7 research outputs found
Photoinitiated Nitric Oxide-Releasing Tertiary S -Nitrosothiol-Modified Xerogels
The synthesis of a tertiary thiol-bearing silane precursor (i.e., N-acetyl penicillamine propyltrimethoxysilane or NAPTMS) to enable enhanced NO storage stability at physiological temperature is described. The novel silane was co-condensed with alkoxy- and alkylalkoxysilanes under varied synthetic parameters (e.g., water to silane ratio, catalyst and solvent concentrations, and reaction time) to evaluate systematically the formation of stable xerogel films. The resulting xerogels were subsequently nitrosated to yield tertiary RSNO-modified coatings. Total NO storage ranged from 0.87–1.78 µmol cm−2 depending on the NAPTMS concentration and xerogel coating thickness. Steric hindrance near the nitroso functionality necessitated the use of photolysis to liberate NO. The average NO flux for irradiated xerogels in physiological buffer at 37 °C was ~23 pmol cm−2 s−1 (20% NAPTMS balance TEOS xerogel film cast using 30 µL). The biomedical utility of the photo-initiated NO-releasing films was illustrated by their ability to both reduce Pseudomonas aeruginosa adhesion by ~90% relative to control interfaces and eradicate the adhered bacteria
Fluorinated benzalkylsilane molecular rectifiers
We report on the synthesis and electrical properties of nine new alkylated silane self-assembled monolayers (SAMs) – (EtO)3Si(CH2)nN = CHPhX where n = 3 or 11 and X = 4-CF[subscript 3], 3,5-CF[subscript 3], 3-F-4-CF[subscript 3], 4-F, or 2,3,4,5,6-F, and explore their rectification behavior in relation to their molecular structure. The electrical properties of the films were examined in a metal/insulator/metal configuration, with a highly-doped silicon bottom contact and a eutectic gallium-indium liquid metal (EGaIn) top contact. The junctions exhibit high yields (>90%), a remarkable resistance to bias stress, and current rectification ratios (R) between 20 and 200 depending on the structure, degree of order, and internal dipole of each molecule. We found that the rectification ratio correlates positively with the strength of the molecular dipole moment and it is reduced with increasing molecular length.National Science Foundation (U.S.) (Award ECCS 1254757)Wake Forest University (Pilot Research Grant
Examination of bacterial resistance to exogenous nitric oxide
While much research has been directed to harnessing the antimicrobial properties of exogenous NO, the possibility of bacteria developing resistance to such therapy has not been thoroughly studied. Herein, we evaluate potential NO resistance using spontaneous and serial passage mutagenesis assays. Specifically, Staphylococcus aureus, Methicillin-resistant S. aureus (MRSA), Staphylococcus epidermidis, Escherichia coli, and Pseudomonas aeruginosa were systematically exposed to NO-releasing 75mol% MPTMS-TEOS nitrosothiol particles at or below minimum inhibitory concentration (MIC) levels. In the spontaneous mutagenesis assay, bacteria that survived exposure to lethal concentrations of NO showed no increase in MIC. Similarly, no increase in MIC was observed in the serial passage mutagenesis assay after exposure of these species to sub-inhibitory concentrations of NO through 20 d
Photoinitiated Nitric Oxide-Releasing Tertiary <i>S</i>-Nitrosothiol-Modified Xerogels
The synthesis of a tertiary thiol-bearing silane precursor
(i.e., <i>N</i>-acetyl penicillamine propyltrimethoxysilane
or NAPTMS)
to enable enhanced NO storage stability at physiological temperature
is described. The novel silane was co-condensed with alkoxy- or alkylalkoxysilanes
under varied synthetic parameters (e.g., water to silane ratio, catalyst
and solvent concentrations, and reaction time) to evaluate systematically
the formation of stable xerogel films. The resulting xerogels were
subsequently nitrosated to yield tertiary RSNO-modified coatings.
Total NO storage ranged from 0.87 to 1.78 μmol cm<sup>–2</sup> depending on the NAPTMS concentration and xerogel coating thickness.
Steric hindrance near the nitroso functionality necessitated the use
of photolysis to liberate NO. The average NO flux for irradiated xerogels
(20% NAPTMS balance TEOS xerogel film cast using 30 μL) in physiological
buffer at 37 °C was ∼23 pmol cm<sup>–2</sup> s<sup>–1</sup>. The biomedical utility of the photoinitiated NO-releasing
films was illustrated by their ability to both reduce <i>Pseudomonas
aeruginosa</i> adhesion by ∼90% relative to control interfaces
and eradicate the adhered bacteria
Role of Size and Shape on Biofilm Eradication for Nitric Oxide-Releasing Silica Nanoparticles
Nitric
oxide (NO), a reactive free radical, has proven effective
in eradicating bacterial biofilms with reduced risk of fostering antibacterial
resistance. Herein, we evaluated the efficacy of NO-releasing silica
nanoparticles against Gram-negative <i>Pseudomonas aeruginosa</i> and Gram-positive <i>Staphylococcus aureus</i> biofilms
as a function of particle size and shape. Three sizes of NO-releasing
silica nanoparticles (i.e., 14, 50, and 150 nm) with identical total
NO release (∼0.3 μmol/mg) were utilized to study antibiofilm
eradication as a function of size. To observe the role of particle
shape on biofilm killing, we varied the aspect ratio of the NO-releasing
silica particles from 1 to 8 while maintaining constant particle volume
(∼0.02 μm<sup>3</sup>) and NO-release totals (∼0.7
μmol/mg). Nitric oxide-releasing particles with decreased size
and increased aspect ratio were more effective against both <i>P. aeruginosa</i> and <i>S. aureus</i> biofilms, with
the Gram-negative species exhibiting the greatest susceptibility to
NO. To further understand the influence of these nanoparticle properties
on NO-mediated antibacterial activity, we visualized intracellular
NO concentrations and cell death with confocal microscopy. Smaller
NO-releasing particles (14 nm) exhibited better NO delivery and enhanced
bacteria killing compared to the larger (50 and 150 nm) particles.
Likewise, the rod-like NO-releasing particles proved more effective
than spherical particles in delivering NO and inducing greater antibacterial
action throughout the biofilm
Examination of bacterial resistance to exogenous nitric oxide
While much research has been directed to harnessing the antimicrobial properties of exogenous NO, the possibility of bacteria developing resistance to such therapy has not been thoroughly studied. Herein, we evaluate potential NO resistance using spontaneous and serial passage mutagenesis assays. Specifically, Staphylococcus aureus, Methicillin-resistant S. aureus (MRSA), Staphylococcus epidermidis, Escherichia coli, and Pseudomonas aeruginosa were systematically exposed to NO-releasing 75mol% MPTMS-TEOS nitrosothiol particles at or below minimum inhibitory concentration (MIC) levels. In the spontaneous mutagenesis assay, bacteria that survived exposure to lethal concentrations of NO showed no increase in MIC. Similarly, no increase in MIC was observed in the serial passage mutagenesis assay after exposure of these species to sub-inhibitory concentrations of NO through 20 d