Intercalation mode

The term intercalation was first described in 1982 and it was found that intercalators shows a high affinity to double-stranded DNA structures because they prefer to locate between two adjacent pairs of bases [38], Intercalator molecules usually have planar aromatic rings, for example, some antibiotics such as daunomycin destroy deoxyribose-phosphate structure. These molecules are stabilized by r-bonds with bases [39], 

Intercalators have generally high DNA-binding constants (partition coefficients), and therefore after the interaction between intercalator compound and double helix, a conformational change occurs onto DNA that gives a very favorable free energy of complex formation [14], On the other hand, in bis-intercalators, for example, Echinomycin, two intercalative interactions perform via covalent bonds between aromatic rings of the molecule and DNA [14]. 

7-dimethyl-amino-l,2-benzophenoxazinium salt (Meldola s blue [MDB]) is also used as an electrochemical hybridization mediator [40-43] and an analysis of its intercalation mechanism has been reported by Reid etal [44]. 

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However, such intercalation involves the insertion of a flat molecule, with a ir-electron system, between the ir-electron systems of the bases of DNA. Therefore a buckled molecule and/or a methyl group will not fit well in such an intercalation mode. Thus, since the buckled molecules (with a methyl group in the bay region) are more carcinogenic, we concluded that complete intercalation of the hydrocarbon between the bases of DNA is not a likely mechanism for carcinogenicity, since the less planar molecules are more active in terms of carcinogenic activity. However, as we shall show later, it is possible that the planar portion of the PAH may lie between the bases of DNA in a semi-intercalation mode the methyl groups, if present, probably do not take part in this semi-intercalation. 

The effect of the position of side chains on the intercalation kinetics of anthra-quinones,101 which are related to the aromatic moiety of daunomycin (13), was studied with the stopped flow SDS sequestration technique. Guest molecules 14—17 can have two different intercalation modes, a classic mode where both side chains are located in the same groove of the DNA helix (14 and 16) or a threading mode where the side chains are located in opposite grooves of the DNA (15 and 17) (Scheme 7). The relative position of intercalated 14 with respect to the DNA bases was suggested to be the same as for 13. 

The interaction of the tetracationic [M(4-TRPyP)]" species with calf thymus DNA was studied by UV-Vis and luminescence spectroscopy (168, 169, 240). Dramatic changes were observed in the absorption and emission spectra, as shown in Fig. 25, indicating that the interaction occurs in two steps. When the relative concentration of DNA is low, the Soret band decreases steeply while the luminescence increases a bit, consistent with the predominance of the electrostatic interaction mode. Nevertheless, as the relative concentration of DNA increases, the Soret band shifts to the red and there is a large enhancement of fluorescence, consistent with an intercalation mode. The equilibrium constants for both processes was determined as ti = 1.5 x 10 and7t2 = 2.5 x Zn(4-TRPyP) also in-... 

A simple model has been used to calculate the frequencies of the new modes appearing after Li intercalation. The intercalation mode is given by ... 

Burret PA, Jouanne M, Julien C (1989) Theoretical calculations and Raman spectrum of intercalation modes in Li/lnSe. Z Phys B Condensed Matter 76 451 55... 

These small upfield shifts are similar to the nonspecific Mg + ion effects on the duplex signals in tRNA (Gueron and Shulman, 1975 Gorenstein et al, 1981). This further supports the hypothesis that large (>2 ppm) downfield shifts are only observed for the intercalation mode of drug binding. 

Raman spectra have also been reported on ropes of SWCNTs doped with the alkali metals K and Rb and with the halogen Br2 [30]. It is found that the doping of CNTs with alkali metals and halogens yield Raman spectra that show spectral shifts of the modes near 1580 cm" associated with charge transfer. Upshifts in the mode frequencies are observed and are associated with the donation of electrons from the CNTs to the halogens in the case of acceptors, and downshifts are observed for electron charge transfer to the CNT from the alkali metal donors. These frequency shifts of the CNT Raman-active modes can in principle be u.sed to characterise the CNT-based intercalation compound for the amount of intercalate uptake that has occurred on the CNT wall. 

Searcey et al. have just published additional work that supports an intercalative mode of binding, at least for partial azinomycin structures. They performed DNA unwinding assays with 77 and designed prodrug analogue 95 and conclude that both compounds bind weakly to DNA through intercalation [151],... 

Lerf A (2004) Different modes and consequences of electron transfer in intercalation compounds. J Phys Chem Sol 65 553-563... 

The most important aspect of coralyne is its ability to inhibit DNA relaxation in a fashion significantly similar to the most potent antitumour alkaloid camptothecin, which is known to exert this property [242], Presumably, the most notable biological action of these alkaloids appears to be topoisomerase inhibition [238-242], which has direct relevance to their DNA intercalating property. In this context. Pilch et al. [167] described a mixed binding mode model (Fig. 16) in which the protoberberine structure constitutes portions that can intercalate or bind to the minor groove of DNA. Wang et al. [240] demonstrated that coralyne (Ci) and several of its derivatives (Ce to Ch) (Scheme 5), including the partial saturated... 

Furthermore, it is often possible to extract from the structural analysis of solid solvates a significant information on solvation patterns and their relation to induced structural polymorphism. An interesting illustration has been provided by crystal structure determinations of solvated 2,4-dichloro-5-carboxy-benzsulfonimide (5)35). This compound contains a large number of polar functions and potential donors and acceptors of hydrogen bonds and appears to have only a few conformational degrees of freedom associated with soft modes of torsional isomerism. It co-crystallizes with a variety of solvents in different structural forms. The observed modes of crystallization and molecular conformation of the host compound were found to be primarily dependent on the nature of the solvent environment. Thus, from protic media such as water and wet acetic acid layered structures were formed which resemble intercalation type compounds. 

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