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Biological and Biophysical Studies on Ruthenium Complexes

Anna Mårtensson (Institutionen för kemi och kemiteknik, Fysikalisk kemi)
Göteborg : Chalmers University of Technology, 2015.

Small molecules that interact with DNA through intercalation are attractive candidates for treatments against cancer and microbial infections. Octahedral ruthenium(II) polypyridyl complexes, being substitution-inert, readily synthesized and coordinately saturated, has the potential of being developed in to a new family of drugs. By modifying the ligands coordinated to the centered ruthenium atom, it is possible to alter the DNA-binding properties, such as selectivity towards a particular sequence. This thesis presents two aspects of the properties of intercalating ruthenium(II) polypyridyl complexes. The first study investigates the DNA interactions of a novel dppz-ruthenium-centered complex with a tridentate ligand. In contrast to more “traditional” complexes with tris-bidentate structures, this complex is not chiral, thus eliminating the need of separating Δ and Λ racemic mixtures. In addition, the single coordination site left free on the ruthenium atom provides another dimension of fine-tuning complex-DNA interaction, a desirable property in the on-going quest for improved DNA sequence specificity. Using both spectroscopic and calorimetric methods, detailed information about the DNA binding thermodynamics and binding geometry was provided. Linear and circular dichroism, as well as isotropic absorption indicated that the metal complex binds to DNA from the minor groove with the dppz ligand intercalated between the base pairs. It was possible to have an excellent global fit for the calorimetric and absorption titration data using a simple cooperative binding model with only one binding geometry. The second study focused on how chirality affect the DNA binding properties of a ruthenium complex. This was done by evaluating the antimicrobial activity of an enantiopure tris-bidentate complex and its binuclear dimer. Both enantiomers of the mononuclear complex showed a high inhibitory and bactericidal effect comparable to clinically available antibiotics against the Gram-positive bacterial model. More interestingly though was the significantly higher antimicrobial activity seen in the Δ-form compared to Λ, strongly indicating a DNA binding mode of action.

Nyckelord: DNA, ruthenium complex, intercalation, circular dichroism, linear dichroism, isothermal titration calorimetry, antimicrobial, metal susceptibility

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Denna post skapades 2015-05-18.
CPL Pubid: 217187


Institutioner (Chalmers)

Institutionen för kemi och kemiteknik, Fysikalisk kemi


Nanovetenskap och nanoteknik
Fysikalisk kemi

Chalmers infrastruktur

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Inkluderade delarbeten:

Binding of Ru(terpyridine)(pyridine)dipyridophenazine to DNA studied with polarized spectroscopy and calorimetry


Datum: 2015-06-09
Tid: 10:00
Lokal: KS101
Opponent: Moa Sandberg Wranne, Ying Lee

Ingår i serie

Licentiatuppsatser vid Institutionen för kemi- och bioteknik, Chalmers tekniska högskola 1652