Limits...
Electronic circular dichroism behavior of chiral Phthiobuzone.

Li L, Wang L, Si Y - Acta Pharm Sin B (2014)

Bottom Line: It was found that solvation changed both the conformational distribution and the ECD spectrum of each conformer.The ECD behavior of the bis(thiosemicarbazone) chromophore in a chiral environment is also discussed.Our results indicate that ECD spectroscopy may be a useful tool for the stereochemical evaluation of chiral drugs.

View Article: PubMed Central - PubMed

Affiliation: Beijing Key Laboratory of Active Substances Discovery and Druggability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.

ABSTRACT
Phthiobuzone is a bis(thiosemicarbazone) derivative with a single chiral center which has been used as a racemate in the clinical treatment of herpes and trachoma diseases. In this study, its two enantiomers were prepared from chiral amino acids and their absolute configurations were investigated by electronic circular dichroism (ECD) combined with modern quantum-chemical calculations using time-dependent density functional theory. It was found that solvation changed both the conformational distribution and the ECD spectrum of each conformer. The theoretical ECD spectra of the two enantiomers were in good agreement with the experimentally determined spectra of the corresponding isomers in dimethyl sulfoxide. The ECD behavior of the bis(thiosemicarbazone) chromophore in a chiral environment is also discussed. Our results indicate that ECD spectroscopy may be a useful tool for the stereochemical evaluation of chiral drugs.

No MeSH data available.


Related in: MedlinePlus

Comparison of experimental ECD spectrum of chiral 1 in DMSO (After blue shift 20 nm).
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4590302&req=5

f0020: Comparison of experimental ECD spectrum of chiral 1 in DMSO (After blue shift 20 nm).

Mentions: The overall UV and ECD spectra of 1 shown in Fig. 4 were obtained by averaging the ECD spectra of each conformer using Boltzmann statistics. Based on our experience and on the literature, a lower level basis set can sometimes give better concordance with the experimental data due to the error compensation in the calculation19,20. Thus, the ECD spectra of the enantiomers of 1 were also calculated at the B3LYP/6–31G(d) level using the optimized geometries at the B3LYP/6–31+G(d,p) level in DMSO. Since the TDDFT method has a tendency to underestimate the excitation energy, it is necessary to perform a correction to compensate for systematic computational errors. In this case, the long wavelength absorption band at 349 nm was used for wavelength correction. After a blue shift of 20 nm, the calculated ECD spectra of the enantiomers of 1 were in good agreement with their corresponding experimental ECD spectra. In the gas phase, the theoretical and experimental ECD spectra differed greatly from those in DMSO indicating that solvation has a major effect on both the conformational distribution and excitation properties.


Electronic circular dichroism behavior of chiral Phthiobuzone.

Li L, Wang L, Si Y - Acta Pharm Sin B (2014)

Comparison of experimental ECD spectrum of chiral 1 in DMSO (After blue shift 20 nm).
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4590302&req=5

f0020: Comparison of experimental ECD spectrum of chiral 1 in DMSO (After blue shift 20 nm).
Mentions: The overall UV and ECD spectra of 1 shown in Fig. 4 were obtained by averaging the ECD spectra of each conformer using Boltzmann statistics. Based on our experience and on the literature, a lower level basis set can sometimes give better concordance with the experimental data due to the error compensation in the calculation19,20. Thus, the ECD spectra of the enantiomers of 1 were also calculated at the B3LYP/6–31G(d) level using the optimized geometries at the B3LYP/6–31+G(d,p) level in DMSO. Since the TDDFT method has a tendency to underestimate the excitation energy, it is necessary to perform a correction to compensate for systematic computational errors. In this case, the long wavelength absorption band at 349 nm was used for wavelength correction. After a blue shift of 20 nm, the calculated ECD spectra of the enantiomers of 1 were in good agreement with their corresponding experimental ECD spectra. In the gas phase, the theoretical and experimental ECD spectra differed greatly from those in DMSO indicating that solvation has a major effect on both the conformational distribution and excitation properties.

Bottom Line: It was found that solvation changed both the conformational distribution and the ECD spectrum of each conformer.The ECD behavior of the bis(thiosemicarbazone) chromophore in a chiral environment is also discussed.Our results indicate that ECD spectroscopy may be a useful tool for the stereochemical evaluation of chiral drugs.

View Article: PubMed Central - PubMed

Affiliation: Beijing Key Laboratory of Active Substances Discovery and Druggability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.

ABSTRACT
Phthiobuzone is a bis(thiosemicarbazone) derivative with a single chiral center which has been used as a racemate in the clinical treatment of herpes and trachoma diseases. In this study, its two enantiomers were prepared from chiral amino acids and their absolute configurations were investigated by electronic circular dichroism (ECD) combined with modern quantum-chemical calculations using time-dependent density functional theory. It was found that solvation changed both the conformational distribution and the ECD spectrum of each conformer. The theoretical ECD spectra of the two enantiomers were in good agreement with the experimentally determined spectra of the corresponding isomers in dimethyl sulfoxide. The ECD behavior of the bis(thiosemicarbazone) chromophore in a chiral environment is also discussed. Our results indicate that ECD spectroscopy may be a useful tool for the stereochemical evaluation of chiral drugs.

No MeSH data available.


Related in: MedlinePlus