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Pathogenic fungi are an increasing health threat due to the rise in drug resistance. The limited number of antifungals currently available and growing incidence of multi-drug-resistant fungi has caused rising healthcare costs and a decreased quality of life for patients with fungal infections. Nitric oxide (NO) has previously been shown to act as an antimicrobial agent, albeit with a limited understanding of the effects of the NO-release kinetics against pathogenic fungi. Herein, the antifungal effects of four nitric oxide-releasing small molecules were studied against the pathogenic fungi Candida albicans, Candida auris, Cryptococcus neoformans, and Aspergillus fumigatus, to demonstrate the broad-spectrum antifungal activity of NO. A bolus dose of NO was found to eradicate fungi after 24 h, where nitric oxide donors with shorter half-lives achieved antifungal activity at lower concentrations and thus had wider selectivity indexes. Each NO donor was found to cause a severe surface destruction of fungi, and all NO donors exhibited compatibility with currently prescribed antifungals against several different fungi species. [ABSTRACT FROM AUTHOR]

A summer outreach program, which was implemented for the first time in the summer of 2004, that provided middle school girls with an opportunity to conduct college-level analytical chemistry experiments under the guidance of female graduate students is explained. The program proved beneficial to participants at each level.

An amperometric fluorinated xerogei-derived nitric oxide (NO) microelectrode is described. A range of fluorine-modified xerogel polymers were synthesized via the cohydrolysis and condensation of alkylalkoxy--and fluoro-alkoxysilanes. Such polymers were evaluated as NO sensor membranes to identify the optimum composition for maximizing NO permeability while providing sufficient selectivity for NO in the presence of common interfering species. By taking advantage of both the versatility of sol--gel chemistry and the 'poly(tetrafluoroethylene)-like' high NO permselective properties of the xerogels, the performance of the fluorinated xerogel-derived sensors was excellent, surpassing all miniaturized NO sensors reported to date. In contrast to previous electrochemical NO sensor designs, xerogel-based NO microsensors were fabricated using a simple, reliable dip-coating procedure. An optimal permselective membrane was achieved by synthesizing xerogels of methyltrimethoxysilane (MTMOS) and 20% (heptadecafluoro-1,1,2,2-tetrahydrodecyl)tri-methoxysilane (17FrMS, balance MTMOS) under acid-catalyzed conditions. The resulting NO microelectrode had a conical tip of ~20/[micro]m in diameter and ~55 [micro]m in length and exhibited sensitivities of 7.91 pA x [nM.sup.-1] from 0.2 to 3.0 nM ([R.sup.2] = 0.9947) and 7.60 nA x [micro][M.sup.-1] from 0.5 to 4.0 [micro]M ([R.sup.2] = 0.9999), detection limit of 83 pM (S/N= 3), response time ([t.sub.95%]) of

Xerogel sensing films were synthesized via sol--gel chemistry were used to fabricate optical nitroxyl (HNO) sensors. Selective detection of HNO in solution was achieved by monitoring the rates of manganese(III) meso-tetrakis-(4-sulfonatophenyl) porphyrinate ([Mn.sup.III]TPPS) reductive nitrosylation in the anaerobic interior of aminoalkoxysilane-derived xerogel films. Nitroxyl permeability in sensor films deposited in round-bottom 96-well plates was enhanced via incorporation of trimethoxysilyl-terminated poly(amidoamine-organosilicon) dendrimers in the xerogel network. The selectivity of [Mn.sup.III]TPPS for HNO, the overall sensitivity, and the working dynamic range of the resulting sensors were characterized. The HNO-sensing microtiter plates were used to quantify pH-dependent HNO generation by the recently described HNO-donor sodium 1-(isopropylamino)diazene-1-ium-1,2-diolate (IPA/ NO), and compare HNO production efficiency between IPA/NO and Angeli's salt, a traditional HNO-donor.

A xerogel-based optical pH sensor capable of releasing low levels of nitric oxide (NO) and measuring changes in solution pH is reported. Through simple dip-coating procedures, aminoalkoxysilane-based xerogel films modified with N-diazeniumdiolate NO donor precursors and the fluorescent pH indicator seminaphthorhodamine-1 carboxylate (SNARF-1) were sequentially deposited onto optical fibers. The resulting sensors were characterized by fast and linear response to pH throughout the physiological range (pH 7.0-7.8). Real-time chemiluminescence measurements confirmed that the presence of the overlying SNARF-1-containing TMOS layer did not have an inhibitory effect on N-diazeniumdiolate formation or NO release, and the NO-releasing coatings were capable of maintaining NO fluxes >0.4 pmol/[cm.sub.2] s up to 16 h. In vitro blood compatibility studies using porcine platelets confirmed the expected thromboresistivity of the NO-releasing xerogel coatings.

The preparation and characterization of nitric oxide (NO) releasing dendrimer conjugates from primary and secondary amine functionalized dendrimers are reported. It is observed that the total NO released from secondary amine conjugates is significantly greater than from the primary amine parent dendrimers due to the enhanced stability of secondary amine diazeniumdiolates.

The initial phase of fibrin formation, thrombin-catalyzed fibrinopeptide cleavage, from adsorbed fibrinogen is examined using surface plasmon resonance and liquid chromatography-mass spectrometry. Fibrinogen adsorbed on negatively charged surfaces (carboxyl-terminated self-assembled monolayers) released a smaller amount of fibrinopeptides, at a reduced rate relative to those of hydrophobic, hydrophilic, and positively charged surfaces (methyl-, hydroxyl-, and amine-terminated self-assembled monolayers, respectively).

An amperometric sol-gel derived nitric oxide microsensor is described. Several silicon-based xerogel membranes are evaluated to identify the optimum composition for maximizing NO permeability while providing sufficient selectivity for NO in the presence of common interfering species. Xerogel permeability and selectivity are further manipulated as a function of reaction/processing conditions. In addition, the effects of incorporating Nation into the xerogel matrix on sensor performance and the stability of the ensuing xerogel/Nafion hybrid film are evaluated. The optimal permselective membrane is achieved by catalyzing polycondensation of the xerogel composed of methyltrimethoxysilane and (aminoethylaminomethyl)-phenethyltrimethoxysilane and Nation with NO gas. The resulting NO microsensor exhibits a sensitivity of 0.17 [+ or -] 0.02 pA/nM (from 25 to 800 nM, r = 0.9991), detection limit of 25 nM (S/N = 3), response time of 9 s ([t.sub.95%], a NO concentration change from 400 to 500 nM), selectivnap ity (log [K.sup.amp.sub.NOj]) of

A potentiometric sol-gel derived (xerogel) pH sensor based on covalently attached amine groups is described. The sensor consists of a Ag/AgCl electrode coated with a hybrid aminosilane/alkylsilane xerogel film. Various combinations of aminosilanes and alkylsilanes are evaluated for their potentiometric response to pH. The optimal sensor design is composed of (aminoethylaminomethyl)phenethyltrimethoxysilane and methyltrimethoxysilane. This sensor exhibits near-Nerstian response (-55 mV x [decade.sup.-1]), responds rapidly ([less than or equal to] 3 s) to changes in pH, and has [H.sup.+] selectivity coefficients (log [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII.]) of -13 and -11 for interfering j cations [Na.sup.+] and [K.sup.+], respectively. In vitro platelet adhesion tests indicate that the xerogel coatings are more blood compatible than conventional poly(vinyl chloride) and poly(urethane) ion-selective electrode coatings.

A hybrid sol--gel/polyurethane glucose biosensor that releases nitric oxide is developed and characterized. The biosensor consists of a platinum electrode coated with four polymeric membranes including the following: (1) sol--gel with immobilized glucose oxidase (GOx); (2) polyurethane to protect the enzyme; (3) NO donor-modified sol--gel particle-doped polyurethane; and (4) polyurethane. This configuration was developed due to the drastic reduction in sensitivity observed for NO donor-modified sol--gel film-based glucose sensors. For the hybrid sol--gel/polyurethane biosensor, sol--gel particles are first modified with the NO donor and then incorporated into a polyurethane layer that is coated onto the preimmobilized GOx electrode. In this manner, the GOx layer is not exposed to the harsh conditions necessary to impart NO release ability to the biosensor, and only a minimal decrease in sensitivity due to the NO release is observed. The glucose response of the NO-releasing glucose biosensor and its NO generation profiles are reported. In addition, the stability of the sol--gel particles in the supporting polyurethane membrane is discussed.

The in vitro analytical performance of fluorescence-based oxygen sensing polymeric films prepared with silicone rubbers that spontaneously release nitric oxide (NO) is examined. The use of NO-release polymers for fabricating functional optical sensors is proposed as a potential solution to lingering biocompatibility and concomitant performance problems encountered with prototype intravascular optical oxygen sensors. Plasticized silicone rubber films formulated with two distinct types of diazeniumdiolate NO donors release NO for more than 24 h. The optical oxygen sensing films prepared by doping these NO release polymeric materials with oxygen indicators (pyrene/ perylene donor/acceptor pair) display different analytical responses, as compared to controls without NO release capability. Nonlinear Stern--Volmer behavior is observed for single-layer NO release oxygen sensors owing to heterogeneous environments for the pyrene/perylene pair and a concomitant quenching of the fluorescence by excess amine sites in such films. In contrast, a dual-layer configuration using an underlying NO-release silicone rubber layer covered with a second polymeric layer containing the fluorescent indicators is shown to yield identical sensitivity and linearity toward oxygen as conventional non-NO-releasing oxygen sensing films, while still providing surface NO fluxes necessary to yield more thromboresistive devices.