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Novel materials for the phototherapeutic release of the bioregulator nitric oxide (nitrogen monoxide) are described. Also reported is a method for scanning these materials with a focused NIR beam to induce photouncaging while minimizing damage from local heating. The new materials consist of poly(dimethylsiloxane) composites with near-infrared-to-visible upconverting nanoparticles (UCNPs) that are cast into a biocompatible polymer disk (PD). These PDs are then impregnated with the photochemical nitric oxide precursor Roussin's black salt (RBS) to give UCNP_RBS_PD devices that generate NO when irradiated with 980 nm light. When the UCNP_RBS_PD composites were irradiated with NIR light through filters composed of porcine tissue, physiologically relevant NO concentrations were released, thus demonstrating the potential of such devices for minimally invasive phototherapeutic applications.

Described is the photoluminescence (PL) of water-soluble CdSe/ZnS core/shell quantum dots (QDs) as perturbed by salts of the chromium(III) complexes trans-Cr(cyclam)Cl2+ (1), trans-Cr(cyclam)(ONO)2+ (2), and trans-Cr(cyclam)(CN)2+ (3) (cyclam = 1,4,8,11-tetraazacyclo-tetradecane). The purpose is to probe the characteristics of such QDs as antennae for photosensitized release of bioactive agents (in the present case, the bioregulatory molecule NO) from transition metal centers. Addition of 1 or 2 to a QD solution results in concentration-dependent quenching of the band edge emission, but 3 has a minimal effect. Added KCl strongly attenuates the quenching by 1, and this suggests that the Cr(III) cations and the QDs form electrostatic assemblies via ion pairing on the negatively charged QD surfaces. Quenching by 2, a known photochemical NO precursor, was accompanied by photosensitized NO release. All three, however, do quench the broad red emission ( approximately 650-850 nm) attributed to radiative decay of surface trapped carriers. The effect of various concentrations of 1 on time-resolved PL and absorbance were explored using ultrafast spectroscopic methods. These observations are interpreted in terms of the Förster resonance energy-transfer mechanism for quenching of the band edge PL by multiple units of 1 or 2 at the QD surface, whereas quenching of the low-energy trap emission occurs via a charge-transfer pathway.

The synthesis, characterization, photochemistry, and two-photon photophysical properties of a new dye-derivatized iron sulfur nitrosyl cluster Fe2(mu-RS)2(NO)4 (AFX-RSE, RS = 2-thioethyl ester of N-phenyl-N-(3-(2-ethoxy)phenyl)-7-(benzothiazol-2-yl)-9,9-diethyl-fluoren-2-yl-amine) were investigated. Under continuous photolysis, AFX-RSE decomposes with modest quantum yields (Phi(diss) = (4.9 +/- 0.9) x 10(-3) at lambda(irr) = 436 nm) as measured from the loss of the nitrosyl bands in the IR absorbance spectrum. Nitric oxide (NO) was qualitatively demonstrated to be photochemically produced via single-photon excitation through the use of an NO-specific electrode. Steady-state luminescence measurements have shown that AFX-RSE fluorescence is about 88% quenched relative to the model compound AF-tosyl. This is attributed to a relatively efficient energy transfer from the excited states of the antenna chromophores to the dinuclear metal center, with the subsequent production of NO. In addition, the two-photon absorption (TPA) cross sections (delta) were measured for the AF-chromophores via the two-photon excitation (TPE) photoluminescence technique using a femtosecond excitation source. The TPA cross section of AFX-RSE was found with this technique to be delta = 246 +/- 8 GM (1 GM = 10(-50) cm4 s photon(-1) molecule(-1)).

The experiments described here demonstrate the use of two-photon excitation (TPE) to sensitize nitric oxide (NO) release from a dye-derivatized iron/sulfur/nitrosyl cluster Fe2(mu-RS)2(NO)4 (Fluor-RSE, RS = 2-thioethyl ester of fluorescein) with near-infrared (NIR) light in the form of femtosecond pulses from a Ti:sapphire laser. TPE at 800 nm leads both to weak fluorescence from the organic chromophore at lambda(max) = 532 nm and to NO labilization from the cluster. Since the emission from the reference compound Fluor-Et (the ethyl ester of fluorescein) under identical conditions (50/50 CH3CN/phosphate buffer (1 mM) at pH 7.4) is considerably more intense, the weaker emission from Fluor-RSE and the NO generation indicate that the fluorescein excited states initially formed by TPE are largely quenched by energy transfer to the cluster core. The two-photon absorption (TPA) cross section of Fluor-RSE at 800 nm was determined to be delta = 63 +/- 7 GM via the TPA photoluminescence technique. This can be compared to the TPA cross section of 36 GM reported for fluorescein dye in pH 11 aqueous solution and of 32 +/- 3 GM for Fluor-Et measured under conditions comparable to those used for Fluor-RSE. Pulse intensity dependence studies showed that the quantity of NO released from the latter as the result of NIR photoexcitation follows a quadratic relationship to excitation intensity, consistent with the expectation for a TPE process. These studies demonstrate the potential utility of a two-photon antenna for sensitization of the photochemical release of an active agent (in this case, NO) from a photoactive pro-drug.

The synthesis, characterization, photochemistry, and two-photon photophysical properties of a new dye-derivatized iron sulfur nitrosyl cluster Fe2(μ-RS)2(NO)4 (AFX-RSI=, RS = 2-thioethyl ester of N-phenyl-N-(3-(2-ethoxy)phenyl)-7-(benzothiazol-2-yl)-9,9-diethyl-fluoren-2-yl-amine) were investigated. Under continuous photolysis, AFX-RSE decomposes with modest quantum yields (Ωdiss = (4.9 ± 0.9) × 10-3 at λ-irr = 436 nm) as measured from the loss of the nitrosyl bands in the IR absorbance spectrum. Nitric oxide (NO) was qualitatively demonstrated to be photochemically produced via single-photon excitation through the use of an NO-specific electrode. Steady-state luminescence measurements have shown that AFX-RSE fluorescence is about 88% quenched relative to the model compound AF-tosyl. This is attributed to a relatively efficient energy transfer from the excited states of the antenna chromophores to the dinuclear metal center, with the subsequent production of NO. In addition, the two-photon absorption (TPA) cross sections (b) were measured for the AF-chromophores via the two-photon excitation (TPE) photoluminescence technique using a femtosecond excitation source. The TPA cross section of AFX-R$E was found with this technique to be δ = 246 ± 8 GM (1 GM = 10-50 cm4 s photon-1 molecule-1). [ABSTRACT FROM AUTHOR]