206 research outputs found
Evaluation panel “Chimie moléculaire for ”French National Research Agency (ANR) 2022
No full textANR is the project-based funding agency for research in France
Interaction of tributyltin(IV) chloride and related [Bu3 Sn(LSM)] complex with rat leukocytes and erythrocytes: effect on DNA and on plasma membrane
No full textThe discovery of the antitumor activity of cisplatin led several research groups to investigate the possible
therapeutic applications of othermetal-based compounds. Organotin(IV) complexes have been developed
from organotin compounds that were employed in industry and agriculture as stabilizers and pesticides,
respectively. A careful choice of the ligand coordinated to an organotin(IV) fragment can modulate the
activity of the organotin(IV) complex and minimize its drawbacks.With this aim, the tributyltin(IV) complex
[Bu3Sn(LSM)] (LSM= bis(1-methyl-1H-imidazol-2-ylthio)acetate) was synthesized and its in vitro
effects on rat blood cells were compared with those of the analogous tributyltin(IV) compound without
the anionic ligand.
Comet-assay results show that both the tributyltin(IV) chloride (TBTC) and the complex [Bu3Sn(LSM)]
can induce DNA damage in leukocytes, but a stronger effect was observed in the presence of the organotin(
IV) complex. Moreover, lipid-hydroperoxide formation in leukocyte plasma membranes increases
more in the presence of [Bu3Sn(LSM)] compared with TBTC, while TBTC can change the lipid order and
packing of leukocytes and, partially, erythrocyte plasma membranes. The treatment of whole blood with
these two compounds shows a preferential oxidative effect of TBTC on erythrocyte plasma membranes
and erythrocyte oxidative processes, which influence the induction of DNA damage in leukocytes. The
different hydrophobic characters and the different extents of steric hindrance of TBTC and [Bu3Sn(LSM)]
influence the capacity of the two compounds to cross the plasma membrane and affect the pathways that
lead to DNA damage
XAFS studies on copper(I) complexes containing scorpionate ligands
No full textX-ray Absorption Spectroscopy (XAS) has been used to probe the local structure of copper(I) complexes containing scorpionate ligands. The EXAFS analysis, performed by using the GNXAS package, has permitted the identification of the local environment of the copper site. Copper is found to be 4-fold coordinated with two sets of Cu-N and Cu-P interactions describing a quasi-planar figure, in the case of {Cu[(C6H5) 2PCH2CH2P(C6H5) 2][H2B(tzNO2)2]}. An additional coordination is revealed for the copper complex of bis(1,2,4-triazol-1-yl) acetate due to the interaction of the copper with the acetate of the scorpionate ligand. XANES spectra behavior confirms the occurrence of copper in the +1 oxidation state
Copper in diseases and treatments, and copper-based anticancer strategies.
No full textCopper 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
Zinc coordination complexes as anticancer agents
No full textZinc, present in all forms of life, is an essential element for humans. It is one of the most abundant metals in our body. Because of its importance, any malfunctions of its homeostasis can lead to different disease states, also related to the development of cancer. On the other hand, several Zn complexes have been recognized for their biological activities principally for preventive effects on infectious diseases and for low toxicity. Among different applications in medicinal chemistry, zinc-based complexes have shown to be appealing as anticancer drugs with low toxicity or as photosensitizers in Photo Dynamic Therapy. Here we present an overview of Zn coordination complexes proposed in the last six years as anticancer agents, trying to find a correlation between their chemical features and biological activity, and to evidence the potential perspectives of their use. Despite the great amount of work done in this field, this is the first exhaustive review on antitumor zinc complexes, that might be of wide interest for the researchers in the design and synthesis of new antitumor zinc-based drugs alternative to platinum derivatives
Applications of Scorpionate Ligands in Enzyme Modeling and Biological Studies
No full textForty-three years ago Swiatoslaw Trofimenko in a truthfully seminal paper introduced the “Boron-Pyrazole Chemistry”. It is likely that even Trofimenko could not have foreseen the true immensity of the field that was to spring from his pioneering discovery of the poly(pyrazolyl)borates or “scorpionates” ligands. In fact, tris(pyrazolyl)borates are a very useful class of monoanionic, nitrogen-based, auxiliary ligands in coordination, organometallic and bioinorganic chemistry. They readily coordinate, usually as face-capping tridentate ligands, to a wide variety of metal ions affording stable metal complexes. Furthermore, it is possible to modify the steric and electronic properties of these ligands quite easily by varying the number and nature of substituents on the pyrazolyl rings and on the boron atom, thereby providing a convenient avenue to finetune the properties at the tris(pyrazolyl)borate ligand bound metal center. Actually, more than 3000 papers have appeared in the intervening years concerned with the coordination chemistry of this versatile class of ligands. In surveying this literature notes a recurrent feature is the acknowledgement to Jerry Trofimenko for generously providing samples of his ligands to help others initiate work. This generosity has no doubt played a role in the wider embrace of these ligands and stands as an example to enforce the name of Trofimenko’s ligands.
Scorpionates have been extensively used in biomimetic chemistry as spectator ligands, which modulate the electronic and steric properties of the metal ion and of the co-ligands or actor ligands, but are not directly involved in the metal-based reactivity. A common approach for obtaining synthetic analogues of the type [{XYZ}M-L] (e.g., L = OH, H2O, Cys, etc.) involves the application of tridentate ligands which incorporate the requisite X, Y, and Z donor groups to mimic the protein residues that bind metals at the active site. In particular, tripodal ligands in which the X, Y, and Z groups are attached to a common tetrahedral (or trigonal pyramidal) center have proven to be of particular benefit for several reasons: a) tripodal ligands enforce the “facial” binding that is required to create a tetrahedral metal center; b) tripodal ligands typically possess only a single relevant binding conformation; c) as a consequence of the directional nature of tripodal ligands, it is possible to incorporate substituents that directly influence the steric environment about the metal center; d) the substituents on these ligands can be readily modified to provide a means to influence both the size of the coordination pocket and the electronic properties of the metal center. One of the most versatile tripodal ligand typology that can be utilized for biomimetic purposes is represented by the scorpionates. The pyrazole rings of these ligands can in fact be considered as good models of the histidine residues of proteins, and their spatial disposition provide the steric arrangements found in many active sites. In addition, from a synthetic point of view, the steric and electronic properties of these ligands can be easily modulated by placing opportune substituents in close proximity of the N donor atoms. In recent years complexes of scorpionate ligands were successfully used to mimic the activity of enzymes containing various metals such as vanadium, manganese, iron, cobalt, nickel, copper, zinc, molybdenum and tungsten. With this ever-growing wealth of scorpionate-supported coordination and bioinorganic chemistry, this issue would provide a valuable resource for chemists and biologist, clarifying the properties of metal complexes with scorpionate ligands with biological activity or used as models for active sites of enzymes and proteins.
The structural and functional characteristics of copper complexes with scorpionate ligands used as synthetic analogues for the binding sites of copper proteins are the subject of the first review. The specific Cu-binding sites examined are: the T3 binuclear and the T2 mononuclear sites of dioxygen-binding proteins, the T1 sites of electron-transfer in blue copper proteins, and the T2 site of nitrite reductase. The second review presents an overview of the active site structure for manganese redox proteins and their model compounds, including the study of manganese(II/III) complexes with pyrazoles and poly(pyrazolyl)borates and the investigation of the biological activity of some Mn-complexes. The third review focuses on the biological uses of methimazole based soft scorpionates and their potential for further study. At the centre of this report is the importance of the sulfur donor set. It becomes evident that the success of this system in modelling bioinorganic motifs stems from a number features of the ligand: the charge does not reside solely on the sulphur atoms, the ligand is not subject to facile oxidation to disulfide and finally it has the ability alter its denticity. In the fourth review some aspects of mononuclear zinc and iron enzymes inhibitor studies with zinc scorpionate ligands have been summarized. In particular this review focus on pharmacological relevant zinc and their scorpionate models, further discussing the chances to extend such biomimetic studies to iron enzymes and scorpionate complexes thereof. The structural and functional properties of group 6 metal complexes with scorpionate ligands, used as synthetic analogues for the binding sites of the molybdenum and tungsten enzymes, are the subject of the last review, together with an introductive overview on the bioinorganic application of scorpionate metal complexes.
This issue “Applications of Scorpionate Ligands in Enzyme Modeling and Biological Studies” has analyzed the chemical diversity exhibited by some metal complexes of scorpionate ligands and the overall progress on synthetic analogues of enzyme centers, focusing primarily on systems in which coordination spheres contain poly(pyrazolyl)borate ligands
Copper Complexes as Anticancer Agents
No full textMetal-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
Zinc(II), cadmium(II) and mercury(II) derivatives of bis(4-halopyrazol-l-yl)alkanes: synthesis, spectroscopic characterization and behaviour in solution
No full textThe interaction between various bis(4-halopyrazol-1-yl)alkanes L (L* = bis(3,5-dimethyl-4-chloropyrazol-1-yl)methane, L# = bis(4-bromopyrazol-1-yl)methane, L° = bis(4-chloropyrazol-1-yl)methane) and zinc(II), cadmium(II) and mercury(II) acceptors gave 1 : 1 [LMX2] (L = L*, M = Zn, X = Cl, Br, I, NO3 or CF3CO2; L = L*, M = Cd, X = Cl or Br; L = L*, M = Hg, X = Cl, Br or I; L = L#, M = Zn, X = Cl, Br, I or NO3; L = L#, M = Cd, X = Cl, Br, I or NO3; L = L#, M = Hg, X = Cl or Br; L = L°, M = Zn, X = Cl, M = Cd, X = I, M = Hg, X = Br), 3 : 2 [(L*)3{Zn(CF3SO3)2} 2]·3H2O and [(L*)3{Cd(NO3)2} 2]·2H2O, 2 : 1 [L2M]X2 (L = L*, M = Zn or Cd, X = ClO4 or BF4; L = L*, M = Hg, X = ClO4; L = L#, M = Zn, X = ClO4 or CF3SO3, M = Cd, X = ClO4 or BF4; L = L , M = Cd, X = BF4) and finally 3 : 1 [(L#)3Zn](BF4)2 adducts; these derivatives have been characterized through elemental analyses, spectral data (IR, 1H and 13C NMR in the case of the sufficiently soluble derivatives), conductivities and molecular weight measurements. Comparison is made with the results obtained with other bis(pyrazol-1-yl)alkanes
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