Circular Dichroism Studies on Anthracycline Antitumor Compounds. Relationship between the Molecular Structure and the Spectroscopic Data

Abstract

The band assignment of the circular dichroism (CD) spectra of anthracyclines can provide us with the tools to study the interaction of these molecules with biomolecules, such as DNA and membranes, and also with metal ions. This paper reports the CD spectra of 17 anthracycline derivatives and the tentative assignment of the bands to specific electronic transitions. The deprotonation of some anthracyclines, such as doxorubicin, daunorubicin, and idarubicin, have been also studied in order to characterize the electronic transitions involved in the acid-base process. Our evidence suggests the following assignment. The position of the band assigned to pi-->pi transition, polarized along the short axis of the molecule ( approximately 290 nm), does not depend on the hydroxyl group at C(11) (presence and/or ionization state), whereas the position of the band assigned to the pi-->pi transition ( approximately 480 nm), polarized along the long axis, is strongly dependent on it. Concerning the n-->pi transitions, the bands at approximately 320 and approximately 350 nm have a strong contribution of the n-->pi C(12)=O transition and the n-->pi C(5)=O transition, respectively.

Interaction of Uranyl Ions with Daunorubicin and Adriamycin

“…Additionally, the intensity of the band at 317 nm is exactly the same as the original band at 290 nm, while C(6)ϪOH deprotonation is followed by a decrease in the intensity of this band. [27] Such a decrease in the energy of the πǞπ* transitions along the sort axis of the chromophore has previously been observed in the case of Sn IV with Adr. [30] The authors saw no evidence for participation of the phenolic groups, despite the fact that a shift of the band at 290 nm to higher wavelengths accompanied the complexation of Adr to Sn IV .…”

“…In contrast, the red shift of the UV band from 290 to 320 nm in the CD spectra is characteristic of the deprotonation of the second phenolic group at C(6). [27] A more detailed examination of these spectra reveal that this is not the case, however, since neither the red shift for the band at 350 nm nor the bathochromic shift of the main visible band from 450 to about 620 nm can account for this deprotonation. Additionally, the intensity of the band at 317 nm is exactly the same as the original band at 290 nm, while C(6)ϪOH deprotonation is followed by a decrease in the intensity of this band.…”

“…The formation of more than one species is evident for most of the metal ions examined, the predominance of which depends on the metal-toligand molar ratio, the pH, and the dielectric constant of the solvent. However, spectroscopic analysis, especially the CD spectra, can provide many detailed characteristics of the complexes formed, [27] while NMR spectroscopy has also proved to be a powerful tool for the study of these systems. [14,28] In pure water and under our experimental conditions most anthracyclines exist in the fully protonated and dimeric state.…”

“…The bathochromic shifts of the visible absorption and CD spectra bands show that complexation takes place to the drug's chromophore after deprotonation of either the C(11) or C(6) phenolic groups, in order of acidity. [19] The position of the absorption bands at 560Ϫ600 nm can account for the deprotonation of the first phenolic group [27] and coordination to UO 2 2ϩ through the oxygens of the [C (11)ϪO Ϫ , C(12)ϭO] donor site, forming a six-member chelate ring. In contrast, the red shift of the UV band from 290 to 320 nm in the CD spectra is characteristic of the deprotonation of the second phenolic group at C(6).…”

Structure of metal adducts of anthracyclines probed by absorption, circular dichroism and paramagnetic NMR

“…An analogous shift, a sign of drastic changes of the ligand electronic features, occurred in the daunorubicin absorption spectrum acquired under basic deprotonating conditions. 41 Since the coordination of different lanthanides produces spectral changes (Vis absorption and 1 H NMR) similar to those generated by Ca 2C , we can consider the complexes of the two types of ion to be isomorphous.…”