepared and characterized by alkaline-earth ((43)Ca and (87)Sr) solid-state NMR experiments in a magnetic field of 21.1 T. In the 11 compounds studied as part of this work, a range of coordination motifs are observed including nitrogen atom binding to Ca(2+) and Sr(2+), a binding mode which has not been investigated previously by (43)Ca or (87)Sr solid-state NMR. (43)Ca isotopic enrichment has enabled the full characterization of the (43)Ca electric field gradient (EFG) and chemical shift tensors of the two calcium sites in calcium p-aminosalicylate (Ca(pams)), where both NMR interactions are affected by the presence of a nitrogen atom in the first coordination sphere of one of the metal sites. The (43)Ca isotropic chemical shift is sensitive to the Ca-N distance as exemplified by the NMR parameters of a second form of Ca(pams) and density functional theory (DFT) calculations. Studies of the strontium analogue, Sr(pams), confirm a similar sensitivity of the (87)Sr EFG tensor to the presence or absence of nitrogen in the first coordination sphere. To our knowledge, this is the first systematic (87)Sr NMR study of strontium complexes featuring organic ligands. The |CQ((87)Sr)| values are found to be sensitive to the coordination number about Sr(2+). In general, this work has also established a larger data set of reliable experimental |CQ((43)Ca)| values which correlate well with those obtained using gauge-including projector-augmented-wave (GIPAW) DFT calculations. It is found that the use of a recently recommended quadrupole moment for (43)Ca, -44.4 mbarn, improves the agreement with experimental values. This contribution lays the groundwork for the interpretation of (43)Ca and (87)Sr NMR spectra of more challenging systems, particularly where nitrogen-alkaline earth metal bonding is occurring.

Cobalt fluorocarbenes: cycloaddition reactions with tetrafluoroethylene and reactivity of the perfluorometallacyclic products.

Cobalt fluorocarbene complexes CpCo(═CFR(F))(PPh2Me) (Cp = η(5)-C5H5, R(F) = F or CF3) react with tetrafluoroethylene to give the metallacyclobutanes CpCo(κ(2)-CFR(F)CF2CF2-)(PPh2Me) in the first examples of cycloaddition reactions between perfluoroalkenes and metal perfluorocarbenes. The metallacyclic products undergo a variety of reactions upon activation of the C-F bonds, including Brønsted acid-catalyzed C-F/Co-C scrambling. Implications for metal-catalyzed metathesis and polymerization of perfluoroalkenes are discussed.

Insight into magnesium coordination environments in benzoate and salicylate complexes through 25Mg solid-state NMR spectroscopy.

We report on the (25)Mg solid-state nuclear magnetic resonance (NMR) characterization of a series of magnesium complexes featuring Mg(2+) ions in organic coordination environments. Six compounds have been synthesized with benzoate and salicylate ligands, which are typically used as linkers in metal organic frameworks (MOFs). The use of ultrahigh-field solid-state NMR has revealed a relatively large range of values for the (25)Mg quadrupolar coupling constant, CQ((25)Mg), in these compounds. In contrast to some previously studied inorganic Mg(2+) complexes, the values of CQ((25)Mg) in organic Mg(2+) complexes are well rationalized by the degree of octahedral strain of the "MgO6" coordination polyhedra. (13)C and (25)Mg isotropic chemical shifts were also found to be sensitive to the binding mode of the carboxylate ligands. The experimental findings are corroborated by gauge-including projector-augmented-wave (GIPAW) density functional theory (DFT) computations, and these have allowed for an interpretation of the experimentally observed trend in the CQ((25)Mg) values and for the visualization of the EFG tensor principal components with respect to the molecular structure. These new insights may prove to be valuable for the understanding and interpretation of (25)Mg NMR data for Mg(2+) ions in organic binding environments such as those found in MOFs and protein-divalent metal binding sites.