Partially Sulfated Pillar[5]Arenes: Synthesis and Molecular Recognition Properties.

We report the synthesis and characterization of sulfated pillar[5]arene hosts (P5S-P5S) that differ in the number of sulfate substituents. All five P5S hosts display high solubility in water (73-131 mM) and do not undergo significant self-association according to H NMR dilution experiments. The x-ray crystal structures of P5S, P5S ⋅ MeHDA, P5S ⋅ MeHDA, and P5S ⋅ MeHDA reveal one intracavity molecule of MeHDA and several external molecules of MeHDA which form a network of close methonium ⋅ ⋅ ⋅ sulfate interactions.

Insoluble Acyclic Cucurbit[n]uril-Type Receptors Capture Iodine from the Vapor Phase.

Nuclear energy makes large contributions toward meeting global energy needs, but societal concerns remain high given the impacts of the intended release of radioactive materials including I and I. In this paper we explore the use of a homologous series of acyclic CB[n] type hosts (H1-H4) as adsorbents of iodine from the vapor phase. We find that H2-H4, but not H1 - perform well in this application with uptake capacities of 2.

NASC 2023: Showcasing Diversity in North American Supramolecular Chemistry.

Diversity in supramolecular chemistry can showcase itself in many ways. This includes the diversity of thought and topics covered in research (from fundamental science to applications in biology and materials), as well as the diversity of people (e.g.

The Missing Trial Variable: A Case Report on Dietary Modification in a Patient with Durable Complete Remission After an Immunotherapy Clinical Trial for Metastatic Bladder Cancer.

A patient with metastatic bladder cancer has had an ongoing 9-year complete remission on a clinical trial of immunotherapy with nivolumab and ipimumab, but he also was following an intensive dietary and nutritional supplement regimen. Whether this combination or the immunotherapy alone brought about his good outcome is unknown but could be clarified in future trials by improved data collection about dietary and supplement choices.

Acyclic Cucurbit[n]uril Receptors Function as Solid State Sequestrants for Organic Micropollutants.

The accumulation of organic micropollutants (OMP) in aquatic systems is a major societal problem that can be addressed by approaches including nanofiltration, flocculation, reverse osmosis and adsorptive methods using insoluble materials (e.g. activated carbon, MOFs, nanocomposites).

Pillar[6]MaxQ functions as an sequestrant for rocuronium and vecuronium.

The binding affinity of pillar[6]MaxQ toward a panel of neuromuscular blockers and neurotransmitters was measured in phosphate buffered saline by isothermal titration calorimetry and H NMR spectroscopy. efficacy studies showed that P6MQ sequesters rocuronium and vecuronium and reverses their influence on the recovery of the train-of-four (TOF) ratio.

The CDC Foundation's COVID-19 emergency response pilot project: a case study in knowledge brokering for older adults and caregivers.

Objective: The coronavirus disease 2019 (COVID-19) public health emergency has disproportionately affected older adults and their caregivers, requiring evidence-based and coordinated efforts to meet their health and social needs. This paper describes the role of the CDC Foundation as a knowledge broker working with public health partners to rapidly meet the unmet health, social, and other needs of older adults and caregivers during the COVID-19 pandemic. Type of program or service: Qualitative case study using the Role Model for Knowledge Brokering framework to describe a project that translated public health research into practice during the COVID-19 pandemic response.

A Brief History of Glandular Therapy: More Than Just Thyroid.

In the late 1800s, treatment with thyroid extract caused dramatic improvement in patients with myxedema. Shortly thereafter, multiple other glandular extracts became available, both individually and in combinations. Their use gradually fell into disfavor, partly due to overpromotion by the manufacturers.

Pillar[6]MaxQ: A Potent Supramolecular Host for Sequestration of Methamphetamine and Fentanyl.

Pillar[6]MaxQ (P6AS) functions as an sequestration agent for methamphetamine and fentanyl. We use H NMR, isothermal titration calorimetry, and molecular modelling to deduce the geometry and strength of the P6AS•drug complexes. P6AS forms tight complexes with fentanyl (K=9.

More than a participant in trials of cell and gene therapy: Hearing the voices of people living with neurodegenerative diseases.

With the advent of novel advanced therapy medicinal products (ATMPs) for neurodegenerative diseases, their pathway to clinical trials and the therapeutic landscape has highlighted some new challenges, many of which are outlined in other chapters of this volume. The practical considerations of all these aspects from basic research and animal models through to clinical trials and eventual clinical implementation are significant. By and large, the major voices surrounding these challenges are the scientists and clinical teams who both develop the interventions and design and deliver the clinical trials to test these novel ATMPs.

Molecular recognition of methylated amino acids and peptides by Pillar[6]MaxQ.

We report the molecular recognition properties of Pillar[]MaxQ (P[]MQ) toward a series of (methylated) amino acids, amino acid amides, and post-translationally modified peptides by a combination of H NMR, isothermal titration calorimetry, indicator displacement assays, and molecular dynamics simulations. We find that P6MQ is a potent receptor for -methylated amino acid side chains. P6MQ recognized the H3K4Me peptide with = 16 nM in phosphate buffered saline.

DNA Strand Displacement Driven by Host-Guest Interactions.

Base-pair-driven toehold-mediated strand displacement (BP-TMSD) is a fundamental concept employed for constructing DNA machines and networks with a gamut of applications─from theranostics to computational devices. To broaden the toolbox of dynamic DNA chemistry, herein, we introduce a synthetic surrogate termed host-guest-driven toehold-mediated strand displacement (HG-TMSD) that utilizes bioorthogonal, cucurbit[7]uril (CB[7]) interactions with guest-linked input sequences. Since control of the strand-displacement process is salient, we demonstrate how HG-TMSD can be finely modulated via changes to the structure of the input sequence (including synthetic guest head-group and/or linker length).

Double-Cavity Nor-Seco-Cucurbit[10]uril Enables Efficient and Rapid Separation of Pyridine from Mixtures of Toluene, Benzene, and Pyridine.

Benzene, toluene and pyridine are widely used as essential raw materials in industry and laboratory research, with stringent purity requirements. Herein, we show that solid double-cavity host nor-seco-cucurbit[10]uril (ns-Q[10]) functions as an efficient adsorption separator for pyridine; benzene and toluene can be obtained in >99.9 % purity by this method.

New Synthetic Route to Water-Soluble Prism[5]arene Hosts and Their Molecular Recognition Properties.

We report that the direct macrocyclization of naphthalene monomers bearing ethyl ester functional groups delivers prism[5]arene derivatives, which can be deprotected to yield water-soluble prism[5]arenes (H1 and H3). H NMR spectroscopy showed that dicationic guests bind with the hydrophobic cores buried inside the anisotropic magnetically shielding cavity. Isothermal titration calorimetry measurements showed that H1 and H3 are high-affinity hosts in PBS-buffered water with K values exceeding 10  M for a select guest.

Pancreatic Proteolytic Enzymes and Cancer: New Support for an Old Theory.

In 1905, the embryologist John Beard first proposed that pancreatic proteolytic enzymes had potential as a treatment for cancer. His theories were dismissed by the medical world a decade later, but various practitioners have kept the concept alive through the publication of case reports of cancer patients treated with pancreatic proteolytic enzymes. In the last 2 decades, studies of the role of proteases in physiology have made it clear that they do more than digest food.

Voltage-Gated Membranes Incorporating Cucurbit[]uril Molecular Containers for Molecular Nanofiltration.

Smart voltage-gated nanofiltration membranes have enormous potential for on-demand and precise separation of similar molecules, which is an essential element of sustainable water purification and resource recovery. However, the existing voltage-gated membranes are hampered by limited selectivity, stability, and scalability due to electroactive monomer dimerization. Here, for the first time, the host-guest recognition properties of cucurbit[7]uril (CB[7]) are used to protect the viologen derivatives and promote their assembly into the membrane by interfacial polymerization.

Thermodynamics of Pillararene•Guest Complexation: Blinded Dataset for the SAMPL9 Challenge.

We report an investigation of the complexation between a water soluble pillararene host (WP6) and a panel of hydrophobic cationic guests (G1 - G20) by a combination of H NMR spectroscopy and isothermal titration calorimetry in phosphate buffered saline. We find that WP6 forms 1:1 complexes with K values in the 10 - 10 M range driven by favorable enthalpic contributions. This thermodynamic dataset serves as blinded data for the SAMPL9 challenge.

Anthracene-Walled Acyclic CB[n] Receptors: in vitro and in vivo Binding Properties toward Drugs of Abuse.

We report studies of the interaction of six acyclic CB[n]-type receptors toward a panel of drugs of abuse by a combination of isothermal titration calorimetry and H NMR spectroscopy. Anthracene walled acyclic CB[n] host (M3) displays highest binding affinity toward methamphetamine (K =15 nM) and fentanyl (K =4 nM). Host M3 is well tolerated by Hep G2 and HEK 293 cells up to 100 μM according to MTS metabolic and adenylate kinase release assays.

Androgen Effects on Neural Plasticity.

Androgens are synthesized in the brain, gonads, and adrenal glands, in both sexes, exerting physiologically important effects on the structure and function of the central nervous system. These effects may contribute to the incidence and progression of neurological disorders such as autism spectrum disorder, schizophrenia, and Alzheimer's disease, which occur at different rates in males and females. This review briefly summarizes the current state of knowledge with respect to the neuroplastic effects of androgens, with particular emphasis on the hippocampus, which has been the focus of much of the research in this field.

Whole adrenal extract for Addison's disease in the 1920s: Where is the cortisol?

Prior to the development of synthetic corticosteroids, Addison's disease was treated with oral dessicated whole adrenal glands or crude extracts. These products could not have contained meaningful amounts of cortisol, yet some patients improved. There may be something in whole glands that can stimulate failing adrenals to make cortisol.

Binding Methylarginines and Methyllysines as Free Amino Acids: A Comparative Study of Multiple Host Classes.

Methylated free amino acids are an important class of targets for host-guest chemistry that have recognition properties distinct from those of methylated peptides and proteins. We present comparative binding studies for three different host classes that are each studied with multiple methylated arginines and lysines to determine fundamental structure-function relationships. The hosts studied are all anionic and include three calixarenes, two acyclic cucurbiturils, and two other cleft-like hosts, a clip and a tweezer.

In Vitro and In Vivo Sequestration of Methamphetamine by a Sulfated Acyclic CB[n]-Type Receptor.

We report the synthesis of two new acyclic sulfated acyclic CB[n]-type receptors (TriM0 and Me TetM0) and investigations of their binding properties toward a panel of drugs of abuse (1-13) by a combination of H NMR spectroscopy and isothermal titration calorimetry. TetM0 is the most potent receptor with K ≥10  M toward methamphetamine, fentanyl, MDMA and mephedrone. TetM0 is not cytotoxic toward HepG2 and HEK 293 cells below 100 μM according to MTS metabolic and adenylate kinase release assays and is well tolerated in vivo when dosed at 46 mg kg .