Room Temperature Regioselective Debenzylative Cycloetherification Reaction.

A regio- and stereoselective debenzylative cycloetherification (DBCE) reaction of protected hexoses to form stereodefined hydroxylated tetrahydrofurans of synthetic utility has been investigated under very mild room temperature reaction conditions. This study revealed the potential application of the DBCE reaction of simple, abundant starting materials to access stereochemically rich tetrahydrofuran compounds under mild reaction conditions.

Toward the Clinical Translation of Safe Intravenous Long Circulating Iodinated Lipid Nanoemulsion Contrast Agents for CT Imaging.

Current clinical small molecule x-ray CT agents are effective but pose risks such as nephrotoxicity, short blood circulation time, limiting scan durations, potential thyroid impact, and immune responses. These challenges drive the development of kidney-safe x-ray nanoparticle (NP)-based contrast agents (CAs), though translation to clinical practice is hindered by chemical complexities and potential toxicity. We have engineered an intravenous, injectable, and safe blood pool NP-based CT CAs at a clinical-equivalent dose of ∼300 mgI/kg (∼2 mL/kg), ideal for vascular and hepatic imaging which are limited by clinical agents.

Cycloaddition of Phenyltriazolinedione with Carbazole-Alkynes and Yne-Carbamates to Access Diazacyclobutenes.

Previously, we described the synthesis of stable, bicyclic examples of the rather rare diazacyclobutene (DCB) motif by means of a cycloaddition between triazolinediones and electron-rich thiolated alkynes. Here, we report the investigation of the cycloaddition of triazolinediones with related electron-rich yne-carbamates and carbazole-alkynes. Bicyclic DCBs arising from yne-carbamates were isolated in 8-65% yield, while those arising from carbazole-alkynes were isolated in 28-59% yield.

Enolase inhibitors as therapeutic leads for infection.

Infections with the pathogenic free-living amoebae can lead to life-threatening illnesses including catastrophic primary amebic meningoencephalitis (PAM). Efficacious treatment options for these infections are lacking and the mortality rate remains >95% in the US. Glycolysis is very important for the infectious trophozoite lifecycle stage and inhibitors of glucose metabolism have been found to be toxic to the pathogen.

Enhancing drug delivery with supramolecular amphiphilic macrocycle nanoparticles: selective targeting of CDK4/6 inhibitor palbociclib to melanoma.

Drug delivery systems based on amphiphilic supramolecular macrocycles have garnered increased attention over the past two decades due to their ability to successfully formulate nanoparticles. Macrocyclic (MC) materials can self-assemble at lower concentrations without the need for surfactants and polymers, but surfactants are required to form and stabilize nanoparticles at higher concentrations. Using MCs to deliver both hydrophilic and hydrophobic guest molecules is advantageous.

Enhancing Drug Delivery with Supramolecular Amphiphilic Macrocycle Nanoparticles: Selective Targeting of CDK4/6 Inhibitor Palbociclib to Melanoma.

Drug delivery systems based on amphiphilic supramolecular macrocycles have garnered increased attention over the past two decades due to their ability to successfully formulate nanoparticles. Macrocyclic (MC) materials can self-assemble at lower concentrations without the need for surfactants and polymers, but surfactants are required to form and stabilize nanoparticles at higher concentrations. Using MCs to deliver both hydrophilic and hydrophobic guest molecules is advantageous.

Correction: Removal of metals and inorganics from rendered fat using polyamine-modified cellulose nanocrystals.

[This corrects the article DOI: 10.1039/D3SU00116D.].

Enolase Inhibitors as Early Lead Therapeutics against .

Glucose metabolism is critical for the African trypanosome, , serving as the lone source of ATP production for the bloodstream form (BSF) parasite in the glucose-rich environment of the host blood. Recently, phosphonate inhibitors of human enolase (ENO), the enzyme responsible for the interconversion of 2-phosphoglycerate (2-PG) to phosphoenolpyruvate (PEP) in glycolysis or PEP to 2-PG in gluconeogenesis, have been developed for the treatment of glioblastoma multiforme (GBM). Here, we have tested these agents against ENO (ENO) and found the compounds to be potent enzyme inhibitors and trypanocides.

Glucose metabolism in the pathogenic free-living amoebae: Tempting targets for treatment development.

Pathogenic free-living amoebae (pFLA) are single-celled eukaryotes responsible for causing intractable infections with high morbidity and mortality in humans and animals. Current therapeutic approaches include cocktails of antibiotic, antifungal, and antimicrobial compounds. Unfortunately, the efficacy of these can be limited, driving the need for the discovery of new treatments.

Predicting Antioxidant Synergism via Artificial Intelligence and Benchtop Data.

Lipid oxidation is a major issue affecting products containing unsaturated fatty acids as ingredients or components, leading to the formation of low molecular weight species with diverse functional groups that impart off-odors and off-flavors. Aiming to control this process, antioxidants are commonly added to these products, often deployed as combinations of two or more compounds, a strategy that allows for lowering the amount used while boosting the total antioxidant capacity of the formulation. While this approach allows for minimizing the potential organoleptic and toxic effects of these compounds, predicting how these mixtures of antioxidants will behave has traditionally been one of the most challenging tasks, often leading to simple additive, antagonistic, or synergistic effects.

A cathepsin C-like protease mediates the post-translation modification of secretory proteins for optimal invasion and egress.

Microbial pathogens use proteases for their infections, such as digestion of proteins for nutrients and activation of their virulence factors. As an obligate intracellular parasite, must invade host cells to establish its intracellular propagation. To facilitate invasion, the parasites secrete invasion effectors from microneme and rhoptry, two unique organelles in apicomplexans.

Lignocellulosic-Based Nanoparticles with Photoluminescent Properties for Bioimaging.

Natural and renewable resources from plants or animals are an important source of biomaterials due to their biocompatibility and high availability. Lignin is a biopolymer present in the biomass of plants, where it is intertwined and cross-linked with other polymers and macromolecules in the cell walls, generating a lignocellulosic material with potential applications. We have prepared lignocellulosic-based nanoparticles with an average size of 156 nm that exhibit a high photoluminescence signal when excited at 500 nm with emission in the near-infrared (NIR) region at 800 nm.

Exploring the interactive mechanism of acarbose with the amylase SusG in the starch utilization system of the human gut symbiont Bacteroides thetaiotaomicron through molecular modeling.

The α-amylase, SusG, is a principal component of the Bacteroides thetaiotaomicron (Bt) starch utilization system (Sus) used to metabolize complex starch molecules in the human gastrointestinal (GI) tract. We previously reported the non-microbicidal growth inhibition of Bt by the acarbose-mediated arrest of the Sus as a potential therapeutic strategy. Herein, we report a computational approach using density functional theory (DFT), molecular docking, and molecular dynamics (MD) simulation to explore the interactive mechanism between acarbose and SusG at the atomic level in an effort to understand how acarbose shuts down the Bt Sus.

Comparison between nanocellulose-polyethylenimine composites synthesis methods towards multiple water pollutants removal: A review.

Nanocellulose/polyethylenimine composites have attracted growing attention due to their versatility as new materials for application in different fields. Water remediation is one of the traditional applications of these composites and their investigation as adsorbents for single water pollutants is well established. However, most water resources such as rivers, lakes, and even oceans contain complex mixtures of pollutants.

A cathepsin C-like protease post-translationally modifies secretory proteins for optimal invasion and egress.

Unlabelled: Microbial pathogens use proteases for their infections, such as digestion of proteins for nutrients and activation of their virulence factors. As an obligate intracellular parasite, must invade host cells to establish its intracellular propagation. To facilitate invasion, the parasites secrete invasion effectors from microneme and rhoptry, two unique organelles in apicomplexans.

Cellulose-based hydrogels towards an antibacterial wound dressing.

Hydrogels are promising candidates for wound healing bandages because they can mimic the native skin microenvironment. Additionally, there is increasing growth in the use of naturally derived materials and plant-based biomaterials to produce healthcare products with healing purposes because of their biocompatibility and biodegradation properties. In this study, cellulose extracted from biodiverse sources in Ecuador was used as the raw material for the fabrication of hydrogels with enhanced antifouling properties.

Radiopaque Iodosilane-Coated Lipid Hybrid Nanoparticle Contrast Agent for Dual-Modality Ultrasound and X-ray Bioimaging.

Here, we report the synthesis of robust hybrid iodinated silica-lipid nanoemulsions (HSLNEs) for use as a contrast agent for ultrasound and X-ray applications. We engineered iodinated silica nanoparticles (SNPs), lipid nanoemulsions, and a series of HSLNEs by a low-energy spontaneous nanoemulsification process. The formation of a silica shell requires sonication to hydrolyze and polymerize/condensate the iodomethyltrimethoxysilane at the oil/water interface of the nanoemulsion droplets.

Telescoped Oxidation and Cycloaddition of Urazoles to Access Diazacyclobutenes.

Our previous method to access the diazacyclobutene scaffold did not allow for modification of the substituent originating from the 1,2,4-triazoline-3,5-dione component. We have circumvented this challenge and expanded access to additional structural diversity of the scaffold. A telescoped urazole oxidation and Lewis acid-catalyzed cyclization provided R-substituted diazacyclobutenes.

Oxadiazon Derivatives Elicit Potent Intracellular Growth Inhibition against by Disrupting Heme Biosynthesis.

Infections of can cause severe and sometimes fatal diseases in immunocompromised individuals. The heme biosynthesis pathway is required for intracellular growth and pathogenesis, making it an appealing therapeutic target. We synthesized a small library of derivatives of the herbicide oxadiazon, a known inhibitor of the penultimate reaction within the heme biosynthesis pathway in plants, catalyzed by protoporphyrinogen oxidase (PPO).

Scaled Synthesis of Polyamine-Modified Cellulose Nanocrystals from Bulk Cotton and Their Use for Capturing Volatile Organic Compounds.

We have previously demonstrated that cellulose nanocrystals modified with poly(ethylenimine) (PEI--CNC) are capable of capturing volatile organic compounds (VOCs) associated with malodors. In this manuscript, we describe our efforts to develop a scalable synthesis of these materials from bulk cotton. This work culminated in a reliable protocol for the synthesis of unmodified cellulose nanocrystals (CNCs) from bulk cotton on a 0.

Bimodal Ultrasound and X-ray Bioimaging Properties of Particulate Calcium Fluoride Biomaterial.

Ultrasound (US) and X-ray imaging are diagnostic methods that are commonly used to image internal body structures. Several organic and inorganic imaging contrast agents are commercially available. However, their synthesis and purification remain challenging, in addition to posing safety issues.

In Situ Photopolymerization of Acrylamide Hydrogel to Coat Cellulose Acetate Nanofibers for Drug Delivery System.

In this study we developed electrospun cellulose acetate nanofibers (CANFs) that were loaded with a model non-steroidal anti-inflammatory drug (NSAID) (ibuprofen, Ib) and coated with poly(acrylamide) (poly-AAm) hydrogel polymer using two consecutive steps: an electrospinning process followed by photopolymerization of AAm. Coated and non-coated CANF formulations were characterized by several microscopic and spectroscopic techniques to evaluate their physicochemical properties. An analysis of the kinetic release profile of Ib showed noticeable differences due to the presence or absence of the poly-AAm hydrogel polymer.

Polytetrafluoroethylene-like Nanoparticles as a Promising Contrast Agent for Dual Modal Ultrasound and X-ray Bioimaging.

Various noninvasive imaging techniques are used to produce deep-tissue and high-resolution images for biomedical research and clinical purposes. Organic and inorganic bioimaging agents have been developed to enhance the resolution and contrast intensity. This paper describes the synthesis of polytetrafluoroethylene-like nanoparticles (PTFE≈ NPs), their characterization, biological activity, and bioimaging properties.