Natural Isotopic Abundance Research Articles

Gold-FISH enables targeted NanoSIMS analysis of plant-associated bacteria.

Bacteria colonize plant roots and engage in reciprocal interactions with their hosts. However, the contribution of individual taxa or groups of bacteria to plant nutrition and fitness is not well characterized due to a lack of insitu evidence of bacterial activity. To address this knowledge gap, we developed an analytical approach that combines the identification and localization of individual bacteria on root surfaces via gold-based insitu hybridization with correlative NanoSIMS imaging of incorporated stable isotopes, indicative of metabolic activity. We incubated Kosakonia strain DS-1-associated, gnotobiotically grown rice plants with 15 N-N2 gas to detect insitu N2 fixation activity. Bacterial cells along the rhizoplane showedheterogeneous patterns of 15 N enrichment, ranging from the natural isotope abundance levels up to 12.07 at% 15 N (average and median of 3.36 and 2.85 at% 15 N, respectively, n = 697 cells). The presented correlative optical and chemical imaging analysis is applicable to a broad range of studies investigating plant-microbe interactions. For example, it enables verification of the insitu metabolic activity of host-associated commercialized strains or plant growth-promoting bacteria, thereby disentangling their role in plant nutrition. Such data facilitate the design of plant-microbe combinations for improvement of crop management.

Detection of pyridine derivatives by SABRE hyperpolarization at zero field

Nuclear magnetic resonance (NMR) spectroscopy is a powerful analytical tool used in modern science and technology. Its novel incarnation, based on measurements of NMR signals without external magnetic fields, provides direct access to intramolecular interactions based on heteronuclear scalar J-coupling. The uniqueness of these interactions makes each zero-field NMR spectrum distinct and useful in chemical fingerprinting. However, the necessity of heteronuclear coupling often results in weak signals due to the low abundance of certain nuclei (e.g., 15N). Hyperpolarization of such compounds may solve the problem. In this work, we investigate molecules with natural isotopic abundance that are polarized using non-hydrogenative parahydrogen-induced polarization. We demonstrate that spectra of hyperpolarized naturally abundant pyridine derivatives can be observed and uniquely identified whether the same substituent is placed at a different position of the pyridine ring or different constituents are placed at the same position. To do so, we constructed an experimental system using a home-built nitrogen vapor condenser, which allows for consistent long-term measurements, crucial for identifying naturally abundant hyperpolarized molecules at a concentration level of ~1 mM. This opens avenues for future chemical detection of naturally abundant compounds using zero-field NMR.

Accuracy and precision of ESI-Orbitrap-IRMS observations of hours to tens of hours via reservoir injection

Orbitrap isotope ratio mass spectrometry (Orbitrap-IRMS) has recently been applied to high-precision, natural-abundance isotope ratio measurements of a diverse range of compounds, including amino acids, oxyanions, fatty acids, and metals. These measurements can characterize many isotope ratios simultaneously at high (≈1.0‰) precision. In a successful experiment, observed precision will track the shot-noise limit and be limited by experimental time. Some isotope ratios, for example those involving 17O in organic compounds or multiply-substituted (‘clumped’) isotopologues, require experimental times of hours to tens of hours to achieve desired precision, while current sample introduction techniques focus on observations on the order of seconds to tens of minutes. In this study, we characterize Orbitrap-IRMS performance for three long duration measurements (individual acquisitions ≥1 h and as long as 24 h) using an automated reservoir injection system coupled to a Q Exactive HF Orbitrap with an electrospray ionization (ESI) source. First, we characterize long-term intra-measurement stability through a 24-h long measurement of acetone. We report the following isotope ratios and precisions (as acquisition errors, errors on the observed ratio within this measurement (σAE)): 13C/12C (σAE = 0.07‰), 17O/16O (σAE = 1.1‰), 18O/16O (σAE = 0.3‰), and 13C13C/12C (σAE = 0.65‰). The σAE of each tracks the shot noise limit throughout and is limited by the challenging conditions (high resolution and low numbers of ions per scan) required for 17O/16O measurement in the presence of 13C via Orbitrap. Second, we characterize inter-measurement stability via a sequence of seven 75-min analyses of perchlorate. We observe the following ratios and acquisition errors: 37Cl/35Cl (σAE = 0.09‰); 17O/16O (σAE = 1.6‰); 18O/16O (σAE = 0.7‰), 37Cl17O/35Cl16O (σAE = 2.7‰), and 37Cl18O/35Cl16O (σAE = 1.2‰). However, we find that inter-measurement drift between acquisitions limits our accuracy and precision for standardized measurements (i.e., error on reported δ values) to ≈1‰ for the 37Cl/35Cl measurement. Hence, the benefits of low σAE may not be fully realized. Third, we demonstrate accuracy via sample/standard comparisons of a methionine sample with 13C enrichment of ≈20‰ relative to a known standard. Using a sequence of seven 60-min analyses, we recover the following isotope ratios and standardized precisions (i.e., error on reported δ values, denoted propagated acquisition errors, σPAE): 33S/32S (σPAE = 1.0‰), 34S/32S (σPAE = 0.7‰), 15N/14N (σPAE = 2.1‰), 2H/1H (σPAE = 3.2‰),13C/12C (σPAE = 0.4‰), 18O/16O (σPAE = 1.6‰), &13C13C/12C (σPAE = 2.8‰) with confirmation of accurate results for the known 13C/12C and 13C13C/12C enrichments. Together, our results demonstrate the viability of Orbitrap-IRMS for long duration measurements of diverse sample types via an automated reservoir injection system. Inter-measurement stability remains a challenge; we expect our methods to be most applicable to extended measurements of hard-to-observe properties, such as 17O in organics and clumped isotopologues.

Biochar application significantly increases soil organic carbon under conservation tillage: an 11-year field experiment

Biochar application and conservation tillage are significant for long-term organic carbon (OC) sequestration in soil and enhancing crop yields, however, their effects on native soil organic carbon (native SOC) without biochar carbon sequestration in situ remain largely unknown. Here, an 11-year field experiment was carried out to examine different biochar application rates (0, 30, 60, and 90 Mg ha−1) on native SOC pools (native labile SOC pool I and II, and native recalcitrant SOC) and microbial activities in calcareous soil across an entire winter wheat–maize rotation. The proportions of C3 and C4-derived native SOC mineralization were quantified using soil basal respiration (SBR) combined with 13C natural isotope abundance measurements. The results showed that 39–51% of the biochar remained in the top 30 cm after 11 years. Biochar application rates significantly increased native SOC and native recalcitrant SOC contents but decreased the proportion of native labile SOC [native labile SOC pool I and II, dissolved organic carbon (DOC), and microbial biomass carbon (MBC)]. Biochar application tended to increase the indicators of microbial activities associated with SOC degradation, such as SBR, fluorescein diacetate hydrolysis activity, and metabolic quotient (qCO2). Meanwhile, higher biochar application rates (B60 and B90) significantly increased the C4-derived CO2 proportion of the SBR and enhanced C4-derived native SOC mineralization. The effect of the biochar application rate on the content and proportion of native SOC fractions occurred in the 0–15 cm layer, however, there were no significant differences at 15–30 cm. Soil depth also significantly increased native labile SOC pool I and II contents and decreased qCO2. In conclusion, the biochar application rate significantly increased native SOC accumulation in calcareous soil by enhancing the proportion of native recalcitrant SOC, and biochar application and soil depth collectively influenced the seasonal turnover of native SOC fractions, which has important implications for long-term agricultural soil organic carbon sequestration.Graphical

Enhanced Solar CO2 Photoreduction to Formic Acid by Platinum Immobilization on Bipyridine Covalent Triazine Framework with Defects

AbstractThe immobilization and structural analysis of platinum nanoparticles on a nitrogen‐rich, bipyridine‐containing covalent triazine framework (bpyCTF) having structural defects are disclosed by taking advantage of 15N solid‐state nuclear magnetic resonance measurements at natural 15N isotope abundance and X‐ray photoelectron spectroscopic analyses. The photocatalyst (Pt@bpyCTF) with structural defects reduces CO2 to formic acid (FA) at a rate of 152 µmol h−1g−1 and a selectivity higher than 95% over CO and H2 in water under simulated solar light. The presence of amine defects and the immobilization of Pt cause improvement in the photocurrent density and CO2 capture capacity (≈8% by weight) despite the moderate surface area (0.54 cm3 g−1)of the photocatalyst. Theoretical models and density functional theory calculations are employed to investigate the possible CO2 reduction reaction (CO2RR) mechanisms. Considering the exceptional CO2 capture capacity and high FA production using only CO2‐bubbled water, this work highlights the great potential of nitrogen‐rich CTFs for photocatalyzed CO2RRs under green conditions.

Coupling geochemical and microbial molecular techniques to reveal catchment-scale nitrate yield and fluvial export dynamics

The disturbance of reactive nitrogen (N) on ecosystems and biogeochemical cycles is now one of the most severe environmental problems worldwide. Nitrate (NO3−) is usually a dominant reactive N species in river ecosystems. Excessive NO3− concentrations in rivers have led to eutrophication and consequent ecological and environmental damages. Quantifying catchment-scale NO3− yield and export dynamics is crucial for effective remediation of river NO3− pollution. Frequently, natural abundance isotopes of NO3− in a river (δ15N/δ18O-NO3−) are applied to identify sources and potential transformations of NO3− at a catchment scale, while microbial molecular techniques and 15N pairing experiments are employed to reveal the NO3− production and removal processes and their underlying mechanisms in microenvironments (e.g., sediments and soils). In this study, we developed a novel protocol that couples these complementary geochemical and molecular techniques to quantify catchment-scale NO3− yield and fluvial export dynamics. The protocol links microscopic processes with catchment-scale geochemical characteristics to explicitly describe the NO3− cycling processes and their underlying abiotic and biotic mechanisms within a catchment. We applied the protocol to the Dadu and Jiazela catchments on the Qinghai-Tibet Plateau, and demonstrated the effectiveness of the protocol in determining NO3− yield and export dynamics in the catchments.

Albany K‐Feldspar: A New Pb Isotope Reference Material

Lead isotopes are a powerful and versatile tool to elucidate fundamental geological problems related to the formation and evolution of continental crust. K‐feldspar is a popular target for Pb isotope measurement as it is prevalent in many rock types and tends to capture the initial Pb isotope composition of its parental magma. We present data for a new Pb isotope reference material: Albany K‐feldspar; as well as updated data for Shap K‐feldspar. Results of Pb double‐spike TIMS for Albany K‐feldspar are 206Pb/204Pb = 16.7872 ± 0.0062, 207Pb/204Pb = 15.5640 ± 0.0056, and 208Pb/204Pb = 36.6600 ± 0.0168 (2s). TIMS measurement results for Shap K‐feldspar indicate two isotopically distinct Pb populations. LA‐MC‐ICP‐MS, with a spatial resolution as high as 15 μm, indicates a homogeneous Pb isotopic composition in Albany K‐feldspar. In accord with previous studies, our results show that scatter in the measured Pb isotope ratios, related to the low natural isotopic abundance of 204Pb, along with the effect of isobaric 204Hg‐204Pb interference, increases at lower count rates. However, the mean Pb isotope ratios measured via LA‐MC‐ICP‐MS using a range of spot sizes are in excellent agreement with TIMS results thus highlighting the feasibility of Pb isotope determination via LA‐MC‐ICP‐MS to access geological information preserved in small crystals, including mineral inclusions.

Thermoluminescence properties of Dy3+-Doped Li2O–CaO–P2O5 glasses for neutron detection

In this study, we fabricated Dy3+-doped Li2O–CaO–P2O5 glasses using 6Li or nLi (nLi: containing 6Li or 7Li isotopes in natural abundance) to develop a new thermoluminescent material for neutron detection. Their thermoluminescence (TL) properties were investigated using X-ray and thermal neutron irradiation. TL glow peaks were observed at 366 K after X-ray irradiation, and the observed TL intensities of the nLi and 6Li glasses were similar, indicating that these materials have similar sensitivities to X-rays. A TL glow peak was observed at between 373 K and 400 K after neutron irradiation, and the TL intensities of the 6Li glass were significantly higher than those of the nLi glass, indicating that high-energy particles generated in the 6Li (n, α)3H reaction efficiently induced TL. The thermal neutron fluence and TL intensity derived from the 6Li (n, α)3H reaction in the neutron fluence range of 1.0 × 106–1.0 × 1011 neutrons/cm2 showed good linear correlation. These glasses are expected to be applied in TL dosimetry for X-rays, gamma rays, and thermal neutrons.

Fungi in ant-plant interactions: a key to enhancing plant nutrient-acquisition strategies.

This article is a Commentary on Gegenbauer et al. (2023), 238: 2210–2223.

A Design and Optimization Methodology for Liquid Metal Fast Reactors

A liquid metal fast reactor (LMFR) design and optimization methodology (DOM) has been developed. The methodology effectively explores a search space by initially sampling the search space, excluding invalid design samples prior to performing expensive multiphysics analysis, and then performing local searches of the design space. The design samples are evaluated using the multiphysics capabilities of the LUPINE LMFR simulation suite. Two studies have been performed to demonstrate DOM. First, the Westinghouse long-life core lead fast reactor (WLFR) is optimized. This reactor is 950 MW th and fueled with uranium nitride (UN) fuel which has a natural nitrogen isotopic abundance. The objective of the optimization is the reduction of the levelized fuel cycle cost (LFCC) while complying with the design constraints. Considering the challenges associated with using natural nitrogen in nitride fuel, a second study was performed to design a competitive 15N-enriched UN-fueled long-life core LFR. Based on this design, the cost of the 15N enrichment process necessary to achieve a competitive LFCC was calculated.

Isotope Effects on the Optical Phonons of Cubic Boron Phosphide

The ratio of boron isotopes (10B and 11B) affects the thermal conductivity of cubic borides because of the phonon scattering. There are two signals appearing in the Raman spectra of cubic boron phosphide (c‐BP) single crystals with natural boron isotope abundance. One is a sharp peak with high intensity and small linewidth, which has been identified as a TO‐LO‐mixed mode; the other is a small peak in the low‐frequency side with quite low intensity and large linewidth, which is difficult to be observed in isotope‐purified crystals and with an unclear origin. Herein, in order to clarify the isotope effects on optical phonons and to identify the origin of the small peak in c‐BP, the Raman spectra of isotope‐tailored c‐BP single crystals in the range from nearly pure c‐10BP to nearly pure c‐11BP are analyzed in detail. Both the frequency and linewidth of the TO‐LO‐mixed mode are closely related to the boron isotope ratio under the isotopic average mass effect and mass disorder effect. The small Raman peak is also isotope dependent. It originates from LO phonon scattering at the non‐origin of the Brillouin zone under the isotopic mass disorder effect.

Nitrate dynamics in a forested catchment on the southeastern Tibetan Plateau: A study integrating natural-abundance isotopic, 15N pairing, and microbial molecular techniques

The nitrate (NO3–) dynamics on the Tibetan Plateau, one of the most climatic sensitive regions on Earth, has not yet been well understood. This study synthesized natural-abundance isotopes, 15N pairing techniques, and microbial functional genes to systematically elucidate the NO3− cycling dynamics as well as their biotic and abiotic driving mechanisms in a pristine forested catchment on the Tibetan Plateau. The river’s natural-abundance isotopes showed that mineralization-nitrification of soil organic nitrogen was the major source of NO3− in the river, while significant NO3− removal occurred in the catchment. The 15N pairing experiments support the river’s isotopes and quantitatively showed that nitrification was prevalent in soil, but more than half of the nitrification-derived NO3− was removed. In turn, the river isotopes verified the representativeness of the in-soil processes in the catchment. Structural equation models suggested nitrification and denitrification (the major NO3− removal pathway) were largely regulated by microbial functional gene abundances, which in turn were regulated by varying abiotic factors. In addition, the fluvial NO3– export rates in the sub-catchments were significantly correlated with the river runoff, highlighting the role of hydrological conditions and associated soil leaching in regulating fluvial NO3– fluxes. This study shows that combining multi-disciplinary techniques can achieve a more comprehensive understanding of NO3− dynamics at the catchment scale.

Isotope Effects and the Atmosphere.

Chemical physics plays a large role in determining the isotopic compositions of gases in Earth's atmosphere, which in turn provide fundamental insights into the sources, sinks, and transformations of atmospheric gases and particulates and their influence on climate. This review focuses on the kinetic and photolysis isotope effects relevant to understanding the isotope compositions of atmospheric ozone, carbon dioxide, methane, nitrous oxide, and other gases and their historical context. The discussion includes non-mass-dependent isotope compositions of oxygen-containing species and a brief overview of the recent growth of clumped isotope measurements at natural isotopic abundances, that is, of molecules containing more than one rare isotope. The intention is to introduce chemistry researchers to the field of using isotope compositions as tracers of atmospheric chemistry and climate both today and back in time through ice and rock records and to highlight the outstanding research questions to which experimental and theoretical physical chemists can contribute. Expected final online publication date for the Annual Review of Physical Chemistry, Volume 74 is April 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Hyperfine structure and isotope shifts of xenon measured for near-infrared transitions with Doppler-free saturated absorption spectroscopy

Hyperfine structure and isotope shifts of Xe were investigated with Doppler-free saturated absorption spectroscopy for all transitions in the 820-841 nm spectral interval. The Xe samples were commercial gases of natural isotopic abundances. The measurements were performed by employing a widely tunable narrow line Ti:sapphire laser. The hyperfine structures for 129Xe and 131Xe were well resolved. For the transitions with the wavelengths in vacuum near 820.860 nm and 841.150 nm also isotope shifts of the even isotopes were clearly observed. The modeling of the shapes of the observed absorption lines qualitatively reproduces experimental spectral profiles. The measured absorption peaks of the hyperfine structure and isotope shifts of Xe isotopes present characteristic spectral fingerprints for their identification. Eventually, quantitative spectral analysis will provide isotopic abundances of natural, as well as radioactive Xe gas samples.

Anthropogenic impacts on the nitrate pollution in an urban river: Insights from a combination of natural-abundance and paired isotopes

Urban rivers are often characterized by high nitrate (NO3−) loadings. High NO3− loadings cause water quality and ecological damages, which undermines the sustainable development of cities. To date, the drivers of these high NO3− loadings remain unclear. This study, for the first time, integrated natural-abundance isotopes (δ15 N/δ18O–NO3− and δD/δ18O–H2O) and 15N-pairing techniques to comprehensively reveal the anthropogenic impacts on the NO3− pollution in an urban river. Natural-abundance isotopes suggested that in both the wet and dry seasons, the NO3− was predominantly from the conservative mixing of different sources, and biological NO3− removal was minor. The 15N-pairing experiments supported the natural-abundance isotope data, quantitatively showing that in-soil nitrification was prevailing, while NO3− removal processes (denitrification, anammox, and dissimilatory NO3− reduction to ammonium) were weak. A Bayesian isotope-mixing model showed that soil sources (soil organic nitrogen and chemical fertilizer) dominated the NO3− in the upper reaches, while in the lower reaches, the impermeable riparian zone short-circuited the access of soils to the river. Here, the wastewater treatment plants became a significant source of NO3−. This study quantitatively revealed the drivers of high NO3− loadings in an urban river, and generated important clues for effective NO3− pollution control and remediation in urban rivers.

The absorption spectrum of nitrous oxide between 7250 and 7653 cm−1

We revisit the weak absorption spectrum of natural nitrous oxide between 7250 and 7653 cm−1 for which rovibrational assignments were previously reported in Lu et al. (doi:10.1016/j.jqsrt.2012.03.005). Our main goal is to provide intensity information for the high number of lines detected by cavity ring down spectroscopy in the region. Line parameters of about 4180 transitions were retrieved from a line-by-line profile adjustment. They belong to 69 bands of the 14N216O, 14N15N16O, 15N14N16O, and 14N218O isotopologues, present in natural isotopic abundance in the sample. Eight bands are newly reported. The band-by-band analysis allowed for the determination of refined values of the rovibrational parameters of a total of 68 upper vibrational states. Eight 14N216O bands were found to be affected by local rovibrational perturbations and a total of 31 extra lines due to an intensity transfer could be identified. The comparison with the recent NOSL-296 and Ames line lists is discussed in detail. The overall agreement is very satisfactory. As concerns line intensities, the NOSL and Ames lists show both specific advantages and drawbacks which are discussed.

Efficient SABRE-SHEATH Hyperpolarization of Potent Branched-Chain-Amino-Acid Metabolic Probe [1-13C]ketoisocaproate.

Efficient 13C hyperpolarization of ketoisocaproate is demonstrated in natural isotopic abundance and [1-13C]enriched forms via SABRE-SHEATH (Signal Amplification By Reversible Exchange in SHield Enables Alignment Transfer to Heteronuclei). Parahydrogen, as the source of nuclear spin order, and ketoisocaproate undergo simultaneous chemical exchange with an Ir-IMes-based hexacoordinate complex in CD3OD. SABRE-SHEATH enables spontaneous polarization transfer from parahydrogen-derived hydrides to the 13C nucleus of transiently bound ketoisocaproate. 13C polarization values of up to 18% are achieved at the 1-13C site in 1 min in the liquid state at 30 mM substrate concentration. The efficient polarization build-up becomes possible due to favorable relaxation dynamics. Specifically, the exponential build-up time constant (14.3 ± 0.6 s) is substantially lower than the corresponding polarization decay time constant (22.8 ± 1.2 s) at the optimum polarization transfer field (0.4 microtesla) and temperature (10 °C). The experiments with natural abundance ketoisocaproate revealed polarization level on the 13C-2 site of less than 1%-i.e., one order of magnitude lower than that of the 1-13C site-which is only partially due to more-efficient relaxation dynamics in sub-microtesla fields. We rationalize the overall much lower 13C-2 polarization efficiency in part by less favorable catalyst-binding dynamics of the C-2 site. Pilot SABRE experiments at pH 4.0 (acidified sample) versus pH 6.1 (unaltered sodium [1-13C]ketoisocaproate) reveal substantial modulation of SABRE-SHEATH processes by pH, warranting future systematic pH titration studies of ketoisocaproate, as well as other structurally similar ketocarboxylate motifs including pyruvate and alpha-ketoglutarate, with the overarching goal of maximizing 13C polarization levels in these potent molecular probes. Finally, we also report on the pilot post-mortem use of HP [1-13C]ketoisocaproate in a euthanized mouse, demonstrating that SABRE-hyperpolarized 13C contrast agents hold promise for future metabolic studies.

Solvent Effects Used for Optimal Simultaneous Analysis of Amino Acids via 19F NMR Spectroscopy.

19F NMR has been extensively used in simultaneous analysis of multicomponent due to its 100% natural isotope abundance, high NMR-sensitivity, and wide-range chemical shifts. The solvent effects are usually observed in NMR spectroscopy and cause large changes in 19F chemical shifts. Herein, we propose that the simultaneous analysis of a complex mixture can be achieved using solvent effects via 19F NMR spectroscopy, such as a mixture solution of amino acids (AAs). AAs are not only cell-signaling molecules, but are also considered as biomarkers of some diseases. Hence, the analysis of AAs is important for human health and the diagnosis of diseases. In this work, the key to the success of sensing 19 biogenic AAs is the use of 2-fluorobenzaldehyde (2FBA) as a highly sensitive derivatizing agent and solvent effects to produce distinguishable 19F NMR signals. As a result, the resolution of 19F NMR spectroscopy of multiple 2FBA-labeled AAs is obviously higher than other methods based on 19F NMR. Moreover, 14 and 18 AAs can be satisfactorily differentiated and unambiguously identified in different complicated media supporting the growth of mammalian cells. Furthermore, quantification of the concentration of AAs can be made, and the limit of detection reaches 10 μM. Our work provides new insights into the simultaneous analysis of a multicomponent mixture based on solvent effects by 19F NMR spectroscopy.

Solid-State NMR Characterization of Lyophilized Formulations of Monoclonal Antibody Therapeutics.

Monoclonal antibodies (mAbs) are an important and growing class of biotherapeutic drugs. Method development for the characterization of critical quality attributes, including higher-order structure (HOS), of mAbs remains an area of active inquiry. Recently, solution-state nuclear magnetic resonance (NMR) spectroscopy has received increased attention and is a means for reliable, high-resolution HOS characterization of aqueous-based preparations of mAbs. While mAbs are predominantly formulated in solution, up to 20% are prepared as solid amorphous powders and techniques for the robust characterization of HOS in the solid state remain limited. We propose here the use of solid-state NMR (ssNMR) fingerprinting to inform directly on the HOS of solid preparations of mAbs. Using lyophilized samples of the NISTmAb reference material prepared with different formulation conditions, we demonstrate that 1H-13C cross-polarization (hC-CP) buildup spectral series at natural isotopic abundance mAb samples are sensitive to differences in formulation. We also demonstrate that principal component analysis (PCA) can be used to differentiate the samples from one another in a user-independent manner while also highlighting areas where expert analysis can provide structural details about important molecular interactions in solid-phase protein formulations. Results from this study contribute to establishing the foundation for the use of ssNMR for HOS characterization of solid-phase biotherapeutics.

Natural and enriched Cr target development for production of Manganese-52

52Mn is a promising PET radiometal with a half-life of 5.6 days and an average positron energy of 242 keV. Typically, chromium of natural isotope abundance is used as a target material to produce this isotope through the nat/52Cr(p,n)52Mn reaction. While natural Cr is a suitable target material, higher purity 52Mn could be produced by transitioning to enriched 52Cr targets to prevent the co-production of long-lived 54Mn (t1/2 = 312 day). Unfortunately, 52Cr targets are not cost-effective without recycling processes in place, therefore, this work aims to explore routes to prepare Cr targets that could be recycled. Natural Cr foils, metal powder pellets, enriched chromium-52 oxide and Cr(III) electroplated targets were investigated in this work. Each of these cyclotron targets were irradiated, and the produced 52Mn was purified, when possible, using a semi-automated system. An improved purification by solid-phase anion exchange from ethanol-HCl mixtures resulted in recoveries of 94.5 ± 2.2% of 52Mn. The most promising target configuration to produce a recyclable target was electroplated Cr(III). This work presents several pathways to optimize enriched Cr targets for the production of high purity 52Mn.