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Absolute configurations of spiroiminodihydantoin and allantoin stereoisomers: comparison of computed and measured electronic circular dichroism spectra.

ABSTRACT: The assignment of absolute configurations is of critical importance for understanding the biochemical processing of DNA lesions. The diastereomeric spiroiminodihydantoin (Sp) lesions are oxidation products of guanine and 8-oxo-7,8-dihydroguanine (8-oxoG), and the absolute configurations of the two diastereomers, Sp1 and Sp2, have been evaluated by experimental and computational optical rotatory dispersion (ORD) methods. In order to support our previous assignments by the ORD method, we calculated the electronic circular dichroism spectra (ECD) of the Sp stereoisomers. Comparison of the experimentally measured and computed ECD spectra indicates that Sp1 has (-)-S absolute configuration, while Sp2 has (+)-R absolute configuration. Thus, the S and R assignments, based on the ECD spectra of Sp1 and Sp2, are consistent with our previous assignments of absolute configurations. To further test the validity of this approach, we performed a proof-of-principle computation of the ECD and ORD of the R and S enantiomers of allantoin (similar in chemical composition to Sp) of known absolute configurations. The calculations provide the correct assignment of the absolute configurations of the allantoin enantiomers, indicating that the computational TDDFT approach is robust for identifying the absolute configurations of allantoins and probably the Sp stereoisomers, as has been shown previously for other organic molecules.

SUBMITTER: Ding S

PROVIDER: S-EPMC4030679 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature

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Absolute configurations of spiroiminodihydantoin and allantoin stereoisomers: comparison of computed and measured electronic circular dichroism spectra.

Ding Shuang S Jia Lei L Durandin Alexander A Crean Conor C Kolbanovskiy Alexander A Shafirovich Vladimir V Broyde Suse S Geacintov Nicholas E NE

Chemical research in toxicology 20090601 6

The assignment of absolute configurations is of critical importance for understanding the biochemical processing of DNA lesions. The diastereomeric spiroiminodihydantoin (Sp) lesions are oxidation products of guanine and 8-oxo-7,8-dihydroguanine (8-oxoG), and the absolute configurations of the two diastereomers, Sp1 and Sp2, have been evaluated by experimental and computational optical rotatory dispersion (ORD) methods. In order to support our previous assignments by the ORD method, we calculate ...[more]

PMID: 19485408

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Project description:Estrogen components of some hormone replacement formulations have been implicated in the initiation of breast cancer. Some of these formulations contain equine estrogens such as equilin and equilenin that are metabolized to the genotoxic catechol 4-hydroxyequilenin (4-OHEN). Auto-oxidation generates the o-quinone form that reacts with dC and dA in oligodeoxynucleotides to form unusual stable cyclic bulky adducts, with four different stereoisomers identified for each base adduct. The dC and dA adducts have the same unsaturated bicyclo[3.3.1]nonane type linkage site with identical stereochemical characteristics. Stereochemical effects may play an important part in the biological consequences of the formation of 4-OHEN-DNA adducts, and the assignment of the absolute configurations of the stereoisomeric 4-OHEN-dC and -dA adducts is therefore needed to understand structure-function relationships. We used density functional theory (DFT) to compute the specific optical rotations and electronic circular dichroism (ECD) spectra of the four 4-OHEN-C stereoisomers, and the results were compared with experimentally measured optical rotatory dispersion (ORD) and ECD spectra. The predicted ORD curves for the four stereoisomeric base adducts reproduced the shapes and signs of experimental spectra in the transparent spectral region. The stereochemistry of the C3' atom was determined by comparison of the calculated and experimental ORD and ECD spectra, and the stereochemistry of C2' was determined by mass spectrometric methods. Combining the ORD and mass spectrometry data, the absolute configurations of the four 4-OHEN-C and the stereochemically identical -dC adducts have been identified. The molecular architecture of the linkage site at the 4-OHEN-C/A and 4-OHEN-dC/dA is identical, and it is shown that the deoxyribose group does not substantially contribute to the optical activities. The absolute configurations of the 4-OHEN-dA adducts were thus deduced by comparing the experimental ORD with computed ORD values of 4-OHEN-A adducts.

Dataset Information

Absolute configurations of spiroiminodihydantoin and allantoin stereoisomers: comparison of computed and measured electronic circular dichroism spectra.

Publications

Absolute configurations of spiroiminodihydantoin and allantoin stereoisomers: comparison of computed and measured electronic circular dichroism spectra.

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