Metallointercalator-DNA Conjugates: Synthesis and Application in Investigations of DNA-Mediated Electron and Energy Transfer

Author: Holmlin, R. Erik

Year: 1998

Degree: Dissertation (Ph.D.)

Advisor: Barton, Jacqueline K.

Committee Members: Carreira, Erick Moran; Zewail, Ahmed H.; Bercaw, John E.; Gray, Harry B.; Barton, Jacqueline K.

Option: Chemistry

DOI: 10.7907/d46y-nm88

Abstract

The DNA base stack offers a unique medium for long-range charge transfer (CT). Dipyridophenazine (dppz) complexes of Os(II) were characterized as a new class of luminescent DNA probes and applied in mechanistic studies of DNA-mediated electron transfer (ET). The product of ET between [Os(phen)2(dppz)]2+ and [Rh(phi)2(bpy)]3+ (phi = phenanthrenequinone diimine) was spectroscopically characterized to confirm the mechanism of ET in quenching reactions on DNA. The rate of photoinduced ET is > 3 x 1010 s-1 and the rate of recombination is ~1010 s-1 for several donor-acceptor pairs. The rate and efficiency of ET depend sensitively on the DNA binding properties of the reactants and DNA sequence, which underscores the importance of π-stacking interactions in ET through the DNA base stack.

To investigate long-range DNA-mediated CT in well defined molecular assemblies, a methodology was developed to tether metallointercalators to the 5', 3', or both termini of oligonucleotides on a solid support. This method permits the construction of metallointercalator-DNA conjugates possessing metal complexes that vary in photochemical and photophysical properties, as well as structure. These diverse properties were exploited to characterize the intercalation of the tethered complexes and the chemical composition of the materials.

Several CT reactions in modified duplexes were investigated. Rh-modified oligonucleotides were employed to introduce a photoexcited hole into the DNA π-stack at a precise location and initiate remote oxidative repair of thymine dimer lesions in duplex DNA. The yield of repair was sensitive to the stacking of the photooxidant and the intervening bases, but not distance. Here, the DNA bases mediate CT over long-range (26 Å) and serve as a reactant. The yield of photoinduced ET between [M(phen)2(dppz)]2+ (M = Os, Ru) and [Rh(phi)2(bpy)]3+ derivatives tethered to opposite ends of oligoduplexes (14-18 bp) was modest (≤ 15%) and sensitive to sequence and orientational isomer. This lower efficiency of ET compared with studies of metallointercalators bound noncovalently to DNA may reflect the inhibition of stacking introduced by the tether.

The DNA base stack has been shown also to mediate triplet energy transfer (TET), which consists of simultaneous hole transfer and ET. The yield of subnanosecond DNA-mediated TET between Ru(II) and Os(II) metallointercalators tethered to DNA is found to be remarkably sensitive to the stacking of the metal complexes in the duplex, and the stacking of the intervening bases. TET is observed over a distances ranging from 27-40 Å and requires intercalated reactants. The distance dependence for subnanosecond TET in duplexes 14-18 bp in length is extremely shallow, especially for TET, which required two CT events. These studies illustrate the facility of CT through the DNA base stack and the sensitivity of several DNA-mediated CT reactions π-stacking of the reactants and the medium.

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