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Laser spectroscopic study of estrogen and its hydrated clusters in a supersonic jet
○Fumiya Morishima, Yoshiya Inokuchi, Takayuki EbataGraduate School of Science, Hiroshima Univ.
IntroductionIntroduction
A
D
D
Fukuzawa et al. Journal of Computational Chemistry
• In estrogen receptor• In estrogen receptor
Cegelski et al. Drug Development Research
• In membrane• In membrane
estriol(E3)
A
D
estrone(E1)
A
D
β-estradiol(E2)
A
D
estrogen estrogen
B
C
B
C
B
C12
3 4 56
7
8
910
1112
1314
15
16
17
18
3
16
17
3
16
17
IntroductionIntroduction
Investigate the structure of bare estrogen and itshydrated clusters to clarify their hydrogen bonding ability.
estriol(E3)
A
D
estrone(E1)
A
D
β-estradiol(E2)
A
D
estrogen estrogen
B
C
B
C
B
C
3
16
17
3
16
17
3
16
17
Experimental and ComputationalExperimental and Computational
vacuum chamber
He gas
IR laser
UV laser
~4 atm
Supersonic jet
Vacuum chamber
heater temperatureheater temperature
estrone : ~150℃
estradiol : ~130℃
estriol : ~190℃
Electronic spectra LIF
To differentiate bands UV-UV hole-burning(HB)
Vibrational spectra IR-UV double resonance
experimentalexperimental
Quantum chemical calculation M05-2X / 6-311++G**
S1-S0 Electronic Spectra of Bare EstrogenS1-S0 Electronic Spectra of Bare Estrogen
3520035150351003505035000
band 1
band 3
band 2
band aband bband cband d
band 1band 2
a b cd
1 2
1 23 4
56
7 8 9
UV wavenumber / cm-1
LIF and UV-UV HB spectra of bare estrogenLIF and UV-UV HB spectra of bare estrogen
Number ofconformer
= 4
= 6 or more?
= 2
Each conformer of estrogen originates from orientation of OH group(s)
estrone
estradiol
estriol
3800370036003500
IR Spectra of Bare EstroneIR Spectra of Bare Estrone
UV wavenumber / cm-1
1 2
1
23657
3658
IR wavenumber / cm-1
IR spectra in the regionof OH stretching vibrationIR spectra in the regionof OH stretching vibration
cis-estrone
trans-estrone
estrone(E1)
cis-estrone
trans-estrone
3520035150351003505035000
A
DNumber ofconformer = 2
LIF
3520035150351003505035000
cis-estrone
1 2
UV wavenumber / cm-1
Assignment for cis- and trans- Conformation of EstroneAssignment for cis- and trans- Conformation of Estrone
trans-estrone
Comparison of LIF spectra of estrone and results of TD-DFT calculationComparison of LIF spectra of estrone and results of TD-DFT calculation
cis-estrone trans-estrone
3520035150351003505035000
band 1
band 3
band 2
band aband bband cband d
band 1band 2
a b cd
1 2
1 23 4
56
7 8 9
UV wavenumber / cm-1
estrone
estradiol
estriol
Assignment for cis- and trans- Conformation of EstrogenAssignment for cis- and trans- Conformation of Estrogen
cis- trans-
37503700365036003550
IR Spectra of Bare EstradiolIR Spectra of Bare Estradiol
UV wavenumber / cm-1
ab c
d
a
b
c
d
IR wavenumber / cm-1
β-estradiol(E2)
3656
3655
3657
3658
3642
3641
A-ring OHD-ring OH
A-ring OH stretching vibrations… A-ring OH stretching vibrations…
a, c show two bands b, d show only one band.
A
D
estrone(E1)
AD
3520035150351003505035000
IR spectra in the regionof OH stretching vibrationIR spectra in the regionof OH stretching vibration
Number ofconformer = 4
cis- trans-
LIF
16
17
Conformations of A-ring & D-ringConformations of A-ring & D-ring
anti: ~14cm-1 gauche(+): 0cm-1
H1 6 C 1 3 C
H
M e
O1 7 C H
1 6 C 1 3 C
H
M e
O1 7 C
gauche(-): ~73cm-1
H
1 6 C 1 3 C
H
M e
O1 7 C
• cis• trans
• anti• gauche(+)
anti gauche(+)
H1 6 C 1 3 C
H
M e
O1 7 C H
1 6 C 1 3 C
H
M e
O1 7 C
Four conformers
cistrans
antigauche(+)×
Conformations of A-ring & D-ringConformations of A-ring & D-ring
16
17
3520035150351003505035000
Assignment of D-ring OH ConformationsAssignment of D-ring OH Conformations
a b
c d
3800370036003500 3800370036003500
D-ring OH A-ring OH
IR wavenumber / cm-1
UV wavenumber / cm-1
a : antib : gauche(+) c : anti
d : gauche(+)
3656 3655
3657 3658
3642
3641
cis-anti
trans-gauche(+)
cis-gauche(+)
trans-anti
d: trans-gauche(+)b: cis-gauche(+)
a: cis-anti c: trans-anti
35050 35100 35150 35200
UV wavenum ber / cm -1
ab c
d
cis-anti
trans-gauche(+)
cis-gauche(+) trans-anti
Assignment of bare estradiolAssignment of bare estradiol
With water vapor
Without water vapor
Hydrated Cluster of Estradiol on A-ringHydrated Cluster of Estradiol on A-ring
UV wavenumber / cm-1
AB
CD
ab c
d
LIF and UV-UV HB spectraof monohydrated cluster of estradiolLIF and UV-UV HB spectraof monohydrated cluster of estradiol
β-estradiol(E2)
35200351003500034900348003470034600
band B
band C
band D
Red shift = 350 cm-1
~340 cm-1
38003700360035003400IR wavenumber / cm-1
38003700360035003400IR wavenumber / cm-1
IR Spectra of Hydrated Clusters of Estradiol on A-ringIR Spectra of Hydrated Clusters of Estradiol on A-ring
trans-anti-(H2O)
3641band C
trans-anti-(H2O)
trans-anti
ν3(H2O)
36573641
3527
3746
ν1(H2O)trans-gauche(+)
-(H2O)
band D
trans-gauche(+)
ν3(H2O)
3657
3658
35273746
ν1(H2O)
trans-gauche(+)-(H2O)
UV wavenumber / cm-134850348003475034700
C
DLIF
A
B
Each conformer forms hydrogen bondon A-ring OH as proton donor.
ν(D-ring)ν(A-ring) ν(D-ring)ν(A-ring)
** *
3520035150351003505035000
Another Isomer of Hydrated Cluster of EstradiolAnother Isomer of Hydrated Cluster of Estradiol
ab c
d
H1 6 C 1 3 C
H
M e
O1 7 C
OH
H
1 6 C 1 3 C
H
M e
O1 7 C
H
OH
Hgauche(+) typeproton donor
anti typeproton acceptor
B
C
D
Different patterns of hydrogen bond are conceivable for D-ring OH
3520035150351003505035000
37503700365036003550 37503700365036003550
IR Spectra of Bare EstriolIR Spectra of Bare Estriol
UV wavenumber / cm-1
IR wavenumber / cm-1
IR spectra in the regionof OH stretching vibration
IR spectra in the regionof OH stretching vibration
1
2
3
4
5
6
7
8
9
12
34
5
6
7 8 9
estriol(E3)
3723
37213538
3535
3722
3657
3656
3658
3663
3645
3644
3536
3655
3656
3657
3658 3664
3658
3658
3644
3644
A-ring OH
cis region
trans region
IR wavenumber / cm-1
A-ring OH
Band 1 - 6 Bare estriol
Band 7 - 9 Hydrated clusteror its vibronic band
A
Dcis- trans-
LIF
Predicted Conformers of Bare cis-EstriolPredicted Conformers of Bare cis-Estriol
Conformational nameRelative energy / cm-1
17
16
3c_16a_17a810
3c_16g-_17a208
3c_16g+_17a740
3c_16a_17g+796
3c_16g-_17g+0.00
3c_16g+_17g+466
3c_16a_17g-243
3c_16g+_17g-46.3
Intramolecularhydrogen bondIntramolecularhydrogen bond
3c_16a_17a810
3c_16g-_17a208
3c_16g+_17a740
3c_16a_17g+796
3c_16g-_17g+0.00
3c_16g+_17g+466
3c_16a_17g-243
3c_16g+_17g-46.3
Conformational nameRelative energy / cm-1
1 6 C 1 7 C
1 3 CO
1 8 C
H
H H
H1 6 C 1 7 C
1 3 C
O
1 8 C
H
HHH
1 6 C 1 7 C
1 3 C
O
1 8 C
H
H H
H
H
1 6 C 1 7 C
1 3 C
O
1 8 C
H
HH 1 6 C 1 7 C
1 3 CO
1 8 C
H
H
H
H1 6 C 1 7 C
1 3 C
O
1 8 C
H
HH
H
H
1 6 C 1 7 C
1 3 CO
1 8 C
H
H H
H
1 6 C 1 7 C
1 3 C
O
1 8 C
H
H
H
Predicted Conformers of Bare cis-EstriolPredicted Conformers of Bare cis-Estriol
380037503700365036003550
IR Spectra of Bare cis-EstriolIR Spectra of Bare cis-Estriol
3
2
1
IR wavenumber / cm-1
3520035150351003505035000UV wavenumber / cm-1
12
3estriol(E3)
3c_16g-_17g+
3c_16g-_17a
3c_16g+_17g-
3
17
16
3658
3662
3656
3657
3643
3645
Comparison of IR spectra of cis-estriol and results of frequency calculationComparison of IR spectra of cis-estriol and results of frequency calculation
3c_16g-_17g+0.00
1 6 C 1 7 C
1 3 CO
1 8 C
H
H H
H
3c_16g+_17g-46.3
1 6 C 1 7 C
1 3 C
O
1 8 C
H
HHH
3c_16g-_17a208
1 6 C 1 7 C
1 3 C
O
1 8 C
H
H H
H
Bare estriol
Form the intramolecular
hydrogen bond
between16OH and 17OH
LIFcis-
SummarySummary
estrone(E1) β-estradiol(E2) estriol(E3)
monomer
Assign the conformation of bare estrogen.
Estriol forms intramolecular hydrogen bond
1:1 hydrated cluster of estradiol
On A-ringEach conformer forms hydrogen bondon A-ring OH.
On D-ringDifferent pattern of hydrogen bond are conceivable.
Future work Hydrated clusters of estrone / estriol Methoxy estrogen
H1 6 C 1 3 C
H
M e
O1 7 C
OH
H
1 6 C 1 3 C
H
M e
O1 7 C
H
OH
H
Thank you for kindly listening to my presentationand my poor English
Relative energy of bare estroneRelative energy of bare estrone
/ cm-1
anti gauche(-)gauche(+)
Relative energy of bare estradiolRelative energy of bare estradiol
/ cm-1
H1 6 C 1 3 C
H
M e
O1 7 C H
1 6 C 1 3 C
H
M e
O1 7 C
H
1 6 C 1 3 C
H
M e
O1 7 C
35200351503510035050
* * *
3480034700
UV wavenumber / cm-1
≈
estradiol(A)-H2O
estradiol(monomer)
estradiol(D)-H2O
Relative energy of clusters
/ cm-1
3c_16g-_17g+ 0.003c_16g+_17g- 46.33c_16g-_17a 2083c_16a_17g- 243
3c_16g+_17g+ 4663c_16g+_17a 7403c_16a_17g+ 7963c_16a_17a 810
3t_16g-_17g+ 22.43t_16g+_17g- 46.33t_16g-_17a 2073t_16a_17g- 249
3t_16g+_17g+ 4643t_16g+_17a 7303t_16a_17a 796
3t_16a_17g+ 805
1 6 C 1 7 C
1 3 CO
1 8 C
H
H
H
H1 6 C 1 7 C
1 3 C
O
1 8 C
H
HH
H
H
1 6 C 1 7 C
1 3 CO
1 8 C
H
H H
H
1 6 C 1 7 C
1 3 C
O
1 8 C
H
H
H
1 6 C 1 7 C
1 3 CO
1 8 C
H
H H
H1 6 C 1 7 C
1 3 C
O
1 8 C
HH
HH
1 6 C 1 7 C
1 3 C
O
1 8 C
H
H H
H
H
1 6 C 1 7 C
1 3 C
O
1 8 C
H
HH
Relative energy of bare estriolRelative energy of bare estriol
Intramolecular hydrogen bond
16g-_17g+ 16g+_17g- 16g-_17a 16a_17g-
16g+_17g+ 16g+_17a 16a_17a 16a_17g+
/ cm-1
IR Spectra of Bare EstrogenIR Spectra of Bare Estrogen
estradiol
estrone
estriol
71238
9456
1
2
a
b
c
d
IR wavenumber / cm-1
IR spectra in the region of OH stretching vibrationIR spectra in the region of OH stretching vibration
37503700365036003550
cis-anti
trans-anti trans-gauche(+)
cis-gauche(+)
Predicted ConformersPredicted Conformers
M05-2X / 6-311++G**
~410 cm-1
~260 cm-1
Barrier between each D-ring conformation of estradiolBarrier between each D-ring conformation of estradiol
~820 cm-1
Without ZPE correction
H1 6 C 1 3 C
H
M e
O1 7 C
H
1 6 C 1 3 C
H
M e
O1 7 C
H
1 6 C 1 3 C
H
M e
O1 7 C
810 cm-1
cistrans
Rotation of A-ring OHRotation of A-ring OH
Without ZPE correction
π(HOMO)
π(HOMO)
π*(LUMO)
π*(LUMO)
cis-anti
trans-anti
HOMO and LUMO of EstradiolHOMO and LUMO of Estradiol
35200351503510035050UV wavenumber / cm -1
cis-antitrans-gauche(+)
cis-gauche(+)
trans-anti
a
bc
d
cis-anti
trans-gauche(+)
cis-gauche(+)trans-anti
Assignment of A-ring OH conformationsAssignment of A-ring OH conformations
estradiol(estradiol(DD)-H)-H22OO
Estradiol(D)-H2O
cis-antitrans-gauche(+)cis-gauche(+)
trans-anti
* * *
35200351503510035050U V wa venum be r / c m
-1
cis-anti
trans-gauche(+)cis-gauche(+)trans-anti
H1 6 C 1 3 C
H
M e
O1 7 C
OH
H
1 6 C 1 3 C
H
M e
O1 7 C
H
OH
Hgauche(+) typeproton donor
anti typeproton acceptor
red shift
blue shift
3240032000316003120030800 31800314003100030600
1-cis-naphthol
1-trans-naphthol
2-trans-naphthol
2-cis-naphthol
M05-2X / 6-311++G**
TD-DFT calculationTD-DFT calculation
352503520035150351003505035000
TD-DFT Calculation for conformers of bare estriolTD-DFT Calculation for conformers of bare estriol
UV wavenumber / cm-1
trans- 16g+_17g- 16g+_17a 16g+_17g+ 16a_17g- 16a_17a 16g-_17a 16a_17g+ 16g_17g+
Position / cm-1 35140 35141 35144 35146 35149 35150 35153 35155
Relative energy / cm-1 46 730 464 249 796 207 805 22
21
3
5
46
cis- 16g+_17g- 16g+_17a 16g+_17g+ 16a_17g- 16a_17a 16g-_17a 16a_17g+ 16g_17g+
Position / cm-1 35051 35054 35057 35058 35061 35061 35065 35067
Relative energy / cm-1 46 740 466 243 810 208 0 796
cis- trans-
Lifetime
Time / ns
Time / ns95908580757065605550
80757065605550
Monomer
Cluster
τ = 5 ns
τ = 15 ns
Predicted Conformers of Bare trans-EstriolPredicted Conformers of Bare trans-Estriol
Conformational nameRelative energy / cm-1
3
17
16
3t_16a_17a796
3t_16g-_17a207
3t_16g+_17a730
3t_16a_17g+805
3t_16g-_17g+22.4
3t_16g+_17g+464
3t_16a_17g-249
3t_16g+_17g-46.3
Predicted Conformers of Bare trans-EstriolPredicted Conformers of Bare trans-Estriol
3t_16a_17a796
3t_16g-_17a207
3t_16g+_17a730
3t_16a_17g+805
3t_16g-_17g+22.4
3t_16g+_17g+464
3t_16a_17g-249
3t_16g+_17g-46.3
Conformational nameRelative energy / cm-1
1 6 C 1 7 C
1 3 CO
1 8 C
H
H H
H1 6 C 1 7 C
1 3 C
O
1 8 C
H
HHH
1 6 C 1 7 C
1 3 C
O
1 8 C
H
H H
H
H
1 6 C 1 7 C
1 3 C
O
1 8 C
H
HH 1 6 C 1 7 C
1 3 CO
1 8 C
H
H
H
H1 6 C 1 7 C
1 3 C
O
1 8 C
H
HH
H
H
1 6 C 1 7 C
1 3 CO
1 8 C
H
H H
H
1 6 C 1 7 C
1 3 C
O
1 8 C
H
H
H
375036503550IR wavenumber / cm-1
7
1238
9456
IR spectra of Bare EstriolIR spectra of Bare Estriol
16g-_17g+
16g+_17g-
16g-_17a
16a_17g-
16g+_17g+
16g+_17a
16a_17a16a_17g+
1 6 C 1 7 C
1 3 CO
1 8 C
1 6 C 1 7 C
1 3 C
O
1 8 C
1 6 C 1 7 C
1 3 CO
1 8 C
1 6 C 1 7 C
1 3 CO
1 8 C
1 6 C 1 7 C
1 3 C
O
1 8 C
1 6 C 1 7 C
1 3 C
O
1 8 C
1 6 C 1 7 C
1 3 C
O
1 8 C
1 6 C 1 7 C
1 3 C
O
1 8 C
16g-_17g+
16g+_17g-
16g-_17a
16a_17g-
16g+_17g+
16g+_17a
16a_17a
16a_17g+
cis region
trans region
Intramolecula
rhydrogen bond
Relative Energy of Monohydrated Estriol IsomersRelative Energy of Monohydrated Estriol Isomers
3t_16g+_17g-_(A)-H2O 3t_16g+_17g-_(D)-H2O
0.00 cm-1~1,000 cm-1
More stable
Relative Energy of Monohydrated Estradiol IsomersRelative Energy of Monohydrated Estradiol Isomers
cis-gauche(+)-(A)-H2O
cis-gauche(+)-(D)-H2O
cis-anti-(D)-H2O
0.00 cm-1
~330 cm-1
~460 cm-1
More stable
cis-anti-(A)-H2O62.9cm-1