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Review
, 21 Suppl 1 (0 1), E231-41

Absolute Configurations of DNA Lesions Determined by Comparisons of Experimental ECD and ORD Spectra With DFT Calculations

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Review

Absolute Configurations of DNA Lesions Determined by Comparisons of Experimental ECD and ORD Spectra With DFT Calculations

Shuang Ding et al. Chirality.

Abstract

The usefulness of modern density functional theory (DFT) methods is considered for establishing the absolute configurations of DNA lesions by comparisons of computed and experimentally measured optical rotatory dispersion (ORD) and electronic circular dichroism (ECD) spectra. Two rigid, structurally different DNA lesions (two spiroiminodihydantoin stereoisomers and four equine estrogen 4-hydoxyequilenin-DNA stereoisomeric adducts) have been investigated. In all cases, the signs and shapes of the computed ORD spectra reproduced the experimentally measured ORD spectra, although the magnitudes of the computed and experimental ORD values do not coincide exactly. The computed ECD spectra also reproduced the shapes of the experimental ECD spectra rather well, but are blue-shifted by 10-20 nm. Since the assignments of the absolute configurations of the DNA lesions studied based on computed and experimental ORD and ECD spectra are fully consistent with one another, the computational DFT method shows significant promise for determining the absolute configurations of DNA lesions. Establishing the stereochemistry of DNA lesions is highly useful for understanding their biological impact, especially when sufficient amounts of material are not available for other methods of structural characterization.

Figures

Figure 1
Figure 1
Comparisons of chemical structures of estrone and equine estrogens, the metabolite 4-hydroxyequilenin, and the stereochemical properties of 4-OHEN-C and -A adducts.
Figure 2
Figure 2
Structures of spiroiminodihydantoins.
Figure 3
Figure 3
Block diagram of ORD spectrometer.
Figure 4
Figure 4
ORD of amino acids measured using the apparatus depicted in Figure 3. Concentrations: 1g/100mL in 0.1N HCl. The results are presented in terms of molar rotation units to facilitate comparison with the previous work of Iizuka,E. and Yang, J.T., Biochemistry, 3, 1519 (1964).
Figure 5
Figure 5
Top panel: Comparisons of computed 4-OHEN-C3 and -C4 adduct ORD spectra (circles) and experimentally measured ORD spectra (solid lines) of C3 and C4 adducts (see the text). Middle and bottom panels: Computed 4-OHEN-C3 and -C4 adduct ECD spectra (dashed lines), and comparisons with experimentally measured ECD spectra (solid lines) of C3 and C4 adducts (see the text).
Figure 6
Figure 6
Top panel: Comparisons of computed S- and R-Sp ORD spectra (circles), and experimentally measured ORD spectra (solid lines). Middle and bottom panels: Computed R- and S-Sp ECD spectra (dashed lines), and comparisons with experimentally measured ECD spectra (solid lines). The experimental CD spectra are expressed in mdeg/per absorbance unit at 230 nm (1.0 cm optical pathlength).

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