Transition Metal Complexes and Their Interaction with Nucleic-acids

The Transition Elements (d block) and Inner Transition Elements (f block)

Introduction
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Heavy metal interface in metalloregulatory proteins and in doing so disrupt gene expression. Example: Cisplatin (Anti-cancer drug)

Heavy metal toxicity in an environment arises due to covalent interactions of metal ions with nucleic acids.

Transition Metal Complexes (Coordination Complexes) NAMI-A: NAMI is the acronym for New Anti-tumour Metastasis Inhibitor; -A means that this is the first of a series.

Aqueous Oxo-anions of Transition Elements

One of the most characteristic chemical properties of these elements is the occurrence of multiple oxidation states. Mn(II) Mn(VI) Mn(VII)

Mn(VII)

V(V)

Cr(VI)

Structure of DNA

Structure of DNA
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DNA is a coiled structure composed of nitrogen bases arranged in a helical manner. DNA may be single helix as in 174 or double helix as in humans and others eukaryotes. In double helix DNA, the two antiparallel polynucleotide strands are interwined in a helix, stabilized through hydrogen bonding between purines and pyrimidines.

Structure Of Nucleic Acids

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Nucleic acids are built with nucleotides and four different nucleic acid bases that are; Monomer---nucleotides o Nitrogenous bases o Purines (Adenine and Guanine) o Pyrimidines (Cytosine and Thymine) o Sugar o Ribose o Deoxyribose o Phosphates o +nucleoside=nucleotide

Intercalation of Metal Complexes with

Nucleic Acids
Intercalation of metal complexes with nucleic acids is mainly of 3 types: 1. Coordination. 2. Intercalation. 3. Hydrogen bonding.
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Coordination
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Most metal complexes interact with nucleic acids by forming a coordination bond between soft metal ions and nucleophilic positions of the bases. E.g. cis-(NH3)2Pt Platinum centre coordinates with N7 position of guanine bases. Other nucleophilic sites coordinated by soft metal ions are N7 position of Adenine, N3 position of Cytosine, etc

Intercalation
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Highly selective interaction arises by a weaker non-covalent interaction of ligands of coordinatively saturated metal complexes with nucleic acid. E.g. Planar aromatic heterocyclic ligands such as phenanthroline. These can stick between DNA base pairs, stabilized through dipole-dipole interactions. Free energy of stabilization is 210 K cal

Hydrogen Bonding
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Hydrogen bonding interactions between of coordinated ligands with the polynucleotide arise with phosphate oxygen atom. E.g. Hydrogen bonding between oxygen atoms of phosphate (oligonucleotide) and amine hydrogen's of cobalt hexamine complex.

Techniques in Monitor Binding

Tris(phenanthroline)

Techniques employed for studying the binding of coordination complex are mainly of 3 types: 1. Visible Spectroscopy 2. NMR Spectroscopy 3. Gel Electrophoresis These are easily explained by tris(phenanthroline).
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Visible Spectroscopy
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Colours of coordination provide a useful and sensitive spectroscopic fundamental reactions. Tris(phenanthroline) metal complexes in their interaction with nucleic acids are highly coloured because of intense metal-to-ligand charge transfer. (max = 447nm). These complexes are very much photoluminescent at max= 610nm. On binding with nucleic acids this transitions are perturbed.

NMR Spectroscopy
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In NMR technique the binding of DNA oligonucleotide provides resonance shifts variations in H-NMR. These variations are used empirically to watch the dynamics of association and to gain some structural insights into the binding modes of the complexes on the helix. These kinds of experiments have been performed with tris(phenanthroline) complexes of ruthenium-II and rhodium-III.

Gel Electrophoresis
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Gel electrophoresis experiments permits an assessment of change in nucleic acid conformation through its change in gel mobility. In Gel electrophoresis, the supercoiled form of DNA-I is differentiated from nickel DNA (form II) in an agarose gel because of different mobilities. The supercoiled molecule moves easily through gelatinous matrix to the positive pole, whereas nickel species is more floppy and is thus inhibited in its travel down the gel.

Application of Nuclease activity metal complexes

Function Of Carbonic Anhydrase Carbonic anhydrase, enzyme found in red blood cells, gastric mucosa, pancreatic cells, and renal tubules that catalyzes the interconversion of carbon dioxide (CO2) and carbonic acid (H2CO3). Carbonic anhydrase plays an important role in respiration by influencing CO2 transport in the blood. The enzyme also functions in the formation of hydrochloric acid by the stomach.

Zinc Fingers

Function of Zinc Fingers

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A zinc finger is a small protein structural motif that is characterized by the coordination of one or more zinc ions in order to stabilize the fold. Zinc finger proteins are among the most abundant proteins in eukaryotic genomes. Their functions are extraordinarily diverse and include DNA recognition, RNA packaging, transcriptional activation, regulation of apoptosis, protein folding and assembly, and lipid binding.

Haemoglobin

Function of Haemoglobin
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Hemoglobin is an iron-protein compound in red blood cells that gives blood its red color and transports oxygen, carbon dioxide, and nitric oxide. About 70 percent of your body's iron is found in the red blood cells of your blood called hemoglobin. Hemoglobin interacts with nitric oxide (NO) to regulate the blood pressure.

Myoglobin

Function of Myoglobin
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Myoglobin is an iron and oxygen binding protein found in the muscle tissue of vertebrates in general and in almost all mammals. Only time Myoglobin is found in the bloodstream is when it is released following muscle injury. Only one site to attach with oxygen as compared to Haemoglobin where, there are four sites for attachment.

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