Medicinal Chemistry of Drugs with N-Oxide Functionalities

Journal of Medicinal Chemistry, Год журнала: 2024, Номер 67(7), С. 5168 - 5184

Опубликована: Март 29, 2024

Molecules with N-oxide functionalities are omnipresent in nature and play an important role Medicinal Chemistry. They synthetic or biosynthetic intermediates, prodrugs, drugs, polymers for applications drug development surface engineering. Typically, the group is critical biomedical of these molecules. It may provide water solubility decrease membrane permeability immunogenicity. In other cases, has a special redox reactivity which targeting and/or cytotoxicity. Many underlying mechanisms have only recently been discovered, number N-oxides healthcare field rapidly growing. This Perspective article gives short summary properties their synthesis. also provides discussion current explains basic molecular responsible biological activity.

Язык: Английский

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Atomistic Insights into the Ionic Response and Mechanism of Antifouling Zwitterionic Polymer Brushes

Small, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 9, 2024

Zwitterionic polymer brushes are not a practical choice since their ionic response mechanisms unclear, despite great potential for surface antifouling modification. Therefore, atomic force microscopy and molecular dynamics simulations investigated the of electrical properties, hydration protein adhesion three types zwitterionic brushes. The PMPC (poly(2-methacryloyloxyethyl phosphorylcholine)) PSBMA (poly(sulfobetaine methacrylate)) in salt solution exhibits significant accumulation cations, which results positive shift potential. In contrast, demonstrates no notable change Furthermore, divalent Ca

Язык: Английский

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The Case for Poly(ylides) as a Class of Charge-Neutral, Hydrophilic Polymers with Applications in Biomaterials Science

Biomaterials Science, Год журнала: 2024, Номер unknown

Опубликована: Янв. 1, 2024

Many applications of biomaterials require hydrophilic polymers as building blocks, including hydrogels and nanomedicinal devices. Besides enabling sufficient swelling properties in aqueous environments, provide hydration layers, which are considered a major requirement when designing non-fouling surfaces materials. For the last few decades, polyethylene glycol has been seen gold standard for such applications. However, reports on its stability immunogenicity have urged chemists to identify alternatives with comparable or superior properties. In addition biopolymers, zwitterionic gained increasing attention by effectively offering an overall charge-neutral scaffold capable forming strong layers. Driven enhanced understanding structure-property relationship materials, poly(ylides) emerged new class polymers. By having negative charge adjacent positive charge, ylides offer not only minimal dipole moment but also maintain their nature. Despite some early synthesis during 1980s, polymeric were largely overlooked polymers, utility unique blocks design tools remained elusive. recent years, several groups reported

Язык: Английский

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Decoration of 1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid (DOTA) with N‐oxides increases the T₁ relaxivity of Gd‐complexes

ChemistryOpen, Год журнала: 2024, Номер 13(7)

Опубликована: Янв. 15, 2024

Abstract High complex stability and longitudinal relaxivity of Gd‐based contrast agents are important requirements for magnetic resonance imaging (MRI) because they ensure patient safety contribute to measurement sensitivity. Charged zwitterionic Gd 3+ ‐complexes the well‐known chelator 1,4,7,10‐tetraazacyclododecane‐1,4,7,10‐tetraacetic acid (DOTA) provide an excellent basis development safe sensitive agents. In this report, we describe synthesis DOTA‐NOx, a DOTA derivative with four N ‐oxide functionalities via “click” functionalization tetraazide DOTAZA. The resulting complexes Gd‐DOTA‐NOx Eu‐DOTA‐NOx stable compounds in aqueous solution. NMR‐spectroscopic characterization revealed high excess twisted square antiprismatic (TSAP) coordination geometry over (SAP). was found be r 1 =7.7 m −1 s (1.41 T, 37 °C), unusually value comparable weight. We attribute steric influence ordering effect on outer sphere water molecules surrounding generated by strongly hydrated groups. Moreover, against transchelation EDTA (200 eq) period 36 h, it has similar vitro cell toxicity as clinically used DOTA‐based GBCAs.

Язык: Английский

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Low-Fouling and Antibacterial Polymer Brushes via Surface-Initiated Polymerization of a Mixed Zwitterionic and Cationic Monomer

Langmuir, Год журнала: 2023, Номер 39(49), С. 17959 - 17971

Опубликована: Ноя. 30, 2023

The use of surface-grafted polymer brushes with combined low-fouling and antibacterial functionality is an attractive strategy to fight biofilm formation. This report describes a new styrene derivative combining quaternary ammonium group sulfobetaine in one monomer. Surface-initiated polymerization this monomer on titanium polyethylene (PE) base material gave bifunctional brush layers. Grafting was achieved via surface-initiated atom transfer radical from or heat-induced free-radical plasma-activated PE. Both techniques charged layers thickness over 750 nm, as confirmed by ToF-SIMS-SPM measurements. chemical composition the polymers XPS FT-IR analysis. surface charge, characterized ζ potential, positive at different pH values, number solvent-accessible excess groups found be ∼1016 N+/cm2. led strong activity against Gram-positive Gram-negative bacteria that superior structurally related contact-active polymeric brush. In addition activity, good properties dual-function were found. dual most likely due combination antifouling sulfobetaines. both allows preparation operationally simple techniques.

Язык: Английский

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Polyethylene Terephthalate (PET) Primary Degradation Products Affect c-di-GMP-, cAMP-Signaling, and Quorum Sensing (QS) in Vibrio gazogenes DSM 21264

Опубликована: Фев. 7, 2025

Global plastic pollution in oceans and estuaries is increasing rapidly it’s well known that bacteria colonize particles of all sizes. _Vibri_o spp. are frequently found as part the plastisphere. We recently showed _Vibrio gazogenes_ DSM 21264 harbors a promiscuous esterase designated PET6. now provide evidence _pet6_ gene expressed under wide range environmental conditions its native host. However, PET- PE-grown biofilms expression was not affected by type surface. The transcription sufficient to allow enzyme production release µM amounts mono-(2-hydroxyethyl) terephthalate (MHET) terephthalic acid (TPA) already after 24 hours incubation on PET foil. Notably, highest observed planktonic lifestyle presence bis(2-hydroxyethyl) (BHET) one primary degradation products PET. BHET further hydrolyzed PET6 UlaG, lactonase had been be involved degradation. Elevated concentrations major signaling circuits bacterial quorum sensing (QS), c-di-GMP cAMP-CRP signaling. This resulted failure form biofilms, synthesis red pigment prodigiosin altered colony morphologies. While very impact, TPA interfered mainly with QS attenuating CAI-I autoinducer synthase gene. These observations imply potential role nutritional signals may affect growth survival IMPORTANCE: study provides first secretes an active hydrolase degrades polymer using when growing foils microplastic particles. have profound impact global QS, _V. capability marine environment.

Язык: Английский

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Water-Soluble Sulfur-Ylide-Functionalized Polyacrylamides for Antibacterial Surface Applications

Langmuir, Год журнала: 2025, Номер unknown

Опубликована: Март 24, 2025

Surface fouling induced by biomolecules and microorganisms remains a persistent challenge in materials science, particularly healthcare applications, where biofilm formation on medical devices may lead to infections antimicrobial resistance. Antifouling strategies typically rely the of either hydration layers or cytotoxic for direct effects. Recent advances zwitterionic polymers derived from ylides offer promising yet unexplored toolbox construction antifouling coatings. While N-oxide-based have been extensively studied as building blocks materials, sulfur-ylide-based precise underlying mechanisms remain underexplored despite their broader chemical versatility. Here, we present fully water-soluble acrylamide-based poly(sulfur ylide) compare its properties those previously reported hydrophobic polystyrene-derived analogues. Notably, ylides) retain efficacy surfaces but lose cytotoxicity solution, unlike counterpart. Computational studies reveal that dipole moment sulfur is environmentally responsive, stabilizing environments. Genetic analysis confirms outer membrane destabilization both suggests hydrophobicity polystyrene backbone promotes stronger interactions. We suggest future work should focus elucidating additional interactions, including supramolecular behaviors amphiphilic ylides, refine structure–property relationships optimize properties.

Язык: Английский

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Interaction of Grafted Polymeric N-oxides with Charged Dyes

Langmuir, Год журнала: 2025, Номер unknown

Опубликована: Апрель 24, 2025

Grafted polymeric N-oxides have recently attracted interest for antifouling applications, drug delivery, wastewater purification, and electronic devices. Their function depends on the efficiency of grafting process following postgrafting oxidation step. These two parameters govern solvent-accessible charge density surface, an important parameter, which is notoriously hard to determine. In this study, a novel colorimetric quantitative assay was developed. It allows determination surface grafted N-oxides. The method based adsorption acid fuchsin (AF) through reversible electrostatic interactions between positively charged nitrogen atoms N-oxide functionality sulfonate groups dye. thus pH-switchable properties Adsorption achieved at pH value 3, where are almost fully protonated (typical pKa 4-5). AF desorbed from 7 quantified via visible spectroscopy (UV-vis) 556 nm determine amount surface-grafted functional groups. Charge densities diverse by free radical polymerization polyethylene (PE) were determined be in range 1-3 × 1015 N+-O-/cm2. Notably, can form covalent bonds with electron-deficient triarylmethane dyes like AF. This nucleophilic reactivity does not compromise proposed assay, but it may relevance dye desorption purification.

Язык: Английский

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Durable plasma-mediated zwitterionic grafting on polymeric surfaces for implantable medical devices

Communications Materials, Год журнала: 2024, Номер 5(1)

Опубликована: Март 5, 2024

Abstract Adverse body reactions to blood-contacting medical devices endanger patient safety and impair device functionality, with events invariably linked nonspecific protein adsorption due suboptimal material biocompatibility. To improve the durability of such devices, herein we propose a strategy for introducing stable zwitterionic grafts onto polymeric surfaces via plasma functionalization. The resulting zwitterion-grafted substrates exhibit long-lasting superhydrophilicity, enabling antifouling anti-thrombogenic properties. We demonstrate successful modification surface elemental composition, morphology, hydrophilicity, while retaining underlying mechanical properties substrate. Furthermore, optimise fabrication process ensure modifications at least three months after fabrication. This decreases fibrinogen by approximately 9-fold, thrombosis almost 75% when applied commercial polyurethane. Moreover, this is universally applicable wide range materials, even those chemistry as polytetrafluoroethylene.

Язык: Английский

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Polyamino Acid Based Zwitterionic Coating can Inhibit Coagulation and Inflammation Through Anti‐Fouling and Restoring Microenvironment

Macromolecular Bioscience, Год журнала: 2024, Номер 25(1)

Опубликована: Ноя. 8, 2024

Abstract Protein adhesion and thrombosis formation caused by limited surface properties pose great challenges to biomedical implants. Although various hydrophilic coating or drug release coatings are reported, the single cannot cope with cases under condition of complex physiological environment, which causes effect is limited. In this study, a polyamino acid‐derived zwitterionic constructed eliminate reactive oxygen species (ROS) in microenvironment. It demonstrated that has excellent hydrophilicity, stability, lubricity, can obviously prevent protein adhesion. At same time, hydrogen peroxide maintain stability The vivo vitro experiments show good biocompatibility, inhibits thrombus. Amino acid zwitterion prevents deposition, alleviates inflammatory process, inhibit thrombosis, reduces risk implantable medical devices, prolongs their service time. Hence, work paves new way develop amino based polymer reduce implant complications.

Язык: Английский

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