homochirality, seed of terrestrial life - MSU Chemistry

Transcription

Organic seminar - Michigan State University
HOMOCHIRALITY,
SEED OF TERRESTRIAL LIFE
Hadi Gholami
October 23, 2013
H 3N
H 3N
http://www.desktopcrunch.com/wp-content/uploads/wallpapers/
iPek©!Random/Digital-Universe-Earth-Desktop-Wallpaper.jpg
H 3N
COO
COO
H 3N
COO
COO
Chirality
1840s - Louis Pasteur studied the crystalline and solution forms of (±)-tartaric acid
1894 - The introduction of the word “chiral” by Lord Kelvin
Chiral comes from the Greek word “Χείρ, Chir” meaning “HAND”
(S)
“Sinister”
LEFT
(R)
“Rectus”
RIGHT
Hands are non-superimposable mirror images
e
Types of Chirality
Point chirality
H
NH 2
H 2N
H
CO 2H
H 3C
CO 2H
H 3C
(S)
(R)
Types of Chirality
Helical chirality
Point chirality
H
NH 2
H 2N
H
CO 2H
H 3C
CO 2H
H 3C
(S)
(R)
(M)
(P)
(M)
Types of Chirality
Helical chirality
Point chirality
H
NH 2
H 2N
H
CO 2H
H 3C
CO 2H
H 3C
(R)
(S)
(P)
(M)
Axial chirality
O 2N
CO 2H
NO 2
HO 2C
HO 2C
O 2N
NH 2
H
H
(M)
Me
C
H
H
(P)
Me
H
H
Me
C
H
(P)
H
NH 2
H 2N
H
Me
(M)
(P)
(M)
H 2N
NO 2
CO 2H
(M)
H
L
H
H
L
L
L
(P)
(M)
Different Chirality, Different Properties?
O
O
O
O
*
*
H
H
(R) Spearmint oil
O
H 3N
H H
N
O
O
O
H 3N
O
H H
N
H
O
O
O
H
(S) Caraway oil
S,S-isomer of Aspartame
Different Smell
R,R-isomer of Aspartame
Different Taste
*
*
(R) Limonene
(S) Limonene
http://karolinas.net/en/home/limonene-a-diploma-thesis-topic-c57.htm
Pharmaceuticals: Chirality matters!
O
N
O
O
*
O
NH
O
(S)-Thalidomide
(S)-isomer had the desired
antinausea effects
O
HN
*
O
N
O
(R)-Thalidomide
(R)-form caused fetal
abnormalities
http://blogs.smithsonianmag.com/smartnews/2012/09/thalidomide-manufacturer-finally-apologizes-for-birth-defects-survivorssay-its-not-enough/
Pharmaceuticals: Chirality matters!
O
N
O
O
*
O
NH
O
(S)-Thalidomide
(S)-isomer had the desired
antinausea effects
O
HN
*
O
N
O
(R)-Thalidomide
(R)-form caused fetal
abnormalities
http://blogs.smithsonianmag.com/smartnews/2012/09/thalidomide-manufacturer-finally-apologizes-for-birth-defects-survivorssay-its-not-enough/
Homochirality and Life
Homochirality: Nature selects almost exclusively one enantiomer over the other as
building blocks for living organisms.
HO
OR
O
OH
D-Sugar
Yoon, C. et al. Proc. Natl Acad. Sci. USA 1988, 85, 6332.
HO
OR
O
OH
D-Sugar
H 2N
H
CO2H
R
L - Amino Acid
Wang, W. et al. Science 2012, 338, 1340.
Yoon, C. et al. Proc. Natl Acad. Sci. USA 1988, 85, 6332.
Progression of Homochirality on Earth
Inducing Initial
Enantio Imbalance
Amplification of
Initial ee
Expansion of
Chiral Pool
Inducing Initial
Enantio Imbalance
Amplification of
Initial ee
Expansion of
Chiral Pool
Inducing Initial
Enantio Imbalance
Amplification of
Initial ee
By chance .....
Circularly Polarized Light (Chiral Light)
and many more ...
Expansion of
Chiral Pool
It’s all about light?
From Prebiotic Soup to Chiral Organisms...
Biological world started
Prebiotic
Life as we know today
Biological evolution
3.6-3.8 billion
years ago
Enantiomeric imbalance was induced by polarized light, either somewhere in
the universe (extraterrestrial) or directly on earth (terrestrial) resulting in small
excess of one enantiomer of the biological building blocks over the other
(chiral excess).
Stanley Miller’s Experiment
Light Storm
Energy from the
spark drives the
reaction between
molecules
Water vapor was
provided into the
artificial atmosphere
Organic molecules including
some amino acids were
detected after a few days
http://www.studyblue.com/notes/note/n/exam-3-flashcards/deck/2577056
Revised Stanley Miller’s Experiment
UV photolysis of the mixture on ice
H2O:CH3OH:NH3:HCN
20:2:1:1
HPLC Trace
Relative Emission
Serine
Glycine
Ethanolamine
Alanine
No light source
w/o mixture ice
Retention Time (min)
Bernstein,M. P.; Dworkin, J. P.; Sandford, S. A.; Cooper, G.W.; Allamandola, L. J., Nature, 2002 416, 401
Revised Stanley Miller’s Experiment
Relative Emission
Serine
UV photolysis of the mixture on ice
H2O:CH3OH:NH3:HCN
- Light can induce biological
20:2:1:1
building block formation.
HPLC Trace
- Non-chiral light cannot
induce enantio excess
(Homochirality)
Glycine
Ethanolamine
Alanine
No light source
w/o mixture ice
Retention Time (min)
Bernstein,M. P.; Dworkin, J. P.; Sandford, S. A.; Cooper, G.W.; Allamandola, L. J., Nature, 2002 416, 401
What is Chiral Light?
Polarizing
Filter
Linear
Polarized
Light
Light
http://www.photophysics.com/tutorials/circular-dichroism-cd-spectroscopy/1-understanding-circular-dichroism
Polarizing
Filter
Linear
Polarized
Light
Light
Linear Polarized Light
z-axis
y-axis
x-axis
Polarizing
Filter
Linear
Polarized
Light
Light
Linear Polarized Light
z-axis
y-axis
x-axis
Circularly Polarized Light (Chiral Light)
Induction of Chirality on Molecules by Circularly Polarized Light
hν
6π - Con.
I2
O2
H
D+L
D+L
D + L Conformations
Reaction
1
2
3
4
H
Wavelength Irridiated (nm)
410
390
370
290
Circularity of Light, %
75 (RCP)
75 (RCP)
75 (RCP)
75 (LCP)
Optical yield, %
2.00
1.96
1.77
- 0.42
RCP, Right Handed Circular Polarized Light / LCP, Linear Polarized Light
Bernstein, W. J.; Calvin, M.; Buchardt, O. J. Am. Chem. Soc. 1971, 94, 494.
But is There Any Circularly Polarized Light in the Universe?
Total IR
intensity
Percentage
of circular
polarization
Bailey, J. et al. Science 1998, 281, 672.
Creation of Chiral Excess by Circularly Polarized Light
Marcellus, P. et. al. Astrophys. J. Lett., 2011, L27, 727
Measured Enantiomeric Excesses for 13C-Alanine
Linearly polarized light
(LPL)
ee L-Ala (%)
-0.04
Left-handed circularly polarized light
(L-CPL)
Right-handed circularly polarized light
(R-CPL)
ee L-Ala (%)
+0.71
Marcellus, P. et. al. Astrophys. J. Lett. 2011, L27, 727.
ee L-Ala (%)
-1.34
Can you Induce Chiral Excess in a Racemic Solution Using
Circularly Polarized Light?
O
O
O
NH 2
HO
L-CPL
HO
NH 2
L-Leu
1
R-CPL
NH 2
HO
6.8 eV
182 nm
6.8 eV
182 nm
Reaction
Irradiation with
L-CP (red line) and RCPSR (blue line)
D-Leu
D-Leu
D,L-Leu
Irradiation
-
L-Leu
ee (D-Leucine) [%]
0.00
2
L-CPL
-0.88
3
R-CPL
2.60
Enantiomeric excesses obtained after irradiation
of racemic leucine with circularly polarized light.
15.0
15.2
15.4
15.6
time (min)
Meierhenrich, U. J. et al. Angew Chem Int. Ed. 2005, 44, 5630.
15.8
16.0
Why Enantiomers Interact Differently with Circularly
Polarized Light
d-Ala (red), l-Ala (blue)
g : anisotropy factor
ε : extinction coefficient
d-Val (orange) and l-Val (black)
Thick lines: Anisotropy spectra
Thin lines : corresponding eeL
H 2N
*
CO2H
Valine
Meinert, C. et. al. Angew. Chem. Int. Ed. 2012, 51, 44..
Transfer of Chiral Molecules
α-methyl L-amino acids were found on meteorites
H 2N
CO2H
Me
Me
H 2N
CO2H
Me
Me
Me
Et
ee : 2.8%
ee : 7%
H 2N
Me
CO2H
Pr
ee : 2.8%
H 2N
Me
CO2H
Et
ee : 15.2%
Cronin, J. R.; Pizzarello, S. Science 1997, 275, 951.
Breslow, R.; Cheng, Z-L. Proc. Natl Acad. Sci. USA 2009, 106, 9144.
H 2N
H
CO2H
R
L - Amino acid
How The Small Enantiomeric Excess Can Get Amplified?
Inducing Initial
Enantio Imbalance
Amplification of
Initial ee
Expansion of
Chiral Pool
2 proposed pathways:
Autocatalysis: Increase of ee via autocatalytic reactions
Crystallization:
i. Enrichment of enantiomeric purity by conglomerate crystallization in solid phase
ii. Racemic crystallization driven enantio-enrichment of the liquid phase
Demonstration of Autocatalysis
Autocatalysis: The chiral substrate acts as a catalyst for its self-production while
suppressing synthesis of its enantiomer.
N
OH
N
N
N
(S)-1
with low
enantiomeric enrichment
N
O Zn
2
asymmetric
autocatalyst
OH
N
(S)-1
with High enantiomeric enrichment
N
O
N
3
Proposed reaction scheme of asymmetric autocatalyst of (S)-1
Frank, F. C. Biochim. Biophys. Acta 1953, 11, 459–463.
Soai, K.; Shibata,T.; Morioka, H.; Choji,K. Nature 1995, 378, 767.
+
Zn
2
(S)-1
(R)-1
(S)-1 and (R)-1 isomers
N
OH
N
(S)-1
Initial
A1
A2
A3
condition (39% ee) (76% ee) (89% ee)
(5% ee, S)
Asymmetric autocatalysis of chiral alkanol (1).
Soai, K.; Shibata,T.; Morioka, H.; Choji, K. Nature 1995, 378, 767.
(S)-1 and (R)-1 isomers
N
OH
N
(S)-1
Initial
A1
A2
A3
condition (39% ee) (76% ee) (89% ee)
(5% ee, S)
Asymmetric autocatalysis of chiral alkanol (1).
ee. of newly formed product (S)-1 (%)
(S)-1
(R)-1
Positive non-linear effect
(amplyfing asymetric autocatalysis)
90
80
70
60
50
40
30
20
10
0
0 10 20 30 40 50 60 70 80 90
ee. of catalyst (S)-1 (%)
Relation between the ee of catalyst (S)-1 and
ee of the newly formed product (S)-1 in
asymmetric autocatalytic reaction of (S)-1
Soai, K.; Shibata,T.; Morioka, H.; Choji, K. Nature 1995, 378, 767.
Conglomerate Crystallization in Solid Phase
Racemic crystalization: crystals contain a 1 : 1 ratio of D : L enantiomers.
Conglomerate crystallization: A compound can be crystallized in purely one form of its
enantiomer from its racemic mixture in liquid phase.
Molecules in the crystal have a greater affinity for the same enantiomer than for the
opposite enantiomer.
Huang, J.; Yu, L. J. Am. Chem. Soc. 2006, 128, 1873.
Liquid Phase
1:1 enantio ratio
Pure D-enantiomer
crystal
Conglomerat
crystalization
Racemic
crystalization
+
Pure L-enantiomer
crystal
D/L Mix crystal
D-enantiomer
L-enantiomer
Liquid Phase
1:1 enantio ratio
Pure D-enantiomer
crystal
Conglomerat
crystalization
Racemic
crystalization
+
Pure L-enantiomer
crystal
D/L Mix crystal
D-enantiomer
L-enantiomer
Racemic crystals:conglomerates
10:1
on Earth
Liquid Phase
1:1 enantio ratio
Pure D-enantiomer
crystal
Conglomerat
crystalization
Racemic
crystalization
+
Pure L-enantiomer
crystal
D/L Mix crystal
D-enantiomer
L-enantiomer
Racemic crystals:conglomerates
10:1
on Earth
Pasteur: crystals of (+) and (-) sodium ammonium tartrate.
Random Chiral Symmetry Breaking During Conglomerate
Crystallization
solution
solid
Solid-Solution Equilibrium for an
Intrinsically Achiral Molecule
Chiral crystals, L or D in the sample (%)
sodium chlorate (NaClO3), Racemic solution.
Sodium chlorate crystal
Random D or L homochirality from initial symmetric
mixtures of D and L crystals.
Viedma, C. Phys. Rev. Lett. 2005, 94, 065504.
Controlled Chiral Symmetry Breaking During
Conglomerate Crystallization
Enantiomeric crystals, L or D in the sample (%)
sodium chlorate (NaClO3)
Levorotatory, (-) CEE.
Dextrorotatory, (-) CEE
Solutions with initial 5% L-CEE show 100% L-CEE, and solutions with initial 5% DCEE show
100%
D-CEE enantiomeric
in 8 h (600 rpm)
small
initial
crystal
excess (CEE) eventually
Any
gives rise
to total crystal purity disappearing the less abundant enantiomer (100% CEE)
Viedma, C. Phys. Rev. Lett. 2005, 94, 065504.
Conglomerate Crystallization for Molecules with Intrinsic Chirality
solution
solid
chemical
equilibrium
solution
solid
Viedma, C. Astrobiology 2007, 7, 312–319.
Conglomerate Crystallization for Molecules with Intrinsic Chirality
solution
solid
Solid-Solution Equilibrium for a
Chiral Molecule Undergoing
Solution-Phase Racemization
chemical
equilibrium
Viedma, C. Astrobiology 2007, 7, 312–319.
solution
solid
Single Solid Chiral State from a Nearly Racemic Amino Acid Derivative
chemical
equilibrium
Noorduin,W. L. et al. J. Am. Chem. Soc. 2008, 130, 1158.
solution
solid
chemical
equilibrium
solution
solid
DBU
N
Chemical and Physical Equilibria in the
Racemization and
Crystallization / Dissolution Processes
for 1.
O
NH 2
MeOH
or
MeCN
25 °C
N
H 2N
O
(S)-1
(R)-1
(S)-1 (solid)
(R)-1 (solid)
chemical
equilibrium
solution
solid
DBU
N
Chemical and Physical Equilibria in the
Racemization and
Crystallization / Dissolution Processes
for 1.
O
N
MeOH
or
MeCN
25 °C
NH 2
H 2N
O
(S)-1
(R)-1
(S)-1 (solid)
(R)-1 (solid)
N
N
N
H
H 2N
O
DBU
N
NH 2
N
H 2N
O
(S)-1
(R)-1
(S)-1 (solid)
(R)-1 (solid)
solid phase ee (%)
solid phase ee (%)
O
MeOH
or
MeCN
25 °C
time (days)
time (days)
DBU
N
NH 2
N
H 2N
O
(S)-1
(R)-1
(S)-1 (solid)
(R)-1 (solid)
solid phase ee (%)
solid phase ee (%)
O
MeOH
or
MeCN
25 °C
time (days)
time (days)
Attrition-enhanced evolution of solid-phase ee for 1 in
MeCN: starting from initial ee values of 1 as shown
Evolution of Solid Phase Homochirality for a Natural Amino Acid
O
H
L
L
O
HO
L
L
solid phase
OH
O
NH 2
O
OH
O
OH
heat or
heat/glass beads
OH
HO
NH 2 O
D
D
D
D
solid phase
Viedma, C.; Ortiz, J. E.; de Torres, T.; Izumi, T.; Blackmond, D. G. J. Am. Chem. Soc. 2008, 130, 15274.
Evolution of Solid Phase Homochirality for a Natural Amino Acid
O
H
L
L
O
HO
L
L
solid phase
OH
O
NH 2
O
OH
O
OH
heat or
heat/glass beads
OH
HO
NH 2 O
D
D
D
D
solid phase
gradient
heatingtoto160
160˚C°C
gradient heating
isothermal 90
isothermal
at ˚C
90 °C
Viedma, C.; Ortiz, J. E.; de Torres, T.; Izumi, T.; Blackmond, D. G. J. Am. Chem. Soc. 2008, 130, 15274.
Racemic Crystallization Driven Liquid Phase ee Amplification
- Many compounds, including amino acids, their racemates are less soluble than the pure
enantiomers.
slow evaporation
solid removal
water solution
water solution
NH 2
Ph
CO2H
L-phenylalanine
1% ee, ≅500 mg
Racemic crystals
(≅ 400 mg)
solution with 40% ee
L-phenylalanine
Breslow, R.; Levine, M. Proc. Natl Acad. Sci. USA 2006, 103, 12 979.
- Many compounds, including amino acids, their racemates are less soluble than the pure
enantiomers.
slow evaporation
solid removal
water solution
water solution
NH 2
Ph
Racemic crystals
(≅ 400 mg)
CO2H
L-phenylalanine
1% ee, ≅500 mg
slow evaporation
water solution
L-phenylalanine
solid removal
water solution
NH 2
Ph
CO2H
L-phenylalanine
40 % ee, ≅500
Racemic crystals
L-phenylalanine
(≅100 mg)
A solution with a small ee of an amino acid component were allowed to evaporate,
there would be selective precipitation of the racemate crystals, leading to
amplification of the ee concentration in solution.
Component
NH 2
Initial ee, %
10
Final ee, %
90.0
5
91.7
1
87.2
NH 2
10
88.3
* CO2H
5
88.6
1
90.9
* CO2H
D-Phenylalanine
L-Phenylalanine
Enantiomeric concentration amplification of
phenylalanine after two crystallizations from water
Transfer of Chirality
Inducing Initial
Enantio Imbalance
Amplification of
Initial ee
Expansion of
Chiral Pool
Application of chiral amino acid to catalyze the prebiotic synthesis of other biological building
blocks.
Chirality Transfer From α-Methyl Amino Acids
O
CO2
H 3N
+
CH 3
R
O
O
α-keto carboxylates
α-methyl L-valine
Cu2+
CO2
CH 3
N
O
R
O
NH 3
- CO2
H + transfer
from α-methyl valine
+
O
R
CO2
Natural L-amino acids
Levine, M.; Kenesky, C. S.; Mazori, D.; Breslow, R. Org. Lett. 2008, 10, 2433.
Sugars Synthesis Catalyzed with α-Methyl Amino Acids
O
HO
+
H 2N
Me
glycoaldehyde
CO2H
Et
S-isovaline
Asymmetric aldol
O
O
OH
HO
O
OH
HO
OH
L-thereose
O
OH
HO
OH
D-thereose
OH
HO
OH
L-erythrose
OH
D-erythrose
Pizzarello, S.; Weber, A. L. Science 2004, 303, 1151.
O
HO
+
H 2N
Me
glycoaldehyde
CO2H
Et
S-isovaline
Asymmetric aldol
O
O
OH
HO
O
OH
HO
OH
OH
HO
OH
D-thereose
OH
HO
OH
L-erythrose
OH
D-erythrose
Enantiomeric excess (%)
L-thereose
O
Amino acid catalyst (ee)
O
HO
+
H 2N
Me
glycoaldehyde
CO2H
Et
S-isovaline
Asymmetric aldol
O
O
OH
HO
Me
Et
L (s)-Isovaline
O
OH
HO
OH
D-thereose
OH
HO
OH
L-erythrose
OH
D-erythrose
L-thereose
CO2H
OH
HO
OH
H 2N
O
O
HO
+
H 2N
Me
glycoaldehyde
CO2H
Et
S-isovaline
Asymmetric aldol
O
O
OH
HO
Me
Et
L (s)-Isovaline
O
OH
HO
OH
D-thereose
OH
HO
OH
L-erythrose
OH
D-erythrose
L-thereose
CO2H
OH
HO
OH
H 2N
O
H 2N
CO2H
H
L (s)-Valine
Sugars Synthesis Catalyzed with Amino Acids
HO
O
O
+
H
Glycoaldehyde
O
Catalyst
H
H
OH
D-Glyceraldehyde
L-Glyceraldehyde
CO 2H
R
Amino acid
-CH2OH
L-erine
50.3/49.7
-CH3
L-alanine
50.8/49.2
-CH(CH3) 2
L-valine
52.2/47.8
-CH2-C6H 5
L-phenylalanine
52.2/47.8
-CH2-CH(CH3) 2
L-leucine
54.4/45.6
-CH2CH 2CO 2H
L-glutamic acid
60.7/39.3
L-proline
28.9/71.1
CO 2H
OH
OH
H
H 2N
N
H
H
OH
formaldehyde
R
O
Glyceraldehyde ratio D/L
Breslow, R.; Cheng, Z-L. Proc. Natl Acad. Sci. USA 2010, 107, 5723.
pH Dependent Proline Catalyzed Amination of Aldehydes
R1
O
+
R 2O
2C
N
N
CO2R 2
O
1) Catalyst
2) NaBH 4
2
NHCO
R
2
N
O
*
3) NaOH
R2
Catalyst
N
H
N
H
N
H
ee, %
Configuration
85%
(R)
48%
(S)
60%
(S)
CO2H
CO2H
, DBU
CO2 Bu N
4
Blackmond, D. G.; Moran, A.; Hughes, M.; Armstrong, A. J. Am. Chem. Soc. 2010, 132, 7598.
Hein, J. E. et al. Org. Lett. 2011, 13, 5644.
Enantiomeric Excess of Glyceraldehyde in the Presence of Proline and
Prolinate Catalysts
O
L-proline
H
HO
O
O
+
H
Glycoaldehyde
N
H
CO2H
OH
OH
L-Glyceraldehyde (8% ee)
H
formaldehyde
CO2 Bu N
4
N
H
O
H
OH
OH
L-prolinate
D-Glyceraldehyde (13% ee)
O
D-proline
H
HO
O
Glycoaldehyde
N
H
O
+
H
OH
OH
CO2H
D-Glyceraldehyde (9% ee)
H
formaldehyde
N
H
O
CO2 Bu 4N
H
D-prolinate
OH
OH
L-Glyceraldehyde (17% ee)
Hein, J. E.; Blackmond, D. G. Acc. Chem. Res. 2012, 45, 2045.
Conclusion
- We are all surrounded by chiral objects.
- Circularly polarized light can be a chiral template to induce chirality
biologically building blocks.
into
- L-Amino acids (natural and/or unnatural (α-methyl) amino acids) can be one of the
primary chiral product formed in small ee under influence of chiral light.
- Small ee can be amplified via chemical and physical processes.
- L-Amino acids can act as chiral templates to induce chirality into other biological
building blocks (D-sugars).
- It has been proposed that the observed homochirality on earth (L-amino acids and
D-sugars) was selected to match with the overall chirality of this part of the universe.
Acknowledgements
Professor Babak Borhan
Professor Xuefei Huang
Dr. Chryssoula Vassiliou
Group members:
Arvind, Kumar, Carmin, Calvin
Tanya,, Ipek, Maisam, Nastaran, Bardia, Yi,
Eddie, Elizabeth, Jun,, Wei, Ding.
Mina
and
All of you for your attention.

homochirality, seed of terrestrial life - MSU Chemistry

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