New nitric oxide-releasing zwitterions derived from polyamines

Hrabie, Joseph A.; Klose, John R.; Wink, David A.; Keefer, Larry K.

doi:10.1021/jo00058a030

Cited by 569 publications

(521 citation statements)

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“…1 H NMR of AHAP3/NO revealed that the protons adjacent to the secondary amine where diazeniumdiolate formation occurs became deshielded in the presence of the zwitterionic NO donor, shifting downfield from 2.45 ppm to 2.84 ppm. The presence of the diazeniumdiolate on AHAP3/NO was also confirmed via UV-Vis spectroscopy (λ max = 253 nm, characteristic of the diazeniumdiolate absorption maximum 17,25 ) and direct observation of the released NO via chemiluminescence. 26 The presence of the diazeniumdiolate functional group in the nanoparticle scaffold was confirmed via UV absorbance spectroscopy and the direct measurement of NO release.…”

Section: Characterization Of No-releasing Silica Nanoparticles and Prmentioning

confidence: 76%

Bactericidal Efficacy of Nitric Oxide-Releasing Silica Nanoparticles

Hetrick

Shin²,

Stasko³

et al. 2008

ACS Nano

322

380

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The utility of nitric oxide (NO)-releasing silica nanoparticles as a novel antibacterial is demonstrated against Pseudomonas aeruginosa. Nitric oxide-releasing nanoparticles were prepared via co-condensation of tetraalkoxysilane with aminoalkoxysilane modified with diazeniumdiolate NO donors, allowing for the storage of large NO payloads. Comparison of the bactericidal efficacy of the NO-releasing nanoparticles to 1-[2-(carboxylato)pyrrolidin-1-yl]diazen-1-ium-1,2-diolate (PROLI/NO), a small molecule NO donor, demonstrated enhanced bactericidal efficacy of nanoparticle-derived NO and reduced cytotoxicity to healthy cells (mammalian fibroblasts). Confocal microscopy revealed that fluorescently-labeled NO-releasing nanoparticles associated with the bacteria, providing rationale for the enhanced bactericidal efficacy of the nanoparticles. Intracellular NO concentrations were measurable when the NO was delivered from nanoparticles as opposed to PROLI/NO. Collectively, these results demonstrate the advantage of delivering NO via nanoparticles for antimicrobial applications.Keywords nitric oxide; silica nanoparticle; antibacterial; bactericidal; cytotoxicity; reactive nitrogen species; reactive oxygen species Antibiotic resistance has resulted in bacterial infections becoming the most common cause of infectious disease-related death. 1,2 In the United States alone, nearly 2 million people per year acquire infections during a hospital stay, of which approximately 90,000 die. 2 The primary culprits behind such deadly infections are antibiotic-resistant pathogens, which are responsible for approximately 70% of all lethal nosocomial infections. The growing danger of life-threatening infections and the rising economic burden of resistant bacteria have created a demand for new antibacterial therapeutics.The use of nanoparticles as delivery vehicles for bactericidal agents represents a new paradigm in the design of antibacterial therapeutics. To date, most antibacterial nanoparticles have been engineered using traditional antibiotics that are either incorporated within the particle scaffold or attached to the exterior of the particle. In many cases, such particles have exhibited greater efficacy than their constituent antibiotics alone. For example, Gu et al. reported that vancomycin-capped gold nanoparticles exhibited a 64-fold improvement in efficacy over vancomycin alone. 3 Similarly, silver nanoparticles have schoenfisch@unc.edu. Supporting Information Available: Synthesis of FITC-modified silica nanoparticles, AFM analysis of nanoparticle dimensions, scavenging of NO by TSB, and confocal fluorescence microscopy images of PROLI/NO-treated P. aeruginosa cells. This material is available free of charge via the Internet at http://pubs.acs.org. NIH Public AccessAuthor Manuscript ACS Nano. Author manuscript; available in PMC 2013 February 13. shown greater antibacterial activity than silver ion (Ag + ) in solution due to the direct toxicity of the particles and tunable release of Ag + based on nanocomposite size. [4][...

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Section: Characterization Of No-releasing Silica Nanoparticles and Prmentioning

confidence: 76%

Bactericidal Efficacy of Nitric Oxide-Releasing Silica Nanoparticles

Hetrick

Shin²,

Stasko³

et al. 2008

ACS Nano

322

380

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“…A. Hrabie, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, MD; ref. 31). Buffer pH (7.4) and temperature (37°C) were confirmed before each experiment because of the major influence these parameters have on the rate of spermine͞NO decomposition (t 1/2 ϭ 42 min).…”

Section: Generation Of Omentioning

confidence: 99%

Focusing of nitric oxide mediated nitrosation and oxidative nitrosylation as a consequence of reaction with superoxide

Espey

Thomas

Miranda

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

160

138

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The impact of nitric oxide (NO) synthesis on different biological cascades can rapidly change dependent on the rate of NO formation and composition of the surrounding milieu. With this perspective, we used diaminonaphthalene (DAN) and diaminofluorescein (DAF) to examine the nitrosative chemistry derived from NO and superoxide (O 2 ؊ ) simultaneously generated at nanomolar to low micromolar per minute rates by spermine͞NO decomposition and xanthine oxidasecatalyzed oxidation of hypoxanthine, respectively. Fluorescent triazole product formation from DAN B iosynthesis of nitrogen monoxide (NO) from nitric-oxide synthase (NOS)-catalyzed oxidation of L-arginine can lead to selective formation of NO adducts on protein residues, which modulates homeostatic metabolism and affects numerous pathophysiologic responses. N-nitrosamines and S-nitrosothiols are typically formed via donation of a nitrosonium equivalent (NO ϩ ) from dinitrogen trioxide (N 2 O 3 ) to the nucleophilic residue (1). The function of many proteins has been altered by nitrosation in vitro including caspases (2, 3), glyceraldehyde-3-phosphate dehydrogenase (4), the N-methyl-D-aspartate receptor (5, 6), O 6 -methylguanine-DNA-methyltransferase (7, 8), ras (9) and the ryanodine receptor (10).The mechanism through which these modifications may occur in biological systems is a subject of debate. Many have questioned the relevance of nitrosation via NO autoxidation, reasoning that sufficient levels of NO cannot be achieved in vivo to satisfy the rate-limiting step for N 2 O 3 formation, which is second order in [11][12][13][14][15][16][17][18][19][20]. In contrast to NO autoxidation, the reaction between NO and superoxide (O 2 Ϫ ) is first order in both reactants and occurs at near diffusion control (21-24). Much emphasis has been placed on the product of this reaction, peroxynitrite (ONOO Ϫ ), as an important mediator of oxidation and nitration (23)(24)(25)(26)(27)(28). In this study, we tested the hypothesis that ONOO Ϫ may also serve as an intermediary in a pathway leading to formation of NO adducts (e.g., N-nitrosamines, S-nitrosothiols) in vivo.The results suggest that these moieties may be produced through both nitrosation and oxidative nitrosylation dependent mechanisms, which are strongly influenced by the relative rates of NO and O 2 Ϫ formation. Buffer pH (7.4) and temperature (37°C) were confirmed before each experiment because of the major influence these parameters have on the rate of spermine͞NO decomposition (t 1/2 ϭ 42 min). Rates of NO release were determined by measuring oxymyoglobin oxidation (582 nm, ϭ 9,100 M Ϫ1 ⅐cm Ϫ1 ) in PBS solution containing DTPA and HX (HX buffer, ref. 32). Oxymyoglobin was prepared by reducing myoglobin (500 M; Sigma) in water with excess sodium dithionite (Fluka) followed by passage through a Sephadex G-25 column (PD-10; Amersham Pharmacia). Steady-state NO concentrations were also assessed by using a NO selective electrode (World Precision Instruments, Sarasota, FL) controlled by a DUO18 amplifier. Peak ampl...

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“…Both devices exhibited positive Dirac points with p-type characteristics at 0 V solution gate voltage bias (hole-transport branch). We used diethylamine NONOate sodium as a precursor to release NO in PBS (pH ¼ 7.4) [41][42][43] . At neutral pH, each one of these precursor molecules can hydrolyse to generate two molecules of NO, following a first-order reaction kinetics with a half-life time of B2 min (ref.…”

Section: Fabrication and Characterization Of Graphene-hemin Sensorsmentioning

confidence: 99%

Real-time electrical detection of nitric oxide in biological systems with sub-nanomolar sensitivity

et al. 2013

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Real-time monitoring of nitric oxide concentrations is of central importance for probing the diverse roles of nitric oxide in neurotransmission, cardiovascular systems and immune responses. Here we report a new design of nitric oxide sensors based on hemin-functionalized graphene field-effect transistors. With its single atom thickness and the highest carrier mobility among all materials, graphene holds the promise for unprecedented sensitivity for molecular sensing. The non-covalent functionalization through p-p stacking interaction allows reliable immobilization of hemin molecules on graphene without damaging the graphene lattice to ensure the highly sensitive and specific detection of nitric oxide. Our studies demonstrate that the graphene-hemin sensors can respond rapidly to nitric oxide in physiological environments with a sub-nanomolar sensitivity. Furthermore, in vitro studies show that the graphene-hemin sensors can be used for the detection of nitric oxide released from macrophage cells and endothelial cells, demonstrating their practical functionality in complex biological systems.

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New nitric oxide-releasing zwitterions derived from polyamines

Cited by 569 publications

References 0 publications

Bactericidal Efficacy of Nitric Oxide-Releasing Silica Nanoparticles

Bactericidal Efficacy of Nitric Oxide-Releasing Silica Nanoparticles

Focusing of nitric oxide mediated nitrosation and oxidative nitrosylation as a consequence of reaction with superoxide

Real-time electrical detection of nitric oxide in biological systems with sub-nanomolar sensitivity

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