Exploring the Use of Pseudosymmetry in the Design of Higher-Symmetry Crystals of Racemic Compounds.

Organometallic antimony(V) complexes were prepared as model compounds to better understand the interactions of chiral chelating diols with this metalloid. These complexes feature three aryl groups (-xylyl or -tolyl) and a bidentate -2,3-butanediolate. The -xylyl and -tolyl complexes of either enantiomerically pure 2,3-butanediolate or 2,3-butanediolate (compounds -) crystallized in Sohncke space groups, as expected.

Silver 4,4'-Vinylenedipyridine Coordination Polymers: Linker Effects on Formation Thermodynamics and Anion Exchange.

Four new and one previously reported silver 4,4'-vinylenedipyridine (Vpe) coordination polymers were tested as anion exchange materials to assess their potential for pollutant sequestration and compared to analogous silver 4,4'-bipyridine (bipy) coordination polymers. The materials were synthesized using nitrate, tetrafluoroborate, perchlorate, perrhenate, or chromate as the anion to produce cationic coordination polymers with solubilities ranging from 0.0137(7) to 0.

Synthesis and structural characterization of the heavy tricysteinylpnictines, models of protein-bound As(III), Sb(III), and Bi(III).

The heavier group 15 elements As, Sb, and Bi are more restricted in their biochemistry than the nearly ubiquitous lighter congeners N and P, but organisms do encounter compounds of these elements as environmental toxins, starting materials for secondary metabolite biosynthesis, substrates for primary metabolism, or exogenously applied medicines. Under many physiological conditions, these compounds are transformed into pnictogen(III) species, the soft Lewis acidic character of which leads them to interact strongly with biologically relevant soft Lewis bases such as small-molecule thiols or cysteine residues of proteins and peptides. The archetypal complexes As(Cys), Sb(Cys), and Bi(Cys) have been studied in the past but a lack of detailed information about their molecular structures has hampered the analysis of protein structures featuring As(III), Sb(III), and Bi(III) bound to cysteine thiolate residues.

PYTA: a universal chelator for advancing the theranostic palette of nuclear medicine.

To clinically advance the growing arsenal of radiometals available to image and treat cancer, chelators with versatile binding properties are needed. Herein, we evaluated the ability of the py[18]dieneN macrocycle PYTA to interchangeably bind and stabilize Ac, [Lu]Lu, [In]In and [Sc]Sc, a chemically diverse set of radionuclides that can be used complementarily for targeted alpha therapy, beta therapy, single-photon emission computed tomography (SPECT) imaging, and positron emission tomography (PET) imaging, respectively. Through NMR spectroscopy and X-ray diffraction, we show that PYTA possesses an unusual degree of flexibility for a macrocyclic chelator, undergoing dramatic conformational changes that enable it to optimally satisfy the disparate coordination properties of each metal ion.

Reactivity of Tetrel-Functionalized Heptaphosphane Clusters toward Azides.

In this work, the reactivity of tetrel-functionalized phosphorus clusters toward organoazides is probed. Clusters (MeSi)P () and (MeGe)P () were reacted with benzyl azide, phenyl azide, and 4-bromophenyl azide, and it was found that the [RN] (R = benzyl, phenyl, and 4-bromophenyl) unit from the azide inserted into the phosphorus-tetrel bonds on the cluster, accompanied by N elimination. Through control of the azide stoichiometry, the mono-, bis-, and tris-inserted products could be observed, consistent with these insertions proceeding in a stepwise manner.

A Sterically Accessible Monomeric Stibine Oxide Activates Organotetrel(IV) Halides, Including C-F and Si-F Bonds.

Phosphine oxides and arsine oxides are common laboratory reagents with diverse applications that stem from the chemistry exhibited by these monomeric species. Stibine oxides are, in contrast, generally dimeric or oligomeric species because of the reactivity-quenching self-association of the highly polarized stiboryl (Sb=O/Sb-O) group. We recently isolated DippSbO (Dipp = 2,6-diisopropylphenyl), the first example of a kinetically stabilized monomeric stibine oxide, which exists as a bench-stable solid and bears an unperturbed stiboryl group.

Enhancing cognitive recovery in chronic traumatic brain injury through simultaneous allosteric modulation of α7 nicotinic acetylcholine and α5 GABA receptors.

Traumatic brain injury (TBI) leads to changes in the neural circuitry of the hippocampus that result in chronic learning and memory deficits. However, effective therapeutic strategies to ameliorate these chronic learning and memory impairments after TBI are limited. Two pharmacological targets for enhancing cognition are nicotinic acetylcholine receptors (nAChRs) and GABA receptors (GABARs), both of which regulate hippocampal network activity to form declarative memories.

Recent advances in the stabilization of monomeric stibinidene chalcogenides and stibine chalcogenides.

The elucidation of novel bonding situations at heavy p-block elements has greatly advanced recent efforts to access useful reactivity at earth-abundant main-group elements. Molecules with unsaturated bonds between heavier, electropositive elements and lighter, electronegative elements are often highly polarized and competent in small-molecule activations, but the reactivity of these molecules may be quenched by self-association of monomers to form oligomeric species where the polar, unsaturated groups are assembled in a head-to-tail fashion. In this Frontier, we discuss the synthetic strategies employed to isolate monomeric σ,λ-stibinidene chalcogenides (RSbCh) and monomeric σ,λ-stibine chalcogenides (RSbCh).

Carbon monoxide poisoning: A problem uniquely suited to a medicinal inorganic chemistry solution.

Carbon monoxide poisoning is one of the most common forms of poisoning in the world. Although the primary mode of treatment, oxygen therapy, is highly effective in many cases, there are instances in which it is inadequate or inappropriate. Whereas oxygen therapy relies on high levels of a low-affinity ligand (O) to displace a high-affinity ligand (CO) from metalloproteins, an antidote strategy relies on introducing a molecule with a higher affinity for CO than native proteins (K > K).

Variation in pnictogen-oxygen bonding unlocks greatly enhanced Brønsted basicity for the monomeric stibine oxide.

Phosphine oxides and arsine oxides feature highly polarized pnictoryl groups (Pn-O/Pn = O; Pn = P, As) and react as Brønsted bases through O-centered lone pairs. We recently reported the first example of a monomeric stibine oxide, DippSbO (Dipp = diisopropylphenyl), allowing periodic trends in pnictoryl bonding to be extended to antimony for the first time. Computational studies suggest that, as the pnictogen atom becomes heavier, delocalization of electron density from the O-centered lone pairs to the Pn-C σ* orbitals is attenuated, destabilizing the lone pairs and increasing the donor capacity of the pnictine oxide.

Models of the putative antimony(V)-diolate motifs in antileishmanial pentavalent antimonial drugs.

The structures of the pentavalent antimonials, small-molecule Sb-containing drugs used to treat the neglected tropical disease leishmaniasis, remain unknown despite their widespread use for over half a century. These drugs are prepared by combination of an Sb(V) precursor and a sugar derivative and proposed structures frequently invoke a cyclic stiborane motif in which a vicinal diolate ligand chelates an Sb(V) center. As a step towards better understanding the structures of the pentavalent antimonial drugs, a series of cyclic organostiboranes spanning the stereochemical space afforded by a vicinal diolate motif has been synthesized and characterized.

Isolation, bonding and reactivity of a monomeric stibine oxide.

In contrast to phosphine oxides and arsine oxides, which are common and exist as stable monomeric species featuring the corresponding pnictoryl functional group (Pn=O/Pn-O; Pn = P, As), stibine oxides are generally polymeric, and the properties of the unperturbed stiboryl group (Sb=O/Sb-O) remain unexplored. We now report the isolation of the monomeric stibine oxide, DippSbO (where Dipp = 2,6-diisopropylphenyl). Spectroscopic, crystallographic and computational studies provide insight into the nature of the Sb=O/Sb-O bond.

Selective Chromium(VI) Trapping by an Acetate-Releasing Coordination Polymer.

We report the high-capacity and selective uptake of Cr(VI) from water using the coordination polymer silver bipyridine acetate (SBA, [Ag(4,4'-bipy)][CHCO]·3HO). Cr capture involves the release of acetate, and we have structurally characterized two of the product phases that form: silver bipyridine chromate (SBC, SLUG-56, [Ag(4,4'-bipy)][CrO]·3.5HO) and silver bipyridine dichromate (SBDC, SLUG-57, [Ag(4,4'-bipy)][CrO]·HO).

Realgar and arsenene nanomaterials as arsenic-based anticancer agents.

Arsenic trioxide (ATO) is an approved therapy for the treatment of acute promyelocytic leukemia, but the extension of arsenic-based therapies to other types of malignancies, notably tumor-forming cancers, has been slow. Nanodelivery vehicles offer a means of effectively delivering ATO to tumors. Very recently, there has been a series of developments in the formulation of arsenic-based nanomedicines that are not simply loaded with ATO.

The rippled β-sheet layer configuration-a novel supramolecular architecture based on predictions by Pauling and Corey.

The rippled β-sheet is a peptidic structural motif related to but distinct from the pleated β-sheet. Both motifs were predicted in the 1950s by Pauling and Corey. The pleated β-sheet was since observed in countless proteins and peptides and is considered common textbook knowledge.

Synthesis and Functionalization of Challenging -Substituted Aryl Bis-pocket Porphyrins Accessed via Suzuki-Miyaura Cross-Coupling.

Herein we report an investigation into the synthesis, metalation, and functionalization of bis-pocket porphyrins using the Suzuki-Miyaura cross-coupling reaction. Steric limitations to accessing bis-pocket porphyrins were overcome by using this Pd-catalyzed C-C-bond-forming strategy to introduce steric bulk macrocyclization: 2,6-dibromo-4-trimethylsilybenzaldehyde was condensed with pyrrole, and a variety of boronic acids were coupled to the resulting porphyrin in up to 95% yield. Furthermore, we show that these porphyrins can be metalated with a variety of metals and sulfonated to create water-soluble bis-pocket porphyrins.

Biomimetic Total Synthesis and Investigation of the Non-Enzymatic Chemistry of Oxazinin A.

We report the first total synthesis of an antimycobacterial natural product oxazinin A that takes advantage of a multi-component cascade reaction of anthranilic acid and a precursor polyketide containing an aldehyde. The route utilized for the synthesis of the pseudodimeric oxazinin A validates a previously proposed biosynthetic mechanism, invoking a non-enzymatic pathway to the complex molecule. We found a 76 : 10 : 9 : 5 ratio of oxazinin diastereomers from the synthetic cascade, which is an identical match to that found in the fermentation media from the fungus Eurotiomycetes 110162.

A New Amino Acid for Improving Permeability and Solubility in Macrocyclic Peptides through Side Chain-to-Backbone Hydrogen Bonding.

Despite the notoriously poor membrane permeability of peptides, many cyclic peptide natural products show high passive membrane permeability and potently inhibit a variety of "undruggable" intracellular targets. A major impediment to the design of cyclic peptides with good permeability is the high desolvation energy associated with the peptide backbone amide NH groups. While several strategies have been proposed to mitigate this deleterious effect, only few studies have used polar side chains to sequester backbone NH groups.

A crystal-structural study of Pauling-Corey rippled sheets.

Following the seminal theoretical work on the pleated β-sheet published by Pauling and Corey in 1951, the rippled β-sheet was hypothesized by the same authors in 1953. In the pleated β-sheet the interacting β-strands have the same chirality, whereas in the rippled β-sheet the interacting β-strands are mirror-images. Unlike with the pleated β-sheet that is now common textbook knowledge, the rippled β-sheet has been much slower to evolve.

A water-soluble iron-porphyrin complex capable of rescuing CO-poisoned red blood cells.

We describe herein a small-molecule platform that exhibits key properties needed by an antidote for CO poisoning. The design features an iron-porphyrin complex with bulky substituents above and below the macrocyclic plane to provide a hydrophobic pocket for CO binding and to prevent the formation of inactive oxo-bridged dimers. Peripheral charged groups impart water solubility.

Encapsulation of -dodecaiodododecaborate in 2-hydroxypropyl-γ-cyclodextrin prevents hemolysis.

NaBI has many of the properties desired by an X-ray contrast agent but is lethal at the concentrations needed for medical imaging. We demonstrate here that PBS solutions with >50 mM NaBI induce hemolysis, consistent with the previously reported superchaotropic nature of the anion. The presence of <1 equiv.

B Cell Mobilization, Dissemination, Fine Tuning of Local Antigen Specificity and Isotype Selection in Asthma.

In order to better understand how the immune system interacts with environmental triggers to produce organ-specific disease, we here address the hypothesis that B and plasma cells are free to migrate through the mucosal surfaces of the upper and lower respiratory tracts, and that their total antibody repertoire is modified in a common respiratory tract disease, in this case atopic asthma. Using Adaptive Immune Receptor Repertoire sequencing (AIRR-seq) we have catalogued the antibody repertoires of B cell clones retrieved near contemporaneously from multiple sites in the upper and lower respiratory tract mucosa of adult volunteers with atopic asthma and non-atopic controls and traced their migration. We show that the lower and upper respiratory tracts are immunologically connected, with trafficking of B cells directionally biased from the upper to the lower respiratory tract and points of selection when migrating from the nasal mucosa and into the bronchial mucosa.

H-Atom Assignment and Sb-O Bonding of [MesSbOH][OSPh] Confirmed by Neutron Diffraction, Multipole Modeling, and Hirshfeld Atom Refinement.

Neutron wavelength-resolved Laue diffraction experiments permit accurate refinement of the H-atom positions and anisotropic displacement parameters of [MesSbOH][OSPh]. A multipole-based charge density refinement and a topological analysis of the refined electron density were also performed. Hirshfeld atom refinement (HAR) recovers the neutron-determined H-atom parameters, and the quantum-mechanical electron density used in HAR recovers the electron density topology from the refined multipole model.