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AIMS AND OBJECTIVES: This paper aims to undertake a review on the current evidence available on therapeutic hypothermia (TH) following cardiac arrest. BACKGROUND: The use of TH has been associated as a potential treatment for a number of medical conditions including head injury and cerebral vascular accidents. Within the past decade, there have been numerous studies focusing upon the use of hypothermia following cardiac arrest. This paper evaluates the research on the use of TH following cardiac arrest and provides recommendations for clinical practice. Evidence from randomized controlled trials that are reviewed in this paper found that neurological outcome and mortality were significantly improved following inducing hypothermia following cardiac arrest. SEARCH STRATEGIES: The following databases were accessed: Bandolier, Embase, Medline, Science Direct, CINAHL, Blackwell Synergy, Nursing Collection, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews and the National Electronic Library for Health. The following key words were used to search the databases: 'Therapeutic hypothermia', 'Induced hypothermia', 'cooling post cardiac arrest' and 'post cardiac arrest care'. INCLUSION AND EXCLUSION CRITERIA: Only evidences published within the past 10 years and written in English were included. Studies on TH for the treatment of raised intracranial pressure were excluded. CONCLUSIONS: All adult patients who have return of spontaneous circulation and remain unconscious following cardiac arrest should be considered for TH between 32 degrees C and 34 degrees C for at least 12-24 h as this will improve patient mortality and morbidity. Acute hospitals need to devise policies and guidelines on the use of TH following cardiac arrest that include methods on how to achieve effective cooling by cold i.v. infusions, ice packs or purchasing specific cooling mattresses. [ABSTRACT FROM AUTHOR]

This paper aims to discuss the development of a pre-registration high-dependency nursing programme and evaluate its effects on student's perceived learning and confidence in managing critically ill patients. The programme consists of two modules that compliment one another, 'Care of the Acutely III Adult' focuses on a variety of disease processes and subsequent nursing care. Whilst the second module titled 'Caring for the Highly Dependant/Critically III Adult' focuses on assessment skills related to critically ill patients. The paper explores the content and delivery of the modules including the advantages and disadvantages of implementing them. Student evaluation from 59 nursing students found that student's knowledge, assessment skills and management of the critically ill patient had improved since completing the modules. Nurse Consultants, intensive therapy unit matrons and Critical Care Outreach nurses have acknowledged an increase in the number of nursing students identifying and referring critically ill patients to outreach teams. They also stated improvements in nurse recruitment in critical care since commencement of the modules. [ABSTRACT FROM AUTHOR]

This article aims to review the current evidence in relation to acute head injury care. Head injuries are a frequent cause of death and disability in western society with the first 72 h being an important period for prevention of further brain damage. The underlying physiology behind head injury and intracranial pressure will be discussed. The monitoring of intracranial pressure and implications for practice will be addressed. The specialized nursing care and drug therapy management that is necessary for acute head injury patients will be highlighted. Recommendations for practice will be given. [ABSTRACT FROM AUTHOR]

Mass spectrometry is commonly used in the identification of species present in microbial samples, but the high similarity in the peptide composition between strains of a single species has made analysis at the subspecies level challenging. Prior research in this area has employed methods such as Principal Component Analysis (PCA), the k-Nearest Neighbors' (kNN) algorithm, and Pearson correlation. Previously, 1D cross-correlation of mass spectra has been shown to be useful in the classification of small molecule compounds as well as in the identification of peptide sequences via the SEQUEST algorithm and its variants. While direct application of cross-correlation to mass spectral data has been shown to aid in the identification of many other types of compounds, this type of analysis has not been demonstrated in the literature for the purpose of LC-MS based identification of microbial strains. A method of identifying microbial strains is presented here that applies the principle of 2D cross-correlation to LC-MS data. For a set of N = 30 yeast isolate samples representing 5 yeast strains (K-97, S-33, T-58, US-05, WB-06), high-resolution LC-MS-Orbitrap data were collected. Reference spectra were then generated for each strain from the combined data of each sample of that strain. Sample strains were then predicted by computing the 2D cross-correlation of each sample against the reference spectra, followed by application of correction factors measuring the asymmetry of the 2D correlation functions.

Background: The European Food Safety Authority (EFSA) recommended lowering their estimated tolerable daily intake (TDI) for bisphenol A (BPA) 20,000-fold to 0.2  ng / kg  body weight  ( BW ) / day . BPA is an extensively studied high production volume endocrine disrupting chemical (EDC) associated with a vast array of diseases. Prior risk assessments of BPA by EFSA as well as the US Food and Drug Administration (FDA) have relied on industry-funded studies conducted under good laboratory practice protocols (GLP) requiring guideline end points and detailed record keeping, while also claiming to examine (but rejecting) thousands of published findings by academic scientists. Guideline protocols initially formalized in the mid-twentieth century are still used by many regulatory agencies. EFSA used a 21st century approach in its reassessment of BPA and conducted a transparent, but time-limited, systematic review that included both guideline and academic research. The German Federal Institute for Risk Assessment (BfR) opposed EFSA's revision of the TDI for BPA., Objectives: We identify the flaws in the assumptions that the German BfR, as well as the FDA, have used to justify maintaining the TDI for BPA at levels above what a vast amount of academic research shows to cause harm. We argue that regulatory agencies need to incorporate 21st century science into chemical hazard identifications using the CLARITY-BPA (Consortium Linking Academic and Regulatory Insights on BPA Toxicity) nonguideline academic studies in a collaborative government-academic program model., Discussion: We strongly endorse EFSA's revised TDI for BPA and support the European Commission's (EC) apparent acceptance of this updated BPA risk assessment. We discuss challenges to current chemical risk assessment assumptions about EDCs that need to be addressed by regulatory agencies to, in our opinion, become truly protective of public health. Addressing these challenges will hopefully result in BPA, and eventually other structurally similar bisphenols (called regrettable substitutions) for which there are known adverse effects, being eliminated from all food-related and many other uses in the EU and elsewhere. https://doi.org/10.1289/EHP13812.

The macrocyclic proligand [H 4 L][OTf] 2 , which contains four carboxamide functions and two conjugated pyridinium groups, is easily deprotonated by the weak base sodium acetate to give the corresponding neutral proligand [H 2 L]. Metallation of [H 2 L] with iron(II) chloride proceeds rapidly to form the macrocyclic complex, [Fe III Cl(L)]. This is an effective catalyst for the oxidation of the organic dye orange II by hydrogen peroxide in aqueous solution, and the kinetic parameters for this reaction have been determined. In striking contrast to an analogous iron-TAML complex that contains two phenyl groups in place of the two pyridinium groups, [Fe III Cl(L)] is a very active oxidation catalyst at pH 7 and is also highly stable towards acid-promoted demetallation at pH 5 or above. The results show that the two pyridinium groups bring greatly enhanced catalytic properties to [Fe III Cl(L)]., (© 2023 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Food contact materials (FCMs) and food contact articles are ubiquitous in today's globalized food system. Chemicals migrate from FCMs into foodstuffs, so called food contact chemicals (FCCs), but current regulatory requirements do not sufficiently protect public health from hazardous FCCs because only individual substances used to make FCMs are tested and mostly only for genotoxicity while endocrine disruption and other hazard properties are disregarded. Indeed, FCMs are a known source of a wide range of hazardous chemicals, and they likely contribute to highly prevalent non-communicable diseases. FCMs can also include non-intentionally added substances (NIAS), which often are unknown and therefore not subject to risk assessment. To address these important shortcomings, we outline how the safety of FCMs may be improved by (1) testing the overall migrate, including (unknown) NIAS, of finished food contact articles, and (2) expanding toxicological testing beyond genotoxicity to multiple endpoints associated with non-communicable diseases relevant to human health. To identify mechanistic endpoints for testing, we group chronic health outcomes associated with chemical exposure into Six Clusters of Disease (SCOD) and we propose that finished food contact articles should be tested for their impacts on these SCOD. Research should focus on developing robust, relevant, and sensitive in-vitro assays based on mechanistic information linked to the SCOD, e.g., through Adverse Outcome Pathways (AOPs) or Key Characteristics of Toxicants. Implementing this vision will improve prevention of chronic diseases that are associated with hazardous chemical exposures, including from FCMs., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare. For the sake of transparency, the authors list their relationships with various research funders and other organizations in the following. As researchers employed by the Food Packaging Forum Foundation (FPF) (JMB, BG, JM, LZ) or working pro bono as members of the Foundation’s board (TB, JPM, MS) and its Scientific Advisory Board (SAB) (AMA, TJC, KJG, JJH, MVM, OVM, AN, CN, AMS, LT, MW, RTZ), we are reporting that the FPF receives donations from diverse companies that may be affected by the research reported in the enclosed paper. FPF funders have no influence on any of the work at FPF and were not involved in any way in the preparation of this manuscript. TB declares that he serves as the board member of the International Panel on Chemical Pollution (IPCP), the Swedish Toxicological Council and the EU Commission’s Committee on Health, Environmental and Emerging Risks (SCHEER). All those activities are pro bono and have no bearing on the content of the manuscript. None of the aforementioned organizations have had any impact on the content of the manuscript. TJC declares that he is the creator-founder of Sudoc, LLC, which deploys TAML catalysts for many applications and has potential for remediating FCCs in water. JL reports that she receives funding for another research project (ZonMw/Health-Holland Microplastics and Health project MOMENTUM 458001101) of which some partners may be affected by the research reported here. MVM is a paid consultant to the FPF. OVM is one of the representatives of the European Parliament on the European Chemical Agency’s Management Board. JPM is co-founder and board member of Sudoc and he declares to have given all his shares to an irrevocable grantor trust so that he will not benefit financially if the company is successful. AN declares to have received travel reimbursement from universities, NGOs and scientific societies, to speak about endocrine-disrupting chemicals. LNV has received travel reimbursements from universities, governments, NGOs, and industry. She has received research funding from the US National Institutes of Health, the University of Massachusetts Amherst, and NGOs including the Cornell Douglas Foundation, the Allen Family Foundation, and the Great Neck Breast Cancer Coalition. She is a scientific advisor to Sudoc LLC. The FPF foundation board, whose members have no connection with any of the FPF’s funders and receive no remuneration for their work, is legally obliged to guarantee that the work of the FPF is in no way influenced by the interests or views of the funders., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The European Food Safety Authority (EFSA) has revised their estimate of the toxicity of bisphenol A (BPA) and, as a result, have recommended reducing the tolerable daily intake (TDI) by 20 000-fold. This would essentially ban the use of BPA in food packaging such as can liners, plastic food containers, and in consumer products. To come to this conclusion, EFSA used a systematic approach according to a pre-established protocol and included all guideline and nonguideline studies in their analysis. They found that Th-17 immune cells increased with very low exposure to BPA and used this endpoint to revise the TDI to be human health protective. A number of regulatory agencies including the European Medicines Agency (EMA) have written formal disagreements with several elements of EFSA's proposal. The European Commission will now decide whether to accept EFSA's recommendation over the objections of EMA. If the Commission accepts EFSA's recommendation, it will be a landmark action using knowledge acquired through independent scientific studies focused on biomarkers of chronic disease to protect human health. The goal of this Perspective is to clearly articulate the monumental nature of this debate and decision and to explain what is at stake. Our perspective is that the weight of evidence clearly supports EFSA's proposal to reduce the TDI by 20 000-fold., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)

Overlapping principles of embryonic and tumor biology have been described, with recent multi-omics campaigns uncovering shared molecular profiles between human pluripotent stem cells (hPSCs) and adult tumors. Here, using a chemical genomic approach, we provide biological evidence that early germ layer fate decisions of hPSCs reveal targets of human cancers. Single-cell deconstruction of hPSCs-defined subsets that share transcriptional patterns with transformed adult tissues. Chemical screening using a unique germ layer specification assay for hPSCs identified drugs that enriched for compounds that selectively suppressed the growth of patient-derived tumors corresponding exclusively to their germ layer origin. Transcriptional response of hPSCs to germ layer inducing drugs could be used to identify targets capable of regulating hPSC specification as well as inhibiting adult tumors. Our study demonstrates properties of adult tumors converge with hPSCs drug induced differentiation in a germ layer specific manner, thereby expanding our understanding of cancer stemness and pluripotency., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Fe-TAML/peroxide catalysis provides simple, powerful, ultradilute approaches for removing micropollutants from water. The typically rate-determining interactions of H 2 O 2 with Fe-TAMLs (rate constant k I ) are sharply pH-sensitive with rate maxima in the pH 9-10 window. Fe-TAML design or process design that shifts the maximum rates to the pH 6-8 window of most wastewaters would make micropollutant eliminations even more powerful. Here, we show how the different pH dependencies of the interactions of Fe-TAMLs with peroxide or hypochlorite to form active Fe-TAMLs ( k I step) illuminate why moving from H 2 O 2 (p K a , ca. 11.6) to hypochlorite (p K a , 7.5) shifts the pH of the fastest catalysis to as low as 8.2. At pH 7, hypochlorite catalysis is 100-1000 times faster than H 2 O 2 catalysis. The pH of maximum catalytic activity is also moderated by the p K a 's of the Fe-TAML axial water ligands, 8.8, 9.3, and 10.3, respectively, for [Fe{4-NO 2 C 6 H 3 -1,2-(NCOCMe 2 NSO 2 ) 2 CHMe}(H 2 O) n ] - ( 2 ) [ n = 1-2], [Fe{4-NO 2 C 6 H 3 -1,2-(NCOCMe 2 NCO) 2 CF 2 }(H 2 O) n ] - ( 1b ), and [Fe{C 6 H 4 -1,2-(NCOCMe 2 NCO) 2 CMe 2 }(H 2 O) n ] - ( 1a ). The new bis(sulfonamido)-bis(carbonamido)-ligated 2 exhibits the lowest p K a and delivers the largest hypochlorite over peroxide catalytic rate advantage. The fast Fe-TAML/hypochlorite catalysis is accompanied by slow noncatalytic oxidations of Orange II.

At ambient temperatures, neutral pH and ultralow concentrations (low nM), the bis(sulfonamido)bis(amido) oxidation catalyst [Fe{4-NO 2 C 6 H 3 -1,2-( N COCMe 2 N SO 2 ) 2 CHMe}(OH 2 )] - ( 1 ) has been shown to catalyze the addition of an oxygen atom to microcystin-LR. This persistent bacterial toxin can contaminate surface waters and render drinking water sources unusable when nutrient concentrations favor cyanobacterial blooms. In mechanistic studies of this oxidation, while the pH was controlled with phosphate buffers, it became apparent that iron ejection from 1 becomes increasingly problematic with increasing [phosphate] (0.3-1.0 M); 1 is not noticeably impacted at low concentrations (0.01 M). At pH < 6.5 and [phosphate] ≥ 1.0 M, 1 decays quickly, losing iron from the macrocycle. Iron ejection is surprisingly mechanistically complex; the pseudo-first-order rate constant k obs has an unusual dependence on the total phosphate concentration ([P t ]), k obs = k 1 [P t ] + k 2 [P t ] 2 , indicating two parallel pathways that are first and second order in [phosphate], respectively. The pH profiles in the 5.5-8.3 range for k 1 and k 2 are different: bell-shaped with a maximum of around pH 7 for k 1 and sigmoidal for k 2 with higher values at lower pH. Mechanistic proposals for the k 1 and k 2 pathways are detailed based on both the kinetic data and density functional theory analysis. The major difference between k 1 and k 2 is the involvement of different phosphate species, i.e., HPO 4 2- ( k 1 ) and H 2 PO 4 - ( k 2 ); HPO 4 2- is less acidic but more nucleophilic, which favors intramolecular rate-limiting Fe-N bond cleavage. Instead, H 2 PO 4 - acts intermolecularly, where the kinetics suggest that [H 4 P 2 O 8 ] 2- drives degradation.

Aim: The "2022 ACC/AHA Guideline for the Diagnosis and Management of Aortic Disease" provides recommendations to guide clinicians in the diagnosis, genetic evaluation and family screening, medical therapy, endovascular and surgical treatment, and long-term surveillance of patients with aortic disease across its multiple clinical presentation subsets (ie, asymptomatic, stable symptomatic, and acute aortic syndromes)., Methods: A comprehensive literature search was conducted from January 2021 to April 2021, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Library, CINHL Complete, and other selected databases relevant to this guideline. Additional relevant studies, published through June 2022 during the guideline writing process, were also considered by the writing committee, where appropriate., Structure: Recommendations from previously published AHA/ACC guidelines on thoracic aortic disease, peripheral artery disease, and bicuspid aortic valve disease have been updated with new evidence to guide clinicians. In addition, new recommendations addressing comprehensive care for patients with aortic disease have been developed. There is added emphasis on the role of shared decision making, especially in the management of patients with aortic disease both before and during pregnancy. The is also an increased emphasis on the importance of institutional interventional volume and multidisciplinary aortic team expertise in the care of patients with aortic disease., (Copyright © 2022 American College of Cardiology Foundation and the American Heart Association, Inc. Published by Elsevier Inc. All rights reserved.)

Natural products (NPs) encompass a rich source of bioactive chemical entities. Here, we used human cancer stem cells (CSCs) in a chemical genomics campaign with NP chemical space to interrogate extracts from diverse strains of actinomycete for anti-cancer properties. We identified a compound (McM25044) capable of selectively inhibiting human CSC function versus normal stem cell counterparts. Biochemical and molecular studies revealed that McM025044 exerts inhibition on human CSCs through the small ubiquitin-like modifier (SUMO) cascade, found to be hyperactive in a variety of human cancers. McM025044 impedes the SUMOylation pathway via direct targeting of the SAE1/2 complex. Treatment of patient-derived CSCs resulted in reduced levels of SUMOylated proteins and suppression of progenitor and stem cell capacity measured in vitro and in vivo. Our study overcomes a barrier in chemically inhibiting oncogenic SUMOylation activity and uncovers a unique role for SAE2 in the biology of human cancers., Competing Interests: Declaration of interests The authors declare no competing financial interests. However, some authors are inventors of a provisional patent related to unique targeting of human cancer cells using SAE2 and related probe compounds., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The environmental problem stemming from toxic and recalcitrant naphthenic acids (NAs) present in effluents from the oil industry is well characterized. However, despite the numerous technologies evaluated for their destruction, their up-scaling potential remains low due to high implementation and running costs. Catalysts can help cutting costs by achieving more efficient reactions with shorter operating times and lower reagent requirements. Therefore, we have performed a laboratory investigation to assess iron-TAML (tetra-amido macrocyclic ligand) activators to catalyze the oxidation of NAs by activating hydrogen peroxide - considered environmentally friendly because it releases only water as by-product - under ultra-dilute conditions. We tested Fe-TAML/H 2 O 2 systems on (i) model NAs and (ii) a complex mixture of NAs in oil refining wastewater (RWW) obtained from a refining site in Colombia. Given the need for cost-effective solutions, this preliminary study explores sub-stoichiometric H 2 O 2 concentrations for NA mineralization in batch mode and, remarkably, delivers substantial removal of the starting NAs. Additionally, a 72-h semi-batch process in which Fe-TAML activators and hydrogen peroxide were added every 8 h achieved 90-95% removal when applied to model NAs (50 mg L -1 ) and a 4-fold reduction in toxicity towards Aliivibrio fischeri when applied to RWW. Chemical characterization of treated RWW showed that Fe-TAML/H 2 O 2 treatment (i) reduced the concentration of the highly toxic O 2 NAs, (ii) decreased cyclized constituents in the mixture, and (iii) preferentially degraded higher molecular weight species that are typically resistant to biodegradation. The experimental findings, together with the recent development of new TAML catalysts that are far more effective than the TAML catalysts deployed herein, constitute a foundation for cost-effective treatment of NA-contaminated wastewater., 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 © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Oxidative water purification of micropollutants (MPs) can proceed via toxic intermediates calling for procedures for connecting degrading chemical mixtures to evolving toxicity. Herein, we introduce a method for projecting evolving toxicity onto composite changing pollutant and intermediate concentrations illustrated through the TAML/H 2 O 2 mineralization of the common drug and MP, propranolol. The approach consists of identifying the key intermediates along the decomposition pathway (UPLC/GCMS/NMR/UV-Vis), determining for each by simulation and experiment the rate constants for both catalytic and noncatalytic oxidations and converting the resulting predicted concentration versus time profiles to evolving composite toxicity exemplified using zebrafish lethality data. For propranolol, toxicity grows substantially from the outset, even after propranolol is undetectable, echoing that intermediate chemical and toxicity behaviors are key elements of the environmental safety of MP degradation processes. As TAML/H 2 O 2 mimics mechanistically the main steps of peroxidase catalytic cycles, the findings may be relevant to propranolol degradation in environmental waters., Competing Interests: Y.S. and T.J.C. are coinventors on a patent for the latest generation TAML catalysts, allowed in the United States and pending elsewhere—the connection to this work is remote. T.J.C. is the Creator Founder and a Board member of Sudoc, LLC, formed to commercialize applications of the latest generation TAML catalysts. T.J.C.'s Irrevocable Family Trust is an owner of significant holdings in Sudoc, LLC—the vast majority of the Trust's future income is directed to supporting research and education in sustainability science, especially to advancing the rational handling of endocrine disrupting chemicals in our global civilization., (© 2020 The Author(s).)

A cyclic voltammetry study of a series of iron(III) TAML activators of peroxides of several generations in acetonitrile as solvent reveals reversible or quasireversible Fe III/IV and Fe IV/V anodic transitions, the formal reduction potentials (E°') for which are observed in the ranges 0.4-1.2 and 1.4-1.6 V, respectively, versus Ag/AgCl. The slope of 0.33 for a linear E°'(IV/V) against E°'(III/IV) plot suggests that the TAML ligand system plays a bigger role in the Fe III/IV transition, whereas the second electron transfer is to a larger extent an iron-centered phenomenon. The reduction potentials appear to be a convenient tool for analysis of various properties of iron TAML activators in terms of linear free energy relationships (LFERs). The values of E°'(III/IV) and E°'(IV V -1 ) correlate 1) with the pK a values of the axial aqua ligand of iron(III) TAMLs with slopes of 0.28 and 0.06 V, respectively; 2) with the Stern-Volmer constants K SV for the quenching of fluorescence of propranolol, a micropollutant of broad concern; 3) with the calculated ionization potentials of Fe III and Fe IV TAMLs; and 4) with rate constants k I and k II for the oxidation of the resting iron(III) TAML state by H 2 O 2 and reactions of the active forms of TAMLs formed with donors of electrons S, respectively. Interestingly, slopes of log k II versus E°'(III/IV) plots are lower for fast-to-oxidize S than for slow-to-oxidize S. The log k I versus E°'(III/IV) plot suggests that the manmade TAML catalyst can never be as reactive toward H 2 O 2 as a horseradish peroxidase enzyme., (© 2020 Wiley-VCH GmbH.)

Materials have been developed that encapsulate a homogeneous catalyst and enable it to operate as a heterogeneous catalyst in water. A hydrophobic ionic liquid within the material was used to dissolve Fe-TAML and keep it from leaching into the aqueous phase. One-pot processes were used to entrap Fe-TAML in basic ionic liquid gels, and ionic liquid gel spheres structured via a modified Stöber synthesis forming SiO 2 particles of uniform size. Catalytic activity was demonstrated via the oxidative degradation of dyes. Fe-TAML entrapped in a basic ionic liquid gel exhibited consistent activity in five recycles. This discovery of heterogenized H 2 O 2 activators prepared by sol-gel and Stöber processes opens new possibilities for the creation of engineered catalytic materials for water purification.

Studies of the oxidative degradation of picric acid (2,4,6-trinitrophenol) by H 2 O 2 catalyzed by a fluorine-tailed tetraamido macrocyclic ligand (TAML) activator of peroxides [Fe III {4,5-Cl 2 C 6 H 2 -1,2-( N COCMe 2 N CO) 2 CF 2 }(OH 2 )] - ( 2 ) in neutral and mildly basic solutions revealed that oxidative degradation of this explosive demands components of phosphate or carbonate buffers and is not oxidized in their absence. The TAML- and buffer-catalyzed oxidation is subject to severe substrate inhibition, which results in at least 1000-fold retardation of the interaction between the iron(III) resting state of 2 and H 2 O 2 . The inhibition accounts for a unique pH profile for the TAML catalysis with the highest activity at pH 7. Less aggressive TAMLs such as [Fe III {C 6 H 4 -1,2-( N COCMe 2 N CO) 2 CMe 2 }(OH 2 )] - are catalytically inactive. The roles of buffer components in modulating catalysis have been clarified through detailed kinetic investigations of the degradation process, which is first order in the concentration of 2 and shows ascending hyperbolic dependencies in the concentrations of all three participants, i.e., H 2 O 2 , picrate, and phosphate/carbonate. The reactivity trends are consistent with a mechanism involving the formation of double ([LFe III -Q] 2- ) and triple ([LFe III -{Q-H 2 PO 4 }] 3- ) associates, which are unreactive and reactive toward H 2 O 2 , respectively. The binding of phosphate converts [LFe III -Q] 2- to the reactive triple associate. Density functional theory suggests that the stability of the double associate is achieved via both Fe-O phenol binding and π-π stacking. The triple associate is an outer-sphere complex where phosphate binding occurs noncovalently through hydrogen bonds. A linear free energy relationship analysis of the reactivity of the mono-, di-, and trinitro phenols suggests that the rate-limiting step involves an electron transfer from phenolate to an oxidized ironoxo intermediate, giving phenoxy radicals that undergo further rapid oxidation that lead to eventual mineralization.

Bis-sulfonamide bis-amide TAML activator [Fe{4-NO 2 C 6 H 3 -1,2-(NCOCMe 2 NSO 2 ) 2 CHMe}] - (2) catalyzes oxidative degradation of the oxidation-resistant neonicotinoid insecticide, imidacloprid (IMI), by H 2 O 2 at pH 7 and 25 °C, whereas the tetrakis-amide TAML [Fe{4-NO 2 C 6 H 3 -1,2-(NCOCMe 2 NCO) 2 CF 2 }] - (1), previously regarded as the most catalytically active TAML, is inactive under the same conditions. At ultra-low concentrations of both imidacloprid and 2, 62 % of the insecticide was oxidized in 2 h, at which time the catalyst is inactivated; oxidation resumes on addition of a succeeding aliquot of 2. Acetate and oxamate were detected by ion chromatography, suggesting deep oxidation of imidacloprid. Explored at concentrations [2]≥[IMI], the reaction kinetics revealed unusually low kinetic order in 2 (0.164±0.006), which is observed alongside the first order in imidacloprid and an ascending hyperbolic dependence in [H 2 O 2 ]. Actual independence of the reaction rate on the catalyst concentration is accounted for in terms of a reversible noncovalent binding between a substrate and a catalyst, which usually results in substrate inhibition when [catalyst]≪[substrate] but explains the zero order in the catalyst when [2]>[IMI]. A plausible mechanism of the TAML-catalyzed oxidations of imidacloprid is briefly discussed. Similar zero-order catalysis is presented for the oxidation of 3-methyl-4-nitrophenol by H 2 O 2 , catalyzed by the TAML analogue of 1 without a NO 2 -group in the aromatic ring., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Understanding the catalysis of oxidative reactions by TAML activators of peroxides, i. e. iron(III) complexes of tetraamide macrocyclic ligands, advocated a spectrophotometric procedure for quantifying the catalytic activity of TAMLs for colorless targets (k II ', M -1  s -1 ), which is incomparably more advantageous in terms of time, cost, energy, and ecology than NMR, HPLC, UPLC, GC-MS and other similar techniques. Dyes Orange II or Safranin O (S) are catalytically bleached by non-excessive amount of H 2 O 2 in the presence of colorless substrates (S 1 ) according to the rate law: -d[S]/dt=k I k II [H 2 O 2 ][S][TAML]/(k I [H 2 O 2 ]+k II [S]+k II '[S 1 ]). The bleaching rate is thus a descending hyperbolic function of S 1  : v=ab/(b+[S 1 ]). Values of k II ' found from a and b for phenol and propranolol with commonly used TAML [Fe III {o,o'-C 6 H 4 (NCONMe 2 CO) 2 CMe 2 } 2 (OH 2 )] + are consistent with those for S 1 (phenol, propranolol) obtained directly by UPLC. The study sends vital messages to enzymologists and environmentalists., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Chemotherapy-induced peripheral neuropathy (PN) is a disorder damaging the peripheral nervous system (PNS) and represents one of the most common side effects of chemotherapy, negatively impacting the quality of life of patients to the extent of withdrawing life-saving chemotherapy dose or duration. Unfortunately, the pathophysiological effects of PN are poorly understood, in part due to the lack of availability of large numbers of human sensory neurons (SNs) for study. Previous reports have demonstrated that human SNs can be directly converted from primitive CD34 + hematopoietic cells, but was limited to a small-scale product of SNs and derived exclusively from less abundant allogenic sources of cord or drug mobilized peripheral blood (PB). To address this shortcoming, we have developed and report detailed procedures toward the generation of human SN directly converted from conventionally drawn PB of adults that can be used in a high-content screening platform for discovery-based studies of chemotherapy agents on neuronal biology. In the absence of mobilization drugs, cryogenically preserved adult human PB could be induced to (i)SN via development through expandable neural precursor differentiation. iSNs could be transferable to high-throughput procedures suitable for high-content screening applicable to neuropathy for example, alterations in neurite morphology in response to chemotherapeutics. Our study provides the first reported platform using adult PB-derived iSNs to study peripheral nervous system-related neuropathies as well as target and drug screening potential for the ability to prevent, block, or repair chemotherapy-induced PN damage. Stem Cells Translational Medicine 2019;8:1180-1191., (© 2019 The Authors. Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.)

The assembly of organized colonies is the earliest manifestation in the derivation or induction of pluripotency in vitro. However, the necessity and origin of this assemblance is unknown. Here, we identify human pluripotent founder cells (hPFCs) that initiate, as well as preserve and establish, pluripotent stem cell (PSC) cultures. PFCs are marked by N-cadherin expression (NCAD + ) and reside exclusively at the colony boundary of primate PSCs. As demonstrated by functional analysis, hPFCs harbor the clonogenic capacity of PSC cultures and emerge prior to commitment events or phenotypes associated with pluripotent reprogramming. Comparative single-cell analysis with pre- and post-implantation primate embryos revealed hPFCs share hallmark properties with primitive endoderm (PrE) and can be regulated by non-canonical Wnt signaling. Uniquely informed by primate embryo organization in vivo, our study defines a subset of founder cells critical to the establishment pluripotent state., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The adhesion of human epidermal keratinocytes to the implant surface is one of the most critical steps during the patient's recovery from implantation of transcutaneous prosthesis. To improve the success rate of transcutaneous prosthetic implants, we explored a new "top-down" approach to promoting this dynamic adhering process through modulation of upstream cell signaling pathways. To examine the feasibility of this novel approach, we first established an in vitro platform that is capable of providing a non-invasive, real-time, quantitative characterization of the keratinocyte-implant interaction. This platform is based on the dissipation monitoring function of the quartz crystal microbalance with dissipation monitoring (QCM-D) in conjunction with the open-module setup of the QCM-D. We then employed this platform to assess the effects of various pathways-specific modulators on the adhering process of keratinocytes. We demonstrated that this "top-down" approach is as effective in enhancing the adhesion of keratinocytes as the conventional "bottom-up" approach that relies on modifying the substrate surface with the adhesion protein such as fibronectin. We envision that this new "top-down" approach combined with the QCM-D-based in vitro platform will help facilitate the future development of new therapies for enhancing osseointegration and promoting wound healing., (Copyright © 2019 Elsevier Inc. All rights reserved.)

High-valent Fe-OH species are important intermediates in hydroxylation chemistry. Such complexes have been implicated in mechanisms of oxygen-activating enzymes and have thus far been observed in Compound II of sulfur-ligated heme enzymes like cytochrome P450. Attempts to synthetically model such species have thus far seen relatively little success. Here, the first synthetic Fe IV OH n complex has been generated and spectroscopically characterized as either [LFe IV OH] - or [LFe IV OH 2 ] 0 , where H 4 L = Me 4 C 2 (NHCOCMe 2 NHCO) 2 CMe 2 is a variant of a tetra-amido macrocyclic ligand (TAML). The steric bulk provided by the replacement of the aryl group with the -CMe 2 CMe 2 - unit in this TAML variant prevents dimerization in all oxidation states over a wide pH range, thus allowing the generation of Fe IV OH n in near quantitative yield from oxidation of the [LFe III OH 2 ] - precursor.

TAML activators enable unprecedented, rapid, ultradilute oxidation catalysis where substrate inhibitions might seem improbable. Nevertheless, while TAML/H 2 O 2 rapidly degrades the drug propranolol, a micropollutant (MP) of broad concern, propranolol is shown to inhibit its own destruction under concentration conditions amenable to kinetics studies ([propranolol] = 50 μM). Substrate inhibition manifests as a decrease in the second-order rate constant k I for H 2 O 2 oxidation of the resting Fe III -TAML (RC) to the activated catalyst (AC), while the second-order rate constant k II for attack of AC on propranolol is unaffected. This kinetics signature has been utilized to develop a general approach for quantifying substrate inhibitions. Fragile adducts [propranolol, TAML] have been isolated and subjected to ESI-MS, florescence, UV-vis, FTIR, 1 H NMR, and IC examination and DFT calculations. Propranolol binds to Fe III -TAMLs via combinations of noncovalent hydrophobic, coordinative, hydrogen bonding, and Coulombic interactions. Across four studied TAMLs under like conditions, propranolol reduced k I 4-32-fold (pH 7, 25 °C) indicating that substrate inhibition is controllable by TAML design. However, based on the measured k I and calculated equilibrium constant K for propranolol-TAML binding, it is possible to project the impact on k I of reducing [propranolol] from 50 μM to the ultradilute regime typical of MP contaminated waters (≤2 ppb, ≤7 nM for propranolol) where inhibition nearly vanishes. Projecting from 50 μM to higher concentrations, propranolol completely inhibits its own oxidation before reaching mM concentrations. This study is consistent with prior experimental findings that substrate inhibition does not impede TAML/H 2 O 2 destruction of propranolol in London wastewater while giving a substrate inhibition assessment tool for use in the new field of ultradilute oxidation catalysis.

We completed a phase 1 dose-escalation trial to evaluate the safety of a dopamine receptor D2 (DRD2) antagonist thioridazine (TDZ), in combination with cytarabine. Thirteen patients 55 years and older with relapsed or refractory acute myeloid leukemia (AML) were enrolled. Oral TDZ was administered at 3 dose levels: 25 mg (n = 6), 50 mg (n = 4), or 100 mg (n = 3) every 6 hours for 21 days. Intermediate-dose cytarabine was administered on days 6 to 10. Dose-limiting toxicities (DLTs) included grade 3 QTc interval prolongation in 1 patient at 25 mg TDZ and neurological events in 2 patients at 100 mg TDZ (gait disturbance, depressed consciousness, and dizziness). At the 50-mg TDZ dose, the sum of circulating DRD2 antagonist levels approached a concentration of 10 μM, a level noted to be selectively active against human AML in vitro. Eleven of 13 patients completed a 5-day lead-in with TDZ, of which 6 received TDZ with hydroxyurea and 5 received TDZ alone. During this period, 8 patients demonstrated a 19% to 55% reduction in blast levels, whereas 3 patients displayed progressive disease. The extent of blast reduction during this 5-day interval was associated with the expression of the putative TDZ target receptor DRD2 on leukemic cells. These preliminary results suggest that DRD2 represents a potential therapeutic target for AML disease. Future studies are required to corroborate these observations, including the use of modified DRD2 antagonists with improved tolerability in AML patients. This trial was registered at www.clinicaltrials.gov as #NCT02096289., (© 2018 by The American Society of Hematology.)

Human pluripotent stem cells (hPSCs) generate hematopoietic progenitor cells (HPCs) but fail to engraft xenograft models used to detect adult/somatic hematopoietic stem cells (HSCs) from donors. Recent progress to derive hPSC-derived HSCs has relied on cell-autonomous forced expression of transcription factors; however, the relationship of bone marrow to transplanted cells remains unknown. Here, we quantified a failure of hPSC-HPCs to survive even 24 hr post transplantation. Across several hPSC-HPC differentiation methodologies, we identified the lack of CXCR4 expression and function. Ectopic CXCR4 conferred CXCL12 ligand-dependent signaling of hPSC-HPCs in biochemical assays and increased migration/chemotaxis, hematopoietic progenitor capacity, and survival and proliferation following in vivo transplantation. This was accompanied by a transcriptional shift of hPSC-HPCs toward somatic/adult sources, but this approach failed to produce long-term HSC xenograft reconstitution. Our results reveal that networks involving CXCR4 should be targeted to generate putative HSCs with in vivo function from hPSCs., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

The preparation, characterization, and evaluation of a cobalt(III) complex with 13-membered tetraamide macrocyclic ligand (TAML) is described. This is a square-planar (X-ray) S = 1 paramagnetic ( 1 H NMR) compound, which becomes an S = 0 diamagnetic octahedral species in excess d 5 -pyridine. Its one-electron oxidation at an electrode is fully reversible with the lowest E 1/2 value (0.66 V vs SCE) among all investigated Co III TAML complexes. The oxidation results in a neutral blue species which is consistent with a Co III /radical-cation ligand. The ease of oxidation is likely due to the two benzene rings incorporated in the ligand structure (whereas there is just one in many other Co III TAMLs). The oxidized neutral species are unexpectedly EPR silent, presumably due to the π-stacking aggregation. However, they display eight-line hyperfine patterns in the presence of excess of 4- tert -butylpyridine or 4- tert -butyl isonitrile. The EPR spectra are more consistent with the Co III /radical-cation ligand formulation rather than with a Co IV complex. Attempts to synthesize a similar vanadium complex under the same conditions as for cobalt using [V V O(OCHMe 2 ) 3 ] were not successful. TAML-free decavanadate was isolated instead., Competing Interests: Disclosure statement No potential conflict of interest was reported by the authors.

Acute myeloid leukaemia (AML) is distinguished by the generation of dysfunctional leukaemic blasts, and patients characteristically suffer from fatal infections and anaemia due to insufficient normal myelo-erythropoiesis. Direct physical crowding of bone marrow (BM) by accumulating leukaemic cells does not fully account for this haematopoietic failure. Here, analyses from AML patients were applied to both in vitro co-culture platforms and in vivo xenograft modelling, revealing that human AML disease specifically disrupts the adipocytic niche in BM. Leukaemic suppression of BM adipocytes led to imbalanced regulation of endogenous haematopoietic stem and progenitor cells, resulting in impaired myelo-erythroid maturation. In vivo administration of PPARγ agonists induced BM adipogenesis, which rescued healthy haematopoietic maturation while repressing leukaemic growth. Our study identifies a previously unappreciated axis between BM adipogenesis and normal myelo-erythroid maturation that is therapeutically accessible to improve symptoms of BM failure in AML via non-cell autonomous targeting of the niche.

Kinetic studies of the acid-induced ejection of iron(III) show that the more electron-rich tetra-amido-N macrocyclic ligand (TAML) activator [Fe III {(Me 2 CNCOCMe 2 NCO) 2 CMe 2 }OH 2 ] - (4), which does not have a benzene ring in its head component ("beheaded" TAML), is up to 1 × 10 4 times more resistant than much less electron-rich [Fe III {1,2-C 6 H 4 (NCOCMe 2 NCO) 2 CMe 2 }OH 2 ] - (1a) to the electrophilic attack. This counterintuitive increased resistance is seen in both the specific acid (k obs = k 1 [H + ]/(K + [H + ])) and phosphate general acid (k II = (k di K a1 + k tri [H + ])/(K a1 +[H + ])) demetalation pathways. Insight into this reactivity puzzle was obtained from coupling kinetic data with theoretical density functional theory modeling. First, although 1a and related complexes are six-coordinate in water, 4 has a strong tendency to repel the second aqua ligand favoring [LFe(OH 2 )] - and making appropriate the comparison of monoaqua-4 with diaqua-1a in the demetalation process. Second, dearomatization exerts a strong effect on the highest occupied molecular orbital (HOMO) energy of five-coordinate monoaqua-4, the presumed target in proton-induced demetalation, stabilizing it by ca. 51 kJ mol -1 compared with monoaqua-1a. Third, the monoaqua-4 HOMO is localized over the N-p π system of all four N donors in contrast with monoaqua-1a, where N-p π contributions from the head amides only mix with the aromatic ring π system. Fourth, addition of a second water ligand to monoaqua-1a giving [LFe(OH 2 ) 2 ] - reshapes the monoaqua-1a HOMO by shifting its entire locus from the head to the tail diamido-N section-this HOMO is by 54 kJ mol -1 less stable than the monoaqua-4 HOMO. These features provide the foundations for mechanistic conclusions concerning demetalation that (i) axial water ligands enable a favored path in the six-coordinate case of 1a, where a proton "slides" toward the Fe-N bond and (ii) early and late transition states are realized for 4 and 1a, respectively, with a larger free energy of activation for the beheaded TAML activator 4.

Targeting of human cancer stem cells (CSCs) requires the identification of vulnerabilities unique to CSCs versus healthy resident stem cells (SCs). Unfortunately, dysregulated pathways that support transformed CSCs, such as Wnt/β-catenin signaling, are also critical regulators of healthy SCs. Using the ICG-001 and CWP family of small molecules, we reveal Sam68 as a previously unappreciated modulator of Wnt/β-catenin signaling within CSCs. Disruption of CBP-β-catenin interaction via ICG-001/CWP induces the formation of a Sam68-CBP complex in CSCs that alters Wnt signaling toward apoptosis and differentiation induction. Our study identifies Sam68 as a regulator of human CSC vulnerability., (Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.)

TAML activators of peroxides are iron(III) complexes. The ligation by four deprotonated amide nitrogens in macrocyclic motifs is the signature of TAMLs where the macrocyclic structures vary considerably. TAML activators are exceptional functional replicas of the peroxidases and cytochrome P450 oxidizing enzymes. In water, they catalyze peroxide oxidation of a broad spectrum of compounds, many of which are micropollutants, compounds that produce undesired effects at low concentrations-as with the enzymes, peroxide is typically activated with near-quantitative efficiency. In nonaqueous solvents such as organic nitriles, the prototype TAML activator gave the structurally authenticated reactive iron(V)oxo units (Fe V O), wherein the iron atom is two oxidation equivalents above the Fe III resting state. The iron(V) state can be achieved through the intermediacy of iron(IV) species, which are usually μ-oxo-bridged dimers (Fe IV Fe IV ), and this allows for the reactivity of this potent reactive intermediate to be studied in stoichiometric processes. The present review is primarily focused at the mechanistic features of the oxidation by Fe V O of hydrocarbons including cyclohexane. The main topic is preceded by a description of mechanisms of oxidation of thioanisoles by Fe V O, because the associated studies provide valuable insight into the ability of Fe V O to oxidize organic molecules. The review is opened by a summary of the interconversions between Fe III , Fe IV Fe IV , and Fe V O species, since this information is crucial for interpreting the kinetic data. The highest reactivity in both reaction classes described belongs to Fe V O. The resting state Fe III is unreactive oxidatively. Intermediate reactivity is typically found for Fe IV Fe IV ; therefore, kinetic features for these species in interchange and oxidation processes are also reviewed. Examples of using TAML activators for C-H bond cleavage applied to fine organic synthesis conclude the review.

It was shown previously (Chem. Eur. J. 2015, 21, 1803) that the rate of hydrogen atom abstraction, k, from ethylbenzene (EB) by TAML complex [Fe V (O)B*] - (1) in acetonitrile exhibits a large kinetic isotope effect (KIE ∼ 26) in the experimental range 233-243 K. The extrapolated tangents of ln(k/T) vs T -1 plots for EB-d 10 and EB gave a large, negative intercept difference, Int(EB) - Int(EB-d 10 ) = -34.5 J mol -1 K -1 for T -1 → 0, which is shown to be exclusively due to an isotopic mass effect on tunneling. A decomposition of the apparent activation barrier in terms of electronic, ZPE, thermal enthalpic, tunneling, and entropic contributions is presented. Tunneling corrections to ΔH ⧧ and ΔS ⧧ are estimated to be large. The DFT prediction, using functional B3LYP and basis set 6-311G, for the electronic contribution is significantly smaller than suggested by experiment. However, the agreement improves after correction for the basis set superposition error in the interaction between EB and 1. The kinetic model employed has been used to predict rate constants outside the experimental temperature range, which enabled us to compare the reactivity of 1 with those of other hydrogen abstracting complexes.

Human pluripotent stem cells (hPSCs) have been reported in naive and primed states. However, the ability to generate mature cell types remains the imperative property for utility of hPSCs. Here, we reveal that the naive state enhances self-renewal while restricting lineage differentiation in vitro to neural default fate. Molecular analyses indicate expression of multiple lineage-associated transcripts in naive hPSCs that failed to predict biased functional differentiation capacity. Naive hPSCs can be converted to primed state over long-term serial passage that permits recovery of multi-germ layer differentiation. Suppression of OCT4 but not NANOG allows immediate recovery directly from naive state. To this end, we identified chemical inhibitors of OCT4 that restore naive hPSC differentiation. Our study reveals unique cell-fate restrictions in human pluripotent states and provides an approach to overcome these barriers that harness both efficient naive hPSC growth while maintaining in vitro differentiation essential for hPSC applications., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

TAML activators enable homogeneous oxidation catalysis where the catalyst and substrate (S) are ultradilute (pM-low μM) and the oxidant is very dilute (high nM-low mM). Water contamination by exceptionally persistent micropollutants (MPs), including metaldehyde (Met), provides an ideal space for determining the characteristics and utilitarian limits of this ultradilute catalysis. The low MP concentrations decrease throughout catalysis with S oxidation (k II ) and catalyst inactivation (k i ) competing for the active catalyst. The percentage of substrate converted (%Cvn) can be increased by discovering methods to increase k II /k i . Here we show that NaClO extends catalyst lifetime to increase the Met turnover number (TON) 3-fold compared with H 2 O 2 , highlighting the importance of oxidant choice as a design tool in TAML systems. Met oxidation studies (pH 7, D 2 O, 0.01 M phosphate, 25 °C) monitored by 1 H NMR spectroscopy show benign acetic acid as the only significant product. Analysis of TAML/NaClO treated Met solutions employing successive identical catalyst doses revealed that the processes can be modeled by the recently published relationship between the initial and final [S] (S 0 and S ∞ , respectively), the initial [catalyst] (Fe Tot ) and k II /k i . Consequently, this study establishes that ΔS is proportional to S 0 and that the %Cvn is conserved across all catalyst doses in multicatalyst-dose processes because the rate of the k II process depends on [S] while that of the k i process does not. A general tool for determining the Fe Tot required to effect a desired %Cvn is presented. Examination of the dependence of TON on k II /k i and Fe Tot at a fixed S 0 indicates that for any TAML process employing Fe Tot < 1 × 10 -6 M, small catalyst doses are not more efficient than one large dose.

Studies of the new tetra-amido macrocyclic ligand (TAML) activator [Fe III {(Me 2 CNCOCMe 2 NCO) 2 CMe 2 }OH 2 ] - (4) in water in the pH range of 2-13 suggest its pseudo-octahedral geometry with two nonequivalent axial H 2 O ligands and revealed (i) the anticipated basic drift of the first pK a of water to 11.38 due to four electron-donating methyl groups alongside (ii) its counterintuitive enhanced resistance to acid-induced iron(III) ejection from the macrocycle. The catalytic activity of 4 in the oxidation of Orange II (S) by H 2 O 2 in the pH range of 7-12 is significantly lower than that of previously reported TAML activators, though it follows the common rate law (v/[Fe III ] = k I k II [H 2 O 2 ][S]/(k I [H 2 O 2 ] + k II [S]) and typical pH profiles for k I and k II . At pH 7 and 25 °C the rate constants k I and k II equal 0.63 ± 0.02 and 1.19 ± 0.03 M -1 s -1 , respectively. With these new values for pK a , k I and k II establishing new high and low limits, respectively, the rate constants k I and k II were correlated with pK a values of all TAML activators. The relations log k = log k 0 + α × pK a were established with log k 0 = 13 ± 2 and 20 ± 4 and α = -1.1 ± 0.2 and -1.8 ± 0.4 for k I and k II , respectively. Thus, the reactivity of TAML activators across four generations of catalysts is predictable through their pK a values.

Foams are a common material for high-energy-density physics experiments because of low, tunable densities, and being machinable. Simulating these experiments can be difficult because the equation of state is largely unknown for shocked foams. The focus of this experiment was to develop an x-ray scattering platform for measuring the equation of state of shocked foams on OMEGA EP. The foam used in this experiment is resorcinol formaldehyde with an initial density of 0.34 g/cm 3 . One long-pulse (10 ns) beam drives a shock into the foam, while the remaining three UV beams with a 2 ns square pulse irradiate a nickel foil to create the x-ray backlighter. The primary diagnostic for this platform, the imaging x-ray Thomson spectrometer, spectrally resolves the scattered x-ray beam while imaging in one spatial dimension. Ray tracing analysis of the density profile gives a compression of 3 ± 1 with a shock speed of 39 ± 6 km/s. Analysis of the scattered x-ray spectra gives an upper bound temperature of 20 eV.

The unique properties of entirely aliphatic TAML activator [Fe III {(Me 2 CNCOCMe 2 NCO) 2 CMe 2 }OH 2 ] - (3), namely the increased steric bulk of the ligand and the unmatched resistance to the acid-induced demetalation, enables the generation of high-valent iron derivatives in pure water at any pH. An iron(V)oxo species is readily produced with NaClO at pH values from 2 to 10.6 without any observable intermediate. This is the first reported example of iron(V)oxo formed in pure water. At pH 13, iron(V)oxo is not formed and NaClO oxidizes 3 to an iron(IV)oxo derivative.