Design, Structure-Activity Relationships, and Computational Modeling Studies of a Series of α-Helix Biased, Ultra-Short Glucagon-like Peptide-1 Receptor Agonists.

A systematic structure-activity and computational modeling analysis of a series of glucagon-like peptide-1 receptor (GLP-1R) agonists based upon an ultra-short GLP-1 peptide, H-His-Aib-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Bip-Bip-NH2, was conducted. This highly potent 11-mer peptide led to a deeper understanding of the α-helical bias of strategic α-methylation within the linear parent template as well as optimization of GLP-1R agonist potency by 1000-fold. These data were correlated with previously reported co-structures of both full-length GLP-1 analogs and progenitor N-terminal GLP-1 fragment analogs related to such ultra-short GLP-1R agonist peptides.

Isolated Neutral Organic Radical Unveiled Solvent-Radical Interaction in Highly Reducing Photocatalysis.

Diffusion-limited kinetics is a key mechanistic debate when consecutive photoelectron transfer (conPET) is discussed in photoredox catalysis. In-situ generated organic photoactive radicals can access catalytic systems as reducing as alkaline metals that can activate remarkably stable bonds. However, in many cases, the extremely short-lived transient nature of these doublet state open-shell species has led to debatable mechanistic studies, hindering adoption and development.

Metal complex-based probes for the detection of chloride ions.

Chloride ions play vital roles in a variety of biological and environmental processes, making their accurate and efficient detection critical for both research and practical applications. In this perspective, we explore the recent advancements in the development of metal complex-based probes for chloride ion detection, with a focus on complexes involving transition and lanthanide metals. These probes offer remarkable selectivity and sensitivity, achieved through diverse mechanisms such as metal coordination, hydrogen bonding, electrostatic interactions, and halogen or chalcogen bonding.

Solvent-Free Silsesquioxane Self-Welding for 3D Printing Multi-Refractive Index Glass Objects.

The growing interest in 3D printing of silica glass has spurred substantial research efforts. Our prior work utilizing a liquid silica resin (LSR) demonstrated high printing accuracy and resolution. However, the resin's sensitivity to moisture posed limitations, restricting the printing environment.

Surface Magnetic Stabilization and the Photoemission Chiral-Induced Spin-Selectivity Effect.

The spinterface mechanism was suggested as a possible origin for the chirality-induced spin-selectivity (CISS) effect and was used to explain and reproduce, with remarkable accuracy, experimental data from transport experiments showing the CISS effect. Here, we apply the spinterface mechanism to explain the appearance of magnetization at the interface between nonmagnetic metals and chiral molecules, through the stabilization of otherwise fluctuating magnetic moments. We show that the stabilization of surface magnetic moments occurs for a wide range of realistic parameters and is robust against dephasing.

Gold Tripyrrindione: Redox Chemistry and Reactivity with Dichloromethane.

The identification of ligands that stabilize Au(III) centers has led to the isolation of complexes for applications in catalysis, gold-based therapeutics, and functional materials. Herein, we report the coordination of gold by tripyrrin-1,14-dione, a linear tripyrrole with the scaffold of naturally occurring metabolites of porphyrin-based protein cofactors (e.g.

Gaussians for Electronic and Rovibrational Quantum Dynamics.

The assumptions underpinning the adiabatic Born-Oppenheimer (BO) approximation are broken for molecules interacting with attosecond laser pulses, which generate complicated coupled electronic-nuclear wave packets that generally will have components of electronic and dissociation continua as well as bound-state contributions. The conceptually most straightforward way to overcome this challenge is to treat the electronic and nuclear degrees of freedom on equal quantum-mechanical footing by invoking the BO approximation at all. Explicitly correlated Gaussian (ECG) basis functions have proved successful for non-BO calculations of stationary molecular states and energies, reproducing rovibrational absorption spectra with very high accuracy.

Transition Path Sampling Study of Engineered Enzymes That Catalyze the Morita-Baylis-Hillman Reaction: Why Is Enzyme Design so Difficult?

It is hoped that artificial enzymes designed in laboratories can be efficient alternatives to chemical catalysts that have been used to synthesize organic molecules. However, the design of artificial enzymes is challenging and requires a detailed molecular-level analysis to understand the mechanism they promote in order to design efficient variants. In this study, we computationally investigate the mechanism of proficient Morita-Baylis-Hillman enzymes developed using a combination of computational design and directed evolution.

UV-curable thiol-ene system for broadband infrared transparent objects.

Conventional infrared transparent materials, including inorganic ceramic, glass, and sulfur-rich organic materials, are usually processed through thermal or mechanical progress. Here, we report a photo-curable liquid material based on a specially designed thiol-ene strategy, where the multithiols and divinyl oligomers were designed to contain only C, H, and S atoms. This approach ensures transparency in a wide range spectrum from visible light to mid-wave infrared (MWIR), and to long-wave infrared (LWIR).

Bio-inspired Compact, High-resolution Snapshot Hyperspectral Imaging System with 3D Printed Glass Lightguide Array.

To address the major challenges to obtain high spatial resolution in snapshot hyperspectral imaging, 3D printed glass lightguide array has been developed to sample the intermediate image in high spatial resolution and redistribute the pixels in the output end to achieve high spectral resolution. Curved 3D printed lightguide array can significantly simplify the snapshot hyperspectral imaging system, achieve better imaging performance, and reduce the system complexity and cost. We have developed two-photon polymerization process to print glass lightguide array, and demonstrated the system performance with biological samples.

High-Throughput Deconvolution of Native Protein Mass Spectrometry Imaging Data Sets for Mass Domain Analysis.

Protein mass spectrometry imaging (MSI) with electrospray-based ambient ionization techniques, such as nanospray desorption electrospray ionization (nano-DESI), generates data sets in which each pixel corresponds to a mass spectrum populated by peaks corresponding to multiply charged protein ions. Importantly, the signal associated with each protein is split among multiple charge states. These peaks can be transformed into the mass domain by spectral deconvolution.

Site-Selective Modification of Secondary Amine Moieties on Native Peptides, Proteins, and Natural Products with Ynones.

Site-selective modification of biologically relevant secondary amines in peptides, proteins, and natural products has been challenging due to the similar reactivity between primary and secondary amines. Even for the secondary amines, their reactivities are significantly influenced by their structures and environment. Herein, we report a ynone Michael bioconjugation method for selective modification of secondary amines in unprotected peptides and proteins and complex natural products.

Design of Tetrazolium Cations for the Release of Antiproliferative Formazan Chelators in Mammalian Cells.

Cancer cells generally present a higher demand for iron, which plays crucial roles in tumor progression and metastasis. This iron addiction provides opportunities to develop broad spectrum anticancer drugs that target iron metabolism. In this context, prochelation approaches are investigated to release metal-binding compounds under specific conditions, thereby limiting off-target toxicity.

Targeting iron to contrast cancer progression.

An altered metabolism of iron fuels cancer growth, invasion, metastasis, and recurrence. Ongoing research in cancer biology is delineating a complex iron-trafficking program involving both malignant cells and their support network of cancer stem cells, immune cells, and other stromal components in the tumor microenvironment. Iron-binding strategies in anticancer drug discovery are being pursued in clinical trials and in multiple programs at various levels of development.

Multicenter interactions and ligand field effects in platinum(II) tripyrrindione radicals.

The tripyrrin-1,14-dione biopyrrin, which shares the scaffold of several naturally occurring heme metabolites, is a redox-active platform for metal coordination. We report the synthesis of square planar platinum(II) tripyrrindiones, in which the biopyrrin binds as a tridentate radical and the fourth coordination position is occupied by either aqua or -butyl isocyanide ligands. These complexes are stable through chromatographic purification and exposure to air.

Aroylhydrazone Glycoconjugate Prochelators Exploit Glucose Transporter 1 (GLUT1) to Target Iron in Cancer Cells.

Glycoconjugation strategies in anticancer drug discovery exploit the high expression of glucose transporters in malignant cells to achieve preferential uptake and hence attractive pharmacological characteristics of increased therapeutic windows and decreased unwanted toxicity. Here we present the design of glycoconjugated prochelators of aroylhydrazone AH1, an antiproliferative scavenger that targets the increased iron demand of rapidly proliferating malignant cells. The constructs feature a monosaccharide (d-glucose, d-glucosamine, or glycolytic inhibitor 2-deoxy-d-glucose) connected at the C2 or C6 position via a short linker, which masks the chelator through a disulfide bond susceptible to intracellular reduction.

Free-Energy Surfaces of Two Cardiac Thin Filament Conformational Changes during Muscle Contraction.

The troponin core is an important regulatory complex in cardiac sarcomeres. Contraction is initiated by a calcium ion binding to cardiac troponin C (cTnC), initiating a conformational shift within the protein, altering its interactions with cardiac troponin I (cTnI). The change in cTnC-cTnI interactions prompts the C-terminal domain of cTnI to dissociate from actin, allowing tropomyosin to reveal myosin-binding sites on actin.

High-Precision Printing of Complex Glass Imaging Optics with Precondensed Liquid Silica Resin.

3D printing of optics has gained significant attention in optical industry, but most of the research has been focused on organic polymers. In spite of recent progress in 3D printing glass, 3D printing of precision glass optics for imaging applications still faces challenges from shrinkage during printing and thermal processing, and from inadequate surface shape and quality to meet the requirements for imaging applications. This paper reports a new liquid silica resin (LSR) with higher curing speed, better mechanical properties, lower sintering temperature, and reduced shrinkage, as well as the printing process for high-precision glass optics for imaging applications.

On the Fundamental Polymer Chemistry of Inverse Vulcanization for Statistical and Segmented Copolymers from Elemental Sulfur.

In this concept review, the fundamental and polymerization chemistry of inverse vulcanization for the preparation of statistical and segmented sulfur copolymers, which have been actively developed and advanced in various applications over the past decade is discussed. This concept review delves into a discussion of step-growth polymerization constructs to describe the inverse vulcanization process and discuss prepolymer approaches for the synthesis of segmented sulfur polyurethanes. Furthermore, this concept review discusses the advantages of inverse vulcanization in conjunction with dynamic covalent polymerization and post-polymerization modifications to prepare segmented block copolymers with enhanced thermomechanical and flame retardant properties of these materials.

{Moco}, (n = 0-8): A general formalism for describing the highly covalent molybdenum cofactor of sulfite oxidase and related Mo enzymes.

Over 50 molybdenum enzymes in three distinct families (sulfite oxidase, xanthine oxidase, DMSO reductase) are known, and representative X-ray crystal structures are available for all families. Structural analogues that replicate the coordination about the Mo atom in the absence of surrounding protein have been synthesized and characterized. The properties of metal complexes of non-innocent dithiolene ligands and their oxidized counter parts, dithiones, are summarized.

PNJ scaffolds promote microenvironmental regulation of glioblastoma stem-like cell enrichment and radioresistance.

Glioblastoma (GBM) brain tumors contain a subpopulation of self-renewing multipotent Glioblastoma stem-like cells (GSCs) that are believed to drive the near inevitable recurrence of GBM. We previously engineered temperature responsive scaffolds based on the polymer poly(-isopropylacrylamide--Jeffamine M-1000 acrylamide) (PNJ) for the purpose of enriching GSCs from patient-derived samples. Here, we used PNJ scaffolds to study microenvironmental regulation of self-renewal and radiation response in patient-derived GSCs representing classical and proneural subtypes.

Rationalizing energy level alignment by characterizing Lewis acid/base and ionic interactions at printable semiconductor/ionic liquid interfaces.

Charge transfer and energy conversion processes at semiconductor/electrolyte interfaces are controlled by local electric field distributions, which can be especially challenging to measure. Herein we leverage the low vapor pressure and vacuum compatibility of ionic liquid electrolytes to undertake a layer-by-layer, ultra-high vacuum deposition of a prototypical ionic liquid EMIM (1-ethyl-3-methylimidazolium) and TFSI (bis(trifluoromethylsulfonyl)-imide) on the surfaces of different electronic materials. We consider a case-by-case study between a standard metal (Au) and four printed electronic materials, where interfaces are characterized by a combination of X-ray and ultraviolet photoemission spectroscopies (XPS/UPS).

Synthesis and In Vitro Characterization of Glycopeptide Drug Candidates Related to PACAP.

The search for efficacious treatment of neurodegenerative and progressive neuroinflammatory diseases continues, as current therapies are unable to halt or reverse disease progression. PACAP represents one potential therapeutic that provides neuroprotection effects on neurons, and also modulates inflammatory responses and circulation within the brain. However, PACAP is a relatively long peptide hormone that is not trivial to synthesize.