Selective damage to hyphal form through light-induced delivery of nitric oxide to Candida albicans colonies.

Candida albicans, an opportunistic fungal pathogen, causes severe to life-threatening infections in immunocompromised hosts (e.g. HIV patients, burn victims). Conversion of the commensal yeast form to the invasive hyphal form, triggered by environmental cues, initiates such episodes. Although the antifungal activity of nitric oxide (NO) has been established, very few convenient NO-donating systems for treating C. albicans infection have been reported. In this work, a biocompatible NO-donating material that delivers NO upon illumination with visible light has been employed to eradicate C. albicans in a dose-dependent way. Careful studies on the yeast and hyphal forms with this NO donor have revealed that the hyphal form is more susceptible to NO exposure than the yeast variety. Results of this work suggest that materials of this type could find use in thwarting invasion of the hyphal form of the fungus in cases of invasive C. albicans infection.

Light-triggered eradication of Acinetobacter baumannii by means of NO delivery from a porous material with an entrapped metal nitrosyl.

A photoactive manganese nitrosyl, namely [Mn(PaPy(3))(NO)](ClO(4)) ({Mn-NO}), has been loaded into the columnar pores of an MCM-41 host. Strong interaction between the polar nitrosyl and the -OH groups on the host wall leads to excellent entrapment of the NO donor within the porous host. With the aluminosilicate-based host (Al-MCM-41), the loading is further enhanced due to electrostatic interaction of the cationic species with the aluminum sites. The extent of loading has been determined via analytical techniques including N(2) adsorption/desorption isometry. Powder X-ray diffraction studies on the loaded materials afford patterns typical of an ordered mesoporous silicate consisting of a hexagonal array of unidimensional channels (with slight loss of crystallinity). Elemental mapping of the loaded particles confirms the incorporation of {Mn-NO} into the porous MCM-41 structure and attests to the homogeneity of the guest molecule distribution throughout individual particles. When suspensions of the loaded materials in saline solution are exposed to low-power (10-100 mW) visible light, rapid release of NO is observed. With continuous exposure, a steady release of 50-80 µM of NO is attained with 5 mg of material/mL buffer within 5 min, and the NO flux is maintained for a period of ~60 min. Rapid bursts of 5-10 µM NO are noted with short light pulses. Loss of either the nitrosyl or its photoproduct(s) from these materials in biological media is minimal over long periods of time. The NO release profiles suggest potential use of these powdery biocompatible materials as NO donors where the delivery of NO (a strong antibiotic) could be controlled via the exposure of light. Such prediction has been confirmed with the successful eradication of both drug-susceptible and drug-resistant Acinetobacter baumannii in a soft-tissue infection model through light-triggered NO delivery.

Synthesis, characterization, and light-controlled antibiotic application of a composite material derived from polyurethane and silica xerogel with embedded photoactive manganese nitrosyl.

The synthesis of a light-sensitive polyurethane-based composite material (PUX-NO) is described. In its polyurethane medium, PUX-NO contains entrapped silica xerogel particles in which a photoactive manganese nitrosyl has been incorporated. Green flexible films of PUX-NO readily release nitric oxide (NO) only when exposed to low power (mW) visible light. Incorporation of the nitrosyl in the xerogel not only retains the nitrosyl (NO donor) within the composite material but also provides the right extent of hydration. Pre-swelled films of PUX-NO have water content close to 30 Wt % and such films can be stored for months under slightly moist condition without loss in NO-delivering capacity. The NO-releasing parameters of the film have been determined. The NO-releasing capacity of PUX-NO films can be conveniently altered by changing the amount of the nitrosyl as well as the thickness of the films. Patches of PUX-NO film have been successfully employed to reduce drastically bacterial loads of both gram-positive and gram-negative bacteria including methicillin-resistant Staphylococcus aureus and Acinetobacter baumannii under the total control of light. Effective control of infections by these bacterial pathogens via delivery of proper doses of NO only to the sites of infection appears feasible with PUX-NO films.

Dye-tethered ruthenium nitrosyls containing planar dicarboxamide tetradentate N4 ligands: effects of in-plane ligand twist on NO photolability.

To examine the steric effects of the in-plane ligands in dye-sensitized {RuNO}(6) nitrosyls on their NO photolability, two new ligands, namely, 1,2-Bis(pyridine-2-carboxamido)-4,5-dimethoxybenzene (H(2)(OMe)(2)bpb) and 1,2-Bis(Isoquinoline-1-carboxamido)-4,5-dimethoxybenzene (H(2)(OMe)(2)IQ1, H's are dissociable carboxamide protons) have been designed and synthesized. The syntheses and spectroscopic properties of {RuNO}(6) nitrosyls derived from these two ligands, namely, [((OMe)(2)bpb)Ru(NO)(Cl)] (4-Cl), [((OMe)(2)IQ1)Ru(NO)(Cl)] (5-Cl), [((OMe)(2)bpb)Ru(NO)(Resf)] (4-Resf), and [((OMe)(2)IQ1)Ru(NO)(Resf)] (5-Resf), are reported. The structures of 5-Cl, 4-Resf, and 5-Resf have been determined by X-ray crystallography. Removal of the in-plane ligand twist in the quinoline-based R(2)bQb(2-) ligand frame (because of steric interactions between the extended quinoline ring systems) in both R(2)bpb(2-) and R(2)IQ1(2-) (pyridine and 1-isoquinoline rings, respectively, instead of quinoline rings in the equatorial plane) results in enhanced solution stability, as well as higher quantum yield values for NO photorelease upon exposure to 500 nm light. Both dye-tethered {RuNO}(6) nitrosyls 4-Resf and 5-Resf exhibit greater sensitivity to visible light compared to the chloro-bound species 4-Cl and 5-Cl. In addition, the dye-tethered nitrosyls are fluorescent and hence can be used as trackable NO donors in cellular studies.