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Single-molecule magnets represent the ultimate size limit for spin-based information storage and processing; however, such applications require large spin relaxation barriers and blocking temperatures. Ongoing efforts to synthesize single-molecule magnets with higher barriers must take into consideration key physical parameters, such as spin ground state, S, and axial zero-field splitting parameter, D, which are both correlated to the barrier height. A third critical parameter that has received less attention is the exchange coupling constant, J. This constant determines the degree of separation between spin ground state and excited states, which must be sufficiently large in a single-molecule magnet to maintain slow magnetization dynamics at elevated temperatures, and also serves to shut down fast quantum relaxation pathways. Toward this end, one synthetic strategy to engender strong magnetic exchange is the incorporation of radical ligands into metal complexes. Within these complexes, the presence of direct exchange between paramagnetic ligand and metal units can result in exceptionally strong magnetic coupling, much stronger in fact than more common superexchange interactions. This review article provides a survey of radical ligand-containing single-molecule magnets, with a brief overview of other classes of metal-ligand radical complexes that could be exploited in the design of new single-molecule magnets. Furthermore, ligand-field and electronic structure considerations in dictating exchange strength and slow magnetic relaxation are highlighted, with the aim of helping to guide the synthesis of future radical ligand-containing single-molecule magnets with even stronger exchange coupling.

Stereoradiographs have been used on occasion for three-dimensional reconstruction and measurement of objects in radiology and radiotherapy. The lack of a good stereoradiographic technique has limited the uses of steroradiographic exposures. In this paper, the principle of the double-image is outlined and a method of applying this principle to stereoradiographic exposures is developed. A computer program has been developed from geometrical considerations to analyze the stereobronchogram and to calculate the dimensions of the objects in question. The applications of this technique are discussed and its use in evaluating lung casts is described.

The pressure dependence of the HOMO-LUMO transition energy and the frequency of the longest wavelength longitudinal optical vibration of 45 Å diameter CdSe clusters in methanol-ethanol solution have been measured up to 50 kbar. The LO mode shifts to higher frequency at a rate of 0.43 cm -1/kbar, which corresponds to a Grüneisen parameter of 1.1. The HOMO-LUMO transition shifts to higher energy at 4.5 meV/kbar, yielding a deformation potential of 2.3 eV. The pressure dependence of these properties closely resemble those of the corresponding bulk solid, confirming the point of view that the lattice properties of these clusters resemble those of the bulk, even though the optical properties are quite distinct. © 1988 American Institute of Physics.

We describe a synthesis of nanometer-sized clusters of CdSe using organometallic reagents in inverse micellar solution and chemical modification of the surface of these cluster compounds. In particular we show how the clusters grow in the presence of added reagents and how the surface may be terminated and passivated by the addition of organoselenides. Passivation of the surface allows for the removal of the cluster molecules from the reaction medium and the isolation of organometallic molecules which are zinc blende CdSe clusters terminated by covalently attached organic ligands. Preliminary cluster characterization via resonance Raman, infrared, and NMR spectroscopy, X-ray diffraction, transmission electron microscopy, and size-exclusion chromatography is reported. © 1988, American Chemical Society. All rights reserved.

The resonance Raman spectrum of 45( + - 3) Å diameter CdSe clusters was measured. The incident photons were resonant with the HOMO-LUMO transition in the clusters. At low temperature, one mode at 205 cm-1 is observed, as well as two overtones, with the integrated areas under these peaks in the ratio of 9:3:1. This mode is assigned as the longest wavelength longitudinal optical vibration of the cluster. The strength of the coupling between the lowest electronic excited state and the LO vibration is found to be 20 times weaker in these clusters than in the bulk solid. The CdSe cluster resonance Raman spectrum is shown to be consistent with the recently measured homogeneous cluster absorption spectrum. © 1989 American Institute of Physics.

High-resolution extracellular electrophysiology is the gold standard for recording spikes from distributed neural populations, and is especially powerful when combined with optogenetics for manipulation of specific cell types with high temporal resolution. We integrated these approaches into prototype Neuropixels Opto probes, which combine electronic and photonic circuits. These devices pack 960 electrical recording sites and two sets of 14 light emitters onto a 1 cm shank, allowing spatially addressable optogenetic stimulation with blue and red light. In mouse cortex, Neuropixels Opto probes delivered high-quality recordings together with spatially addressable optogenetics, differentially activating or silencing neurons at distinct cortical depths. In mouse striatum and other deep structures, Neuropixels Opto probes delivered efficient optotagging, facilitating the identification of two cell types in parallel. Neuropixels Opto probes represent an unprecedented tool for recording, identifying, and manipulating neuronal populations.

We report the development of an azanide ( - NH 2 ) surrogate which enables the facile conversion of electron-deficient (hetero)aryl halides into primary N-aryl amines under transition-metal-free conditions. The designed amidine reagent is easy to prepare, bench stable, and undergoes facile N-arylation under basic conditions at 40 °C. Intermediate N-aryl amidines are readily cleaved to form N-aryl amines in situ through hydrolysis or base-promoted elimination. The developed surrogate is a safer and more selective alternative to existing anionic N-nucleophiles, such as alkali metal amides or azide salts., (© 2024 The Author(s). Chemistry - A European Journal published by Wiley-VCH GmbH.)

Accurate tracking of the same neurons across multiple days is crucial for studying changes in neuronal activity during learning and adaptation. Advances in high-density extracellular electrophysiology recording probes, such as Neuropixels, provide a promising avenue to accomplish this goal. Identifying the same neurons in multiple recordings is, however, complicated by non-rigid movement of the tissue relative to the recording sites (drift) and loss of signal from some neurons. Here, we propose a neuron tracking method that can identify the same cells independent of firing statistics, that are used by most existing methods. Our method is based on between-day non-rigid alignment of spike-sorted clusters. We verified the same cell identity in mice using measured visual receptive fields. This method succeeds on datasets separated from 1 to 47 days, with an 84% average recovery rate., Competing Interests: AY, JC, AL, MO, AC, TH No competing interests declared, (© 2023, Yuan et al.)

Wetlands play a disproportionate role in the global climate as major sources and sinks of greenhouse gases. Herbicides are the most heavily used agrochemicals and are frequently detected in aquatic ecosystems, with glyphosate and 2,4-Dichlorophenoxyacetic acid (2,4-D), representing the two most commonly used worldwide. In recent years, these herbicides are being used in mixtures to combat herbicide-tolerant noxious weeds. While it is well documented that herbicide use for agriculture is expected to increase, their indirect effects on wetland greenhouse gas dynamics are virtually unknown. To fill this knowledge gap, we conducted a factorial microcosm experiment using low, medium, and high concentrations of glyphosate or 2,4-D, individually and in combination to investigate their effects on wetland methane, carbon dioxide, and nitrous oxide fluxes. We predicted that mixed herbicide treatments would have a synergistic effect on greenhouse gases compared to individual herbicides. Our results showed that carbon dioxide flux rates and cumulative emissions significantly increased from both individual and mixed herbicide treatments, whereas methane and nitrous oxide dynamics were less affected. This study suggests that extensive use of glyphosate and 2,4-D may increase carbon dioxide emissions from wetlands, which could have implications for climate change., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The purpose of this study was to evaluate the efficacy and safety of intragastric administration of small volumes of sodium enema solution containing phosphorus as phosphorus replacement therapy in critically ill patients with traumatic injuries who required continuous enteral nutrition. Adult patients (>17 years of age) who had a serum phosphorus concentration <3 mg/dL (0.97 mmol/L) were evaluated. Patients with a serum creatinine concentration >1.4 mg/dL (124 µmol/L) were excluded. Patients were given 20 mL of saline enema solution intragastrically, containing 34 mmol of phosphorus and mixed in 240 mL water. A total of 55% and 73% of patients who received one ( n = 22) or two doses ( n = 11) had an improvement in the serum phosphorus concentration, respectively. The serum phosphorus concentration increased from 2.5 [2.1, 2.8] mg/dL (0.81 [0.69, 0.90] mmol/L) to 2.9 [2.2, 3.0] mg/dL (0.94 [0.71, 0.97 mmol/L) for those who received two doses ( p = 0.222). Excluding two patients with a marked decline in serum phosphorus by 1.3 mg/dL (0.32 mmol/L) resulted in an increase in the serum phosphorus concentration from 2.3 [2.0, 2.8] mg/dL (0.74 [0.65, 0.90] mmol/L) to 2.9 [2.5, 3.2] mg/dL (0.94 [0.81, 1.03] mmol/L; n = 9; p = 0.012). No significant adverse effects were noted. Our data indicated that intragastric phosphate administration using a small volume of saline enema solution improved the serum phosphorus concentrations in most patients.

Accurate tracking of the same neurons across multiple days is crucial for studying changes in neuronal activity during learning and adaptation. Advances in high density extracellular electrophysiology recording probes, such as Neuropixels, provide a promising avenue to accomplish this goal. Identifying the same neurons in multiple recordings is, however, complicated by non-rigid movement of the tissue relative to the recording sites (drift) and loss of signal from some neurons. Here we propose a neuron tracking method that can identify the same cells independent of firing statistics, that are used by most existing methods. Our method is based on between-day non-rigid alignment of spike sorted clusters. We verified the same cell identity in mice using measured visual receptive fields. This method succeeds on datasets separated from one to 47 days, with an 84% average recovery rate., Competing Interests: Declaration of interests The authors declare no competing interests.

To understand the neural basis of behavior, it is essential to sensitively and accurately measure neural activity at single neuron and single spike resolution. Extracellular electrophysiology delivers this, but it has biases in the neurons it detects and it imperfectly resolves their action potentials. To minimize these limitations, we developed a silicon probe with much smaller and denser recording sites than previous designs, called Neuropixels Ultra ( NP Ultra ). This device samples neuronal activity at ultra-high spatial density (~10 times higher than previous probes) with low noise levels, while trading off recording span. NP Ultra is effectively an implantable voltage-sensing camera that captures a planar image of a neuron's electrical field. We use a spike sorting algorithm optimized for these probes to demonstrate that the yield of visually-responsive neurons in recordings from mouse visual cortex improves up to ~3-fold. We show that NP Ultra can record from small neuronal structures including axons and dendrites. Recordings across multiple brain regions and four species revealed a subset of extracellular action potentials with unexpectedly small spatial spread and axon-like features. We share a large-scale dataset of these brain-wide recordings in mice as a resource for studies of neuronal biophysics. Finally, using ground-truth identification of three major inhibitory cortical cell types, we found that these cell types were discriminable with approximately 75% success, a significant improvement over lower-resolution recordings. NP Ultra improves spike sorting performance, detection of subcellular compartments, and cell type classification to enable more powerful dissection of neural circuit activity during behavior., Competing Interests: Declaration of interests CK holds an executive position, and has a financial interest, in Intrinsic Powers, Inc., a company whose purpose is to develop a device that can be used in the clinic to assess the presence and absence of consciousness in patients. This does not pose any conflict of interest with regard to the work undertaken for this publication. BR, CML, and BD are employees of IMEC vzw, a nonprofit research institute that manufactures, sells, and distributes the Neuropixels probes, at cost, to the research community. IMEC vzw holds patents US10811542B2, US10044325B2, and US9384990B2 related to the Neuropixels 1.0 technology that is built upon in this work. All other authors have no competing interests.

Freshwater benthic algae form complex mat matrices that can confer ecosystem benefits but also produce harmful cyanotoxins and nuisance taste-and-odor (T&O) compounds. Despite intensive study of the response of pelagic systems to anthropogenic change, the environmental factors controlling toxin presence in benthic mats remain uncertain. Here, we present a unique dataset from a rapidly urbanizing community (Kansas City, USA) that spans environmental, toxicological, taxonomic, and genomic indicators to identify the prevalence of three cyanotoxins (microcystin, anatoxin-a, and saxitoxin) and two T&O compounds (geosmin and 2-methylisoborneol). Thereafter, we construct a random forest model informed by game theory to assess underlying drivers. Microcystin (11.9 ± 11.6 µg/m 2 ), a liver toxin linked to animal fatalities, and geosmin (0.67 ± 0.67 µg/m 2 ), a costly-to-treat malodorous compound, were the most abundant compounds and were present in 100 % of samples, irrespective of land use or environmental conditions. Anatoxin-a (8.1 ± 11.6 µg/m 2 ) and saxitoxin (0.18 ± 0.39 µg/m 2 ), while not always detected, showed a systematic tradeoff in their relative importance with season, an observation not previously reported in the literature. Our model indicates that microcystin concentrations were greatest where microcystin-producing genes were present, whereas geosmin concentrations were high in the absence of geosmin-producing genes. Together, these results suggest that benthic mats produce microcystin in situ but that geosmin production may occur ex situ with its presence in mats attributable to adsorption by organic matter. Our study broadens the awareness of benthic cyanobacteria as a source of harmful and nuisance metabolites and highlights the importance of benthic monitoring for sustaining water quality standards in rivers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Cyanobacterial blooms present substantial challenges to managers and threaten ecological and public health. Although the majority of cyanobacterial bloom research and management focuses on factors that control bloom initiation, duration, toxicity, and geographical extent, relatively little research focuses on the role of loss processes in blooms and how these processes are regulated. Here, we define a loss process in terms of population dynamics as any process that removes cells from a population, thereby decelerating or reducing the development and extent of blooms. We review abiotic (e.g., hydraulic flushing and oxidative stress/UV light) and biotic factors (e.g., allelopathic compounds, infections, grazing, and resting cells/programmed cell death) known to govern bloom loss. We found that the dominant loss processes depend on several system specific factors including cyanobacterial genera-specific traits, in situ physicochemical conditions, and the microbial, phytoplankton, and consumer community composition. We also address loss processes in the context of bloom management and discuss perspectives and challenges in predicting how a changing climate may directly and indirectly affect loss processes on blooms. A deeper understanding of bloom loss processes and their underlying mechanisms may help to mitigate the negative consequences of cyanobacterial blooms and improve current management strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

The hippocampus is critical for recollecting and imagining experiences. This is believed to involve voluntarily drawing from hippocampal memory representations of people, events, and places, including maplike representations of familiar environments. However, whether representations in such "cognitive maps" can be volitionally accessed is unknown. We developed a brain-machine interface to test whether rats can do so by controlling their hippocampal activity in a flexible, goal-directed, and model-based manner. We found that rats can efficiently navigate or direct objects to arbitrary goal locations within a virtual reality arena solely by activating and sustaining appropriate hippocampal representations of remote places. This provides insight into the mechanisms underlying episodic memory recall, mental simulation and planning, and imagination and opens up possibilities for high-level neural prosthetics that use hippocampal representations.

Plastic debris is thought to be widespread in freshwater ecosystems globally 1 . However, a lack of comprehensive and comparable data makes rigorous assessment of its distribution challenging 2,3 . Here we present a standardized cross-national survey that assesses the abundance and type of plastic debris (>250 μm) in freshwater ecosystems. We sample surface waters of 38 lakes and reservoirs, distributed across gradients of geographical position and limnological attributes, with the aim to identify factors associated with an increased observation of plastics. We find plastic debris in all studied lakes and reservoirs, suggesting that these ecosystems play a key role in the plastic-pollution cycle. Our results indicate that two types of lakes are particularly vulnerable to plastic contamination: lakes and reservoirs in densely populated and urbanized areas and large lakes and reservoirs with elevated deposition areas, long water-retention times and high levels of anthropogenic influence. Plastic concentrations vary widely among lakes; in the most polluted, concentrations reach or even exceed those reported in the subtropical oceanic gyres, marine areas collecting large amounts of debris 4 . Our findings highlight the importance of including lakes and reservoirs when addressing plastic pollution, in the context of pollution management and for the continued provision of lake ecosystem services., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Materials that simultaneously exhibit permanent porosity and high-temperature magnetic order could lead to advances in fundamental physics and numerous emerging technologies. Herein, we show that the archetypal molecule-based magnet and magnonic material V(TCNE) 2 (TCNE = tetracyanoethylene) can be desolvated to generate a room-temperature microporous magnet. The solution-phase reaction of V(CO) 6 with TCNE yields V(TCNE) 2 ·0.95CH 2 Cl 2 , for which a characteristic temperature of T * = 646 K is estimated from a Bloch fit to variable-temperature magnetization data. Removal of the solvent under reduced pressure affords the activated compound V(TCNE) 2 , which exhibits a T * value of 590 K and permanent microporosity (Langmuir surface area of 850 m 2 /g). The porous structure of V(TCNE) 2 is accessible to the small gas molecules H 2 , N 2 , O 2 , CO 2 , ethane, and ethylene. While V(TCNE) 2 exhibits thermally activated electron transfer with O 2 , all the other studied gases engage in physisorption. The T * value of V(TCNE) 2 is slightly modulated upon adsorption of H 2 ( T * = 583 K) or CO 2 ( T * = 596 K), while it decreases more significantly upon ethylene insertion ( T * = 459 K). These results provide an initial demonstration of microporosity in a room-temperature magnet and highlight the possibility of further incorporation of small-molecule guests, potentially even molecular qubits, toward future applications., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

The brain is arguably the most powerful computation system known. It is extremely efficient in processing large amounts of information and can discern signals from noise, adapt, and filter faulty information all while running on only 20 watts of power. The human brain's processing efficiency, progressive learning, and plasticity are unmatched by any computer system. Recent advances in stem cell technology have elevated the field of cell culture to higher levels of complexity, such as the development of three-dimensional (3D) brain organoids that recapitulate human brain functionality better than traditional monolayer cell systems. Organoid Intelligence (OI) aims to harness the innate biological capabilities of brain organoids for biocomputing and synthetic intelligence by interfacing them with computer technology. With the latest strides in stem cell technology, bioengineering, and machine learning, we can explore the ability of brain organoids to compute, and store given information (input), execute a task (output), and study how this affects the structural and functional connections in the organoids themselves. Furthermore, understanding how learning generates and changes patterns of connectivity in organoids can shed light on the early stages of cognition in the human brain. Investigating and understanding these concepts is an enormous, multidisciplinary endeavor that necessitates the engagement of both the scientific community and the public. Thus, on Feb 22-24 of 2022, the Johns Hopkins University held the first Organoid Intelligence Workshop to form an OI Community and to lay out the groundwork for the establishment of OI as a new scientific discipline. The potential of OI to revolutionize computing, neurological research, and drug development was discussed, along with a vision and roadmap for its development over the coming decade., Competing Interests: TH is employed by, and inventor on a patent by Johns Hopkins University on the production of brain organoids, which is licensed to AxoSim, New Orleans, LA, USA, and receives royalty shares. TH also consults to AxoSim. LS is employed by Johns Hopkins University and consults to AxoSim, New Orleans, LA, USA. JS is employed by, and inventor on a patent by the University of Luxembourg on the production of midbrain organoids, which is licensed to OrganoTherapeutics SARL, Esch-sur-Alzette, Luxembourg. JLC and BC were employed by AxoSim Inc., New Orleans, LA, United States. JS is also co-founder and shareholder of OrganoTherapeutics SARL. AM is employed by the University of California, San Diego and is co-founder and has equity interest in TISMOO, a company dedicated to genetic analysis and human brain organogenesis, focusing on therapeutic applications customized for autism spectrum disorders and other neurological disorders origin genetics. The terms of this arrangement have been reviewed and approved by the University of California, San Diego, in accordance with its conflict of interest policies. BK is employed by Cortical Labs Pty Ltd., Melbourne, Australia, and is an inventor on patents for technology related this paper and holds shares in Cortical Labs Pty Ltd., Melbourne, Australia. No specific funding or other incentives were provided for involvement in this publication. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Morales Pantoja, Smirnova, Muotri, Wahlin, Kahn, Boyd, Gracias, Harris, Cohen-Karni, Caffo, Szalay, Han, Zack, Etienne-Cummings, Akwaboah, Romero, Alam El Din, Plotkin, Paulhamus, Johnson, Gilbert, Curley, Cappiello, Schwamborn, Hill, Roach, Tornero, Krall, Parri, Sillé, Levchenko, Jabbour, Kagan, Berlinicke, Huang, Maertens, Herrmann, Tsaioun, Dastgheyb, Habela, Vogelstein and Hartung.)

A wide range of techniques in neuroscience involve placing individual probes at precise locations in the brain. However, large-scale measurement and manipulation of the brain using such methods have been severely limited by the inability to miniaturize systems for probe positioning. Here, we present a fundamentally new, remote-controlled micropositioning approach composed of novel phase-change material-filled resistive heater micro-grippers arranged in an inchworm motor configuration. The microscopic dimensions, stability, gentle gripping action, individual electronic control, and high packing density of the grippers allow micrometer-precision independent positioning of many arbitrarily shaped probes using a single piezo actuator. This multi-probe single-actuator design significantly reduces the size and weight and allows for potential automation of microdrives. We demonstrate accurate placement of multiple electrodes into the rat hippocampus in vivo in acute and chronic preparations. Our robotic microdrive technology should therefore enable the scaling up of many types of multi-probe applications in neuroscience and other fields., Competing Interests: RS, MB M.B. and R.D.S. have applied for intellectual property patent protection on the devices and principles described in this work ("Positioning apparatus and gripping apparatus", US20200046317A1), IK, ST, AL, TH No competing interests declared, (© 2022, Smith et al.)

David Schindler and his colleagues pioneered studies in the 1970s on the role of phosphorus in stimulating cyanobacterial blooms in North American lakes. Our understanding of the nuances of phosphorus utilization by cyanobacteria has evolved since that time. We review the phosphorus utilization strategies used by cyanobacteria, such as use of organic forms, alternation between passive and active uptake, and luxury storage. While many aspects of physiological responses to phosphorus of cyanobacteria have been measured, our understanding of the critical processes that drive species diversity, adaptation and competition remains limited. We identify persistent critical knowledge gaps, particularly on the adaptation of cyanobacteria to low nutrient concentrations. We propose that traditional discipline-specific studies be adapted and expanded to encompass innovative new methodologies and take advantage of interdisciplinary opportunities among physiologists, molecular biologists, and modellers, to advance our understanding and prediction of toxic cyanobacteria, and ultimately to mitigate the occurrence of blooms., (© The Author(s) 2022. Published by Oxford University Press on behalf of FEMS.)

Oxygen is a critical gas in numerous industries and is produced globally on a gigatonne scale, primarily through energy-intensive cryogenic distillation of air. The realization of large-scale adsorption-based air separations could enable a significant reduction in associated worldwide energy consumption and would constitute an important component of broader efforts to combat climate change. Certain small-scale air separations are carried out using N 2 -selective adsorbents, although the low capacities, poor selectivities, and high regeneration energies associated with these materials limit the extent of their usage. In contrast, the realization of O 2 -selective adsorbents may facilitate more widespread adoption of adsorptive air separations, which could enable the decentralization of O 2 production and utilization and advance new uses for O 2 . Here, we present a detailed evaluation of the potential of metal-organic frameworks (MOFs) to serve as O 2 -selective adsorbents for air separations. Drawing insights from biological and molecular systems that selectively bind O 2 , we survey the field of O 2 -selective MOFs, highlighting progress and identifying promising areas for future exploration. As a guide for further research, the importance of moving beyond the traditional evaluation of O 2 adsorption enthalpy, Δ H , is emphasized, and the free energy of O 2 adsorption, Δ G , is discussed as the key metric for understanding and predicting MOF performance under practical conditions. Based on a proof-of-concept assessment of O 2 binding carried out for eight different MOFs using experimentally derived capacities and thermodynamic parameters, we identify two existing materials and one proposed framework with nearly optimal Δ G values for operation under user-defined conditions. While enhancements are still needed in other material properties, the insights from the assessments herein serve as a guide for future materials design and evaluation. Computational approaches based on density functional theory with periodic boundary conditions are also discussed as complementary to experimental efforts, and new predictions enable identification of additional promising MOF systems for investigation., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Carbon, nitrogen, and phosphorus are critical macroelements in freshwater systems. Historically, researchers and managers have focused on inorganic forms, based on the premise that the organic pool was not available for direct uptake by phytoplankton. We now know that phytoplankton can tap the organic nutrient pool through a number of mechanisms including direct uptake, enzymatic hydrolysis, mixotrophy, and through symbiotic relationships with microbial communities. In this review, we explore these mechanisms considering current and projected future anthropogenically-driven changes to freshwater systems. In particular, we focus on how naturally- and anthropogenically- derived organic nutrients can influence phytoplankton community structure. We also synthesize knowledge gaps regarding phytoplankton physiology and the potential challenges of nutrient management in an organically dynamic and anthropogenically modified world. Our review provides a basis for exploring these topics and suggests several avenues for future work on the relation between organic nutrients and eutrophication and their ecological implications in freshwater systems., (Copyright © 2022. Published by Elsevier Ltd.)

Exogenous ketone esters have demonstrated the capacity to increase oxygen availability during acute hypoxic exposure leading to the potential application of their use to mitigate performance declines at high altitudes. Voluntary hypoventilation (VH) with exercise reliably reduces oxygen availability and increases carbon dioxide retention without alterations to ambient pressure or gas content. Utilizing a double-blind randomized crossover design, fifteen recreational male distance runners performed submaximal exercise (4 × 5 min; 70% VO 2 Max) with VH. An exogenous ketone ester (KME; 573 mg⋅kg -1 ) or iso-caloric flavor matched placebo (PLA) was consumed prior to exercise. Metabolites, blood gases, expired air, heart rate, oxygen saturation, cognition, and perception metrics were collected throughout. KME rapidly elevated R -β-hydroxybutyrate and reduced blood glucose without altering lactate production. KME lowered pH, bicarbonate, and total carbon dioxide. VH with exercise significantly reduced blood (SpO 2 ) and muscle (SmO 2 ) oxygenation and increased cognitive mean reaction time and respiratory rate regardless of condition. KME administration significantly elevated respiratory exchange ratio (RER) at rest and throughout recovery from VH, compared to PLA. Blood carbon dioxide (PCO 2 ) retention increased in the PLA condition while decreasing in the KME condition, leading to a significantly lower PCO 2 value immediately post VH exercise (IPE; p = 0.031) and at recovery ( p = 0.001), independent of respiratory rate. The KME's ability to rapidly alter metabolism, acid/base balance, CO 2 retention, and respiratory exchange rate independent of respiratory rate changes at rest, during, and/or following VH exercise protocol illustrates a rapid countermeasure to CO 2 retention in concert with systemic metabolic changes., Competing Interests: AK is a consultant for Simply Good Foods Inc. DD’A is co-owner of Ketone Technologies LLC, providing scientific consulting and public speaking on ketogenic therapies, and receives royalties in accordance with University of South Florida policy patent policy. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Prins, Buxton, McClure, D’Agostino, Ault, Welton, Jones, Atwell, Slack, Slack, Williams, Blanchflower, Kannel, Faulkner, Szmaciasz, Croll, Stanforth, Harris, Gwaltney and Koutnik.)

State-of-the-art silicon probes for electrical recording from neurons have thousands of recording sites. However, due to volume limitations there are typically many fewer wires carrying signals off the probe, which restricts the number of channels that can be recorded simultaneously. To overcome this fundamental constraint, we propose a method called electrode pooling that uses a single wire to serve many recording sites through a set of controllable switches. Here we present the framework behind this method and an experimental strategy to support it. We then demonstrate its feasibility by implementing electrode pooling on the Neuropixels 1.0 electrode array and characterizing its effect on signal and noise. Finally we use simulations to explore the conditions under which electrode pooling saves wires without compromising the content of the recordings. We make recommendations on the design of future devices to take advantage of this strategy., (© 2021. The Author(s).)

Measuring the dynamics of neural processing across time scales requires following the spiking of thousands of individual neurons over milliseconds and months. To address this need, we introduce the Neuropixels 2.0 probe together with newly designed analysis algorithms. The probe has more than 5000 sites and is miniaturized to facilitate chronic implants in small mammals and recording during unrestrained behavior. High-quality recordings over long time scales were reliably obtained in mice and rats in six laboratories. Improved site density and arrangement combined with newly created data processing methods enable automatic post hoc correction for brain movements, allowing recording from the same neurons for more than 2 months. These probes and algorithms enable stable recordings from thousands of sites during free behavior, even in small animals such as mice., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Metal-organic frameworks represent the ultimate chemical platform on which to develop a new generation of designer magnets. In contrast to the inorganic solids that have dominated permanent magnet technology for decades, metal-organic frameworks offer numerous advantages, most notably the nearly infinite chemical space through which to synthesize predesigned and tunable structures with controllable properties. Moreover, the presence of a rigid, crystalline structure based on organic linkers enables the potential for permanent porosity and postsynthetic chemical modification of the inorganic and organic components. Despite these attributes, the realization of metal-organic magnets with high ordering temperatures represents a formidable challenge, owing largely to the typically weak magnetic exchange coupling mediated through organic linkers. Nevertheless, recent years have seen a number of exciting advances involving frameworks based on a wide range of metal ions and organic linkers. This review provides a survey of structurally characterized metal-organic frameworks that have been shown to exhibit magnetic order. Section 1 outlines the need for new magnets and the potential role of metal-organic frameworks toward that end, and it briefly introduces the classes of magnets and the experimental methods used to characterize them. Section 2 describes early milestones and key advances in metal-organic magnet research that laid the foundation for structurally characterized metal-organic framework magnets. Sections 3 and 4 then outline the literature of metal-organic framework magnets based on diamagnetic and radical organic linkers, respectively. Finally, Section 5 concludes with some potential strategies for increasing the ordering temperatures of metal-organic framework magnets while maintaining structural integrity and additional function.

The use of radical bridging ligands to facilitate strong magnetic exchange between paramagnetic metal centers represents a key step toward the realization of single-molecule magnets with high operating temperatures. Moreover, bridging ligands that allow the incorporation of high-anisotropy metal ions are particularly advantageous. Toward these ends, we report the synthesis and detailed characterization of the dinuclear hydroquinone-bridged complexes [(Me 6 tren) 2 M II 2 (C 6 H 4 O 2 2- )] 2+ (Me 6 tren = tris(2-dimethylaminoethyl)amine; M = Fe, Co, Ni) and their one-electron-oxidized, semiquinone-bridged analogues [(Me 6 tren) 2 M II 2 (C 6 H 4 O 2 - ˙)] 3+ . Single-crystal X-ray diffraction shows that the Me 6 tren ligand restrains the metal centers in a trigonal bipyramidal geometry, and coordination of the bridging hydro- or semiquinone ligand results in a parallel alignment of the three-fold axes. We quantify the p -benzosemiquinone-transition metal magnetic exchange coupling for the first time and find that the nickel(ii) complex exhibits a substantial J < -600 cm -1 , resulting in a well-isolated S = 3/2 ground state even as high as 300 K. The iron and cobalt complexes feature metal-semiquinone exchange constants of J = -144(1) and -252(2) cm -1 , respectively, which are substantially larger in magnitude than those reported for related bis(bidentate) semiquinoid complexes. Finally, the semiquinone-bridged cobalt and nickel complexes exhibit field-induced slow magnetic relaxation, with relaxation barriers of U eff = 22 and 46 cm -1 , respectively. Remarkably, the Orbach relaxation observed for the Ni complex is in stark contrast to the fast processes that dominate relaxation in related mononuclear Ni II complexes, thus demonstrating that strong magnetic coupling can engender slow magnetic relaxation., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Catalytic heme active sites of enzymes are sequestered by the protein superstructure and are regulated by precisely defined outer coordination spheres. Here, we emulate these protective functions in the porphyrinic metal-organic framework PCN-224 by post-synthetic acetylation and subsequent hydroxylation of the Zr 6 nodes. A suite of physical methods demonstrates that both transformations preserve framework structure, crystallinity, and porosity without modifying the inner coordination spheres of the iron sites. Single-crystal X-ray analyses establish that acetylation replaces the mixture of formate, benzoate, aqua, and terminal hydroxo ligands at the Zr 6 nodes with acetate ligands, and hydroxylation affords nodes with seven-coordinate, hydroxo-terminated Zr 4+ ions. The chemical influence of these reactions is probed with heme-catalyzed cyclohexane hydroxylation as a model reaction. By virtue of passivated reactive sites at the Zr 6 nodes, the acetylated framework oxidizes cyclohexane with a yield of 68(8)%, 2.6-fold higher than in the hydroxylated framework, and an alcohol/ketone ratio of 5.6(3)., (This journal is © The Royal Society of Chemistry 2020.)

The elucidation of magnetostructural correlations between bridging ligand substitution and strength of magnetic coupling is essential to the development of high-temperature molecule-based magnetic materials. Toward this end, we report the series of tetraoxolene-bridged Fe II 2 complexes [(Me 3 TPyA) 2 Fe 2 ( R L)] n + (Me 3 TPyA = tris(6-methyl-2-pyridylmethyl)amine; n = 2: OMe LH 2 = 3,6-dimethoxy-2,5-dihydroxo-1,4-benzoquinone, Cl LH 2 = 3,6-dichloro-2,5-dihydroxo-1,4-benzoquinone, Na 2 [ NO 2 L] = sodium 3,6-dinitro-2,5-dihydroxo-1,4-benzoquinone; n = 4: SMe 2 L = 3,6-bis(dimethylsulfonium)-2,5-dihydroxo-1,4-benzoquinone diylide) and their one-electron-reduced analogues. Variable-temperature dc magnetic susceptibility data reveal the presence of weak ferromagnetic superexchange between Fe II centers in the oxidized species, with exchange constants of J = +1.2(2) (R = OMe, Cl) and +0.3(1) (R = NO 2 , SMe 2 ) cm -1 . In contrast, X-ray diffraction, cyclic voltammetry, and Mössbauer spectroscopy establish a ligand-centered radical in the reduced complexes. Magnetic measurements for the radical-bridged species reveal the presence of strong antiferromagnetic metal-radical coupling, with J = -57(10), -60(7), -58(6), and -65(8) cm -1 for R = OMe, Cl, NO 2 , and SMe 2 , respectively. The minimal effects of substituents in the 3- and 6-positions of R L x -• on the magnetic coupling strength is understood through electronic structure calculations, which show negligible spin density on the substituents and associated C atoms of the ring. Finally, the radical-bridged complexes are single-molecule magnets, with relaxation barriers of U eff = 50(1), 41(1), 38(1), and 33(1) cm -1 for R = OMe, Cl, NO 2 , and SMe 2 , respectively. Taken together, these results provide the first examination of how bridging ligand substitution influences magnetic coupling in semiquinoid-bridged compounds, and they establish design criteria for the synthesis of semiquinoid-based molecules and materials.

Metal-organic frameworks with amidic linkers often exhibit exceptional physical properties, but, owing to their strong metal-nitrogen bonds, are exceedingly challenging to isolate through direct synthesis. Here, we report a route to access metal-diamidobenzoquinone frameworks from their dihydroxobenzoquinone counterparts via postsynthetic linker exchange. The parent compounds (Me 2 NH 2 ) 2 [M 2 L 3 ] (M = Zn, Mn; H 2 L = 2,5-dichloro-3,6-dihydroxo-1,4-benzoquinone) undergo linker exchange upon exposure to a solution of monodeprotonated 2,5-diamino-3,6-dibromo-1,4-benzoquinone or 2,5-diamino-3,6-dichloro-1,4-benzoquinone, proceeding through single-crystal-to-single-crystal reactions. The presence of both types of linker in the resulting frameworks is confirmed by a combination of NMR, Raman, and energy-dispersive X-ray (EDX) spectroscopies. Moreover, the extent of linker exchange in the Zn frameworks is quantified using 13 C NMR spectroscopy, and spatially resolved EDX spectroscopy reveals the two types of linker to be homogeneously distributed within a crystal. Finally, we propose a tentative mechanism of linker exchange based on p K a measurements, considerations of framework solubility, and powder X-ray diffraction analysis. This work provides the first method to exchange organic linkers with different donor atoms in metal-organic frameworks and in doing so demonstrates exchange between linkers with donor atoms differing in acidity by a remarkable 11 units of p K a . Together, these results offer a potentially general synthetic strategy toward new materials with exotic metal-linker coordination modes.

Although CMOS fabrication has enabled a quick evolution in the design of high-density neural probes and neural-recording chips, the scaling and miniaturization of the complete data-acquisition systems has happened at a slower pace. This is mainly due to the complexity and the many requirements that change depending on the specific experimental settings. In essence, the fundamental challenge of a neural-recording system is getting the signals describing the largest possible set of neurons out of the brain and down to data storage for analysis. This requires a complete system optimization that considers the physical, electrical, thermal and signal-processing requirements, while accounting for available technology, manufacturing constraints and budget. Here we present a scalable and open-standards-based open-source data-acquisition system capable of recording from over 10,000 channels of raw neural data simultaneously. The components and their interfaces have been optimized to ensure robustness and minimum invasiveness in small-rodent electrophysiology.

The paramagnetic cyano-bridged complex PhB( t BuIm) 3 Fe-NC-Mo(N t BuAr) 3 (Ar = 3,5-Me 2 C 6 H 3 ) is readily assembled from a new four-coordinate, high-spin ( S = 2) iron(II) monocyanide complex and the three-coordinate molybdenum(III) complex Mo(N t BuAr) 3 . X-ray diffraction and IR spectroscopy reveal that delocalization of unpaired electron density into the cyanide π* orbitals leads to a reduction of the C-N bond order. Direct current (dc) magnetic susceptibility measurements, supported by electronic structure calculations, demonstrate the presence of strong antiferromagnetic exchange between spin centers, with a coupling constant of J = -122(2) cm -1 . To our knowledge, this value represents the strongest magnetic exchange coupling ever to be observed through cyanide. These results demonstrate the ability of low-coordinate metal fragments to engender extremely strong magnetic exchange coupling through cyanide by virtue of significant π-backbonding into the cyanide ligand.

The classic approach to measure the spiking response of neurons involves the use of metal electrodes to record extracellular potentials. Starting over 60 years ago with a single recording site, this technology now extends to ever larger numbers and densities of sites. We argue, based on the mechanical and electrical properties of existing materials, estimates of signal-to-noise ratios, assumptions regarding extracellular space in the brain, and estimates of heat generation by the electronic interface, that it should be possible to fabricate rigid electrodes to concurrently record from essentially every neuron in the cortical mantle. This will involve fabrication with existing yet nontraditional materials and procedures. We further emphasize the need to advance materials for improved flexible electrodes as an essential advance to record from neurons in brainstem and spinal cord in moving animals., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Electrophysiology is the most used approach for the collection of functional data in basic and translational neuroscience, but it is typically limited to either intracellular or extracellular recordings. The integration of multiple physiological modalities for the routine acquisition of multimodal data with microelectrodes could be useful for biomedical applications, yet this has been challenging owing to incompatibilities of fabrication methods. Here, we present a suite of glass pipettes with integrated microelectrodes for the simultaneous acquisition of multimodal intracellular and extracellular information in vivo, electrochemistry assessments, and optogenetic perturbations of neural activity. We used the integrated devices to acquire multimodal signals from the CA1 region of the hippocampus in mice and rats, and show that these data can serve as ground-truth validation for the performance of spike-sorting algorithms. The microdevices are applicable for basic and translational neurobiology, and for the development of next-generation brain-machine interfaces.

Structural and spectroscopic characterization of the dimeric iron hydride complex [Ph 2 B( t BuIm) 2 FeH] 2 reveals an unusual structure in which a tetrahedral iron(II) site ( S = 2) is connected to a square planar iron(II) site ( S = 1) by two bridging hydride ligands. Magnetic susceptibility reveals strong ferromagnetic coupling between iron centers, with a coupling constant of J = +110(12) cm -1 , to give an S = 3 ground state. High-frequency and -field electron paramagnetic resonance (HFEPR) spectroscopy confirms this model. A qualitative molecular orbital analysis of the electronic structure, as supported by electronic structure calculations, reveals that the observed spin configuration results from the orthogonal alignment of two geometrically distinct four-coordinate iron fragments held together by highly covalent hydride ligands.

Semiquinoid radical bridging ligands are capable of mediating exceptionally strong magnetic coupling between spin centers, a requirement for the design of high-temperature magnetic materials. We demonstrate the ability of sulfur donors to provide much stronger coupling relative to their oxygen congeners in a series of dinuclear complexes. Employing a series of chalcogen donor-based bis(bidentate) benzoquinoid bridging ligands, the series of complexes [(TPyA) 2 Cr 2 ( R L 4- )] 2+ ( O LH 4 = 1,2,4,5-tetrahydroxybenzene, OS LH 4 = 1,2-dithio-4,5-dihydroxybenzene, S LH 4 = 1,2,4,5-tetrathiobenzene, TPyA = tris(2-pyridylmethyl)amine) was synthesized. Variable-temperature dc magnetic susceptibility data reveal the presence of weak antiferromagnetic superexchange coupling between Cr III centers in these complexes, with exchange constants of J = -2.83(3) ( O L 4- ), -2.28(5) ( OS L 4- ), and -1.80(2) ( S L 4- ) cm -1 . Guided by cyclic voltammetry and spectroelectrochemical measurements, chemical one-electron oxidation of these complexes gives the radical-bridged species [(TPyA) 2 Cr 2 ( R L 3-• )] 3+ . Variable-temperature dc susceptibility measurements in these complexes reveal the presence of strong antiferromagnetic metal-semiquinoid radical coupling, with exchange constants of J = -352(10) ( O L 3-• ), - 401(8) ( OS L 3-• ), and -487(8) ( S L 3-• ) cm -1 . These results provide the first measurement of magnetic coupling between metal ions and a thiosemiquinoid radical, and they demonstrate the value of moving from O to S donors in radical-bridged metal ions in the design of magnetic molecules and materials.

We report a cobalt-based paramagnetic chemical exchange saturation transfer (PARACEST) magnetic resonance (MR) probe that is able to selectively bind and quantitate the concentration of Ca 2+ ions under physiological conditions. The parent LCo complex features CEST-active carboxamide groups and an uncoordinated crown ether moiety in close proximity to a high-spin pseudo-octahedral Co II center. Addition of Na + , Mg 2+ , K + , and Ca 2+ leads to binding of these metal ions within the crown ether. Single-crystal X-ray diffraction and solid-state magnetic measurements reveal the presence of a cation-specific coordination environment and magnetic anisotropy of Co II , with axial zero-field splitting parameters for the Na + - and Ca 2+ -bound complexes differing by over 90%. Owing to these differences, solution-based measurements under physiological conditions indicate reversible binding of Na + and Ca 2+ to give well-separated CEST peaks at 69 and 80 ppm for [LCoNa] + and [LCoCa] 2+ , respectively. Dissociation constants for different cation-bound complexes of LCo, as determined by 1 H NMR spectroscopy, demonstrate high selectivity toward Ca 2+ . This finding, in conjunction with the large excess of Na + in physiological environments, minimizes interference from related cations, such as Mg 2+ and K + . Finally, variable-[Ca 2+ ] CEST spectra establish the ratio between the CEST peak intensities for the Ca 2+ - and Na + -bound probes (CEST 80 ppm /CEST 69 ppm ) as a measure of [Ca 2+ ], providing the first example of a ratiometric quantitation of Ca 2+ concentration using PARACEST. Taken together, these results demonstrate the ability of transition metal PARACEST probes to afford a concentration-independent measure of [Ca 2+ ] and provide a new approach for designing MR probes for cation sensing.

Purpose: To develop switchable and tunable labels with high contrast ratio for MRI using magnetocaloric materials that have sharp first-order magnetic phase transitions at physiological temperatures and typical MRI magnetic field strengths., Methods: A prototypical magnetocaloric material iron-rhodium (FeRh) was prepared by melt mixing, high-temperature annealing, and ice-water quenching. Temperature- and magnetic field-dependent magnetization measurements of wire-cut FeRh samples were performed on a vibrating sample magnetometer. Temperature-dependent MRI of FeRh samples was performed on a 4.7T MRI., Results: Temperature-dependent MRI clearly demonstrated image contrast changes due to the sharp magnetic state transition of the FeRh samples in the MRI magnetic field (4.7T) and at a physiologically relevant temperature (~37°C)., Conclusion: A magnetocaloric material, FeRh, was demonstrated to act as a high contrast ratio switchable MRI contrast agent due to its sharp first-order magnetic phase transition in the DC magnetic field of MRI and at physiologically relevant temperatures. A wide range of magnetocaloric materials are available that can be tuned by materials science techniques to optimize their response under MRI-appropriate conditions and be controllably switched in situ with temperature, magnetic field, or a combination of both., (© 2018 International Society for Magnetic Resonance in Medicine.)

Materials with switchable magnetic and electrical properties may enable future spintronic technologies, and thus hold the potential to revolutionize how information is processed and stored. While reversible switching of magnetic order or electrical conductivity has been independently realized in materials, the ability to simultaneously switch both properties in a single material presents a formidable challenge. Here, we report the 2D manganese benzoquinoid framework (Me 4 N) 2 [MnII2(L 2- ) 3 ] (H 2 L = 2,5-dichloro-3,6-dihydroxo-1,4-benzoquinone), as synthesized via post-synthetic counterion exchange. This material is paramagnetic above 1.8 K and exhibits an ambient-temperature electrical conductivity of σ 295 K = 1.14(3) × 10 -13 S cm -1 ( E a = 0.74(3) eV). Upon soaking in a solution of sodium naphthalenide and 1,2-dihydroacenaphthylene, this compound undergoes a single-crystal-to-single-crystal (SC-SC) reduction to give Na 3 (Me 4 N) 2 [Mn 2 L 3 ]. Structural and spectroscopic analyses confirm this reduction to be ligand-based, and as such the anionic framework is formulated as [MnII2(L 3- ˙) 3 ] 5- . Magnetic measurements confirm that this reduced material is a permanent magnet below T c = 41 K and exhibits a conductivity value of σ 295 K = 2.27(1) × 10 -8 S cm -1 ( E a = 0.489(8) eV), representing a remarkable 200 000-fold increase over the parent material. Finally, soaking the reduced compound in a solution of [Cp 2 Fe] + affords Na(Me 4 N)[MnII2(L 2- ) 3 ] via a SC-SC process, with magnetic and electrical properties similar to those observed for the original oxidized material. Taken together, these results highlight the ability of metal benzoquinoid frameworks to undergo reversible, simultaneous redox switching of magnetic order and electrical conductivity.

The employment of an ancillary amine-substituted bisphosphonate ligand affords a dicobalt complex able to quantitate pH with a remarkably high sensitivity of 8.8(5) pH unit-1 at 37 °C through a ratiometric paramagnetic chemical exchange saturation transfer (PARACEST) approach, where the different pH dependences of amine and amide CEST peak intensities are utilized.

Postsynthetic metal exchange represents a powerful synthetic method to generate metal-organic frameworks (MOFs) that are not accessible through direct synthesis, yet it is often hampered by slow reaction kinetics and incomplete exchange. While studies of metal exchange reactions have primarily focused on the transmetalation process, transport of exogenous metal ions into the framework structure represents a critical yet underexplored process. Here, we employ X-ray crystallography, electron microscopy, and energy dispersive X-ray spectroscopy to comprehensively examine the transport of Co 2+ and Zn 2+ ions during postsynthetic metal exchange reactions within the 2D manganese-benzoquinoid framework (Et 4 N) 2 [Mn 2 L 3 ] (H 2 L = 3,6-dichloro-2,5-dihydroxy-1,4-benzoquinone). These studies reveal that exogenous metal ions diffuse primarily through the 1D channel along the crystallographic c axis, and this transport represents the rate-determining step. In addition, the Mn framework exhibits reversible dynamic structure behavior, contracting upon desolvation and then rapidly restoring its original structure and full volume upon resolvation. When conducting metal exchange reactions using a partially desolvated sample, these structural dynamics lead to acceleration of metal transport by up to 2000-fold, improve product purity, and give exchange of a larger fraction of metal sites. Finally, upon performing metal exchange using full-solvated crystals, an intermediate product can be isolated that constitutes a unique example of a 2D material with a gradient vertical heterostructure.

We report three new Co 2 -based paramagnetic chemical exchange saturation transfer (PARACEST) probes with the ability to ratiometrically quantitate pH. A Co II 2 complex, [LCo 2 (etidronate)] - , featuring tetra(carboxamide) and OH-substituted etidronate ligands with opposing pH-dependent CEST peak intensities, was previously shown to exhibit a linear correlation between log(CEST OH /CEST NH ) and pH in the pH range 6.5-7.6 that provided a sensitivity of 0.99(7) pH unit -1 at 37 °C. Here, we demonstrate through a series of CF 3 -functionalized Co II 2 complexes [( X L')Co 2 (etidronate)] - (X = NO 2 , F, Me), that modest changes in the electronic structure of Co II centers through remote ligand substitution can significantly affect the NMR and CEST properties of Co 2 -based PARACEST probes. Variable-pH NMR and CEST analyses reveal that the chemical shifts of the ligand protons are highly affected by the nature of the X substituent. The ratios of OH and NH CEST peak intensities at 115 and 88, 93 and 79, and 88 and 76 ppm for X = NO 2 , F, and Me, respectively, afford pH calibration curves with remarkably high sensitivities of 1.49(9), 1.48(7), and 2.04(5) pH unit -1 across the series. The 1.5-2-fold enhancement in pH sensitivity for the CF 3 -functionalized Co 2 probes stems from the complete separation of the OH and NH CEST peaks. Furthermore, incorporation of electron-withdrawing CF 3 groups shifts the detection window to a more acidic range of pH 6.2-7.4. Finally, the Co II 2 complexes are found to be extremely robust toward substitution and oxidation in aqueous solutions. Taken together, these results highlight the unique ability of transition metal-based PARACEST probes to provide a highly sensitive concentration-independent measure of pH and demonstrate that modest ligand modifications can be a powerful tool for optimizing the pH sensing performance of these probes.