ABSTRACT
Dipeptide (Pro-Gly and Pro-Leu) Zinc(II) complexes 1 and 2 were designed and synthesized for potential use as cancer chemotherapeutic agents. In order to augment the DNA recognition of metallonuclease activity, zinc metal ion was tethered to peptide motif to carry out DNA site specific hydrolytic cleavage. The structural formulation of the complexes 1 and 2 was done by elemental analysis, spectroscopic methods (IR, NMR, electronic) and molar conductance measurements. Their in vitro DNA binding profile was investigated by UV-vis titrations, fluorescence titrations and circular dichroism which revealed that these complexes bind to CT DNA by electrostatic interactions via groove binding mode. Zn(II) Pro-Gly complex 1 showed greater binding affinity to CT DNA as compared to the Zn(II) Pro-Leu complex 2 due to steric constraints in the latter. The supercoiled pBR322 DNA cleavage activity of complex 1, ascertained by gel electrophoresis demonstrated efficient DNA cleaving ability via hydrolytic mechanistic pathway. Further, the molecular docking studies confirmed that complex 1 bind to the minor groove of DNA having AT-rich sequences with relative binding energy of -196.72kJmol(-1).
Subject(s)
DNA Cleavage/drug effects , DNA/metabolism , Dipeptides/chemistry , Organometallic Compounds/chemical synthesis , Organometallic Compounds/metabolism , Zinc/chemistry , Animals , Cattle , Chemistry Techniques, Synthetic , DNA/chemistry , Ethidium/chemistry , Hydrolysis , Models, Molecular , Nucleic Acid Conformation , Organometallic Compounds/chemistry , Organometallic Compounds/pharmacologyABSTRACT
Novel dipeptide complexes Cu(II)-Val-Pro (1), Zn(II)-Val-Pro (2), Cu(II)-Ala-Pro (3) and Zn(II)-Ala-Pro (4) were synthesized and thoroughly characterized using different spectroscopic techniques including elemental analyses, IR, NMR, ESI-MS and molar conductance measurements. The solution stability study carried out by UV-vis absorption titration over a broad range of pH proved the stability of the complexes in solution. In vitro DNA binding studies of complexes 1-4 carried out employing absorption, fluorescence, circular dichroism and viscometric studies revealed the binding of complexes to DNA via groove binding. UV-vis titrations of 1-4 with mononucleotides of interest viz., 5'-GMP and 5'-TMP were also carried out. The DNA cleavage activity of the complexes 1 and 2 were ascertained by gel electrophoresis assay which revealed that the complexes are good DNA cleavage agents and the cleavage mechanism involved a hydrolytic pathway. Furthermore, in vitro antitumor activity of complex 1 was screened against human cancer cell lines of different histological origin.
Subject(s)
Coordination Complexes/chemical synthesis , Coordination Complexes/metabolism , Copper/chemistry , DNA/metabolism , Dipeptides/chemical synthesis , Zinc/chemistry , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Antineoplastic Agents/metabolism , Antineoplastic Agents/pharmacology , Binding, Competitive , Cell Line, Tumor , Cell Proliferation/drug effects , Circular Dichroism , Coordination Complexes/chemistry , Coordination Complexes/pharmacology , DNA/chemistry , Dipeptides/chemistry , Dipeptides/metabolism , Dipeptides/pharmacology , Electrophoresis, Agar Gel , Humans , Magnetic Resonance Spectroscopy , Models, Molecular , Spectrometry, Mass, Electrospray IonizationABSTRACT
New tetrapeptide complexes Cu(II)·Ala-Pro-Ala-Pro (1) and Zn(II)·Ala-Pro-Ala-Pro (2) were synthesized from the reaction of tetrapeptide, Ala-Pro-Ala-Pro and CuCl2/ZnCl2 and were thoroughly characterized by elemental analysis, IR,(1)H and (13)C NMR (in case of 2), ESI-MS, UV and molar conductance measurements. The solution stability study was carried out employing UV-vis absorption titrations over a broad range of pH which suggested the stability of the complexes in solution. In vitro interaction of complexes 1 and 2 with CT-DNA was studied employing UV-vis, fluorescence, circular dichroic and viscometry studies. To throw insight into molecular binding event at the target site, UV-vis titrations of 1 and 2 with mononucleotides of interest viz.; 5'-GMP and 5'-TMP were carried out. Cleavage activity of the complexes with pBR322 plasmid DNA was evaluated by agarose gel electrophoresis and, the electrophoresis pattern demonstrated that both the complexes 1 and 2 are efficient cleavage agents. Further, the Cu(II) complex displayed efficient oxidative cleavage of supercoiled DNA while various reactive oxygen species are responsible for the cleavage in Zn(II) complex.
Subject(s)
Coordination Complexes/chemical synthesis , Coordination Complexes/metabolism , Copper/metabolism , DNA Cleavage , DNA/metabolism , Oligopeptides/chemical synthesis , Oligopeptides/metabolism , Zinc/metabolism , Absorption , Animals , Cattle , Circular Dichroism , Coordination Complexes/chemistry , Electron Spin Resonance Spectroscopy , Electrons , Electrophoresis, Agar Gel , Kinetics , Luminescence , Magnetic Resonance Spectroscopy , Mass Spectrometry , Oligopeptides/chemistry , Protein Binding , Protein Stability , Solutions , Spectrophotometry, Infrared , Spectrophotometry, Ultraviolet , ViscosityABSTRACT
Kalpakkam mini (KAMINI) reactor is the newest research reactor built in India. Operated at the Indira Gandhi Centre for Atomic Research, Kalpakkam, it has the unique distinction of being the only operating pool-type reactor in the world at present fuelled by 233U and aluminium alloy. Neutron spectra have been measured by the multi-foil irradiation method at the beam tube ends of this reactor. The spectra unfolding have been done, by using SAND-II computer code. Thus the total and thermal flux at the beam tube ends have been measured. The theoretical spectrum generated by the computer codes SMAXY and COMESH and WIMS cross-section data library was compared with the measured spectrum for one of the beam tubes and found to match well. A new 620-group cross-section data library generated at our centre was tested with SAND-II for the same set of measurements. Use of the new library results in slightly higher measured total fluxes and smoother spectra shapes.
ABSTRACT
Neutron reflection methods are used in the chemical analysis of bulk samples, especially for the determination of contents in hydrogenous solutions. In these techniques albedo is measured by measuring either the activation of a foil, or count rate from a neutron detector. In the present paper Monte Carlo simulations are performed using this method for the possibility of detecting inadvertent criticality in the reprocessing plants and also estimation of 10B in heavy water, which is used as a moderator in PHWRs.
ABSTRACT
The toxicity of mercury ion, on Chlorella vulgaris, is largely influenced by amino acids. Five amino acids, namely alanine, asparagine, glutamic acid, cysteine and histidine, were added separately to the medium containing static dose of mercury. Survival (%) of the alga was reduced with the increasing concentrations of mercury. Of these five amino acids, cysteine was found to be the most effective while alanine and glutamic acid were the least effective on reducing the toxic effect of mercury on the alga measured in terms of growth, chlorophyll and protein content. The order of detoxification was Alanine < Glutamate < Asparargine < Histidine < Cysteine. Amino acids from ligands with Hg2+ making it less toxic to the alga and produce an additional source of energy for growth and development.
