Cl

Cl

Cl

Cl Cl

Cl

Cl

PCB-183

Toda, M.; Matsumura, C.; Tsurukawa, M.; Okuno, T.; Nakano, T.; Inoue, Y.; Mori, T. J. Phys. Chem. A 2012, 116, 9340.

• (–)-o,p’-DDT is more cytotoxic than (+)-o,p’-DDT. 　 (+)-o,p’-DDD is more cytotoxic than (–)-o,p’-DDD.

44%44%3% 8%

The absolute configurations of o,p'-DDT and o,p'-DDD studied by experimental and theoretical circular dichroisms 

Hiroki Tanaka, Takeshi Nakano, Mitsunobu Toda, Yuki Haga, Masahiro Tsurukawa, Chisato Matsumura, Tadashi Mori and Yoshihisa Inoue

Osaka University and Hyogo prefectural Institute of Environmental Sciences

Chiral insecticides

Experimental and theoretical CD spectra of o,p’-DDT and o,p’-DDD

Summary• Theoretical CD spectra calculated at the

SAC-CI/D95(d)//DFT-D3-TPSS/def2-TZVP reproduced the experimental ones.

• (+)-o,p’-DDT and ( –)-o,p’-DDD have S-configurations.

Theoretical and experimental CD spectra

Enantiomer separation: preparative chiral HPLC on a Daicel Chiralcel OJ-H column eluted with n-hexane/isopropanol (9:1).Spectral measurement: in hexane at 25 °C.

Conformers of o,p’-DDD

Geometry optimization:Energy calculation: Spectral simulation:

o,p’-DDT

ClClCl

*

Cl Cl

o,p’-Dichlorodiphenyl-trichloromethane

(o,p’-DDT)

ClCl

*

Cl Cl

o,p’-Dichlorodiphenyl-dichloromethane

(o,p’-DDD)

insecticide to control malaria and typhus

Wang, C.; Li, Z.; Zhang, Q.; Zhao, M.; Liu, W. Environ. Sci. Technol. 2013, 47, 3909.

Cl

Cl

Cl3C OCOCH3*Acetofenate • For mosquitoes and flies.• S-configuration is more

toxic.

Fipronil• For cockroaches and

ants. • S-configuration is more

toxic.

DDT

Zhao, M.; Liu, W. Environ. Toxicol. Chem. 2009, 28, 578.

The absolute configuration controls pesticidal activities and toxicities.

This work 　 Determination of the absolute configurations of o,p’-DDT and o,p’-DDD

We investigated experimentally and theoretically the CD spectra of o,p’-DDT and o,p’-DDD to unambiguously assign their absolute configurations.

The absolute configuration can be determined by the theoretical calculation.

SAC-CI (Symmetry adapted cluster/configuration interaction)

o,p’-DDD

The bands of thoretical spectra• at longest wavelength: red-shifted because inverse hyperconjugation may

be overestimated.• at shortest wavelength: stronger than experimental ones because the

diffuse function may not be enough.• at 210-250 nm: reproduced the experimental ones satisfactorily.

metabolite of DDT

Evaluated by X-ray crystallography with better refinement parameters (the anomalous dispersion was not taken into account).

Determined by chemical transformation to o,p’-DDT (see above).

• (–)-o,p’-DDT has R-configuration:

• (+)-o,p’-DDD has R-configuration:

Smith, R. A.; Bennett, M. J. Acta Cryst. 1977, B33, 1126.

(R)-(–)-o,p'-DDT

NaBH4

dechlorination(R)-(+)-o,p'-DDD

Buser, H-R.; Muller, M.D. Anal. Chem. 1995, 67, 2691.

DFT-D3-TPSS/def2-TZVPSCS-MP2/def2-TZVPPSAC-CI/D95(d)

(

M-1

cm-1

)

Wavelength (nm)

1st HPLC elute= (+)-o,p'-DDT

2nd HPLC elute=(–)-o,p'-DDT

+50

0

–50

–100200 240 280

10

calc. of (S)-o,p'-DDT

320

(

M-1

cm-1

)

+50

–50

Wavelength (nm)200 240 280

10

–100320

01st HPLC elute= (–)-o,p'-DDD

2nd HPLC elute= (+)-o,p'-DDD

calc. of (S)-o,p'-DDD

(

M-1

cm-1

)

+50

0

–50

Wavelength (nm)200 240 280

10

–100320

ag–

ag+

at

bt

four conformers

B-DNA (tetra model)

RI-CC2 (resolution-of-identity, linear response, approximate coupled cluster)

Cl

ClClCl

H

Cl Cl

H

Cl

Cl

Cl

H Cl

H

Cl

Cl

g–

Cl

Cl H

H

Cl

Cl

g+

a-gauche– (ag–)a-gauche+ (ag+) a-trans (at)

H

Cl Cl

H

ClClb-trans (bt)

= = = =

Ye, J.; Zhao, M.; Liu, J.; Liu, W. Environmental Pollution 2010, 158, 2371.

NF3C

Cl

Cl H2N

CN

SO

F3C

*

Miyahara, T.; Nakatsuji, H.; Sugiyama, H. J. Phys. Chem. A 2013, 117, 42.

• Theoretical CD spectrum of o,p’-DDD was obtained by Boltzmann distribution assumed by the energy gap between various conformers (bg+ and bg– : 0.0%).

• Theoretical CD spectrum of o,p’-DDT is a-form (population of a-form is >99.8%).

• o,p’-DDT1st HPLC fraction: positive ([a]D = +23)2nd HPLC fraction: negative ([a]D = –21)• o,p’-DDD1st HPLC fraction: negative ([a]D = –57)2nd HPLC fraction: positive ([a]D = +61)

Specific rotation

(+)-o,p’-DDT and (–)-o,p’-DDD have S-configuration.(Match the past report)

Cohn, B. A.; Wolff, M. S.; Cirillo, P. M.; Sholtz, R. I. Environ. Health Perspect. 2007, 115, 1406.

• DDT and DDD are POPs.• DDT exposure may cause cancer.

(

M–1

cm

–1)

Wavelength (nm)

HO2CCO2H

HO2C

CO2H

2,6-Anthracenedicarboxylic

acid dimer

Wakai, A.; Fukasawa, H.; Cheng, Y.; Mori, T.; Inoue, Y. J. Am. Chem. Soc. 2012, 134, 4990.

Application to persistent organic pollutants (POPs)