Contributions of Hydroxyethyl Groups to the DNA Binding Affinities of Anthracene Probes

Abstract

Contributions of hydroxyethyl functions to the DNA binding affinities of substituted anthracenes are evaluated by calorimetry and spectroscopy. Isothermal titration calorimetry indicated that binding of the ligands to calf thymus DNA (5 mM Tris buffer, 50 mM NaCl, pH 7.2, 25 degrees C) is exothermic. The binding constants increased from 1.5 x 10(4) to 1.7 x 10(6) M(-1) as a function of increase in the number of hydroxyethyl functions (0-4). DNA binding was accompanied by red-shifted absorption (approximately 630 cm(-1)), strong hypochromism (>65%), positive induced-circular dichroism bands, and negative linear dichroism signals. DNA binding, in general, increased the helix stabilities to a significant extent (DeltaT(m) approximately 7 degrees C, DeltaDeltaH approximately 3 kcal/mol, DeltaDeltaS approximately 6-20 cal/K.mol). The binding constants showed a strong correlation with the number of hydroxyethyl groups present on the anthracene ring system. Analysis of the binding data using the hydrophobicity parameter (Log P) showed a poor correlation between the binding affinity and hydrophobicity. This observation was also supported by a comparison of the affinities of probes carrying N-ethyl (Kb = 0.8 x 10(5) M(-1)) versus N-hydroxyethyl side chains (Kb = 5.5 x 10(5) M(-1)). These are the very first examples of a strong quantitative correlation between the DNA binding affinity of a probe and the number of hydroxyethyl groups present on the probe. These quantitative findings are useful in the rational design of new ligands for high-affinity binding to DNA.

Pyrazolyl–Diamine Ligands That Bear Anthracenyl Moieties and Their Rhenium(I) Tricarbonyl Complexes: Synthesis, Characterisation and DNA‐Binding Properties

“…However, the spectra of These data are consistent with the positive ICD spectra that were recently reported for other amine derivatives of anthracene that have been recognised as DNA intercalators. [13,16,23] In contrast, the molecules that contain the anthracenyl chromophore at the 4-position of the pyrazole ring, Ant-pz*NN (pz* = pz, As an example, the ICD spectra that were obtained for L 4 and complex 9 are presented in Figure 5. This behaviour resembles that which was reported recently by Kumar et al for an anthracenyl derivative that bore 2-hydroxyethylamine substituents at the 9-and 10-positions, a compound that has been proposed to be more likely to be bound to DNA through a groove-binding mode.…”

Arm effects of mononuclear armed cyclen copper complexes on DNA cleavage

“…The results demonstrate that complex 6a is an excellent chemical nuclease, which could cleave plasmid DNA via an oxidative pathway in the absence of any exogenous agents. The side chain on complex 6a appears to bind to the DNA through the p-p stacking binding mode, making 6a to be more efficient than the other complexes in the catalytic cleavage process [40][41][42][43]. …”

The benzo[b]quinolizinium ion as a water-soluble platform for the fluorimetric detection of biologically relevant analytes

“…Unfortunately, anthracene and most of its derivatives are hardly soluble in water, which constitutes a major drawback for the application of this fluorophore in biologically or physiologically relevant media. Although the introduction of appropriate substituents may increase the solubility in aqueous media, [29][30][31][32][33][34] the synthesis of such compounds is often tedious and time-consuming or the solubility-mediating functionalities interfere with the desired photophysical properties of anthracene. With this shortcoming in mind we turned our attention to the isoelectronic, but water-soluble benzo[b]quinolizinium (2a, Chart 1), 35,36 that is also named 4a-azoniaanthracene or acridizinium, in which one bridgehead carbon atom of the anthracene scaffold is replaced with a quaternary nitrogen atom, yielding a permanent positive charge.…”