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

Shuang Ding, Lei Jia, Alexander Durandin, Conor Crean, Alexander Kolbanovskiy, Vladimir Shafirovich, Suse Broyde, Nicholas E. Geacintov

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1189-1193
Number of pages5
JournalChemical Research in Toxicology
Volume22
Issue number6
DOIs
StatePublished - Jun 15 2009

Fingerprint

Allantoin
Stereoisomerism
Optical Rotatory Dispersion
Circular Dichroism
Enantiomers
Guanine
Oxidation
Molecules
spiroiminodihydantoin
DNA
Processing
Chemical analysis

ASJC Scopus subject areas

  • Toxicology

Cite this

Absolute configurations of spiroiminodihydantoin and allantoin stereoisomers : Comparison of computed and measured electronic circular dichroism spectra. / Ding, Shuang; Jia, Lei; Durandin, Alexander; Crean, Conor; Kolbanovskiy, Alexander; Shafirovich, Vladimir; Broyde, Suse; Geacintov, Nicholas E.

In: Chemical Research in Toxicology, Vol. 22, No. 6, 15.06.2009, p. 1189-1193.

Research output: Contribution to journalArticle

Ding, Shuang ; Jia, Lei ; Durandin, Alexander ; Crean, Conor ; Kolbanovskiy, Alexander ; Shafirovich, Vladimir ; Broyde, Suse ; Geacintov, Nicholas E. / Absolute configurations of spiroiminodihydantoin and allantoin stereoisomers : Comparison of computed and measured electronic circular dichroism spectra. In: Chemical Research in Toxicology. 2009 ; Vol. 22, No. 6. pp. 1189-1193.
@article{1d5d033b028c4709b8536fce77cba9a8,
title = "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.",
author = "Shuang Ding and Lei Jia and Alexander Durandin and Conor Crean and Alexander Kolbanovskiy and Vladimir Shafirovich and Suse Broyde and Geacintov, {Nicholas E.}",
year = "2009",
month = "6",
day = "15",
doi = "10.1021/tx900107q",
language = "English (US)",
volume = "22",
pages = "1189--1193",
journal = "Chemical Research in Toxicology",
issn = "0893-228X",
publisher = "American Chemical Society",
number = "6",

}

TY - JOUR

T1 - Absolute configurations of spiroiminodihydantoin and allantoin stereoisomers

T2 - Comparison of computed and measured electronic circular dichroism spectra

AU - Ding, Shuang

AU - Jia, Lei

AU - Durandin, Alexander

AU - Crean, Conor

AU - Kolbanovskiy, Alexander

AU - Shafirovich, Vladimir

AU - Broyde, Suse

AU - Geacintov, Nicholas E.

PY - 2009/6/15

Y1 - 2009/6/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=67449126480&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67449126480&partnerID=8YFLogxK

U2 - 10.1021/tx900107q

DO - 10.1021/tx900107q

M3 - Article

C2 - 19485408

AN - SCOPUS:67449126480

VL - 22

SP - 1189

EP - 1193

JO - Chemical Research in Toxicology

JF - Chemical Research in Toxicology

SN - 0893-228X

IS - 6

ER -