Construction of Functionally Compartmental Inorganic Photocatalyst-Enzyme System via Imitating Chloroplast for Efficient Photoreduction of CO2 to Formic Acid.

Inorganic photocatalyst-enzyme systems are a prominent platform for the photoreduction of CO2 to value-added chemicals and fuels. However, poor electron transfer kinetics and enzyme deactivation by reactive oxygen species in the photoexcitation process severely limit catalytic efficiency. In chloroplast, enzymatic CO2 reduction and photoexcitation are compartmentalized by the thylakoid membrane, which protects enzymes from photodamage, while the tightly integrated photosystem facilitates electron transfer, promoting photocatalysis. By mimicking this strategy, we constructed a novel functionally compartmental inorganic photocatalyst-enzyme system for CO2 reduction to formate. To accomplish efficient electron transfer, we first synthesized an integrated artificial photosystem by conjugation of the cocatalyst (a Rh complex) onto thiophene-modified C3N4 (TPE-C3N4), demonstrating an NADH regeneration rate of 9.33 µM·min-1, 2.33 times higher than that of a homogeneous counterpart. The enhanced NADH regeneration activity was caused by the tightly conjugated structure of the artificial photosystem, enabling rapid electron transfer from TPE-C3N4 to the Rh complex. To protect formate dehydrogenase (FDH) from photoinduced deactivation, FDH was encapsulated into MAF-7, a metal-organic framework (MOF) material, to compartmentalize FDH from the toxic photoexcitation process, similar to the function of the thylakoid membrane. Moreover, the triazole linkers of MAF-7 possess both hydrophilicity and pH-buffering capacity providing a stable microenvironment for FDH, which could enhance enzyme stability in photosynthesis. The synergy between the enhanced electron transfer of TPE-C3N4 for NADH cofactor regeneration and MOF-protection of the redox enzyme enables the construction of a functionally compartmental inorganic photocatalyst-enzyme association system, promoting CO2 photoconversion to formic acid with a yield of 16.75 mM after 9 h of illumination, 3.24 times greater than that of the homogeneous reaction counterpart.

Mechanistic Investigation into DNA Modification by a RuII ,RhIII Bimetallic Complex.

Despite significant progress in the treatment of cancer, there remains an urgent need for more effective therapies that also have less impact on patient wellbeing. Photodynamic therapy employs targeted light activation of a photosensitizer in selected tissues, thereby reducing off-target toxicity. Our group previously reported a RuII ,RhIII bimetallic architecture that displays multifunctional covalent photomodification of DNA in the therapeutic window in an oxygen-independent manner, features that are essential for treating deep and hypoxic tumors. Herein, we explore the mechanism by which a new analogue, [(phen)2 Ru(dpp)Rh(phen)Cl2 ]3+ , or RuII -RhIII , interacts with DNA. We established that RuII -RhIII exhibits "light switch" behavior in the presence of DNA, undergoing strong electrostatic interactions that might involve groove binding. Furthermore, these noncovalent interactions play a major role in the covalent photobinding and photocleavage of DNA, which occur according to an oxygen-independent mechanism. Polymerase chain reaction (PCR) revealed that covalent modification of DNA by RuII -RhIII , especially photobinding, is critical to inhibiting amplification, thus suggesting that the complex could exert its toxic activity by interfering with DNA replication in cells. This new structural motif, with phenanthroline at all three terminal ligand positions, has a number of properties that are promising for the continued refinement of photodynamic-therapy strategies.

The influence of pH on the in vitro permeation of rhodium through human skin.

Workers in precious metals refineries are at risk of exposure to salt compounds of the platinum group metals through inhalation, as well as through the skin. Rhodium salt permeation through the skin has previously been proven using rhodium trichloride (RhCl3) dissolved in synthetic sweat at a pH of 6.5. However, the skin surface pH of refinery workers may be lower than 6.5. The aim of this study was to investigate the influence of pH 6.5 and 4.5 on the in vitro permeation of rhodium through intact Caucasian skin using Franz diffusion cells. A concentration of 0.3 mg mL-1 rhodium was used and analyses were performed using inductively coupled plasma mass spectrometry and inductively coupled plasma optical emission spectrometry. Results indicated a cumulative increase in permeation over 24 h. Rhodium permeation after 12 h was significantly greater at pH 4.5 (1.56 ± 0.24 ng cm-2) than at 6.5 (0.85 ± 0.13 ng cm-2; p = 0.02). At both pH levels, there was a highly significant difference ( p < 0.01) between the mass of rhodium remaining in the skin (1428.68 ± 224.67 ng cm-2 at pH 4.5 and 1029.90 ± 115.96 ng cm-2 at pH 6.5) and the mass that diffused through (0.88 ± 0.17 ng cm-2 at pH 4.5 and 0.62 ± 0.10 ng cm-2 at pH 6.5). From these findings, it is evident that an acidic working environment or low skin surface pH may enhance permeation of rhodium salts, contributing to sensitization and adverse health effects.

Computational Design of New Heterofullerene-Based Biomimetic α-Carbonic Anhydrase Analogues.

The biomimetic CO2 hydration activity of Ru/Rh-doped fullerenes was revealed by using density functional theory calculations. The mechanism of CO2 hydration on the proposed heterofullerenes followed the mechanistic action of α-carbonic anhydrases, and consisted of the adsorption and deprotonation of H2 O, CO2 interaction with hydroxyl groups, CO2 bending, and proton transfer to give the HCO-3 product. Free-energy landscapes for the reaction showed the catalysts to be active for the reaction. H2 O adsorption over the catalysts was exergonic whereas CO2 adsorption over the catalyst-OH complex was observed to be an endergonic process. Intramolecular proton transfer resulting in the final product, HCO-3 , was found to be the rate-limiting step for the reaction on C56 N3 M (M=Ru/Rh), whereas H2 O dissociation was found to be the rate-limiting step for the reaction on C59 M (M=Ru/Rh). C56 N3 M catalysts were found to be superior to C59 M catalysts for biomimetic CO2 hydration, as indicated by the free-energy landscapes and energy requirements.

Enantioselective rhodium/ruthenium photoredox catalysis en route to chiral 1,2-aminoalcohols.

A rhodium-based chiral Lewis acid catalyst combined with [Ru(bpy)3](PF6)2 as a photoredox sensitizer allows for the visible-light-activated redox coupling of α-silylamines with 2-acyl imidazoles to afford, after desilylation, 1,2-amino-alcohols in yields of 69-88% and with high enantioselectivity (54-99% ee). The reaction is proposed to proceed via an electron exchange between the α-silylamine (electron donor) and the rhodium-chelated 2-acyl imidazole (electron acceptor), followed by a stereocontrolled radical-radical reaction. Substrate scope and control experiments reveal that the trimethylsilyl group plays a crucial role in this reductive umpolung of the carbonyl group.

Rhodium Porphyrin Bound to a Merrifield Resin as Heterogeneous Catalyst for the Cyclopropanation Reaction of Olefins.

Cyclopropanation reaction is an important tool for obtaining interesting compounds and can be catalyzed by metalloporphyrins with high syn/anti ratio. The catalyst cannot be recycled and is usually lost during chromatographic separation from the two isomeric products. In this paper a meso-tetraphenylporphyrin rhodium(III) chloride was bound to a Merrifield resin and used to catalyze the cyclopropanation reaction of nine olefins, giving good yields and selectivities of the final products and for the first time, a partial recycling of the catalyst. This new catalytic system will be tested in the future for the synthesis of natural products containing cyclopropyl ring.

Generation, Characterization, and Tunable Reactivity of Organometallic Fragments Bound to a Protein Ligand.

Organotransition metal complexes catalyze important synthetic transformations, and the development of these systems has rested on the detailed understanding of the structures and elementary reactions of discrete organometallic complexes bound to organic ligands. One strategy for the creation of new organometallic systems is to exploit the intricate and highly structured ligands found in natural metalloproteins. We report the preparation and characterization of discrete rhodium and iridium fragments bound site-specifically in a κ(2)-fashion to the protein carbonic anhydrase as a ligand. The reactions of apo human carbonic anhydrase with [Rh(nbd)2]BF4 or [M(CO)2(acac)] (M=Rh, Ir) form proteins containing Rh or Ir with organometallic ligands. A colorimetric assay was developed to quantify rapidly the metal occupancy at the native metal-binding site, and (15)N-(1)H NMR spectroscopy was used to establish the amino acids to which the metal is bound. IR spectroscopy and EXAFS revealed the presence and number of carbonyl ligands and the number total ligands, while UV-vis spectroscopy provided a signature to readily identify species that had been fully characterized. Exploiting these methods, we observed fundamental stoichiometric reactions of the artificial organometallic site of this protein, including reactions that simultaneously form and cleave metal-carbon bonds. The preparation and reactivity of these artificial organometallic proteins demonstrate the potential to study a new genre of organometallic complexes for which the rates and outcomes of organometallic reactions can be controlled by genetic manipulation of the protein scaffold.

The metallobiochemistry of ultratrace levels of platinum group elements in the rat.

The use of platinum, palladium and rhodium (Platinum Group Elements - PGEs) and the possibility of exposure to their ultratrace levels is increasing. In fact, the exponential development of metallic PGE-based nanoparticles (<100 nm in size) opens extraordinary perspectives in the areas of electrocatalysts and catalytic converters, magnetic nanopowders, polymer membranes, cancer therapy, coatings, plastics, nanofibres and textiles. Like other metal-based nanoparticles, exposure to PGEs nanoparticles may result in a release of ultratrace amounts of Pt, Pd, Rh ions in the body whose metabolic fate and toxicity still need to be evaluated. Furthermore, PGEs can act as allergic sensitizers by acting as haptens and inducing both type I and IV allergic reactions. In this work we studied the in vivo metabolic patterns of ultratrace levels of potent allergens and sensitizers PGE halogenated salts. (191)Pt, (103)Pd and (101m)Rh radioisotopes were prepared via cyclotron irradiation and used for radiolabelling Na2(191)PtCl4, Na2(103)PdCl4 and Na2(101m)RhCl6 salts. These anionic chlorocomplexes were intraperitoneally injected into rats (114 ng Pt kg(-1) bodyweight; 24 ng Pd kg(-1) b.w.; 16 ng Rh kg(-1) b.w.). At 16 h post-exposure, PGEs were poorly but significantly retained in all tissues analysed. Kidneys, spleen, adrenal gland, liver, pancreas and small intestine were the organs with the highest Pt, Pd, Rh concentrations. In the blood 30-35% of (103)Pd and (191)Pt and 10% of (101m)Rh were recovered in the plasma, mainly bound to albumin and to a less extent to transferrin. The hepatic and renal intracellular distribution showed the highest recovery of (191)Pt, (103)Pd and (101m)Rh in the nuclear fraction (liver) and in the cytosol (kidney). Chromatographic separation and ultrafiltration experiments on kidney and liver cytosols showed the strong ability of biochemical macromolecules to bind (191)Pt, (103)Pd and (101m)Rh, and being responsible for the retention of the three elements in the body. The link to macromolecules is the basis for the sensitizing capacity of PGEs.

A convergent rhodium-catalysed asymmetric synthesis of tetrahydroquinolines.

Rh-catalysed conjugate additions of 2-aminophenyl boronic acid derivatives were exploited in diastereoselective and asymmetric syntheses of tetrahydroquinolines. In both cases, combinatorial variation of the substitution of the tetrahydroquinoline ring system was possible.

The effects of rhodium on the renal function of female Wistar rats.

In recent years, the increased use of rhodium (Rh) as an active catalyst material in modern three-way automobile catalytic converters has led to a parallel rise in environmental levels of this metal. In spite of this, the literature contains few studies of the effects of Rh on human health. The aim of this study is to assess the effects of Rh on the renal function of female Wistar rats. Our findings show that sub-acute exposure to six increasing concentrations, ranging from 0.001 to 1 mg L(-1), of Rh (III) chloride hydrate in drinking water does not induce alterations in urinary albumin levels, while, at concentrations from 0.1 to 1 mg L(-1), a significant rise in urinary levels of Retinol Binding Protein is evident and an increasing trend in urinary ß2-microglobulin, which becomes significant at 1 mg L(-1), is observed. These results therefore demonstrate a nephrotoxic action of Rh at tubular level in a wide range of doses. Interestingly, because of the recent increase in environmental Rh levels, these findings may have relevant implications both for occupationally exposed subjects and for the general population, especially children.

Cell-selective biological activity of rhodium metalloinsertors correlates with subcellular localization.

Deficiencies in the mismatch repair (MMR) pathway are associated with several types of cancers, as well as resistance to commonly used chemotherapeutics. Rhodium metalloinsertors have been found to bind DNA mismatches with high affinity and specificity in vitro, and also exhibit cell-selective cytotoxicity, targeting MMR-deficient cells over MMR-proficient cells. Ten distinct metalloinsertors with varying lipophilicities have been synthesized and their mismatch binding affinities and biological activities determined. Although DNA photocleavage experiments demonstrate that their binding affinities are quite similar, their cell-selective antiproliferative and cytotoxic activities vary significantly. Inductively coupled plasma mass spectrometry (ICP-MS) experiments have uncovered a relationship between the subcellular distribution of these metalloinsertors and their biological activities. Specifically, we find that all of our metalloinsertors localize in the nucleus at sufficient concentrations for binding to DNA mismatches. However, the metalloinsertors with high rhodium localization in the mitochondria show toxicity that is not selective for MMR-deficient cells, whereas metalloinsertors with less mitochondrial rhodium show activity that is highly selective for MMR-deficient versus proficient cells. This work supports the notion that specific targeting of the metalloinsertors to nuclear DNA gives rise to their cell-selective cytotoxic and antiproliferative activities. The selectivity in cellular targeting depends upon binding to mismatches in genomic DNA.

In vitro investigations of platinum, palladium, and rhodium mobility in urban airborne particulate matter (PM10, PM2.5, and PM1) using simulated lung fluids.

Environmental concentrations of platinum group elements (PGE) have been increasing since the introduction of automotive catalytic converters to control harmful emissions. Assessments of the human health risks of exposures to these elements, especially through the inhalation of PGE-associated airborne particulate matter (PM), have been hampered by a lack of data on their bioaccessibility. The purpose of this study is to apply in vitro methods using simulated human lung fluids [artificial lysosomal fluid (ALF) and Gamble's solution] to assess the mobility of the PGE, platinum (Pt), palladium (Pd), and rhodium (Rh) in airborne PM of human health concern. Airborne PM samples (PM(10), PM(2.5), and PM(1)) were collected in Frankfurt am Main, Germany. For comparison, the same extraction experiments were conducted using the standard reference material, Used Auto Catalyst (monolith) (NIST 2557). Pt and Pd concentrations were measured using isotope dilution ICP-Q-MS, while Rh was measured directly with ICP-Q-MS (in collision mode with He), following established matrix separation and enrichment procedures, for both solid (filtered residues) and extracted sample phases. The mobilized fractions measured for PGE in PM(10), PM(2.5), and PM(1) were highly variable, which can be attributed to the heterogenic nature of airborne PM and its composition. Overall, the mobility of PGE in airborne PM samples was notable, with a mean of 51% Rh, 22% Pt, and 29% Pd present in PM(1) being mobilized by ALF after 24 h. For PM(1) exposed to Gamble's solution, a mean of 44% Rh, 18% Pt, and 17% Pd was measured in solution after 24 h. The mobility of PGE associated with airborne PM was also determined to be much higher compared to that measured for the auto catalyst standard reference material. The results suggest that PGE emitted from automotive catalytic converters are likely to undergo chemical transformations during and/or after being emitted in the environment. This study highlights the need to conduct bioaccessibility experiments using samples collected in the field to enable an adequate assessment of risk.

Catalytic protein modification with dirhodium metallopeptides: specificity in designed and natural systems.

In this study, we present advances in the use of rhodium(II) metallopeptides for protein modification. Site-specific, proximity-driven modification is enabled by the unique combination of peptide-based molecular recognition and a rhodium catalyst capable of modifying a wide range of amino-acid side chains. We explore catalysis based on coiled-coil recognition in detail, providing an understanding of the determinants of specificity and culminating in the demonstration of orthogonal modification of separate proteins in cell lysate. In addition, the concepts of proximity-driven catalysis are extended to include modification of the natural Fyn SH3 domain with metallopeptides based on a known proline-rich peptide ligand. The development of orthogonal catalyst-substrate pairs for modification in lysate, and the extension of these methods to new natural protein domains, highlight the capabilities for new reaction design possible in chemical approaches to site-specific protein modification.

Selective cytotoxicity of rhodium metalloinsertors in mismatch repair-deficient cells.

Mismatches in DNA occur naturally during replication and as a result of endogenous DNA damaging agents, but the mismatch repair (MMR) pathway acts to correct mismatches before subsequent rounds of replication. Rhodium metalloinsertors bind to DNA mismatches with high affinity and specificity and represent a promising strategy to target mismatches in cells. Here we examine the biological fate of rhodium metalloinsertors bearing dipyridylamine ancillary ligands in cells deficient in MMR versus those that are MMR-proficient. These complexes are shown to exhibit accelerated cellular uptake which permits the observation of various cellular responses, including disruption of the cell cycle, monitored by flow cytometry assays, and induction of necrosis, monitored by dye exclusion and caspase inhibition assays, that occur preferentially in the MMR-deficient cell line. These cellular responses provide insight into the mechanisms underlying the selective activity of this novel class of targeted anticancer agents.

Burkavidin: a novel secreted biotin-binding protein from the human pathogen Burkholderia pseudomallei.

The avidin-biotin technology has many applications, including molecular detection; immobilization; protein purification; construction of supramolecular assemblies and artificial metalloenzymes. Here we present the recombinant expression of novel biotin-binding proteins from bacteria and the purification and characterization of a secreted burkavidin from the human pathogen Burkholderia pseudomallei. Expression of the native burkavidin in Escherichia coli led to periplasmic secretion and formation of a biotin-binding, thermostable, tetrameric protein containing an intra-monomeric disulphide bond. Burkavidin showed one main species as measured by isoelectric focusing, with lower isoelectric point (pI) than streptavidin. To exemplify the potential use of burkavidin in biotechnology, an artificial metalloenzyme was generated using this novel protein-scaffold and shown to exhibit enantioselectivity in a rhodium-catalysed hydrogenation reaction.

Accumulation of platinum group elements by the marine gastropod Littorina littorea.

The accumulation and trophic transfer of the platinum group elements (PGE): Rh, Pd and Pt; have been studied in short-term (5 day) exposures conducted in aquaria containing the marine macroalga, Ulva lactuca, and/or the grazing mollusc, Littorina littorea. Metals added to sea water (to concentrations of 20 µg L⁻¹) were taken up by U. lactuca in the order Rh, Pt > Pd and by L. littorea in the order Pd ≥ Pt ≥ Rh, with greatest metal accumulation in the latter generally occurring in the visceral complex and kidney. When fed contaminated alga, accumulation of Rh and Pd by L. littorea, relative to total available metal, increased by an order of magnitude, while accumulation of Pt was not readily detected. We conclude that the diet is the most important vector for accumulation of Rh and Pd, while accumulation of Pt appears to proceed mainly from the aqueous phase.

Nickel, palladium and rhodium induced IFN-gamma and IL-10 production as assessed by in vitro ELISpot-analysis in contact dermatitis patients.

BACKGROUND: Recent attempts to diminish nickel use in most industrial products have led to an increasing utilization of alternative metal compounds for destinations such as the alloys used in orthopaedics, jewellery and dentistry. The present study was undertaken with the aim to evaluate the potential for an allergic response to nickel, palladium and rhodium on the basis of antigen-specific induction of inflammatory/regulatory cytokines, and to characterize, according to the cytokine profiles, the nature of simultaneous positive patch tests elicited in vivo. Peripheral blood mononuclear cells (PBMC) from 40 patients with different patch test results were kept in short term cultures in the presence of optimized concentrations of NiSO4 x 6H2O, PdCl2 and Rh(CH3COO)2. The production of IFN-gamma and IL-10 elicited by metal compounds were analyzed by the ELISpot assay. RESULTS: We found a specific IFN-gamma response by PBMC upon in vitro stimulation with nickel or palladium in well recognized allergic individuals. All controls with a negative patch test to a metal salt showed an in vitro IL-10 response and not IFN-gamma production when challenged with the same compound. Interestingly, all subjects with positive patch test to both nickel and palladium (group 3) showed an in vitro response characterized by the release of IFN-gamma after nickel stimulation and production of IL-10 in response to palladium. CONCLUSION: These results strongly suggest that the different cytokine profiles elicited in vitro reflect different immune responses which may lead to the control of the allergic responses or to symptomatic allergic contact dermatitis. The development of sensitive and specific in vitro assays based on the determination of the cytokine profiles in response to contact allergens may have important diagnostic and prognostic implications and may prove extremely useful in complementing the diagnostic limits of traditional patch testing.

The plant availability of auto-cast platinum group elements.

The introduction of automobile catalysts has raised environmental concern, as this pollution control technology is also an emission source for platinum group elements (PGE). The main aim of this study was to assess soil and grass PGE concentrations in soils adjacent to five road networks. The soil and grass samples were collected from four distances at each site; they were 0, 1, 2 and 5 m from the road edges. The maximum soil Pt, Rh and Pd concentrations were measured at the road perimeters. Pd concentrations were much higher than Pt or Rh, possibly due to differences in its use, emission and/or soil chemistry. Rh and Pt soil concentrations accounted for 66 and 34% (P < 0.01) of the variability observed, respectively, in their plant concentrations. Grass Pd concentrations had no relationship with its total soil concentrations.

Platinum, palladium and rhodium release from vehicle exhaust catalysts and road dust exposed to simulated lung fluids.

The risk associated with the inhalation of platinum group element (PGE) emissions from vehicle exhaust catalysts (VECs) has been investigated by extracting road dust and milled auto catalyst with simulated lung fluids. Gamble's solution (representative of the interstitial fluid of the deep lung) and artificial lysosomal fluid (ALF) (representative of the more acidic environment within the lung) were employed as extraction fluids. The highest PGE release was observed in ALF, implying that inhaled particles would have to be phagocytized before significant amounts of PGEs dissolve. The greatest percentage (up to 88%) of PGEs was released from road dust, possibly due to the presence of mobile PGE species formed in the roadside environment. Pt showed the highest absolute bioavailability, due to its greater concentration in the environmental samples. Pd and Rh had higher percentage of release, however, because of their more soluble nature. From the toxicological perspective, the results demonstrate potential health risks due to the likely formation of PGE-chloride complexes in the respiratory tract, such species having well-known toxic and allergenic effects on human beings and living organisms.

The distribution of automobile catalysts-cast platinum, palladium and rhodium in soils adjacent to roads and their uptake by grass.

The introduction of automobile catalysts has raised environmental concern, as this pollution control technology is also an emission source for the platinum group elements (PGE). The main aim of this study was to assess the concentrations of Pt, Pd, Rh and Au in soil and grass herbage collected adjacent to 5 roads. Soil and grass samples were collected from 4 fixed distances (0, 1, 2 and 5 m) from the road edge at each site. PGE and Au were determined by ICP-MS in all samples after acid digestion. The maximum soil Pt, Rh and Pd concentrations were measured at the road perimeters. Averaged across the sites, the Pt and Rh concentrations of 15.9+/-7.5 microg Pt kg(-1) and 22.40+/-4.73 microg Rh kg(-1) at 0-m distance decreased to 2.04+/-1.7 microg Pt kg(-1) and 3.51+/-1.96 microg Rh kg(-1), respectively at 5-m away from the roads. Pd concentrations were much higher than Pt or Rh, ranging from 120.8+/-12.0 microg Pd kg(-1) (0-m) to 84.2+/-10.9 microg Pd kg(-1) (5-m), possibly due to differences in its use, emission and/or soil chemistry. Au showed little or no change with distance from the roads. However, the average Au concentration of 18.98+/-0.98 microg Au kg(-1) provides clear evidence of some input possibly due to attrition of automobile electronics. No straightforward influence of traffic flow rates on PGE distribution was found. A combination of dispersal impeding local features and slow moving and stop-and-start traffic conditions or fast moving traffic with flat open spaces may have offset the expected impacts. Rh and Pt soil concentration accounted for 66% and 34% (P<0.01) of the variability observed, respectively in their plant concentrations. Grass Pd and Au concentrations had no relationship with their respective soil concentrations.