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The evolution of the UV/Vis spectum of the Tröger's
Base analogue in the presence of increasing concentrations
of DNA appeared almost identical to the changes induced by
protonation of the molecule in acidic medium. This result
would indicate a change in the protonation equilibrium of
the basic molecule due to the interaction with DNA, which
acts as an acidic macromolecule as proposed by Lamm and coll.
Comparison of the circular
dichroism spectra measured in the presence of
CT-DNA and in 3M HCl solution leads to the same
conclusion. The spectra were also recorded for
each enriched enantiomer. In each case very large
changes were observed and characterized by the appearance
of an intense band either positive or negative (depending
on the enantiomer considered) centered respectively at 488
nm and 483 nm. The shapes of the curves are slightly different
which may be indicative of configuration dependent modes of
interaction. For both enantiomers the spectra resemble those
of the protonated species in line with the UV observations.
The magnitude of the induced CD spectra measured for
(-)-TB is slightly greater than that observed
with (+)-TB. This could be indication of
preferential binding of (-)-TB with DNA.
Evolution of the UV/Vis spectra of the
Tröger's Base analogue in the presence of DNA
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As shown in Figure A, large changes of the spectrum were observed, characterized by the appearance of a new broad band centered at 467 nm, whose intensity regularly increased when the DNA to drug ratio r was increased in the range 0-10. These experiments demonstrate that the Tröger's Base analogue interacts with DNA.
The variations are similar to those occurring when the spectrum of TB was recorded at more acidic pH's (Figure B). The simplest interpretation is that the interaction with DNA is accompanied by protonation of the two acridines. The existence of acidic domains surrounding the DNA molecule has already been demonstrated. |
Comparison of the evolution of circular dichroism spectra of
the Tröger's Base analogue
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A) spectra of (+)-TB (solid line) and (-)-TB (dotted line) in pH 3 diluted HCl , c = 10-4 M
B, C, D: spectra recorded in pH 7 phosphate buffer in the presence of various concentrations of CT DNA with the r values given on the spectra (r = DNA(bp)/TB ratio), B) racemic TB, C) (+)-TB, D) (-)-TB In each case, very large changes are observed and characterized by the appearance of an intense band either positive or negative (depending on the enantiomer considered) centered respectively at 488 nm and 483 nm. The shapes of the curves are slightly different which may be indicative of configuration dependent modes of interaction. For both enantiomers the spectra resemble those of the protonated species (Figure A). The magnitude of the induced CD spectra measured for (-)-TB is slightly greater than that observed with (+)-TB. This could be indication of preferential binding of (-)-TB with DNA. |
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[Summary] | [Introduction] | [Synthesis] | [Physico...] | [Enantioselective...] | [Conclusion] |
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