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Functionalized Rhodium Intercalators for DNA Recognition

Terbrueggen, Robert H. and Johann, Timothy W. and Barton, Jacqueline K. (1998) Functionalized Rhodium Intercalators for DNA Recognition. Inorganic Chemistry, 37 (26). pp. 6874-6883. ISSN 0020-1669. https://resolver.caltech.edu/CaltechAUTHORS:20160407-115522359

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Abstract

A series of rhodium complexes containing the phenanthrenequinone diimine (phi) ligand have been prepared which bind DNA by intercalation and, upon photoactivation, promote DNA strand breaks. In this series, the ancillary, nonintercalating bipyridyl or phenanthroline ligands have been functionalized to yield complexes containing guanidinium, amido, or amino groups arranged with defined stereochemistry for site-specific interaction with the DNA bases. Λ-1-[Rh(MGP)_2phi]^(5+) (MGP = 4-(guanidylmethyl)-1,10-phenanthroline) site-specifically targets the 6-base pair sequence 5‘-CATATG-3‘ with a binding affinity of 1 (±0.5) × 10^8 M^(-1) while Δ-1-[Rh(MGP)_2phi]^(5+) displays an affinity of 5 (±2) × 10^7 M^(-1) for 5‘-CATCTG-3‘. Even though these two isomers target sites which differ by only a single base, binding is highly enantioselective. The specificity is derived chiefly from interactions of the pendant guanidinium groups with the DNA bases. For the racemates of 1-[Rh(GEB)_2phi]^(5+) (GEB = (4-(2-guanidylethyl)-4‘-methyl-2,2‘-bipyridine) and 1-[Rh(GPB)_2phi]^(5+) (GPB = (4-(2-guanidylpropyl)-4‘-methyl-2,2‘-bipyridine), photocleavage patterns also show the strongest site of photocleavage as 5‘-CATCTG-3‘, the target site for Δ-1-[Rh(MGP)_2phi]^(5+). Moreover, consistent with the dominance of the guanidinium groups in establishing specificity, significantly enhanced photocleavage is evident for the 1-positional isomer of these complexes, where the guanidinium moieties are directed toward the DNA (above and below the phi ligand) compared to the 2-isomer, in which the guanidinium groups are directed away from the DNA. In contrast to Λ-1-[Rh(MGP)_2phi]^(5+), Λ-1-[Rh(GEB)_2phi]^(5+) shows little cleavage at 5‘-CATATG-3‘; this sensitivity to linker length likely depends on the mode of recognition of 5‘-CATATG-3‘ involving sequence-dependent unwinding of the DNA site. Analogous site-specificity or isomer-specificity is not evident with the complexes which contain pendant amido or amino functionalities. Instead these complexes appear to resemble the parent, unfunctionalized [Rh(phen)_2phi]^(3+) with respect to recognition. Pendant guanidinium functionalities appear to be particularly advantageous in the construction of small molecules which bind DNA with site-specificity.


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URLURL TypeDescription
http://dx.doi.org/10.1021/ic980837jDOIArticle
http://pubs.acs.org/doi/abs/10.1021/ic980837jPublisherArticle
http://pubs.acs.org/doi/suppl/10.1021/ic980837jRelated ItemSupporting Information
ORCID:
AuthorORCID
Barton, Jacqueline K.0000-0001-9883-1600
Additional Information:© 1998 American Chemical Society. Received July 17, 1998. Publication Date (Web): December 3, 1998. We are grateful to the NIH (GM33309) for their financial support of this research and for NRSA training support (R.H.T. and T.W.J.). We also thank Daniel Hall and Dr. Masako Kato for their contributions to optimizing the syntheses and Duncan Odom for manuscript preparation.
Funders:
Funding AgencyGrant Number
NIHGM33309
NIH Predoctoral FellowshipUNSPECIFIED
Issue or Number:26
Record Number:CaltechAUTHORS:20160407-115522359
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20160407-115522359
Official Citation:Functionalized Rhodium Intercalators for DNA Recognition Robert H. Terbrueggen, Timothy W. Johann, and Jacqueline K. Barton Inorganic Chemistry 1998 37 (26), 6874-6883 DOI: 10.1021/ic980837j
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:65986
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:08 Apr 2016 16:22
Last Modified:03 Oct 2019 09:52

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