The Library
Mechanism of interstrand migration of organoruthenium anticancer complexes within a DNA duplex
Tools
Wu, Kui, Luo, Qun, Hu, Wenbing, Li, Xianchan, Wang, Fuyi, Xiong, Shaoxiang and Sadler, P. J. (2012) Mechanism of interstrand migration of organoruthenium anticancer complexes within a DNA duplex. Metallomics, Vol.4 (No.2). pp. 139-148. doi:10.1039/c2mt00162d ISSN 1756-5901.
Research output not available from this repository.
Request-a-Copy directly from author or use local Library Get it For Me service.
Official URL: http://dx.doi.org/10.1039/c2mt00162d
Abstract
Organometallic ruthenium(II) anticancer complexes [(eta(6)-arene)Ru(en)Cl][PF6] (e.g. arene = biphenyl (bip, 1), indane (ind, 2); en = ethylenediamine) bind to N7 of guanine (G) in DNA selectively. The fragment {(eta(6)-bip)Ru(en)}(2+) (1') bound to N7 of one guanine residue at a 14-mer duplex DNA migrates readily to other guanine residues in both the same strand and the complementary strand when the strands are hybridized at elevated temperature. In this work, by applying HPLC coupled to mass spectrometry, the mechanism of such intra- and interstrand migration was investigated using a 15-mer duplex, in which one strand 5'-CTCTCTTG(8)TCTTCTC-3' (I) contained a single guanine (G(8)). The results show that the interstrand migration of complexes 1 and 2 within the duplex involves an SN1 pathway, firstly solvent-assisted dissociation of the initially G(8)-bound adducts I-G(8)-1' and I-G(8)-2' (2' = {(eta(6)-ind)Ru(en)}(2+)) as the rate-controlling step, and secondly the coordination of the dissociated 1' and 2' to guanine bases (G(21) for 1', either G(21) or G(18) for 2') on strand II. The high temperature used to anneal the single strands was found to increase the migration rate. The formation of the duplex acts as a key driving force to promote the dissociation of G(8)-bound 1' and 2' due to the competition of cytosine in II with the en-NH2 groups in 1' and 2' for H-bonding with C6O of guanine. Complex 2 (t(1/2) = 18 h) containing a mono-ringed arene ligand dissociates more readily from the initially binding site G(8) than complex 1 (t(1/2) = 23 h). The extended biphenyl arene ligand which is intercalated into DNA stabilizes the adduct I-G(8)-1'. These results provide new insight into this unusual metal migration, and are of significance for the design and development of more active organometallic ruthenium anticancer complexes.
Item Type: | Journal Article | ||||
---|---|---|---|---|---|
Subjects: | Q Science > QD Chemistry | ||||
Journal or Publication Title: | Metallomics | ||||
Publisher: | Royal Society of Chemistry | ||||
ISSN: | 1756-5901 | ||||
Official Date: | 2012 | ||||
Dates: |
|
||||
Volume: | Vol.4 | ||||
Number: | No.2 | ||||
Page Range: | pp. 139-148 | ||||
DOI: | 10.1039/c2mt00162d | ||||
Status: | Peer Reviewed | ||||
Publication Status: | Published | ||||
Access rights to Published version: | Restricted or Subscription Access | ||||
Funder: | Guo jia zi ran ke xue ji jin wei yuan hui (China) [National Natural Science Foundation of China] (NSFC), China. Guo jia ke xue ji shu bu [Ministry of Science and Technology] (CMST), Chinese Academy of Sciences , European Research Council under the European Community/ERC | ||||
Grant number: | 90713020, 20975103, 21020102039, 21135006(NSFC), 2007CB935601 (CMST), 24363 (ERC) |
Data sourced from Thomson Reuters' Web of Knowledge
Request changes or add full text files to a record
Repository staff actions (login required)
View Item |