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Arhiv Za Higijenu Rada I Toksikologiju Dec 2019Measurable quantities of platinum, palladium, and rhodium, even in remote areas of the planet, evidence the global nature of pollution with these metals, mostly from... (Review)
Review
Measurable quantities of platinum, palladium, and rhodium, even in remote areas of the planet, evidence the global nature of pollution with these metals, mostly from catalytic converters of modern vehicles (other sources are jewellery production, chemical industry, and anticancer drugs). The amount of the platinum group metals (PGMs) emitted from automobile catalysts varies with the type, age, and condition of the engine and the catalyst, as well as the style of driving. Current literature suggests that the concentrations of these metals have increased considerably over the last twenty years, palladium concentrations in particular, as it has been proved more effective catalyst than platinum. However, whether and to what extent the emitted PGMs are toxic for people is still a controversy. The potential health risk from exposure to these elements is most likely for those living in urban environments with busy roads or along major highways. Because of the importance of PGMs and their trace levels in particulate matter, sensitive methods are required for reliable determination. This review discusses particular steps of analytical procedures for PGM quantification in airborne particulate matter and addresses the common preparation, detection, and determination methods.
Topics: Automobiles; Chemical Industry; Environmental Monitoring; Humans; Palladium; Particulate Matter; Platinum; Rhodium
PubMed: 32623861
DOI: 10.2478/aiht-2019-70-3293 -
Chemistry (Weinheim An Der Bergstrasse,... Apr 2022Tumor associated macrophages (TAMs) suppress the cancer immune response and are a key target for immunotherapy. The effects of ruthenium and rhodium complexes on TAMs...
Tumor associated macrophages (TAMs) suppress the cancer immune response and are a key target for immunotherapy. The effects of ruthenium and rhodium complexes on TAMs have not been well characterized. To address this gap in the field, a panel of 22 dirhodium and ruthenium complexes were screened against three subtypes of macrophages, triple-negative breast cancer and normal breast tissue cells. Experiments were carried out in 2D and biomimetic 3D co-culture experiments with and without irradiation with blue light. Leads were identified with cell-type-specific toxicity toward macrophage subtypes, cancer cells, or both. Experiments with 3D spheroids revealed complexes that sensitized the tumor models to the chemotherapeutic doxorubicin. Cell surface exposure of calreticulin, a known facilitator of immunogenic cell death (ICD), was increased upon treatment, along with a concomitant reduction in the M2-subtype classifier arginase. Our findings lay a strong foundation for the future development of ruthenium- and rhodium-based chemotherapies targeting TAMs.
Topics: Cell Line, Tumor; Humans; Immunotherapy; Rhodium; Ruthenium; Triple Negative Breast Neoplasms; Tumor-Associated Macrophages
PubMed: 35235227
DOI: 10.1002/chem.202104430 -
Journal of Nanobiotechnology Feb 2013Magnetic fluids containing superparamagnetic iron oxide nanoparticles represent an attractive platform as nanocarriers in chemotherapy. Recently, we developed a...
BACKGROUND
Magnetic fluids containing superparamagnetic iron oxide nanoparticles represent an attractive platform as nanocarriers in chemotherapy. Recently, we developed a formulation of maghemite nanoparticles coated with rhodium (II) citrate, which resulted in in vitro cytotoxicity enhanced up to 4.6 times when compared to free rhodium (II) citrate formulation on breast carcinoma cells. In this work, we evaluate the antitumor activity and toxicity induced by these formulations in Balb/c mice bearing orthotopic 4T1 breast carcinoma.
METHODS
Mice were evaluated with regard to the treatments' toxicity through analyses of hemogram, serum levels of alanine aminotransferase, iron, and creatinine; DNA fragmentation and cell cycle of bone marrow cells; and liver, kidney and lung histology. In addition, the antitumor activity of rhodium (II) citrate and maghemite nanoparticles coated with rhodium (II) citrate was verified by tumor volume reduction, histology and immunohistochemistry.
RESULTS
Regarding the treatments' toxicity, no experimental groups had alterations in levels of serum ALT or creatinine, and this suggestion was corroborated by the histopathologic examination of liver and kidney of mice. Moreover, DNA fragmentation frequency of bone marrow cells was lower than 15% in all experimental groups. On the other hand, the complexes rhodium (II) citrate-functionalized maghemite and free rhodium (II) citrate led to a marked growth inhibition of tumor and decrease in CD31 and Ki-67 staining.
CONCLUSIONS
In summary, we demonstrated that both rhodium (II) citrate and maghemite nanoparticles coated with rhodium (II) citrate formulations exhibited antitumor effects against 4T1 metastatic breast cancer cell line following intratumoral administration. This antitumor effect was followed by inhibition of both cell proliferation and microvascularization and by tumor tissue injury characterized as necrosis and fibrosis. Remarkably, this is the first published report demonstrating the therapeutic efficacy of maghemite nanoparticles coated with rhodium (II) citrate. This treatment prolonged the survival period of treated mice without inducing apparent systemic toxicity, which strengthens its use for future breast cancer therapeutic applications.
Topics: Alanine Transaminase; Animals; Antineoplastic Agents; Breast Neoplasms; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Citric Acid; Creatinine; DNA Fragmentation; Female; Ferric Compounds; Humans; Immunohistochemistry; Iron; Ki-67 Antigen; Kidney; Liver; Magnetite Nanoparticles; Mice; Mice, Inbred BALB C; Platelet Endothelial Cell Adhesion Molecule-1; Rhodium; Ultraviolet Rays
PubMed: 23414068
DOI: 10.1186/1477-3155-11-4 -
Tumour Biology : the Journal of the... May 2015Breast cancer is one of the most prevalent cancer types among women. The use of magnetic fluids for specific delivery of drugs represents an attractive platform for...
Breast cancer is one of the most prevalent cancer types among women. The use of magnetic fluids for specific delivery of drugs represents an attractive platform for chemotherapy. In our previous studies, it was demonstrated that maghemite nanoparticles coated with rhodium (II) citrate (Magh-Rh2Cit) induced in vitro cytotoxicity and in vivo antitumor activity, followed by intratumoral administration in breast carcinoma cells. In this study, our aim was to follow intravenous treatment to evaluate the systemic antitumor activity and toxicity induced by these formulations in Balb/c mice bearing orthotopic 4T1 breast carcinoma. Female Balb/c mice were evaluated with regard to toxicity of intravenous treatments through analyses of hemogram, serum levels of alanine aminotransferase, iron, and creatinine and liver, kidney, and lung histology. The antitumor activity of rhodium (II) citrate (Rh2Cit), Magh-Rh2Cit, and maghemite nanoparticles coated with citrate (Magh-Cit), used as control, was evaluated by tumor volume reduction, histology, and morphometric analysis. Magh-Rh2Cit and Magh-Cit promoted a significant decrease in tumor area, and no experimental groups presented hematotoxic effects or increased levels of serum ALT and creatinine. This observation was corroborated by the histopathological examination of the liver and kidney of mice. Furthermore, the presence of nanoparticles was verified in lung tissue with no morphological changes, supporting the idea that our nanoformulations did not induce toxicity effects. No studies about the systemic action of rhodium (II) citrate-loaded maghemite nanoparticles have been carried out, making this report a suitable starting point for exploring the therapeutic potential of these compounds in treating breast cancer.
Topics: Alanine Transaminase; Animals; Antineoplastic Agents; Female; Ferric Compounds; Hepatocytes; Kidney; Mammary Glands, Animal; Mammary Neoplasms, Experimental; Mice; Mice, Inbred BALB C; Nanoparticles; Rhodium; Survival Rate
PubMed: 25528215
DOI: 10.1007/s13277-014-2966-x -
Chemistry (Weinheim An Der Bergstrasse,... Mar 2022The use of arylboron reagents in metal-catalyzed domino addition-cyclization reactions is a well-established strategy for the preparation of diverse, highly... (Review)
Review
The use of arylboron reagents in metal-catalyzed domino addition-cyclization reactions is a well-established strategy for the preparation of diverse, highly functionalized carbo- and heterocyclic products. Although rhodium- and palladium-based catalysts have been commonly used for these reactions, more recent work has demonstrated nickel catalysis is also highly effective, in many cases offering unique reactivity and access to products that might otherwise not be readily available. This review gives an overview of nickel-catalyzed arylative cyclizations of alkyne- and allene-tethered electrophiles using arylboron reagents. The scope of the reactions is discussed in detail, and general mechanistic concepts underpinning the processes are described.
Topics: Alkadienes; Alkynes; Catalysis; Cyclization; Indicators and Reagents; Nickel; Rhodium
PubMed: 34986277
DOI: 10.1002/chem.202104230 -
Accounts of Chemical Research Mar 2021By using transition metal catalysts, chemists have altered the "logic of chemical synthesis" by enabling the functionalization of carbon-hydrogen bonds, which have... (Review)
Review
By using transition metal catalysts, chemists have altered the "logic of chemical synthesis" by enabling the functionalization of carbon-hydrogen bonds, which have traditionally been considered inert. Within this framework, our laboratory has been fascinated by the potential for aldehyde C-H bond activation. Our approach focused on generating acyl-metal-hydrides by oxidative addition of the formyl C-H bond, which is an elementary step first validated by Tsuji in 1965. In this Account, we review our efforts to overcome limitations in hydroacylation. Initial studies resulted in new variants of hydroacylation and ultimately spurred the development of related transformations (e.g., carboacylation, cycloisomerization, and transfer hydroformylation).Sakai and co-workers demonstrated the first hydroacylation of olefins when they reported that 4-pentenals cyclized to cyclopentanones, using stoichiometric amounts of Wilkinson's catalyst. This discovery sparked significant interest in hydroacylation, especially for the enantioselective and catalytic construction of cyclopentanones. Our research focused on expanding the asymmetric variants to access medium-sized rings (e.g., seven- and eight-membered rings). In addition, we achieved selective intermolecular couplings by incorporating directing groups onto the olefin partner. Along the way, we identified Rh and Co catalysts that transform dienyl aldehydes into a variety of unique carbocycles, such as cyclopentanones, bicyclic ketones, cyclohexenyl aldehydes, and cyclobutanones. Building on the insights gained from olefin hydroacylation, we demonstrated the first highly enantioselective hydroacylation of carbonyls. For example, we demonstrated that ketoaldehydes can cyclize to form lactones with high regio- and enantioselectivity. Following these reports, we reported the first intermolecular example that occurs with high stereocontrol. Ketoamides undergo intermolecular carbonyl hydroacylation to furnish α-acyloxyamides that contain a depsipeptide linkage.Finally, we describe how the key acyl-metal-hydride species can be diverted to achieve a C-C bond-cleaving process. Transfer hydroformylation enables the preparation of olefins from aldehydes by a dehomologation mechanism. Release of ring strain in the olefin acceptor offers a driving force for the isodesmic transfer of CO and H. Mechanistic studies suggest that the counterion serves as a proton-shuttle to enable transfer hydroformylation. Collectively, our studies showcase how transition metal catalysis can transform a common functional group, in this case aldehydes, into structurally distinct motifs. Fine-tuning the coordination sphere of an acyl-metal-hydride species can promote C-C and C-O bond-forming reactions, as well as C-C bond-cleaving processes.
Topics: Aldehydes; Catalysis; Cobalt; Coordination Complexes; Molecular Structure; Rhodium
PubMed: 33533586
DOI: 10.1021/acs.accounts.0c00771 -
Chemical Communications (Cambridge,... Nov 2007Since the elucidation of the structure of double helical DNA, the construction of small molecules that recognize and react at specific DNA sites has been an area of... (Review)
Review
Since the elucidation of the structure of double helical DNA, the construction of small molecules that recognize and react at specific DNA sites has been an area of considerable interest. In particular, the study of transition metal complexes that bind DNA with specificity has been a burgeoning field. This growth has been due in large part to the useful properties of metal complexes, which possess a wide array of photophysical attributes and allow for the modular assembly of an ensemble of recognition elements. Here we review recent experiments in our laboratory aimed at the design and study of octahedral metal complexes that bind DNA non-covalently and target reactions to specific sites. Emphasis is placed both on the variety of methods employed to confer site-specificity and upon the many applications for these complexes. Particular attention is given to the family of complexes recently designed that target single base mismatches in duplex DNA through metallo-insertion.
Topics: Binding Sites; DNA; Models, Molecular; Molecular Conformation; Organometallic Compounds; Rhodium
PubMed: 17989802
DOI: 10.1039/b710949k -
Accounts of Chemical Research Jan 2020Cycloaddition reactions are a hallmark in organic synthesis because they provide an efficient way to construct highly substituted carbo- and heterocycles found in... (Review)
Review
Cycloaddition reactions are a hallmark in organic synthesis because they provide an efficient way to construct highly substituted carbo- and heterocycles found in natural products and pharmaceutical agents. Most cycloadditions occur under thermal or photochemical conditions, but transition-metal complexes can promote reactions that occur beyond these circumstances. Transition-metal complexation with alkynes, alkenes, allenes, or dienes often alters the reactivity of those π-systems and facilitates access to diverse cycloaddition products. This Account describes our efforts toward the design of novel five-carbon synthons for use in rhodium-catalyzed (5 + ) cycloadditions, which include 3-acyloxy-1,4-enynes (ACEs) for (5 + 1) and (5 + 2) cycloadditions and 3-hydroxy-1,4-enynes (HYEs) for (5 + 1) cycloadditions. Furthermore, this Account includes relevant computational information, mechanistic insights, and applications of these cycloadditions in the synthesis of various highly substituted carbo- and heterocycles. The (5 + ) cycloaddition reactions presented herein share the following common mechanistic features: the 1,2-migration of an acyloxy group in propargyl esters or the ionization of a hydroxyl group in propargylic alcohols, oxidative cyclization to form a metallacycle, insertion of the one- or two-carbon component, and reductive elimination to yield the final product. In conjunction with a cationic rhodium catalyst, we used ACEs for the intramolecular (5 + 2) cycloaddition with tethered alkynes, alkenes, and allenes. In some cases, an electron-deficient phosphine ligand improved the reaction yields, especially when the ACE featured an internal alkyne. We also demonstrated that chirality could be efficiently transferred from a relatively simple starting material to a more complex bicyclic product. Products derived from ACEs with tethered alkenes and allenes contained one or more stereocenters, and high diastereoselectivity was achieved in most of these cases. For ACEs tethered to an allene, the reaction preferentially occurred at the internal alkene. We also switched the positions of the alkene and the alkyne in the 1,4-enyne of our original ACE to provide an inverted ACE variant, which produced products with complementary functionalities. After we successfully developed the Rh-catalyzed intramolecular (5 + 2) cycloaddition, we optimized conditions for the intermolecular version, which required a neutral rhodium catalyst and phosphine ligand. When a terminal alkyne was used as the two-carbon component, high regioselectivity was observed. While investigating the effect of esters on the rate of the intermolecular (5 + 2) cycloadditions, we determined that an electron-rich ester significantly accelerated the reaction. Subsequently, we demonstrated that (5 + 1) cycloadditions undergo this rate enhancement as well in the presence of an ester. Aside from ACEs, we synthesized HYEs in four steps from commercially available 2-aminobenzoic acid for use in the (5 + 1) cycloaddition. Mechanistically, HYEs were designed so that the aniline nitrogen could serve as the nucleophile and the -OH could serve as the leaving group. Using HYEs, we developed a novel method to make substituted carbazoles, dibenzofurans, and tricyclic compounds with a cyclohexadienone moiety. Although the occurrence of transition-metal-catalyzed acyloxy migrations has been known for decades, only recently has their synthetic value been realized. We hope our studies that employ readily available 1,4-enynes as the five-carbon components in (5 + ) cycloadditions can inspire the design of new two-component and multicomponent cycloadditions.
Topics: Alkynes; Carbon; Catalysis; Cycloaddition Reaction; Cycloparaffins; Molecular Structure; Rhodium
PubMed: 31820914
DOI: 10.1021/acs.accounts.9b00477 -
Molecules (Basel, Switzerland) Aug 2020Organosulfur compounds are widely used for the manufacture of drugs and materials, and their synthesis in general conventionally employs nucleophilic substitution... (Review)
Review
Organosulfur compounds are widely used for the manufacture of drugs and materials, and their synthesis in general conventionally employs nucleophilic substitution reactions of thiolate anions formed from thiols and bases. To synthesize advanced functional organosulfur compounds, development of novel synthetic methods is an important task. We have been studying the synthesis of organosulfur compounds by transition-metal catalysis using disulfides and sulfur, which are easier to handle and less odiferous than thiols. In this article, we describe our development that rhodium complexes efficiently catalyze the cleavage of S-S bonds and transfer organothio groups to organic compounds, which provide diverse organosulfur compounds. The synthesis does not require use of bases or organometallic reagents; furthermore, it is reversible, involving chemical equilibria and interconversion reactions.
Topics: Catalysis; Chemistry Techniques, Synthetic; Disulfides; Rhodium; Sulfur; Sulfur Compounds
PubMed: 32784672
DOI: 10.3390/molecules25163595 -
Journal of the American Chemical Society Dec 2022Given the emerging demand to "escape from flatland" for drug discovery, synthetic methods that can efficiently construct complex three-dimensional structures with...
Given the emerging demand to "escape from flatland" for drug discovery, synthetic methods that can efficiently construct complex three-dimensional structures with multi-stereocenters become increasingly valuable. Here, we describe the development of Rh(I)-catalyzed intramolecular annulations between cyclobutanones and 1,5-enyne groups to construct complex C(sp)-rich scaffolds. Divergent reactivities are realized with different catalysts, and excellent diastereo- and enantioselectivity have been achieved. The use of ()-H-binap as the ligand favors forming the bis-bicyclic scaffolds with multiple quaternary stereocenters, while the ()-segphos ligand prefers to generate the tetrahydro-azapinone products. Owing to the versatile reactivity of ketone moieties, these C(sp)-rich scaffolds can be further functionalized. Experimental and computational mechanistic studies support a reaction pathway involving enyne-cyclometallation, 1,2-carbonyl addition, and then β-carbon elimination; the divergent reactivities are dictated by a product-determining Rh-alkyl migratory insertion step.
Topics: Ligands; Rhodium
PubMed: 36399332
DOI: 10.1021/jacs.2c09814