Reversible O-H Bond Activation by Tripodal tris(Nitroxide) Aluminum and Gallium Complexes.

Herein, we report the preparation and characterization of the Group 13 metal complexes of a tripodal tris(nitroxide)-based ligand, designated (TriNOx)M (M = Al (), Ga (), In ()). Complexes and both activate the O-H bond of a range of alcohols spanning a ∼10 p unit range via an element-ligand cooperative pathway to afford the zwitterionic complexes (HTriNOx)M-OR. Structures of these alcohol adduct products are discussed.

Dinuclear Zn-Catalytic System as Brønsted Base and Lewis Acid for Enantioselectivity in Same Chiral Environment.

Zinc (Zn) is a crucial element with remarkable significance in organic transformations. The profusion of harmless zinc salts in the Earth's outer layer qualifies zinc as a noteworthy contender for inexpensive and eco-friendly reagents and catalysts. Recently, widely recognized uses of organo-Zn compounds in the field of organic synthesis have undergone extensive expansion toward asymmetric transformations.

Efficient construction of functionalized pyrroloindolines through cascade radical cyclization/intermolecular coupling.

Pyrroloindolines are important structural units in nature and the pharmaceutical industry, however, most approaches to such structures involve transition-metal or photoredox catalysts. Herein, we describe the first tandem SET/radical cyclization/intermolecular coupling between 2-azaallyl anions and indole acetamides. This method enables the transition-metal-free synthesis of C3a-substituted pyrroloindolines under mild and convenient conditions.

Insertion of Molecular Oxygen into a Gold(III)-Hydride Bond.

The use of molecular oxygen as an oxidant in chemical synthesis has significant environmental and economic benefits, and it is widely used as such in large-scale industrial processes. However, its adoption in highly selective homogeneous catalytic transformations, particularly to produce oxygenated organics, has been hindered by our limited understanding of the mechanisms by which O reacts with transition metals. Of particular relevance are the mechanisms of the reactions of oxygen with late transition metal hydrides as these metal centers are better poised to release oxygenated products.

Construction of C-S and C-Se Bonds from Unstrained Ketone Precursors under Photoredox Catalysis.

A mild photoredox catalyzed construction of sulfides, disulfides, selenides, sulfoxides and sulfones from unstrained ketone precursors is introduced. Combination of this deacylative process with S 2 or coupling reactions provides novel and convenient modular strategies toward unsymmetrical or symmetric disulfides. Reactivity studies favor a bromine radical that initiates a HAT (Hydrogen Atom Transfer) from the aminal intermediate resulting in expulsion of a C-centered radical that is intercepted to make C-S and C-Se bonds.

Cardiometabolic Health in Asian American Children.

Background: The aim was to compare cardiometabolic health between Asian American children and Non-Hispanic White (NHW) children as well as to compare cardiometabolic health among Asian American children by birthplace.

Methods: Children aged 6-17 years enrolled in the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2018 who self-identified as non-Hispanic Asian and NHW were included. Among Asian Americans, place of birth was defined as foreign born vs United States (US) born.

On-DNA hydroalkylation of -vinyl heterocycles photoinduced EDA-complex activation.

The emergence of DNA-encoded library (DEL) technology has provided a considerable advantage to the pharmaceutical industry in the pursuit of discovering novel therapeutic candidates for their drug development initiatives. This combinatorial technique not only offers a more economical, spatially efficient, and time-saving alternative to the existing ligand discovery methods, but also enables the exploration of additional chemical space by utilizing novel DNA-compatible synthetic transformations to leverage multifunctional building blocks from readily available substructures. In this report, a decarboxylative-based hydroalkylation of DNA-conjugated -vinyl heterocycles enabled by single-electron transfer (SET) and subsequent hydrogen atom transfer through electron-donor/electron-acceptor (EDA) complex activation is detailed.

Observing Similarities and Differences in the Properties of Isostructural Niobium(V)/Tantalum(V) Coordination Compounds with Strong Pi-Donor Ligands.

While niobium and tantalum are found together in their mineral ores, their respective applications in technology require chemical separation. Nb/Ta separations are challenging due to the similar reactivities displayed by these metals in the solution phase. Coordination complexes of these metals have been studied in the contexts of catalysis, small-molecule activation, and functional group insertion reactivity; relatively few studies exist directly comparing the properties of isostructural Nb/Ta complexes.

The Effects of Lipids on α-Synuclein Aggregation In Vitro.

The small neuronal protein α-synuclein (αS) is found in pre-synaptic terminals and plays a role in vesicle recycling and neurotransmission. Fibrillar aggregates of αS are the hallmark of Parkinson's disease and related neurodegenerative disorders. In both health and disease, interactions with lipids influence αS's structure and function, prompting much study of the effects of lipids on αS aggregation.

Long-distance tmFRET using bipyridyl- and phenanthroline-based ligands.

With the great progress on determining protein structures over the last decade comes a renewed appreciation that structures must be combined with dynamics and energetics to understand function. Fluorescence spectroscopy, specifically Förster resonance energy transfer (FRET), provides a great window into dynamics and energetics due to its application at physiological temperatures and ability to measure dynamics on the ångström scale. We have recently advanced transition metal FRET (tmFRET) to study allosteric regulation of maltose binding protein and have reported measurements of maltose-dependent distance changes with an accuracy of ~1.

Measuring conformational equilibria in allosteric proteins with time-resolved tmFRET.

Proteins are the workhorses of biology, orchestrating a myriad of cellular functions through intricate conformational changes. Protein allostery, the phenomenon where binding of ligands or environmental changes induce conformational rearrangements in the protein, is fundamental to these processes. We have previously shown that transition metal Förster resonance energy transfer (tmFRET) can be used to interrogate the conformational rearrangements associated with protein allostery and have recently introduced novel FRET acceptors utilizing metal-bipyridyl derivatives to measure long (>20 Å) intramolecular distances in proteins.

Transient susceptibility imaging as a measure of hemodynamic compromise: A pilot study.

Background And Purpose: The purpose of this study was to test the hypothesis that hemodynamically compromised brains exhibit transient changes in magnetic susceptibility throughout the cardiac cycle, and to model these changes using Linear System Theory to extract an index that reflects cerebrovascular reserve.

Materials And Methods: Eleven patients with angiographically-confirmed intracranial atherosclerotic disease with >50% stenosis were imaged with susceptibility weighted, cardiac-gated single shot images of cerebral Oxygen Extraction Fraction (OEF) at different timepoints of the cardiac cycle. Cardiac gating of the OEF acquisition allowed interrogation of oxygenated blood and the detection of changes throughout the cardiac cycle.

Recent Discovery, Development, and Synthetic Applications of Formic Acid Salts in Photochemistry.

The advancement of sustainable photoredox catalysis in synthetic organic chemistry has evolved immensely because of the development of versatile and cost-effective reagents. In recent years, a substantial effort has been dedicated to exploring the utility of formic acid salts in various photochemical reactions. In this context, formates have demonstrated diverse capabilities, functioning as reductants, sources of carbonyl groups, and reagents for hydrogen atom transfer.

Difluoromethyl-1,3,4-oxadiazoles Are Selective, Mechanism-Based, and Essentially Irreversible Inhibitors of Histone Deacetylase .

Histone deacetylase (HDAC6) is an important drug target in oncological and non-oncological diseases. Most available HDAC6 inhibitors (HDAC6i) utilize hydroxamic acids as a zinc-binding group, which limits therapeutic opportunities due to its genotoxic potential. Recently, difluoromethyl-1,3,4-oxadiazoles (DFMOs) were reported as potent and selective HDAC6i but their mode of inhibition remained enigmatic.

The development, content and response process validation of a caregiver-reported severity measure for CDKL5 deficiency disorder.

Background: CDKL5 Deficiency Disorder (CDD) is a severe X-linked developmental and epileptic encephalopathy. Existing developmental outcome measures have floor effects and cannot capture incremental changes in symptoms. We modified the caregiver portion of a CDD clinical severity assessment (CCSA) and assessed content and response-process validity.

Factors associated with receipt of minimally adequate psychotherapy for PTSD at the Veterans Health Administration.

Background: Despite Veterans Health Administration (VHA) efforts, many Veterans do not receive minimally adequate psychotherapy (MAP) for posttraumatic stress disorder (PTSD). It is important to understand factors associated with receipt of PTSD MAP (at least eight sessions) so that we may tailor efforts to increase treatment utilization for those who experience the greatest barriers to care.

Methods: Participants were 2008 post-9/11 Veterans who participated in a nationwide survey and had a PTSD diagnosis documented in the VHA electronic health record (EHR) before 2018.

Pulsed Force Kelvin Probe Force Microscopy through Integration of Lock-In Detection.

Kelvin probe force microscopy measures surface potential and delivers insights into nanoscale electronic properties, including work function, doping levels, and localized charges. Recently developed pulsed force Kelvin probe force microscopy (PF-KPFM) provides sub-10 nm spatial resolution under ambient conditions, but its original implementation is hampered by instrument complexity and limited operational speed. Here, we introduce a solution for overcoming these two limitations: a lock-in amplifier-based PF-KPFM.

Structure and Function of Kdac1, a Class II Deacetylase from the Multidrug-Resistant Pathogen .

Proteomics studies indicate that 10% of proteins in the opportunistic pathogen are acetylated, suggesting that lysine acetyltransferases and deacetylases function to maintain and regulate a robust bacterial acetylome. As the first step in exploring these fascinating prokaryotic enzymes, we now report the preparation and characterization of the lysine deacetylase Kdac1. We show that Kdac1 catalyzes the deacetylation of free acetyllysine and acetyllysine tetrapeptide assay substrates, and we also report the X-ray crystal structures of unliganded Kdac1 as well as its complex with the hydroxamate inhibitor Citarinostat.

Diversifying chemical space of DNA-encoded libraries: synthesis of 2-oxa-1-azaspiro(bicyclo[3.2.0])heptanes on-DNA visible light-mediated energy transfer catalysis.

Azaspiro[3.3]heptanes are valuable synthetic targets for drug discovery programs. The challenges associated with the preparation and diversification of this moiety as compared to other small, saturated rings have led to limited applications of compounds containing this spirocycle.

Combining non-canonical amino acid mutagenesis and native chemical ligation for multiply modifying proteins: A case study of α-synuclein post-translational modifications.

The Parkinson's disease associated protein α-synuclein (αS) has been found to contain numerous post-translational modifications (PTMs), in both physiological and pathological states. One PTM site of particular interest is serine 87, which is subject to both O-linked β-N-acetylglucosamine (gS) modification and phosphorylation (pS), with αS-pS enriched in Parkinson's disease. An often-overlooked aspect of these PTMs is their effect on the membrane-binding properties of αS, which are important to its role in regulating neurotransmitter release.

Integrated 3D Mapping and Diagnosis for the Structural Assessment of Architectural Heritage: Morano's Parabolic Arch.

The architectural heritage of the 20th century is affected by several conservation problems in terms of material preservation, structural analysis, and reuse. Among these, material degradation and durability issues are the ones that have the most effect on the health state and, consequently, the survival of the constructions of the period. In order to conduct a proper analysis for preservation purposes, an interdisciplinary approach is necessary.