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- Wilhelmsson, Marcus, 1974, et al.
(författare)
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Meso stereoisomer as a probe of enantioselective threading intercalation of semirigid ruthenium complex [µ-(11,11'-bidppz)(phen)4Ru2]4
- 2003
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Ingår i: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-5207 .- 1520-6106. ; 107:42, s. 11784-11793
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Tidskriftsartikel (refereegranskat)abstract
- Upon interaction with calf thymus DNA the Lambda,Lambda-enantiomer of the semirigid binuclear ruthenium complex [mu-(11, 11'-bidppz)(phen)(4)Ru-2](4+) has previously been shown to reorganize from an initial groove bound geometry into an intercalative binding mode, threading one of its bulky Ru(phen)(2) moieties through the core of the DNA. We have now found that all three stereoisomers, Delta,Delta; Lambda,Lambda; and Delta,Lambda (meso), are intercalated in their final modes of binding to calf thymus DNA, poly(dA-dT)(2), poly(dG-dC)(2), as well as poly(dI-dC)(2) indicated by linear dichroism, circular dichroism, and luminescence. For all three stereoisomers, studied in detail with poly(dA-dT)(2), the bridging bidppz ligand is intercalated in anti conformation, leaving one Ru(phen)(2) Moiety in each groove. This final binding geometry is characterized by a distinct clockwise roll of the Ru(phen)(2) moiety in the minor groove, similar to the roll earlier observed for the dppz ligand in [Ru(phen)(2)dppz](2+). Using the meso stereoisomer as an enantioselective probe, it is shown that the Lambda moiety prefers to insert itself deeply into the minor groove while the Delta moiety, in the major groove, is somewhat displaced from the center of the DNA helix. The preceding, metastable bound geometries are concluded to be in the major groove for calf thymus DNA, poly(dG-dC)(2), and poly(dI-dC)(2), with the Delta,Delta form displaying an angle of the bidppz bridge relative the DNA helix axis of about 50degrees, whereas the corresponding angles for the meso- and Lambda,Lambda-forms in calf thymus DNA are around 65degrees, suggesting an orientation in the groove more parallel to the bases. By contrast, in poly(dA-dT)(2) none of the stereoisomers exhibits any distinguishable initial groove binding mode, but all seem to bind by threading intercalation directly.
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| 2. |
- Westerlund, Fredrik, 1978, et al.
(författare)
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Micelle-sequestered dissociation of cationic DNA-intercalated drugs: Unexpected surfactant-induced rate enhancement
- 2003
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 1520-5126 .- 0002-7863. ; 125:13, s. 3773-3779
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Tidskriftsartikel (refereegranskat)abstract
- Detergent sequestration using micelles as a hydrophobic sink for dissociated drug molecules is an established technique for determination of dissociation rates. The anionic surfactant molecules are generally assumed not to interact with the anionic DNA and thereby not to affect the rate of dissociation. By contrast, we here demonstrate that the surfactant molecules sodium dodecyl sulfate (SDS), sodium decyl sulfate, and sodium octyl sulfate all induce substantial rate enhancements of the dissociation of intercalators from DNA. Four different cationic DNA intercalators are studied with respect to surfactant-induced dissociation. Except for the smallest intercalator, ethidium, the dissociation rate constants increase monotonically with surfactant concentration both below cmc and (more strongly) above cmc, much more than expected from electrostatic effects of increased counterion concentration. The rate enhancement, most pronounced for the bulky, multicationic, hydrophobic DNA ligands in this study, indicates a reduction of the activation energy for the ligand to pass out from a deeply penetrating intercalation site of DNA. The discovery that surfactants enhance the rate of dissociation of cationic DNA-intercalators implies that rate constants previously determined by micelle-sequestered dissociation may have been overestimated. As an alternative, more reliable method, we suggest instead the addition of excess of dummy DNA as an absorbent for dissociated ligand.
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