Sodium Amide Research Articles

An N‐Heterocyclic Germylene and Stannylene with a 1,1’‐Ferrocenylene Backbone and Dimesitylboryl N‐Substituents

AbstractThe diaminoferrocene derivative fc[NH(BMes2)]2 (1H2; fc=1,1’‐ferrocenylene, Mes=mesityl) was prepared from fc(NH2)2 and Mes2BCl and used for the preparation of the N‐heterocyclic tetrylenes fc{[N(BMes2)]2E} (1E, E=Ge, Sn) via the sodium amide fc[NNa(BMes2)]2 (1Na2), which was obtained from 1H2 and NaN(SiMe3)2. 1H2 is inert towards LiN(SiMe3)2 or nBuLi. Its reaction with nBuLi in the presence of TMEDA afforded the TMEDA‐coordinated lithium amide 1Li2(TMEDA)2. Crystallisation of 1Na2 from THF furnished the adduct 1Na2(THF)3. The reaction of 1Na2 with Me3SiCl afforded 1(SiMe3)2. Attempts to obtain the thiourea fc{[N(BMes2)]2C=S} (1C=S) from 1Na2 and Cl2C=S were not successful. 1C=S is accessible from fc(NH3)Cl2, which is transformed to fc[(NH)2C=S] (2) by reaction with Cl2C=S and NEt3 (4 equiv.), followed by conversion of 2 to fc{[N(SiMe3)]2C=S} (3) with Me3SiCl and NEt3 (2 equiv.) and subsequent reaction of 3 with Mes2BCl. All new compounds except 1Na2 and 2 were structurally characterised by single‐crystal X‐ray diffraction. The N‐boryl substituents of 1E compete efficiently with the EII atom for nitrogen π‐donation, causing comparatively long EII−N bonds and small EII bond angles. 1C=S contains a four‐membered BNCS ring due to intramolecular adduct formation involving the Lewis basic S atom and a Lewis acidic B atom.

Study of GaN solubility in ammonothermal alkaline solution

The solubility of gallium nitride in supercritical ammonia containing an alkaline mineralizer, sodium amide, was investigated. Twenty dissolution processes were carried out at constant ammonia pressure and constant mineralizer concentration. In each process, the solubility of four ammonothermal GaN crystals was analyzed at four different temperatures and five different times. By analyzing the total mass loss of all crystals in a given process, the time interval at which the solubility of GaN stopped changing was determined, indicating the saturated state of the solution. Based on these data, the solubility curve was determined. Retrograde solubility was observed. The impact of surface preparation of GaN samples and its correlation with the quantity of dissolved material was investigated. It was shown that as-grown and optically smooth surfaces dissolved slower than mechanically treated (000-1) GaN surfaces. These are important data for ammonothermal crystallization processes using native GaN seeds with differently prepared (000-1) surfaces.

Alkene Isomerisation Catalysed by a Superbasic Sodium Amide.

Typically catalysed by transition metals, alkene isomerisation is a powerful methodology for preparation of internal olefins. In contrast, the use of more earth abundant main group reagents is limited to activated substrates, requiring high temperatures and excess stoichiometric amounts. Opening a new avenue for progressing this field, here we report applications of bulky sodium amide NaTMP (TMP=2,2,6,6-tetramethylpiperidide) when partnered with tridentate Lewis donor PMDETA (N,N,N',N'',N''-pentamethyldiethylenetriamine) in catalytic alkene isomerisation of terminal olefins under mild reaction conditions. An array of distinct olefins could successfully be isomerised, including unactivated olefins, allylamines, and allylethers, showing the high activity of this partnership. In-depth mechanistic insights provided by X-ray crystallography, real-time nuclear magnetic resonance (NMR) monitoring, and density functional theory (DFT) calculations have unveiled the crucial role of in situ-generated TMP(H) in facilitating efficient isomerisation, and the choice of alkali-metal. Additionally, theoretical studies shed light on the observed E/Z selectivity, particularly accounting for the selective formation of Z-vinyl ethers. The versatility of our method is further demonstrated through the isomerisation of unactivated cycloalkenes, which undergo hydrogen isotope exchange to produce deuterated compounds.

Alkene Isomerisation Catalysed by a Superbasic Sodium Amide

AbstractTypically catalysed by transition metals, alkene isomerisation is a powerful methodology for preparation of internal olefins. In contrast, the use of more earth abundant main group reagents is limited to activated substrates, requiring high temperatures and excess stoichiometric amounts. Opening a new avenue for progressing this field, here we report applications of bulky sodium amide NaTMP (TMP=2,2,6,6‐tetramethylpiperidide) when partnered with tridentate Lewis donor PMDETA (N,N,N′,N′′,N’’‐pentamethyldiethylenetriamine) in catalytic alkene isomerisation of terminal olefins under mild reaction conditions. An array of distinct olefins could successfully be isomerised, including unactivated olefins, allylamines, and allylethers, showing the high activity of this partnership. In‐depth mechanistic insights provided by X‐ray crystallography, real‐time nuclear magnetic resonance (NMR) monitoring, and density functional theory (DFT) calculations have unveiled the crucial role of in situ‐generated TMP(H) in facilitating efficient isomerisation, and the choice of alkali‐metal. Additionally, theoretical studies shed light on the observed E/Z selectivity, particularly accounting for the selective formation of Z‐vinyl ethers. The versatility of our method is further demonstrated through the isomerisation of unactivated cycloalkenes, which undergo hydrogen isotope exchange to produce deuterated compounds.

Development of Sterically Hindered and Basic Sodium Amides for Catalytic Hydrogen Isotope Exchange

AbstractSodium amides are gaining momentum in synthetic chemistry, emerging not only as more sustainable alternatives to lithium amides but also as superior reagents in synthesis and catalysis. Despite recent advances in sodium organometallics, the information available about the constitution of these reagents is very limited. Advancing the understanding on structure/reactivity correlations in sodium amide chemistry, here, we report the synthesis and characterisation of four new sodium amides, with different sterically demanding substituents (adamantyl/trimethylsilyl and dicyclohexyl groups at the nitrogen atom) and different polyamine donors as well as investigate their ability to promote catalytic hydrogen isotope exchange using deuterated benzene as deuterium source. These studies have revealed that sodium dicyclohexylamide in combination with PMDETA (N,N,N’,N’’,N’’‐pentamethyldiethylentriamine) offers only slightly lower deuterium incorporation for non‐activated arenes than sodium 2,2,6,6‐tetramethylpiperidide, which is significantly more expensive and less available.

One-Step Cascade Synthesis of ortho-bay-Imidazolo-Extended Perylene Biscarboximides (OBISIM) and Their Application as Broad-Spectrum Fluorescent Dyes.

A one-step synthesis of perylene dyes with lateral extension by condensed imidazoles in a cascade reaction of sodium amide and benzonitrile is described in which multiple extensions can be controlled by the reaction conditions. The extensions lead to bathochromic shifts in absorption and fluorescence while maintaining high fluorescence quantum yields. The condensed imidazole units cause additional absorption bands in the hypsochromic visible region, resulting in broad-band absorbers. Multiple extensions of the aromatic system enable the NIR spectral approach of the spectra. Energy transfer (fluorescence resonance energy transfer, FRET) of dyads with perylene biscarboximides is very efficient and achieves quantum yields close to unity regardless of the lengths and orientation of the spacer. Applications as broad-band-absorbing fluorescent dyes, such as in solar collectors, are discussed.

Low temperature and facile synthesis of nitrogen-doped hierarchical porous carbon derived from waste polyethylene terephthalate for efficient CO2 capture

Waste polyethylene terephthalate (PET) with high carbon content (>60 wt%) has shown great potential in the field of synthesizing carbon materials for CO2 capture, attracting increasing attention. Herein, an innovative strategy was proposed to synthesize nitrogen-doped hierarchical porous carbon (PC) for CO2 capture using PET as precursor and sodium amide (NaNH2) as both nitrogen dopant and low-temperature activator. As-synthesized N-doped PC exhibited a significantly high micropore volume of 0.755 cm3/g and a rich content of N- and O-containing functional groups, offering ample active sites for CO2 molecules. Further, the adsorbents demonstrated excellent CO2 capture capacity, achieving 5.7 mmol/g (0 °C) and 3.3 mmol/g (25 °C) at 1 bar, respectively. This was primarily attributed to the synergistic effect of narrow micropores filling and electrostatic interactions. Moreover, as-synthesized PC exhibited rapid CO2 adsorption capability, and its dynamic adsorption process was effectively described using a pseudo-second-order kinetic model. After five consecutive cycles, PET-derived PC still maintained ~100 % of adsorption capacity. They also possessed good CO2/N2 selectivity and reasonable isosteric heat of adsorption. Therefore, as-synthesized nitrogen-doped PC is a promising CO2 adsorbent through low-temperature activation of carbonized PET with NaNH2. Such findings have substantial implications for waste plastic recycling and mitigating the greenhouse effect.

High-pressure synthesized perovskite-type CeTaN<sub>2</sub>O and its magnetic and electrical properties

Recently, it has been discovered that the <i>AB</i>(N,O)<sub>3</sub>-type perovskite oxynitrides exhibit excellent dielectric, ferroelectric, and photocatalytic properties, promising for applications in the fields of optoelectronics, energy storage, and communication. Due to the differences in charge, ionic radius, and covalent bonding between N<sup>3–</sup> ion and O<sup>2–</sup> ion, the N substitution for O enhances the <i>B</i>(N,O)<sub>6</sub> octahedron tilting, giving rise to exotic properties and functionalities. However, the current fabrication process for this type of material is rather time-consuming, leading to products with an appreciable quantity of impurities. In this study, using oxide precursors and sodium amide as the nitrogen source, high-purity perovskite-type oxynitride CeTaN<sub>2</sub>O bulk materials are successfully synthesized under high-temperature and high-pressure conditions provided by a cubic-anvil press. The synthesis time decreases to 1 h, achieving rapid production. The lattice structure and physical properties of the obtained samples are comprehensively investigated. X-ray powder diffraction experiments and subsequent Rietveld refinement indicate that the title material shows an orthorhombic crystal structure with the space group of <i>Pnma</i>. The X-ray absorption spectra confirm the charge configuration and the anion composition as Ce<sup>3+</sup>Ta<sup>5+</sup>N<sub>2</sub>O. Magnetization and specific heat measurements reveal that the exchange interactions are mainly antiferromagnetic, with a potential magnetic transition below 2 K. The electrical transport data demonstrate typical semiconductor behaviors, which can be further explained by a three-dimensional variable-range hopping model. Our study paves the way for putting this exotic perovskite oxynitride into practical applications.

New Frontiers in Organosodium Chemistry as Sustainable Alternatives to Organolithium Reagents

AbstractWith their highly reactive respective C−Na and N−Na bonds, organosodium and sodium amide reagents could be viewed as obvious replacements or even superior reagents to the popular, widely utilised organolithiums. However, they have seen very limited applications in synthesis due mainly to poor solubility in common solvents and their limited stability. That notwithstanding in recent years there has been a surge of interest in bringing these sustainable metal reagents into the forefront of organometallics in synthesis. Showcasing the growth in utilisation of organosodium complexes within several areas of synthetic chemistry, this Minireview discusses promising new methods that have been recently reported with the goal of taming these powerful reagents. Special emphasis is placed on coordination and aggregation effects in these reagents which can impart profound changes in their solubility and reactivity. Differences in observed reactivity between more nucleophilic aryl and alkyl sodium reagents and the less nucleophilic but highly basic sodium amides are discussed along with current mechanistic understanding of their reactivities. Overall, this review aims to inspire growth in this exciting field of research to allow for the integration of organosodium complexes within common important synthetic transformations.

New Frontiers in Organosodium Chemistry as Sustainable Alternatives to Organolithium Reagents.

With their highly reactive respective C-Na and N-Na bonds, organosodium and sodium amide reagents could be viewed as obvious replacements or even superior reagents to the popular, widely utilised organolithiums. However, they have seen very limited applications in synthesis due mainly to poor solubility in common solvents and their limited stability. That notwithstanding in recent years there has been a surge of interest in bringing these sustainable metal reagents into the forefront of organometallics in synthesis. Showcasing the growth in utilisation of organosodium complexes within several areas of synthetic chemistry, this Minireview discusses promising new methods that have been recently reported with the goal of taming these powerful reagents. Special emphasis is placed on coordination and aggregation effects in these reagents which can impart profound changes in their solubility and reactivity. Differences in observed reactivity between more nucleophilic aryl and alkyl sodium reagents and the less nucleophilic but highly basic sodium amides are discussed along with current mechanistic understanding of their reactivities. Overall, this review aims to inspire growth in this exciting field of research to allow for the integration of organosodium complexes within common important synthetic transformations.

Low-temperature synthesized hierarchical porous carbon from waste hydrochar with super capacity for dye adsorption

Hydrochar is a by-product of subcritical hydrothermal conversion of biomass for bio-oil production, which has received more and more attention in environmental remediation, but the low porosity of hydrochar severely limits its effective utilization. Herein, a novel method of low-temperature activation of hydrochar with sodium amide (NaNH2) was proposed to enhance its porosity. The resulting hydrochar-derived porous carbon (PC) possessed a large pore volume (1.147 cm3/g) and a high specific surface area of up to 2185.3 m2/g. Further, NaNH2 also increased the relative oxygen content of PC during activation. 2D-FTIR correlation spectra suggested that the change in the infrared signal intensity of -C-O ordinarily occurred before that of aromatic CC as the NaNH2 dosage changed. More importantly, as-prepared PC exhibited excellent adsorption properties for methylene blue (MB), up to 833.33 mg/g, which is mainly attributed to the pore-filling-effect. And the oxygen-containing functional group was also beneficial to improve the adsorption capacity of PC for MB. The adsorption process of MB on as-prepared PC was well described using the Langmuir adsorption isotherm model, indicating that the adsorption process was single-layer adsorption. Undoubtedly, it is a feasible strategy to prepare PC for MB adsorption by low-temperature activation of waste hydrochar with NaNH2.

Electrochemical Stability of Electrode/Electrolyte Interfaces in Metal Borohydride Solid Electrolytes

Meeting the promise of all-solid-state batteries will require solid electrolytes that have high metal ion conductivity, low electronic conductivity, are electrochemically stable at both low and high potential, and have sufficiently high critical current density to avoid metal dendrite penetration. Metal borohydrides comprise a relatively new class of compounds that is being explored for its potential as a solid electrolyte material. Here, we examine the electrochemical thermodynamic stability of sodium amide borohydride (Na2NH2BH4, or NNB) over the potential range 1.5 to 5 V vs. Na/Na+, using electrodynamic methods, X-ray photoelectron spectroscopy (XPS) characterization of the interfacial reaction products1, and electron microscopy characterization of microstructure. We observe the formation of a CEI layer that passivates the NNB electrolyte up to 5V, while the electrolyte is stable without needing additional passivation down to potentials as low as 1.5V. The onset potentials of the CEI formation reactions agree with those predicted by DFT2 and suggest that the resulting CEI is composed of closo-borohydrates, which are a type of metal borohydride with a cage-like structure that holds promise for high sodium ion conductivities3. XPS measurements of atomic compositions in the CEI layer show the formation of these closo-borohydrates and, coupled with charge transfer calculations, predict that the passivating CEI layer is thin (tens of nm). Impedance spectroscopy is performed to characterize the contribution of the CEI layer to the total cell resistance. Several formation cycling methods are explored to show that with appropriate cycling, the passivating layers contribute <10% to electrolyte resistance in the test cells. Acknowledgements: This work was supported as part of the Joint Center for Energy Storage Research, an Energy Innovation Hub funded by the U.S. Department of Energy, Office of Science, Basic Energy Sciences.

Synthesis and Reactivity of Alkali Metal Hydrido-Magnesiate Complexes which Exhibit Group 1 Metal Counter-Cation Specific Stability.

Reactions of the series of alkali metal amides M(HMDS) (M = Li-Cs; HMDS = [N(SiMe3)2]-) with the neutral magnesium(II) hydride compound [Mg(BDIDipp)(μ-H)]2 (BDIDipp = [CH{C(Me)NDipp}2], Dipp = 2,6-iPr2-C6H3) have been carried out. When M = Li or Na, the reactions yielded Mg(BDIDipp)(HMDS) and MH as the primary products. In the sodium amide reaction, [Na2(HMDS)][{Mg(BDIDipp)}2(H)3] was obtained as a low-yield by-product. When M = K-Cs, the reactions gave the group 1 metal hydrido-magnesiates, M2[Mg(BDIDipp)(HMDS)(H)]2·(benzene)n (n = 0 or 1), the thermal stability of which increases with the increasing molecular weight of the alkali metal involved. Reactions of Cs2[Mg(BDIDipp)(HMDS)(H)]2·(benzene) with 18-crown-6 and CO gave the first monomeric alkali metal hydrido-magnesiate [Cs(18-crown-6)][Mg(BDIDipp)(HMDS)(H)] and the ethenediolate complex Cs2[{Mg(BDIDipp)(HMDS)}2(μ-C2H2O2)], respectively. The new synthetic route to alkali metal hydrido-magnesiates described herein may facilitate further reactivity studies of this rare compound class.

Machine-learning-assisted material discovery of oxygen-rich highly porous carbon active materials for aqueous supercapacitors

Porous carbons are the active materials of choice for supercapacitor applications because of their power capability, long-term cycle stability, and wide operating temperatures. However, the development of carbon active materials with improved physicochemical and electrochemical properties is generally carried out via time-consuming and cost-ineffective experimental processes. In this regard, machine-learning technology provides a data-driven approach to examine previously reported research works to find the critical features for developing ideal carbon materials for supercapacitors. Here, we report the design of a machine-learning-derived activation strategy that uses sodium amide and cross-linked polymer precursors to synthesize highly porous carbons (i.e., with specific surface areas > 4000 m2/g). Tuning the pore size and oxygen content of the carbonaceous materials, we report a highly porous carbon-base electrode with 0.7 mg/cm2 of electrode mass loading that exhibits a high specific capacitance of 610 F/g in 1 M H2SO4. This result approaches the specific capacitance of a porous carbon electrode predicted by the machine learning approach. We also investigate the charge storage mechanism and electrolyte transport properties via step potential electrochemical spectroscopy and quasielastic neutron scattering measurements.

On the solubility of boron nitride in supercritical ammonia-sodium solutions

Cubic boron nitride (cBN) is considered to be one of the leading candidates for next generation electronic devices yet has no current synthesis route for single crystals greater than a few mm in size leading to a lack of suitable substrates. New synthesis methods need to be explored, with the ammonothermal method being a potential candidate for synthesis of large area, thick cBN and hexagonal BN (hBN) single crystals. This paper investigates the solubility of BN in supercritical ammonia using sodium amide (NaNH2) as a mineralizer and cBN crystals as feedstock. Solubilities were measured based on mass loss of the feedstock at temperatures from 450—600 deg. C, with pressures of 150–190 MPa, using durations from 24—96 h and with varying amounts of Na. A positive solubility trend is demonstrated with respect to temperature with solubility varying from 0.017—0.050% molBN/molNH3. Solubilities did not vary as a function of time or when>0.07 molNa/L mineralizer content was used suggesting both that equilibrium was reached and the solutions were saturated. These values are high enough to motivate further investigation for solution-based growth of BN.

Uncovering the Untapped Potential of the Use of Sodium Amides for Regioselective Arene Functionalisation.

Alkali-metal amides have become key reagents in synthetic chemistry, with special focus in deprotonation reactions. Despite the higher reactivity found in the heavier sodium and potassium amides, their insolubility and low stability has favoured the use of the more soluble lithium analogues, converting them into the most used non-nucleophilic bases. Studying the coordination effects of Lewis donor molecules such as tridentate amine PMDETA (N,N,N',N'',N''-pentamethyldiethylenetriamine) in combination with the sodium amide NaTMP (TMP = 2,2',6,6'-tetramethylpiperidide), we have been able to unlock the use of these reagents for the functionalisation of arenes, i.e. the deuterium incorporation by hydrogen isotope exchange and the deprotonative borylation of unactivated arenes. These findings show how sodium amides are not just a simple more sustainable replacement of their lithium counterparts, but also that they can display significantly enhanced reactivities allowing for the development of new transformations.

Low-temperature one-step solid state chemical synthesis of GaN nanosheets for conquering polysulfides in Li–S battery

Gallium nitride (GaN) nanosheets have been prepared as an active material for conquering polysulfides in Lithium–Sulfur (Li–S) batteries via one simple synthetic route at 550 °C. The process was carried out in a stainless steel autoclave by using gallium nitrate hydrate, sodium amide and metallic lithium as starting materials. The product was proven to be hexagonal GaN nanosheets by combined X-ray powder diffraction (XRD) pattern and Scanning electron microscopy (SEM). The GaN nanosheets were then used to coat on the Li–S battery separator, and the result proves an effective inhibition of the shutting problem and gives excellent electrochemical properties compared with traditional separators or GaN additives. The battery assembled by GaN coated separator shows good cycling stability with 408 mAh/g and a low capacity fading of 0.6‰ per cycle from 11th to 480th cycle at 2 C due to high utilization of the sulfur-based active species.

Alkylation of N,N-Dibenzylaminoacetonitrile: From Five- to Seven-Membered Nitrogen-Containing Heterocyclic Systems.

The syntheses of several alkaloids and nitrogen-containing compounds including N-Boc-coniine (14b), pyrrolizidine (1), δ-coniceine (2), and pyrrolo[1,2a]azepine (3) are described. New C-C bonds in the α position relative to the nitrogen atom were formed by the alkylation of metalated α-aminonitriles 4 and 6a-c with alkyl iodides possessing the requisite size and functionality. In all of the reported cases, the pyrrolidine ring was formed in the aqueous medium through a favorable 5-exo-tet process involving a primary or a secondary amino group and a terminal δ-leaving group. Conversely, the azepane ring was efficiently formed in N,N-dimethylformamide (DMF), as the preferred aprotic solvent, through an unreported 7-exo-tet cyclization process involving a more nucleophilic sodium amide and a terminal mesylate borne by a saturated six carbon chain unit. In this way, we successfully synthesized pyrrolo[1,2a]azepane 3 and 2-propyl-azepane 14c in good yields from inexpensive and readily available materials without tedious separation methods.

Structural characterization of the 1-metallo-2-t-butyl-1,2-dihydropyridyl rubidium and caesium complexes

With recent reports of alkali metal amides used in homogeneous catalytic chemistry where the reactivity down group one is dependent on the metal identity, esoteric rubidium and caesium amides are finding new admirers amongst chemists who usually study lithium, sodium, and potassium utility amides. Here, as a forerunner to their exploitation in catalysis, we report the X-ray crystallographic and NMR solution structures of the 1-metallo-2-t-butyl-1,2-dihydropyridyl (DHP) complexes of rubidium and caesium, thereby completing the homologous alkali metal series. Crystallized as monosolvated {[Rb(tBuDHP)·THF]2}∞ and hemisolvated {[Cs(tBuDHP)]2·THF}∞, both form spectacular supramolecular structures. While each shares a plethora of metallo-π-contacts with the DHP anion, their subunits differ. The former dimerizes in a ‘slipped’ fashion via interactions between the symmetrically-equivalent Rb centres and the π-system of the adjacent DHP ring, but the latter has distinct Cs centres within its dinuclear subunit, with one Cs engaging in σ-bonding to two tBuDHP anions, whereas the other Cs binds in a more side-on fashion to the π-system of the ring.

Utilization of Hydrotropic Solubilisation Technique for Quantitative Studies of Dexamethasone in Pharmaceutical preparations

Solubility is a crucial characteristic for achieving the appropriate drug concentration in the systemic circulation and demonstrating pharmacological response. Poor water solubility can severely limit drug efficacy, and some medications can even cause negative effects as a result of their poor solubility. Enhancing water solubility can be done through several of methods. Increased water solubility can thus be a beneficial technique for enhancing therapeutic effectiveness and/or reducing side effects. This is true for solutions that are given intravenously, topically, or orally. Increasing the aqueous solubility of drugs that are weakly water soluble can be done in a variety of techniques. Hydrotropy is a solubility enhancement technique that uses hydrotropes such as sodium benzoate, sodium salicylate, sodium citrate, urea, ibuprofen sodium, and niacin amide to improve the solubility of poorly water-soluble drugs. Hydrotropic solubilization was employed in this study to solubilize weakly water-soluble drug like Dexamethasone utilizing hydrotropic agents like sodium benzoate (2M) and sodium salicylate (2M). Dexamethasone has maximum absorbance at 272.05nm, when sodium benzoate is used as a hydrotropic agent. In the 5-25 µg/ml concentration range, this substance follows the beers law. Dexamethasone shows maximum absorbance at 317.10nm, when sodium salicylate is used as a hydrotropic agent. In the concentrations ranging from 5 to 25µg/ml, this substance follows the beers law. The findings of studies have been statistically confirmed, as well as by re-examination studies. According to the ICH guidelines, validation parameters such as linearity, range, and assay were investigated.