Abstract Earth’s field NMR (EFNMR) is a useful modality for low-field NMR spectroscopy due to its availability, portability, and low cost. EFNMR can enable better line width resolution than at high fields primarily due to low magnetic susceptibility broadening. Unfortunately, EFNMR spectra are highly complex due to strong J-coupling effects and can be challenging to interpret without additional information. However, the spectral complexity paired with ultrahigh resolution offers a unique opportunity to fingerprint analytes. Herein, we show that high-field (e.g., 9.4 T) NMR and EFNMR have distinct complementary roles in explaining the NMR interactions that manifest in the respective spectra of complex molecules. Chemical shifts are nearly exclusive to high-field NMR and can enable facile observations of weak J-couplings for cursory spectral assignments, but EFNMR’s ability to resolve high-precision magnitudes and signs of J-couplings is essential for fully and accurately assigning structures with high fidelity. We demonstrate this with an important category of materials, fluorinated fentanyl analogues (i.e., fluorofentanyls) and their precursors. These systems are well suited to study due to their relevance to the synthetic opioid crisis and their similarities to fluorinated pharmaceuticals and biomolecules. Results show assignment of the magnitudes and signs of J-couplings in several fluorinated precursors using both high-field and EFNMR. In select fluorofentanyls, EFNMR can provide information on J-couplings that would otherwise be inaccessible even with 3D experiments at 9.4 T. EFNMR spectra of fluorofentanyls show a strong dependence on J-coupling between 1H or 19F and 14N nuclei, where the effects that manifest in spectra may be used to gain insights into local molecular dynamics and information on 14N electric-field gradient tensors.

A series of Sn2+ coordination compounds with low distortion has been isolated. This enabled the accurate description of Sn-O bonds in a highly symmetrical environment and the evaluation of the Sn2+ ionic radius—a long-sought value for the chemistry books as Sn has been the only nonradioactive cation left out of Shannon’s list of ionic radii [Acta Crystallographica, 1976, 751-767]. The use of Keggin polyoxometalate (POM) ligands allows for the long-term stabilization of the Sn2+ ion at room temperature and in aqueous solutions. Four complexes of Sn2+ with the POMs GaW11O39 9-, SiW11O39 8-, GeW11O39 8-, and PW11O39 7- were synthesized and characterized via single crystal XRD, Raman, FTIR, and solution-state NMR. In the solution state, the POM-induced reduction of Sn4+ to Sn2+ occurs spontaneously and without using any reducing agent. In the four low-valent Sn-POM compounds isolated, Sn2+ is symmetrically sandwiched by two tetradentate POM ligands. The 8-coordinate ionic radius of Sn2+ derived from this series of complexes is 1.184 ± 0.003 Å. Additionally, new POM compounds with ions of comparable sizes or electronic structures, two with Pb2+ and two with Ca2+, were isolated and characterized. Sn2+ stands out as a unique case in the periodic table when compared to isometric Pb2+ and Ca2+ and 26 other cations in analogous POM complexes. All four Sn2+ -POM complexes display Sn2+-O distances of 2.60-2.72 Å, which is about 0.12 Å longer than expected for a cation of its size. Density functional theory calculations show that the anomalously long Sn2+–O distances originate from a stereochemically active lone pair, giving rise to local structural distortions, an isolated Sn-5s/O-2p hybridized electronic state near the Fermi level, and asymmetric electron localization around the Sn center. The combined results from solution-state NMR and crystallography shed light onto the important role of the lone pair of electrons in Sn2+, demonstrating its impact on bonding interactions and overall speciation.

Subetadex-alpha-methyl (SBX-Me), a modified, polyanionic cyclodextrin scaffold, has been evaluated for its utilization as a medical countermeasure (MCM) to neutralize the effects of fentanyl and related opioids. Initial in vitro toxicity assays demonstrate that SBX-Me has a nontoxic profile, comparable to the FDA-approved cyclodextrin-based drug Sugammadex. Pharmacokinetic analysis showed rapid clearance of SBX-Me with an elimination half-life of similar to 7.4 h and little accumulation in major organs. SBX-Me was also evaluated for its ability to counteract the effects of fentanyl, carfentanil, and remifentanil in rats. Recovery times in rats exposed to sublethal fentanyl doses were found to be shorter when treated with SBX-Me after opioid exposure. The recovery times were reduced from similar to 35 to similar to 17 min for fentanyl, similar to 172 to similar to 59 min for carfentanil, and similar to 18 to similar to 12 min for remifentanil. SBX-Me increased the elimination half-life for fentanyl and remifentanil from 5.37 to 6.42 h and 8.24 to 9.74 h, respectively. These data support SBX-Me as a solid platform from which further research can be launched for the development of a MCM against the effects of fentanyl and its analogs. Furthermore, the data suggests that SBX-Me and other analogs are attractive candidates as broad spectrum opioids targeting MCMs.

Pinacolyl alcohol (PA), a key forensic marker for the nerve agent Soman (GD), is a particularly difficult analyte to detect by various analytical methods. In this work, we have explored the reaction between PA and 1,1 '-carbonyldiimidazole (CDI) to yield pinacolyl 1H-imidazole-1-carboxylate (PIC), a product that can be conveniently detected by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-high-resolution mass spectrometry (LC-HRMS). Regarding its GC-MS profile, this new carbamate derivative of PA possesses favorable chromatographic features such as a sharp peak and a longer retention time (RT = 16.62 min) relative to PA (broad peak and short retention time, RT = 4.1 min). The derivative can also be detected by LC-HRMS, providing an avenue for the analysis of this chemical using this technique where PA is virtually undetectable unless present in large concentrations. From a forensic science standpoint, detection of this low molecular weight alcohol signals the past or latent presence of the nerve agent Soman (GD) in a given matrix (i.e., environmental or biological). The efficiency of the protocol was tested separately in the analysis and detection of PA by EI-GC-MS and LC-HRMS when present at a 10 mu g/mL in a soil matrix featured in the 44th PT and in a glycerol-rich liquid matrix featured in the 48th Official Organization for the Prohibition of Chemical Weapons (OPCW) Proficiency Test when present at a 5 mu g/mL concentration. In both scenarios, PA was successfully transformed into PIC, establishing the protocol as an additional tool for the analysis of this unnatural and unique nerve agent marker by GC-MS and LC-HRMS.

An extraction protocol from silt sediment of fentanyl and three analogs: acetylfentanyl, thiofentanyl and acetylthiofentanyl, spiked at two concentrations each and separately (at similar to 1 and similar to 10 mu g/g), is described. In addition, the identity of the fentanyls preliminarily identified by electron ionization gas chromatography-mass spectrometry (EI-GC-MS) analysis, can be corroborated by reacting each opioid in the silt's extract with 2,2,2-trichloroethoxycarbonyl chloride (Troc-Cl). Reaction between Troc-Cl and each opioid generates two unique products that can be used to retrospectively identify the original opioid therefore serving as a corroborating tool for known opioids as well as new, unknown fentanyl analogs.

Organophosphorus (OP) nerve agents are a group of lethal small molecules. Fieldable detection of nerve agents is an on-going challenge that typically relies on mass spectrometry and infrared spectroscopy but not nuclear magnetic resonance (NMR) spectroscopy because of the portability limitations of superconducting magnets. However, Earth’s field NMR (EFNMR) demonstrates a unique signature space for OP compounds and can be made into a portable detector for OP nerve agents. Here we demonstrate a systematic study to develop the EFNMR signature space of 31 nerve-agent-related OP compounds, including surrogates, simulants, synthetic precursors, decomposition products, pesticides, and threat agents identified by the National Institutes of Health. The EFNMR spectral signatures are a diagnostic fingerprint of the molecular structure, and this study establishes the structure–signature relationships of this relatively unexplored signature space. The results indicate that EFNMR is a powerful analytical capability to distinguish and identify the unique structure of OP compounds, including nerve agents. While aimed at detection of nerve agents, this study also lays the foundations of using EFNMR for detection of any OP compound in the laboratory or in the field.

The atomic structure of unusually molecule-rich glasses along the P4Se3-As4Se3 join with 0 to 70 mol% P4Se3 is studied using Raman, 77Se magic-angle-spinning (MAS) and 2D 31P phase adjusted spinning sideband (PASS) nuclear magnetic resonance (NMR) spectroscopy. When taken together, the spectroscopic results indicate the coexistence of cage-like PxAs4-xSe3 molecular moieties and corner-shared P- and As- containing pyramidal network moieties in the structure of these glasses. Increasing substitution of As with P gives rise to a monotonic increase in the total molecule:network ratio, which is shown to be consistent with the compositional variation in the glass transition temperature.

The new Ge(II) cluster [Ge6(μ3-O)4(μ2-OC6H2-2,4,6-Cy3)4](NH3)0.5 (1) and three divalent Group 14 aryloxide derivatives [Ge(OC6H2-2,4,6-Cy3)2]2 (2), [Sn(OC6H2-2,4,6-Cy3)2]2 (3), and [Pb(OC6H2-2,4,6-Cy3)2]2 (4) of the new tricyclohexylphenyloxo ligand, [(-OC6H2-2,4,6-Cy3)2]2 (Cy = cyclohexyl), were synthesized and characterized. Complexes 1-4 were obtained by reaction of the metal bissilylamides M(N(SiMe3)2)2 (M = Ge, Sn, Pb) with 2,4,6-tricyclohexylphenol in hexane at room temperature. If the freshly generated reaction mixture for the synthesis of 2 is stirred in solution for 12 h at room temperature, the cluster [Ge6(μ3-O)4(μ2-OC6H2-2,4,6-Cy3)4](NH3)0.5 (1), which features a rare Ge6O8 core that includes ammonia molecules in non-coordinating positions, is formed. Complexes 3 and 4 were also characterized via119Sn{1H} NMR and 207Pb NMR spectroscopy and feature signals at -280.3 ppm (119Sn{1H}, 25 °C) and 1541.0 ppm (207Pb, 37 °C), respectively. The spectroscopic characterization of 3 and 4 extends known 119Sn parameters for dimeric Sn(II) aryloxides, but data for 207Pb NMR spectra for Pb(II) aryloxides are rare. We present also a rare VT-NMR study of a homoleptic 3-coordinate Pb(II) aryloxide. The crystal structures of 2, 3, and 4 feature interligand H⋯H contacts that are similar in number to those of related transition metal derivatives despite the larger size of the group 14 elements.

There is growing interest in using low-field magnetic resonance experiments for routine chemical characterization. Earth’s field NMR is one such technique that can garner structural information and enable sample differentiation with low cost and highly portable designs. The resulting NMR spectra are primarily influenced by J-couplings, resulting in so-called J-coupled spectra (JCS). Many small molecules include atoms with NMR-active nuclei that are quadrupolar either at natural abundance or are often isotopically enriched (e.g., 2H, 6Li, 11B, 14N, 17O, etc.) where the effects of quadrupolar J-couplings and relaxation on JCS of strongly- and weakly-coupled spin systems have not been explored to date. Herein, using a set of seven fluoropyridine samples with unique substitution and J-couplings, we demonstrate that the 14N relaxation rates can induce drastic line-broadening in the JCS. This includes a previously unexplored unique line broadening mechanism enabled by strongly coupled spins at low-field. Numerical simulations are used to model and refine the magnitudes and signs of J-couplings, as well as indirectly determine the 14N relaxation rates in a single 1D experiment that has a higher fidelity than observed in high-field NMR experiments.

Nuclear magnetic resonance (NMR) spectroscopy routinely characterizes the unique spin systems of molecules using a combination of chemical shift and J-coupling interactions for the H-1 and C-13 nuclei. However, at Earth's magnetic field, chemical shifts are unresolvable and the ability to characterize structure relies solely on the J-couplings. Fortuitously, the J-couplings at Earth's field provides the same spin system information as high field, but only requires detection of the H-1 nucleus. We report the first identification of the multiple natural abundance H-1-C-13 spin systems on organic molecules detected at Earth's magnetic field. The results clearly demonstrate the feasibility of Earth's field NMR to characterize small organic molecules without costly enrichment strategies. (C) 2022 Published by Elsevier Inc.

Structural characterization of the complex [B(β-pinane)3] (1) reveals non-covalent H⋯H contacts that are consistent with the generation of London dispersion energies involving the β-pinane ligand frameworks. The homolytic fragmentations of 1, and camphane and sabinane analogues ([B(camphane)3] (2) and [B(sabinane)3] (3)) were studied computationally. Isodesmic exchange results showed that London dispersion interactions are highly dependent on the terpene's stereochemistry, with the β-pinane framework providing the greatest dispersion free energy (ΔG = -7.9 kcal mol-1) with Grimme's dispersion correction (D3BJ) employed. PMe3 was used to coordinate to [B(β-pinane)3], giving the complex [Me3P-B(β-pinane)3] (4), which displayed a dynamic coordination equilibrium in solution. The association process was found to be slightly endergonic at 302 K (ΔG = +0.29 kcal mol-1).

The inherently quantitative nature of nuclear magnetic resonance (NMR) spectroscopy is one of the most attractive aspects of this analytical technique. Quantitative NMR analyses have typically been limited to high-field (>1 T) applications. The aspects for quantitation at low magnetic fields (<1 mT) have not been thoroughly investigated and are shown to be impacted by the complex signatures that arise at these fields from strong heteronuclear J-couplings. This study investigates quantitation at Earth's magnetic field (∼50 μT) for a variety of samples in strongly, weakly, and uncoupled spin systems. To achieve accurate results in this regime, the instrumentation, experimental acquisition, processing, and theoretical aspects must be considered and reconciled. Of particular note is the constant field nuclear receptivity equation, which has been re-derived in this study to account for strong coupling and quality factor effects. The results demonstrate that the quantitation of homonuclear molecular groups, determination of heteronuclear pseudoempirical formulas, and mixture analysis are all feasible at Earth's magnetic field in a greatly simplified experimental system.

•Application of isotropic-anisotropic correlation 2D NMR.•Short and intermediate -range structure and connectivity in glasses by MATPASS NMR.•Structure of of chalcogenide glasses in S-Se-Te, Ge-Se, As-Se and Si-Se systems.

In recent years, it has been realized that low and ultra-low field (mT-nT magnetic field range) nuclear magnetic resonance spectroscopy can be used for molecular structural analysis. However, spectra are often hindered by lengthy acquisition times or require large sample volumes and high concentrations. Here, we report a low field (50 μT) instrument that employs a linear actuator to shuttle samples between a 1 T prepolarization field and a solenoid detector in a laboratory setting. The current experimental setup is benchmarked using water and 13C-methanol with a single scan detection limit of 2 × 1020 spins (3 µl, 55M H2O) and detection limit of 2.9 × 1019 (200 µl, 617 mM 13C-methanol) spins with signal averaging. The system has a dynamic range of >3 orders of magnitude. Investigations of room-temperature relaxation dynamics of 13C-methanol show that sample dilution can be used in lieu of sample heating to acquire spectra with linewidths comparable to high-temperature spectra. These results indicate that the T1 and T2 mechanisms are governed by both the proton exchange rate and the dissolved oxygen in the sample. Finally, a 2D correlation spectroscopy experiment is reported, performed in the strong coupling regime that resolves the multiple resonances associated with the heteronuclear J-coupling. The spectrum was collected using 10 times less sample and in less than half the time from previous reports in the strong coupling limit.

Chemical analysis via nuclear magnetic resonance (NMR) spectroscopy using permanent magnets, rather than superconducting magnets, is a rapidly developing field. Performing the NMR measurement in the strong heteronuclear J-coupling regime has shown considerable promise for the chemical analysis of small molecules. Typically, the condition for the strong heteronuclear J-coupling regime is satisfied at µT magnetic field strengths and enables high resolution J-coupled spectra (JCS) to be acquired. However, the JCS response to systematic chemical structural changes has largely not been investigated. In this report, we investigate the JCS of C6H6−xFx (x = 0, 1, 2, …, 6) fluorobenzene compounds via simultaneous excitation and detection of 19F and 1H at 51.5 µT. The results demonstrate that JCS are quantitative, and the common NMR observables, including Larmor frequency, heteronuclear and homonuclear J-couplings, relative signs of the J-coupling, chemical shift, and relaxation, are all measurable and are differentiable between molecules at low magnetic fields. The results, corroborated by ab initio calculations, provide new insights into the impact of chemical structure and their corresponding spin systems on JCS. In several instances, the JCS provided more chemical information than traditional high field NMR, demonstrating that JCS can be used for robust chemical analysis.

Controlling both the concentration and the distribution of elements in a given material is often crucial to extracting and optimizing synergistic properties of the various constituents. An interesting class of such multielement materials is metal chalcogenide nanoparticles, which exhibit a wide range of composition-dependent optoelectronic properties including both bandgap-mediated processes and localized surface plasmon resonance properties, each of which is useful in applications ranging from energy conversion to sensing. Because metal chalcogenide nanoparticles can support several different metal elements in a variety of chalcogen lattices, this material class has particularly benefited from the ability to control both atom concentration and atom arrangement to tailor final particle properties. The primary method to access complex, multimetallic chalcogenide particles is via a postsynthetic cation exchange strategy. One-pot syntheses have been less explored to access these complex particles, although this route is desirable for economy and scalability. Here, we compare the composition and morphology outcomes from cation exchange and one-pot preparation approaches using a Cu/Ag/Se system, which is already known to exhibit both binary and ternary metal chalcogenide phases. We show that at similar concentrations of the two metal cations, initial reaction conditions for the one-pot method yield multicomponent nanoparticles, whereas cation exchange yields homogeneous ternary metal chalcogenide structures. We then show that by tuning the precursor oxidation state for the one-pot method, this approach can be used to access homogeneous ternary metal chalcogenide particles that are similar in atom arrangement to the particles obtained using cation exchange. Taken together, our results demonstrate reliable synthetic methods that yield a variety of controlled compositions and composition morphologies in the Cu/Ag/Se system. Importantly, we demonstrate that this entire collection of architectures can all be accessed via a one-pot method simply by modifying metal precursor chemistry. The mechanistic insights gained and the resulting streamlined syntheses outlined indicate pathways to easily scaled, highly tailorable syntheses for rapid translation into downstream technologies.

A new method for measurement of elemental analysis by nuclear magnetic resonance (NMR) of unknown samples is discussed here as a quick and robust means to measure elemental ratios without the use of internal or external calibration standards. The determination of elemental ratios was done by normalizing the signal intensities by the frequency dependent quality factor (and the gyromagnetic ratios (gamma) for each measured nucleus. The correction for the frequency dependence was found by characterizing the output signal of the probe as a function of the quality factor (Q) and the frequency, and the correction for gamma was discussed in a previous study. A Carr-Purcell-Meiboom-Gill (CPMG) pulse sequence was used for evaluation of the relative signal intensities, which allows for derivation of elemental ratios, and was correspondingly used to simultaneously measure the T-2* of samples for an added parameter for more accurate identification of unknown samples.

other SNL personnel in supporting the analysis, particularly from Jennifer Depoy, Abraham Ellis, Derek Hart, Jordan Henry, John Mulder, and Jennifer Trasti. The authors would also like to thank the following government and non-government organiza- tions for their invaluable input to this study: Government Massachusetts Institute of Technology Lincoln Laboratory Construction Engineering Research Laboratory (CERL) Idaho National Laboratory Marine Corps Air Ground Combat Center, Twentynine Palms, California National Renewable Energy Laboratory National Institute of Standards and Technology Pacific Northwest National Laboratory U.S. Army Corps of Engineers U.S. Army Cyber Command U.S. Navy Installations Command Non-Government Customized Energy Solutions Electric Power Research Institute Enchanted Rock ICETEC Integrated Energy Solutions NEC Energy Solutions OpenADR Alliance PJM POWER Engineers Schweitzer Engineering Laboratory Southwest Research Institute Typhoon HIL, Inc. Executive Summary This study describes a long-term cyber security R&D plan to address ICS cyber security for CES. Long-term goals for ICS were assumed to be those that would require significant action and R&D to achieve, as opposed to being addressable by applying existing technology and best practices. Long-term R&D would roughly fall into the window of 5-10 years out. Investing in the identified R&D will posture CES for sustained resilient energy operations well into the future. The gaps were identified using a conventional gap analysis process. The current state of cyber security R&D was surveyed and summarized. Then, the desired future state of ICS cyber security was characterized, in terms of required capabilities for a secure and resilient ICS. Afterward, gaps were identified by comparing the current state of cyber security to the desired end-state. Finally, the gaps were prioritized and paired (where important) with the appropriate communities (industry, vendors, academia, etc.) suitable to address them. The baseline survey of the existing R&D focused on efforts in government, academia, feder- ally funded research and development centers (FFRDCs), and industry (including vendors). One primary source was existing DOE, Department of Homeland Security (DHS), and Department of Defense (DoD) programs, including Cybersecurity for Energy Delivery Systems (CEDS) and Defense Advanced Research Projects Agency (DARPA). Crucial documents from the National In- stitute of Standards and Technology (NIST) were also surveyed. On the academic side, the group included work from the Institute for Information Security & Privacy (IISP) and Trustworthy Cyber Infrastructure for the Power Grid (TCIPG) research consortiums. Numerous other smaller efforts were cataloged as well. Overall, the results show significant attention on the cyber security issues faced by ICS, but with a definite tendency toward near-term solutions, and less defined long-term goals, particularly in terms of needed R&D. The surveyed concepts and goals were used to develop the desired state for long-term ICS cyber security. These were complemented by concepts and frameworks previously used for ICS cyber security. The overall result was the development of a matrix of needed technical capabilities for secure and resilient ICS in the long term. Eighteen cyber security concepts (referred to as "topics" for gap analysis) were identified and sorted according to their positions in the security lifecycle (secure design, reinforced implementation, operation and deployment, or cross-cutting capabilities) and security category (protect, detect, react, or recover). For each topic, a description was provided, as well as other discussion, including a comparison to existing work. The comparisons formed the basis for the gap analysis. Some security topics, although an essential part of a desired secure ICS state in the future, have significant R&D resources alieady working to realize the goal. Others, however, are only partially addressed. Besides the severity of the R&D gap, an important consideration is that perfect security is unattainable; therefore, strong security engineering must be complemented with additional security monitoring. The final rankings for long-term R&D, including specific opportunities and challenges, along with suggestions about which group or groups should be targeted for funding opportunities, are in Chapter of the report. Some of the key results include: 1. Trusted monitors, which act as out-of-band security sentinels, and security analytics, which fuse weak indicators to detect security anomalies, have very high priority for R&D. As men- tioned previously, no system can be completely trusted (or, given the potential ramifications, even reasonably trusted); therefore, monitoring is essential. 2. Virtualization is a key capability for many aspects of ICS cyber security; potential applica- tions include training environments, pre-deployment change testing, red/blue engagement, evaluating tactics-techniques-procedures (TTPs), and others. Virtualization capability would be greatly enhanced with better support for ICS field devices (like relays, programmable logic controllers, etc.) and automated model generation from design or operational system information. 3. Field devices have unique cyber security issues, and are critical to cyber risk given their application: straddling the cyber/physical domains Addressing these issues in an organized fashion (including their virtualization) is a priority R&D gap. This is also an example where industry (particularly vendors) must complement other R&D organizations.