Time-resolved radioluminescence of the Cu(I) cluster Cu4I62-. Different responses to photo, X-ray, ß-ray and α-particle excitation.

Time-resolved radioluminescence (TRRL) properties of the Cu(I) cluster Cu4I62- upon pulsed X-ray, ß-ray or α-particle excitation are described. The longer (>2 µs) TRRL component displays exponential decay comparable to pulsed UV excitation; however, temporal behaviour at shorter times indicates that high local excited state density provides an alternative decay channel.

Correction: 'Redox-mediated carbon monoxide release from a manganese carbonyl-implications for physiological CO delivery by CO releasing moieties' (2021), by Barrett et al.

[This corrects the article DOI: 10.1098/rsos.211022.][This corrects the article DOI: 10.1098/rsos.211022.].

Redox-mediated carbon monoxide release from a manganese carbonyl-implications for physiological CO delivery by CO releasing moieties.

The dynamics of hydrogen peroxide reactions with metal carbonyls have received little attention. Given reports that therapeutic levels of carbon monoxide are released in hypoxic tumour cells upon manganese carbonyls reactions with endogenous H2O2, it is critical to assess the underlying CO release mechanism(s). In this context, a quantitative mechanistic investigation of the H2O2 oxidation of the water-soluble model complex fac-[Mn(CO)3(Br)(bpCO2)]2-, (A, bpCO2 2- = 2,2'-bipyridine-4,4'-dicarboxylate dianion) was undertaken under physiologically relevant conditions. Characterizing such pathways is essential to evaluating the viability of redox-mediated CO release as an anti-cancer strategy. The present experimental studies demonstrate that approximately 2.5 equivalents of CO are released upon H2O2 oxidation of A via pH-dependent kinetics that are first-order both in [A] and in [H2O2]. Density functional calculations were used to evaluate the key intermediates in the proposed reaction mechanisms. These pathways are discussed in terms of their relevance to physiological CO delivery by carbon monoxide releasing moieties.

Nitric Oxide Uncaging from a Hydrophobic Chromium(III) PhotoNORM: Visible and Near-Infrared Photochemistry in Biocompatible Polymer Disks.

Devices consisting of polymer disks (PDs) of optically clear or translucent, medical-grade silicone loaded with a new hydrophobic, oxygen-stable, photoactivated nitric oxide-releasing moiety (photoNORM) are described. The photoNORM is the new O-nitrito chromium(III) complex trans-[Cr(PetA)(ONO)2](BF4) (PetA = 5,14-dimethyl-7,12-diphenyl-1,4,8,11-tetraaza-cyclotetradecane), of which the synthesis, X-ray crystal structure, and solution-phase photochemistry are described. Several different commercially available silicone polymers were tested with this photoNORM, and nitric oxide photouncaging with 451 nm light from these systems is compared. In addition, PDs were loaded with the photoNORM and neodymium-sensitized upconverting nanoparticles (Nd-UCNPs). The Nd-UCNPs absorb NIR light at ∼800 nm and activate NO release from the trans-[Cr(PetA)(ONO)2]+ cation. The use of such ensembles as implants provides a potential strategy for the in vivo uncaging of NO at physiological targets triggered by tissue-transmitting NIR excitation. Also reported are the X-ray crystal structures of cis- and trans-{Cr(PetA)Cl2]Cl.

Near-IR mediated intracellular uncaging of NO from cell targeted hollow gold nanoparticles.

We demonstrate modulation of nitric oxide release in solution and in human prostate cancer cells from a thiol functionalized cupferron (TCF) absorbed on hollow gold nanoshells (HGNs) using near-infrared (NIR) light. NO release from the TCF-HGN conjugates occurs through localized surface heating due to NIR excitation of the surface plasmon. Specific HGN targeting is achieved through cell surface directed peptides, and excitation with tissue penetrating NIR light provides unprecedented spatio-temporal control of NO delivery to biological targets.

A photoCORM nanocarrier for CO release using NIR light.

A water-soluble nanocarrier for a photo-activated CO releasing moiety (photoCORM) that can be triggered with NIR excitation is described. This has an upconversion nanoparticle core encapsulated by an amphiphilic polymer imparting both water solubility and a hydrophobic interior containing the photoCORM trans-Mn(bpy)(PPh3)2(CO)2. Such an ensemble offers a unique strategy for CO delivery to biological targets.

Nitric oxide releasing materials triggered by near-infrared excitation through tissue filters.

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.

Multi-photon excitation in uncaging the small molecule bioregulator nitric oxide.

Multi-photon excitation allows one to use tissue transmitting near-infrared (NIR) light to access excited states with energies corresponding to single-photon excitation in the visible or ultraviolet wavelength ranges. Here, we present an overview of the application of both simultaneous and sequential multi-photon excitation in studies directed towards the photochemical delivery ('uncaging') of bioactive small molecules such as nitric oxide (NO) to physiological targets. Particular focus will be directed towards the use of dyes with high two-photon absorption cross sections and lanthanide ion-doped upconverting nanoparticles as sensitizers to facilitate the uncaging of NO using NIR excitation.

The Extent of Cooperativity of Protein Motions Observed with Elastic Network Models Is Similar for Atomic and Coarser-Grained Models.

Coarse-grained elastic network models have been successful in determining functionally relevant collective motions. The level of coarse-graining, however, has usually focused on the level of one point per residue. In this work, we compare the applicability of elastic network models over a broader range of representational scales. We apply normal mode analysis for multiple scales on a high-resolution protein data set using various cutoff radii to define the residues considered to be interacting, or the extent of cooperativity of their motions. These scales include the residue-, atomic-, proton-, and explicit solvent-levels. Interestingly, atomic, proton, and explicit solvent level calculations all provide similar results at the same cutoff value, with the computed mean-square fluctuations showing only a slightly higher correlation (0.61) with the experimental temperature factors from crystallography than the results of the residue-level coarse-graining. The qualitative behavior of each level of coarse graining is similar at different cutoff values. The correlations between these fluctuations and the number of internal contacts improve with increased cutoff values. Our results demonstrate that atomic level elastic network models provide an improved representation for the collective motions of proteins compared to the coarse-grained models.