Platinum(II) complexes as spectroscopic probes for biomolecules

Avanceña Ratilla, Eva
Major Professor
Nenad M. Kostic
Committee Member
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The use of platinum(II) complexes as tags and probes for biomolecules is indeed advantageous for their reactivities can be made selective for certain purposes through an interplay of mild reaction conditions and of the ligands bound to the platinum;The use of [superscript]195Pt NMR as a method of detecting platinum and its interactions with biomolecules was carried out with the simplest model of platinum(II) tagging to proteins. Variable-temperature [superscript]195Pt NMR spectroscopy proved useful in studying the stereodynamics of complex thioethers like methionine. Its use, however, with large macromolecules, such as proteins, needs to be re-evaluated in view of the potential peptide hydrolysis mediated by platinum as well as the concurrent problems of increased viscosity and relaxation in proteins;The complex, Pt(trpy)Cl[superscript]+, with its chromophore has a greater potential for probing proteins. It is a noninvasive and selective tag for histidine and cysteine residues on the surface of cytochrome c at pH 5. The protein derivatives obtained are separable, and the tags are easily quantitated and differentiated through the metal-to-ligand charge transfer bands which are sensitive to the environment of the tag;Increasing the pH to 7.0 led to the modification by Pt(trpy)Cl[superscript]+ of Arg 91 in cytochrome c. Apparently, Arg 91 which is proximate to an [alpha]-helix has a low pK a. This was the first report for metal-binding to arginines in proteins;Further studies with guanidine-containing ligands as models for arginine modification by Pt(trpy)Cl[superscript]+ showed that guanidine can act as a terminal ligand and as a bridging ligand. The crystal structure of the complex with the oxo-analog or arginine-canavanine (Can), (\Pt(trpy)\2Can) (ClO4)3·5.5H2O, is the first definitive structural proof of metal-binding to guanidines. The two Pt(trpy)[superscript]2+ moieties in the structure are stacked and nearly eclipsed;Owing to the potential utility of Pt(trpy)L[superscript] n+ as electron dense probes of nucleic acid structure, interactions of this bis-Pt(trpy)L[superscript]2+ complex with nucleic acids was evaluated. Indeed, the complex interacts non-covalently with nucleic acids. Its interactions with DNA are not exactly the same as those of its precedents. Most striking is its ability to form highly immobile bands of DNA upon gel electrophoresis.