Polycyclic aromatic hydrocarbons physically intercalate into duplex regions of denatured DNA

Abstract

We have investigated the physical binding of pyrene and benzo[a]pyrene derivatives to denatured DNA. These compounds exhibit a red shift in their absorbance spectra of 9 nm when bound to denatured calf thymus DNA, compared to a shift of 10 nm when binding occurs to native DNA. Fluorescence from the hydrocarbons is severely quenched when bound to both native and denatured DNA. Increasing sodium ion concentration decreases binding of neutral polycyclic aromatic hydrocarbons to native DNA and increases binding to denatured DNA. The direct relationship between binding to denatured DNA and salt concentration appears to be a general property of neutral polycyclic aromatic hydrocarbons. Absorption measurements at 260 nm were used to determine the duplex content of denatured DNA. When calculated on the basis of duplex binding sites, equilibrium constants for binding of 7,8,9,10-tetrahydroxy-7,8,9,10-tetrahydro-benzo[a]pyrene to denatured DNA are an order of magnitude larger than for binding to native DNA. The effect of salt on the binding constant was used to calculate the sodium ion release per bound ligand, which was 0.36 for both native and denatured DNA. Increasing salt concentration increases the duplex content of denatured DNA, and it appears that physical binding of polycyclic aromatic hydrocarbons consists of intercalation into these sites.

The mechanism of antimalarial action of the ruthenium(II)–chloroquine complex [RuCl2(CQ)]2

“…This observation, together with the idea that lipids catalyze heme aggregation within plasmodium food vacuoles [47,48] and with the findings of Egan et al [36] that β-hematin spontaneously forms by rapid self-assembly near octanol-water or lipid-water interfaces can explain the enhanced antimalarial activity of complex 1 both in vitro and in vivo, when compared with CQ. Furthermore, the fact that the complex is active against CQ-resistant strains of P. falciparum may also be related to its greater lipophilicity, in line with previous reports indicating a lowered ability of the mutated transmembrane transporter PfCRT to promote the efflux of highly lipophilic drugs [40,51]. Partition coefficients for a chloroquine diphosphate (CQDP) and b [RuCl 2 (CQ)] 2 (1) in a 1:1 n-octanol-water mixture Interaction of complex 1 with hematin at pH 7.4 Heme aggregation inhibition at different concentrations of CQDP (filled circles) and complex 1 (open circles) in a acetate buffer at pH 5 after 24-h incubation at 37°C and b n-octanol-acetate buffer at pH 4.9 (2:5 by volume) after 30-min incubation at 37 °C Hydrolysis of complex 1…”

“…Absorption spectra were recorded at 330 and 343 nm and the titration was terminated when the intensity at those wavelengths did not change significantly upon further addition of DNA. The simple model often used [40,41] to calculate a single binding constant according to the equation…”

Highly enantioselective DNA-based catalysis

“…1 After dissolution of salmon testes DNA (2 mg/ml), the stock solution was dialyzed extensively against Mops buffer (20 mM pH 6.5) prior to use. The concentration in base pairs was determined spectrophometrically, using ε 260 = 12800 M -1 cm -1 .…”

Alkyl and aryl sulfonyl p-pyridine ethanone oximes are efficient DNA photo-cleavage agents

“…The binding constant, K b , can be obtained by monitoring the changes in the absorbance at the corresponding λ max with increasing concentrations of CT DNA and it is given by the ratio of slope to the y intercept in plots [DNA] / (ε A − ε f ) versus [DNA], according to the Wolfe-Shimer equation [23]:…”