Ashoka G. Samuelson

Bio: Ashoka G. Samuelson is an academic researcher from Indian Institute of Science. The author has contributed to research in topics: Copper & Catalysis. The author has an hindex of 21, co-authored 95 publications receiving 1524 citations. Previous affiliations of Ashoka G. Samuelson include Cornell University.

In Vitro and in Vivo Anticancer Activity of Copper Bis(thiosemicarbazone) Complexes

Abstract: Neutral and cationic copper bis(thiosemicarbazone) complexes bearing methyl, phenyl, and hydrogen, on the diketo-backbone of the ligand have been synthesized. All of them were characterized by spectroscopic methods and in three cases by X-ray crystallography. In vitro cytotoxicity studies revealed that they are cytotoxic unlike the corresponding zinc complexes. Copper complexes Cu(GTSC) and Cu(GTSCHCl) derived from glyoxal-bis(4-methyl-4-phenyl-3-thiosemicarbazone) (GTSCH(2)) are the most cytotoxic complexes against various human cancer cell lines, with a potency similar to that of the anticancer drug adriamycin and up to 1000 fold higher than that of the corresponding zinc complex. Tritiated thymidine incorporation assay revealed that Cu(GTSC) and Cu(GTSCHCl) inhibit DNA synthesis substantially. Cell cycle analyses showed that Cu(GTSC) and Cu(GTSCHCl) induce apoptosis in HCT116 cells. The Cu(GTSCHCl) complex caused distinct DNA cleavage and Topo II alpha inhibition unlike that for Cu(GTSC). In vivo administration of Cu(GTSC) significantly inhibits tumor growth in HCT116 xenografts in nude mice.

Anion-Controlled Nuclearity and Metal−Metal Distances in Copper(I)−dppm Complexes (dppm = Bis(diphenylphosphino)methane)

Abstract: Dicapped triangular copper(I)−dppm complexes Cu3(dppm)3(μ3-X)2+ (X = Cl, Br, and I) and monocapped Cu3(dppm)3(μ3-OH)2+ have been prepared by treating the dimeric Cu2(dppm)2(CH3CN)4(ClO4)2 or Cu2(dppm)2(dmcn)3(BF4)2 (dmcn = dimethylcyanamide) complexes with the corresponding bridging ligand X-. The trimeric complexes Cu3(dppm)3(μ3-OH)(BF4)2 and Cu3(dppm)3(μ3-Cl)2Cl can be converted to dimers Cu2(dppm)2(dmcn)3(BF4)2 and Cu2(dppm)2(dmcn)(Cl)2 by reaction with HBF4, dmcn, and excess dmcn, respectively. The complexes synthesized by the above means, Cu3(dppm)3(μ3-Cl)2ClO4 (1), Cu3(dppm)3(μ3-Br)2ClO4 (2)·2THF, Cu3(dppm)3(μ3-I)2I· 2CH2Cl2·CH3OH (3), and Cu2(dppm)2(dmcn)(Cl)2·2dmcn (4) have been characterized by IR, 1H and 31P{1H} NMR, and solid-state emission spectroscopy. The solid-state molecular structures of complexes 2, 3, and 4 were determined from single-crystal X-ray diffraction studies. Apart from confirming the nuclearity, the structural information reveals interesting variations in the Cu···Cu distance...

The Nature of Bond Critical Points in Dinuclear Copper(I) Complexes

Abstract: Closed-shell contacts between two copper(I) ions are expected to be repulsive. However, such contacts are quite frequent and are well documented. Crystallographic characterization of such contacts in unsupported and bridged multinuclear copper(I) complexes has repeatedly invited debates on the existence of cuprophilicity. Recent developments in the application of Baders theory of atoms-in-molecules (AIM) to systems in which weak hydrogen bonds are involved suggests that the copper(I)copper(I) contacts would benefit from a similar analysis. Thus the nature of electron-density distributions in copper(I) dimers that are unsupported, and those that are bridged, have been examined. A comparison of complexes that are dimers of symmetrical monomers and those that are dimers of two copper(I) monomers with different coordination spheres has also been made. AIM analysis shows that a bond critical point (BCP) between two Cu atoms is present in most cases. The nature of the BCP in terms of the electron density, ?, and its Laplacian is quite similar to the nature of critical points observed in hydrogen bonds in the same systems. The ? is inversely correlated to Cu?Cu distance. It is higher in asymmetrical systems than what is observed in corresponding symmetrical systems. By examining the ratio of the local electron potential-energy density (Vc) to the kinetic energy density (Gc), |Vc|/Gc at the critical point suggests that these interactions are not perfectly ionic but have some shared nature. Thus an analysis of critical points by using AIM theory points to the presence of an attractive metallophilic interaction similar to other well-documented weak interactions like hydrogen bonding.

Mechanism of cytotoxicity of copper(I) complexes of 1,2-bis(diphenylphosphino)ethane.

Abstract: The cytotoxic properties of arylphosphines are regulated by metals. We have synthesized a series of copper(I) complexes of 1,2-bis(diphenylphosphino)ethane (DPPE) and tested their in vitro cytotoxicity in a human lung carcinoma cell line H460. One of the complexes $[Cu_2(DPPE)_3(CH_3CN)_2](ClO_4)_2 (C1)$, showed maximum cytotoxicity comparable to that of adriamycin. Treatment of cells with C1 caused DNA damage in vitro and activated the p53 pathway. Flow cytometry revealed that growth inhibition by C1 was due to a combination of cell cycle arrest and apoptosis. Simultaneous addition of C1 and adriamycin increased the cytotoxicity of either compound, suggesting the potential use of adriamycin in combination with C1. DNA binding and simulation studies suggest that adriamycin binds to DNA synergistically in the presence of C1. Thus, we have identified C1, a copper(I) complex of DPPE, as a potential chemotherapeutic drug for further testing, which could be used either alone or in combination with other chemotherapeutic drugs.

Transformation of carbon dioxide.

Abstract: 4.3. Reaction Mechanism 2373 4.4. Asymmetric Synthesis 2374 4.5. Outlook 2374 5. Alternating Polymerization of Oxiranes and CO2 2374 5.1. Reaction Outlines 2374 5.2. Catalyst 2376 5.3. Asymmetric Polymerization 2377 5.4. Immobilized Catalysts 2377 6. Synthesis of Urea and Urethane Derivatives 2378 7. Synthesis of Carboxylic Acid 2379 8. Synthesis of Esters and Lactones 2380 9. Synthesis of Isocyanates 2382 10. Hydrogenation and Hydroformylation, and Alcohol Homologation 2382

Applications of nanoparticle systems in drug delivery technology

Abstract: The development of nanoparticle-based drug formulations has yielded the opportunities to address and treat challenging diseases. Nanoparticles vary in size but are generally ranging from 100 to 500 nm. Through the manipulation of size, surface characteristics and material used, the nanoparticles can be developed into smart systems, encasing therapeutic and imaging agents as well as bearing stealth property. Further, these systems can deliver drug to specific tissues and provide controlled release therapy. This targeted and sustained drug delivery decreases the drug related toxicity and increase patient’s compliance with less frequent dosing. Nanotechnology has proven beneficial in the treatment of cancer, AIDS and many other disease, also providing advancement in diagnostic testing.

Copper complexes as anticancer agents

Abstract: Metal-based antitumor drugs play a relevant role in antiblastic chemotherapy. Cisplatin is regarded as one of the most effective drugs, even if severe toxicities and drug resistance phenomena limit its clinical use. Therefore, in recent years there has been a rapid expansion in research and development of novel metal-based anticancer drugs to improve clinical effectiveness, to reduce general toxicity and to broaden the spectrum of activity. The variety of metal ion functions in biology has stimulated the development of new metallodrugs other than Pt drugs with the aim to obtain compounds acting via alternative mechanisms of action. Among non-Pt compounds, copper complexes are potentially attractive as anticancer agents. Actually, since many years a lot of researches have actively investigated copper compounds based on the assumption proposal that endogenous metals may be less toxic. It has been established that the properties of copper-coordinated compounds are largely determined by the nature of ligands and donor atoms bound to the metal ion. In this review, the most remarkable achievements in the design and development of copper(I, II) complexes as antitumor agents are discussed. Special emphasis has been focused on the identification of structure-activity relationships for the different classes of copper(I,II) complexes. This work was motivated by the observation that no comprehensive surveys of copper complexes as anticancer agents were available in the literature. Moreover, up to now, despite the enormous efforts in synthesizing different classes of copper complexes, very few data concerning the molecular basis of the mechanisms underlying their antitumor activity are available. This overview, collecting the most significant strategies adopted in the last ten years to design promising anticancer copper(I,II) compounds, would be a help to the researchers working in this field.

Copper in diseases and treatments, and copper-based anticancer strategies.

Abstract: Copper is found in all living organisms and is a crucial trace element in redox chemistry, growth and development. It is important for the function of several enzymes and proteins involved in energy metabolism, respiration, and DNA synthesis, notably cytochrome oxidase, superoxide dismutase, ascorbate oxidase, and tyrosinase. The major functions of copper-biological molecules involve oxidation-reduction reactions in which they react directly with molecular oxygen to produce free radicals. Therefore, copper requires tightly regulated homeostatic mechanisms to ensure adequate supplies without any toxic effects. Overload or deficiency of copper is associated, respectively, with Wilson disease (WD) and Menkes disease (MD), which are of genetic origin. Researches on Menkes and Wilson disorders have provided useful insights in the field of copper homeostasis and in particular into the understanding of intracellular trafficking and distribution of copper at molecular levels. Therapies based on metal supplementation with copper histidine or removal of copper excess by means of specific copper chelators are currently effective in treating MD and WD, respectively. Copper chelation therapy is now attracting much attention for the investigation and treatment of various neurodegenerative disorders such as Alzheimer, Parkinson and CreutzfeldtJakob. An excess of copper appears to be an essential co-factor for angiogenesis. Moreover, elevated levels of copper have been found in many types of human cancers, including prostate, breast, colon, lung, and brain. On these basis, the employment of copper chelators has been reported to be of therapeutic value in the treatment of several types of cancers as anti-angiogenic molecules. More recently, mixtures of copper chelators with copper salts have been found to act as efficient proteasome inhibitors and apoptosis inducers, specifically in cancer cells. Moreover, following the worldwide success of platinum(II) compounds in cancer chemotherapy, several families of individual copper complexes have been studied as potential antitumor agents. These investigations, revealing the occurrence of mechanisms of action quite different from platinum drugs, head toward the development of new anticancer metallodrugs with improved specificity and decreased toxic side effects.