Asymmetric Synthesis of Tetrasubstituted α-Aminophosphonic Acid Derivatives.

Due to their structural similarity with natural α-amino acids, α-aminophosphonic acid derivatives are known biologically active molecules. In view of the relevance of tetrasubstituted carbons in nature and medicine and the strong dependence of the biological activity of chiral molecules into their absolute configuration, the synthesis of α-aminophosphonates bearing tetrasubstituted carbons in an asymmetric fashion has grown in interest in the past few decades. In the following lines, the existing literatures for the synthesis of optically active tetrasubstituted α-aminophosphonates are summarized, comprising diastereoselective and enantioselective approaches.

Introducing N-, P-, and S-donor leaving groups: an investigation of the chemical and biological properties of ruthenium, rhodium and iridium thiopyridone piano stool complexes.

A series of 15 piano-stool complexes featuring either a RuII, RhIII or IrIII metal center, a bidentate thiopyridone ligand, and different leaving groups was synthesized. The leaving groups were selected in order to cover a broad range of different donor atoms. Thus, 1-methylimidazole served as a N-donor, 1,3,5-triaza-7-phosphaadamantane (pta) as a P-donor, and thiourea as a S-donor. Additionally, three complexes featuring different halido leaving groups (Cl, Br, I) were added. Leaving group alterations were carried out with respect to a possible influence on pharmacokinetic and pharmacodynamic parameters, as well as the cytotoxicity of the respective compounds. The complexes were characterized via NMR spectroscopy, X-ray diffraction (where possible), mass spectrometry, and elemental analysis. Cytotoxicity was assessed in 2D cultures of human cancer cell lines by microculture and clonogenic assays as well as in multicellular tumor spheroids. Furthermore, cellular accumulation studies, flow-cytometric apoptosis and ROS assays, DNA plasmid assays, and laser ablation ICP-MS studies for analyzing the distribution in sections of multicellular tumor spheroids were conducted. This work demonstrates the importance of investigating each piano-stool complexes' properties, as the most promising candidates showed advantages over each other in certain tests/assays. Thus, it was not possible to single out one lead compound, but rather a group of complexes with enhanced cytotoxicity and activity.

Bimetallic nanoparticles against multi-drug resistant bacteria.

We discovered two antibacterial bimetallic nanoparticles (AuRh and AuRu NPs), that possess antibacterial activities against multi-drug resistant (MDR) Gram-negative bacteria and can cure wound infections. None of the nanoparticles comprising just one of these metals elements shows any antibiotic activities.

Synthesis, DNA binding and antimicrobial studies on rhodium(II) complexes of dicyandiamide.

The synthesis and characterization on four rhodium(II) complexes with the formula [Rh2(CH3COO)2(AMUH)2(dcda)2](CH3COO)2(1),[Rh2(CH3COO)2(AEUH)2(dcda)2](CH3COO)2(2),[Rh2(CH3COO)2(APrnUH)2(dcda)2](CH3COO)2(3),[Rh2(CH3COO)2(ABnUH)2(dcda)2](CH3COO)2(4), where AMUH = 1-amidino-O-methylurea, AEUH = 1-amidino-O-ethylurea, APrnUH = 1-amidino-O-n-propylurea, ABnUH = 1-amidino-O-n-butylurea, dcda = dicyandiamide are reported. The complexes were prepared by the reaction of dicyandiamide with rhodium(II) acetate in methanol (1), ethanol (2), n-propanol (3) and n-butanol (4) respectively and characterized by various techniques such as C, H, N analysis, FTIR, UV-Visible, EPR, conductance, SEM, EDX, powder XRD pattern and mass spectral studies. The interaction studies of the complexes with CT-DNA suggested the non-intercalative mode of binding for these complexes. The antimicrobial activity of the complexes against the tested microorganisms viz. Bacillus subtilis, Enterococcus faecium, Staphylococcus aureus and Escherichia coli, using the standard antibiotics streptomycin as positive control is also reported.

Rh(III)-Catalyzed C(8)-H Functionalization of Quinolines via Simultaneous C-C and C-O Bond Formation: Direct Synthesis of Quinoline Derivatives with Antiplasmodial Potential.

Here, a facile and efficient protocol for the synthesis of 3-hydroxyquinolin-8-yl propanoates via Rh(III)-catalyzed C(8)-H activation of 2-substituted quinolines has been developed. The reaction proceeds via C(8)-H activation, functionalization with acrylates, followed by intramolecular migration of the oxygen atom from quinoline N-oxides to the acrylate moiety. In this approach, N-oxide plays a dual role of a traceless directing group as well as a source of an oxygen atom for hydroxylation. This catalytic method involves simultaneous formation of new C-C and C-O bonds and is applicable only for C2-substituted quinolines. A catalytically competent five-membered rhodacycle has been characterized, thus revealing a key intermediate in the catalytic cycle. In silico docking studies against Falcipan-2 have revealed that 3a, 3b, 3g, and 3m have better scores. In vitro evaluation of selected compounds against CQ-sensitive pf3D7 and CQ-resistant pfINDO strains provided evidence that 3d (IC50 13.3 µM) and 3g (IC50 9.5 µM) had good promise against Plasmodium falciparum in the in vitro culture. Compound 3g was found to be the most potent on the basis of both in vitro antiplasmodial activity [IC50 9.5 µM ( Pf3D7) and 11.9 µM ( PfINDO), resistance index 1.25] and in silico studies.

Morphology-Controlled Synthesis of Rhodium Nanoparticles for Cancer Phototherapy.

Rhodium nanoparticles are promising transition metal nanocatalysts for electrochemical and synthetic organic chemistry applications. However, notwithstanding their potential, to date, Rh nanoparticles have not been utilized for biological applications; there has been no cytotoxicity study of Rh reported in the literature. In this regard, the absence of a facile and controllable synthetic strategy of Rh nanostructures with various sizes and morphologies might be responsible for the lack of progress in this field. Herein, we have developed a synthetic strategy for Rh nanostructures with controllable morphology through an inverse-directional galvanic replacement reaction. Three types of Rh-based nanostructures-nanoshells, nanoframes, and porous nanoplates-were successfully synthesized. A plausible synthetic mechanism based on thermodynamic considerations has also been proposed. The cytotoxicity, surface functionalization, and photothermal therapeutic effect of manufactured Rh nanostructures were systematically investigated to reveal their potential for in vitro and in vivo biological applications. Considering the comparable behavior of porous Rh nanoplates to that of gold nanostructures that are widely used in nanomedicine, the present study introduces Rh-based nanostructures into the field of biological research.

Monitoring the Reaction Mechanism in Model Biogas Reforming by In†Situ Transient and Steady-State DRIFTS Measurements.

In this work, the reforming of model biogas was investigated on a Rh/MgAl2 O4 catalyst. In situ transient and steady-state diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) measurements were used to gain insight into the reaction mechanism involved in the activation of CH4 and CO2 . It was found that the reaction proceeds through of an initial pathway in which methane and CO2 are both dissociated on Rh metallic sites and additionally a bifunctional mechanism in which methane is activated on Rh sites and CO2 is activated on the basic sites of the support surface via a formate intermediate by H-assisted CO2 decomposition. Moreover, this plausible mechanism is able to explain why the observed apparent activation energy of CO2 is much lower than that of CH4 . Our results suggest that CO2 dissociation facilitates CH4 activation, because the oxygen-adsorbed species formed in the decomposition of CO2 are capable of reacting with the CHx species derived from methane decomposition.

Enantioselective Model Synthesis and Progress toward the Putative Structure of Yuremamine.

An enantioselective model synthesis of the 2,3-dihydro-1H-pyrrolo[1,2-a]indole core of the putative structure of yuremamine is reported in 39% overall yield and 96% ee over five steps. The model synthesis leverages enantioselective, rhodium-catalyzed hydroacylation of an N-vinylindole-2-carboxaldehyde as the key step in the installation of the stereochemical triad. An enantioselective synthesis of a densely functionalized dihydropyrroloindolone that maps onto the putative structure of yuremamine is demonstrated in 26% yield and 97% ee over eight steps.

Formal Synthesis of Gracilamine Using Rh(I)-Catalyzed [3 + 2 + 1] Cycloaddition of 1-Yne-Vinylcyclopropanes and CO.

Reported here is a formal synthesis of gracilamine using Rh(I)-catalyzed [3 + 2 + 1] reaction of yne-VCP (±)-4 and CO. The key reaction gave the cycloadduct (±)-trans-3 with the A-B-C core structure of gracilamine. This advanced intermediate was further transformed to Gao's intermediate (±)-2 via regular transformations to realize the formal synthesis of gracilamine. The present strategy was used to accomplish the asymmetric formal synthesis of gracilamine using chiral substrate (+)-4.

Relative stability and reducibility of CeO2 and Rh/CeO2 species on the surface and in the cavities of γ-Al2O3: a periodic DFT study.

We report the structure and stability of ceria units deposited on the surface of γ-Al2O3 or incorporated in its cavities, as determined by periodic density functional calculations. Ceria species are modeled as CeO2 or Ce2O4 moieties or as a small nanoparticle, Ce13O26, on the (100) and (001) surfaces of a γ-Al2O3 slab. Among the studied structures the incorporation of Ce(4+) ions in cavities of γ-Al2O3 is favored with respect to the ions on the surface only in subsurface cavities of the (100) surface. The calculations also suggested that formation of a surface layer of ceria on the (100) alumina surface is preferable compared to three-dimensional moieties. The deposition of a small ceria nanoparticle on (100) and (001) surfaces of γ-Al2O3 reduces the energy for oxygen vacancy formation to an essentially spontaneous process on the (100) surface, which may be the reason for the experimentally detected large fraction of Ce(3+) ions in the CeO2/γ-Al2O3 systems. The deposition of a single rhodium atom or RhO unit in some of the structures with a CeO2 unit and Ce13O26 showed that spontaneous electron transfer from rhodium to cerium ion occurs, which results in reduction of Ce(4+) to Ce(3+) and the oxidation of rhodium. Only in the presence of deposited rhodium atoms, the incorporated cerium ions can be reduced to Ce(3+).

Asymmetric synthesis of N-allylic indoles via regio- and enantioselective allylation of aryl hydrazines.

The asymmetric synthesis of N-allylic indoles is important for natural product synthesis and pharmaceutical research. The regio- and enantioselective N-allylation of indoles is a true challenge due to the favourable C3-allylation. We develop here a new strategy to the asymmetric synthesis of N-allylic indoles via rhodium-catalysed N-selective coupling of aryl hydrazines with allenes followed by Fischer indolization. The exclusive N-selectivities and good to excellent enantioselectivities are achieved applying a rhodium(I)/DTBM-Segphos or rhodium(I)/DTBM-Binap catalyst. This method permits the practical synthesis of valuable chiral N-allylated indoles, and avoids the N- or C-selectivity issue.

Rhodium nanoparticle-modified screen-printed graphite electrodes for the determination of hydrogen peroxide in tea extracts in the presence of oxygen.

In this work we describe the fabrication of nanostructured electrocatalytic surfaces based on polyethyleneimine (PEI)-supported rhodium nanoparticles (Rh-NP) over graphite screen-printed electrodes (SPEs) for the determination of hydrogen peroxide in the presence of oxygen. Rh-NP, electrostatically stabilized by citrate anions, were immobilized over graphite SPEs, through coulombic attraction on a thin film of positively charged PEI. The functionalized sensors, polarized at 0.0 V vs. Ag/AgCl/3 M KCl, exhibited a linear response to H2O2 over the concentration range from 5 to 600 µmol L(-1) H2O2 in the presence of oxygen. The 3σ limit of detection was 2 µmol L(-1) H2O2, while the reproducibility of the method at the concentration level of 10 µmol L(-1) H2O2 (n=10) and between different sensors (n=4) was lower than 3 and 5%, respectively. Most importantly, the sensors showed an excellent working and storage stability at ambient conditions and they were successfully applied to the determination of H2O2 produced by autooxidation of polylphenols in tea extracts with ageing. Recovery rates ranged between 97 and 104% suggesting that the as-prepared electrodes can be used for the development of small-scale, low-cost chemical sensors for use in on-site applications.

Simultaneous determination of Se, trace elements and major elements in Se-rich rice by dynamic reaction cell inductively coupled plasma mass spectrometry (DRC-ICP-MS) after microwave digestion.

A quick and accurate method was devised to determine Se, As, Ba, Ca, Cd, Cr, Cu, Fe, Mg, Mn, Ni, Pb, Sr and Zn in Se-rich rice samples by microwave digestion and inductively coupled plasma-mass spectrometry (ICP-MS). Spectral interferences on Se were eliminated using methane as a reaction gas in the dynamic reaction cell (DRC). Rhodium was used as an internal standard to compensate for sample matrix effects. A rice-certified reference material (CRM) (GBW 10010) was used to verify the accuracy of the method. The method detection limits were 0.001-0.03 mg/kg, analyte recoveries were 85-108% and precisions (RSDs) ranged from 2.1% to 5.8%. Correlation analysis showed that the Se concentrations in the Se-rich rice samples correlated well with the Cu concentrations (r=0.53, p<0.05).

Studies of asymmetric styrene cyclopropanation with a rhodium(II) metallopeptide catalyst developed with a high-throughput screen.

Dirhodium metallopeptides have been developed as selective catalysts for asymmetric cyclopropanation reactions. A selective ligand sequence has been identified by screening on-bead metallopeptide libraries in a 96-well plate format. Efficient ligand synthesis and screening allows a 200-member library to be created and assayed in less than three weeks. These metallopeptides catalyze efficient cyclopropanation of aryldiazoacetates, providing asymmetric access to cyclopropane products in high diastereoselectivity.

Complementary regioselectivity in Rh(III)-catalyzed insertions of potassium vinyltrifluoroborate via C-H activation: preparation and use of 4-trifluoroboratotetrahydroisoquinolones.

Potassium vinyltrifluoroborate was found to be an efficient partner with benzamide derivatives for Rh(III)-catalyzed annulations. 4-Trifluoroboratotetrahydroisoquinolones were generated under mild conditions, affording a regioisomerically complementary substitution pattern to other alkenes in related reactions. These new boron-containing building blocks were derivatized by N-arylations, retaining the boron substituent for further elaboration.

Synthesis, biochemical evaluation and molecular modeling studies of novel rhodium complexes with nanomolar activity against Platelet Activating Factor.

Two square planar Rh(I) organometallic complexes namely [Rh(L(1))(cod)]Cl (cod = cycloocta-1,5-diene, L(1)=2,2'-pyridylquinoxaline (1-Cl), [Rh(L1)(cod)](NO3) (1-NO(3)) and a series of novel octahedral rhodium(III) complexes of the general formulae mer-[Rh(L(1))Cl(3)(MeOH)] (2) and cis-[Rh(L(2))(2)Cl(2)]Cl (L(2)=4 carboxy 2 (2' pyridyl)quinoline (3), L(3)=2,2' bipyridine 4,4' dicarboxylic acid (4) were synthesized and characterized spectroscopically. All the synthesized compounds including the previously prepared cis-[Rh(L(1))(2)Cl(2)]Cl complex (5) were biologically evaluated as potential inhibitors of the Platelet Activation Factor (PAF) and thrombin induced aggregation. In particular compounds 1-Cl and 1-NO(3) were found to be strong inhibitors of PAF with IC(50) values in the range of 16 nM and 15 nM rendering them good candidates for further investigation. Their potency is comparable to that of the widely used PAF receptor antagonists WEB2170, BN52021, and Rupatadine (IC(50) of 20, 30 and 260 nM respectively). Molecular docking calculations suggest that 1-Cl, 1-NO3 and 2 can be accommodated within the ligand-binding site of PAF receptor and block the activity of PAF. On the other hand, the octahedral rhodium(III) complexes 3-5 that cannot fit the ligand-binding domain, could potentially exhibit their activity at the extracellular domain of the receptor.

Synthesis and antiplasmodial evaluation of novel (4-aminobutyloxy)quinolines.

A variety of 5-, 6- and 8-(4-aminobutyloxy)quinolines as novel oxygen analogues of known 4- and 8-(4-aminobutylamino)quinoline antimalarial drugs was generated from hydroxyquinolines through a three-step approach with a rhodium-catalyzed hydroformylation as the key step. Antiplasmodial assays of these new quinolines revealed micromolar potency for all representatives against a chloroquine-sensitive strain of Plasmodium falciparum, and three compounds showed submicromolar activity against a chloroquine-resistant strain of P. falciparum with IC(50)-values ranging between 150 and 680 nM.

Spin fluctuations of paramagnetic Rh clusters revealed by x-ray magnetic circular dichroism.

The magnetic moment induced on Rh atoms, forming 1.6 nm average diameter clusters, embedded in an Al(2)O(3) matrix, has been determined using x-ray magnetic circular dichroism measurements. The magnetic moment varies linearly with the applied magnetic field. At 2.3 K and under 17 T, the spin magnetic moment amounts to 0.067(2) µ(B)/Rh atom. The orbital moment does not exceed 2% of the spin moment. The susceptibility is highly temperature dependent. This is in agreement with a prediction due to Moriya and Kawabata, that in itinerant electron systems, close to the onset of magnetism, the renormalization of the magnetic susceptibility by electron correlations, leads to a Curie-like behavior.

Hydrodefluorination and hydrogenation of fluorobenzene under mild aqueous conditions.

Fluorinated organic compounds are increasingly used in many applications, and their release to the environment is expected. It is therefore important to find suitable methods for degradation of fluorinated compounds under environmentally relevant conditions. In this study, a simple heterogeneous rhodium-based catalytic system (Rh/Al(2)O(3) and H(2)) for hydrodefluorination and hydrogenation of fluorobenzene under mild aqueous conditions (1 atm of H(2), ambient temperature) was developed and the underlying reaction mechanism was investigated. Fluorobenzene degraded rapidly (t(1/2) ≈ 0.2 h) to form cyclohexane and fluoride (F(-)) as the stable end products, with benzene and cyclohexene observed as intermediates. Cyclohexadiene intermediates were not observed but were expected to form during the hydrogenation of benzene. Three postulated but unobserved fluorinated intermediates were subjected to the catalytic reaction conditions, and it was concluded that they most likely do not form during the fluorobenzene degradation reaction. Isotope labeling experiments showed that the unsaturated intermediates undergo rapid and reversible hydrogenation/dehydrogenation under the reaction conditions and also that fully saturated compounds are unreactive in the catalytic system. Both molecular hydrogen and water were sources of hydrogen in the final cyclohexane product. Kinetic fitting indicated that sorption/desorption of fluorobenzene onto the catalyst surface plays an important role in the mechanism.

Highly regioselective isomerization-hydroaminomethylation of internal olefins catalyzed by Rh complex with Tetrabi-type phosphorus ligands.

A highly regioselective isomerization-hydroaminomethylation of internal olefins has been developed. A 95.3% amine selectivity and 36.2 n/i ratio were obtained for 2-octene with a Tetrabi ligand and Rh(acac)(CO)(2), and a TON of linear amine was achieved of 6837 with a 39.1 n/i ratio of amine. The m-CF(3)-Ph substituted ligand was the best of the applied Tetrabi-type phosphorus ligands for different internal olefins, as up to a 99.2% amine selectivity and 95.6 n/i ratio were obtained for 2-pentene.