title: Light-triggered eradication of Acinetobacter baumannii by means of NO delivery from a porous material with an entrapped metal nitrosyl.
abstract: 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.
authors.affiliation: Department of Chemistry and Biochemistry, University of California-Santa Cruz , Santa Cruz, California 95064, USA.
authors.forename: Brandon J
authors.initials: BJ
authors.lastname: Heilman
authors.forename: Jessica
authors.initials: J
authors.lastname: St John
authors.forename: Scott R J
authors.initials: SR
authors.lastname: Oliver
authors.forename: Pradip K
authors.initials: PK
authors.lastname: Mascharak
mesh_terms: D040981:Acinetobacter baumannii / Q000502:physiology*; D008027:Light; D008670:Metals / Q000008:administration & dosage*; D009569:Nitric Oxide / Q000008:administration & dosage*; D009603:Nitroso Compounds / Q000737:chemistry*
chemical_list: D008670:Metals; D009603:Nitroso Compounds; D009569:Nitric Oxide