The Origin of Chirality Anne-Catherine BédardCharette Group MeetingJan 25th 2012
“Any man who, upon looking down at his bare feet, doesn't laugh, has either no
sense of symmetry or no sense of humour”
(Descartes, cf. Walker 1979)
About Me !Québec Ottawa
Biopharmaceuticals Sciences - COOP
ParisHonours Project
JCEMolChem
Montréal
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Outline
Terrestrial vs Extraterrestrial Theories1.Stereochemistry in Life2.Minority report : opposite handedness3.Difference in energy of enantiomers4.Chirality form polarized light5.Chiral field : Magnetism6.Amplification and transfert of chirality7.Crystallization8.Unidirectional rotation of Earth
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Louis Pasteur
•1848 : Pasteur 1st to draw attention to the homochirality in nature
•Optical purity is inherent to life▫Failure of other planets to yield
optically active material = evidence for the absence of life of complexity comparable to earth’s
•1874 : Van’t Hoff = assymmetry on carbon atom.
•Dextrogyre (+)-D•Levogyre (-)-L
1822-1895 France
Tartaric AcidCO2HHO
CO2HHO
4
Enantiotopic TS
5
R1 H
O 1. MeMgBr
2. H2O
R1
HO
Me MgBrMe MgBr
SiRe
HR1
O
MeH
R1
O
Me
E
Me
OH
R1
HMe
OH
R1
H
EnantiotopicSAME ENERGY
Me
OH
R1
HMe
OH
R1
H
Diastereotopic TS
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H
O1. MeMgBr
2. H2O
HO
Me MgBrMe MgBr
SiRe
E
DiastereotopicDIFFERENT ENERGY
RS
RL
H
RLRSH
RS
RL
H
O H
Me
H
RL
RS
O H
Me
Me
HO
RS
RL
H
H
Me
H
RS
RL
H
OH
Me
HO
RS
RL
H
H
Me
H
RS
RL
H
OH
Biomolecular Homochirality
• Basic elements of biochemistry▫20 (L)-amino acids ▫5 bases (A, G, C, U, T)▫ (D)-Ribose▫ (D)-Glucose▫Fats▫Phosphatides
• Formation of proteins, enzymes, DNA, RNA, sources and storages of metabolic energy !
OHO
HOOH
OH
-D-glucopyranoseOH
CHO
OHH
HHO
OHH
OHH
CH2OH
CHO
OHH
OHH
OHH
OHH
CH2OH
D-glucose D-ribose
H2NOH
O
R(L)-amino acid
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Chirality and Physical Property
R-Carvone : caraway odourS-Carvone : spearmint odour
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Thalidomide (1957-1961)Morning sickness
treatmentCause congenital
abnormalities
NNH
O
O O
O
O
(R)
O
(S)
D-Amino Acids
• Ingestion of D-A.A. in food▫Racemization with vinegar, yogurt, potatoes…
•Enzyme : D-A.A. oxidase•Babies : 60% of D-aspartic acid in prefrontal
cortex at 14th week of gestation▫Decreased by birth to traces amount
•Alzheimer’s : accelerated racemisation of aspartic acid residue
•Racemisation is linked to the process of ageing…•A. A. clock : complementary to 14C-dating method
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H2NOH
O
(L)-aspartic acid
CO2HH
NH2HO
O
(D)-aspartic acid
HO2CH
Racemisation
•Thermodynamically favored process•Gain of entropy (in the solid state)
•Room temperature racemisation of alanine ▫Thousand of years!
H2NOH
O
Me(L)-alanine
H2NOH
O
Me(rac)-alanine
H2NOH
O
Me(R)-alanine
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The Weak (Nuclear) Force – Parity Violation• 4th fundamental force of physics• Influence electrons inside atoms causing them to
travel helical paths that gives all atoms a handedness
• 1013 time weaker than the strong force that holds protons and neutrons in the nucleus
• Discovery in 1956 by • Tsung Dao Lee (Columbia U.) • Chen Ning Yang (Princeton)• Nobel prize of Physics in 1957!• Lee (30) and Yang (34)
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Lee, T. D.; Yang, C. N. Phys Rev 1956, 104, 254
The Weak (Nuclear) Force – Parity Violation• Most familiar effect : β-decay (60Co, 14C)• Inherently left-handed!
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60Coe- () e
60Co 60Ni + e- + e
Conservationof momentum
60Co Beta-Decay – Wu’s Experiment
•If parity is conserved, then the probability of electron emission at θ is equal to that at 180o - θ.
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60Co
Magnetic Field
Parity Conserved
60Co
Magnetic Field
Parity Violated
60Co
spin spin spin
Nuclei polarised through spin alignment in a large magnetic field at 0.01oK
Wu, C. S. and al. Phys Rev 1957, 105, 1413Bonner, W. A. Chirality 2000, 12, 114
Difference in Energy of Enantiomers
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•Femtojoule (10-15) to picojoule (10-12) scale•L-A.A. and D-sugars are more stable !•No experiment has been successful in
confirming the effect.
H F
Me
BrHF
Me
Br
Diastereomers ???
MacDermott, A. J. Orig Life Evol Biosphere, 1995, 25, 191Quack, M. Angew. Chem. Int. Ed. 2002, 41, 4618 Salam, A. J Mol Evol 1991, 33, 105
Chemical effect of polarized radiationPhotochemical asymmetric synthesisPhotochemical decomposition of racemates
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Kagan’s Decomposition of Camphor
20% ee99% decomp
Balavoine, G.; Moradpour, A.; Kagan, H. B. J. Am. Chem. Soc. 1974, 96, 16.
290-370 nm CPL (UV)
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Bonner’s Polarised Light Exp.
•Selective destruction of D enantiomer of A.A. with right circularly polarized light (UV)
•Exact and opposite effect of RCPL and LCPL▫Leucine has the highest molecular absoption
coefficient▫Predicted = 2% ee at 80% photolyzed
Flores, J. J.; Bonner, W. A.; Massey, G. A.; J. Am. Chem. Soc. 1977, 99, 11
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Leucine’s Photolysis
•212.8 m, CPL
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H2NOH
O
H2NOH
OH2N
OH
O
LCPL RCPL
(D) (L)
Photodecomposition vs photosynthesis
Light polarization
% Decomposition
Enantiomeric Excess
RCPL 59 1,98 ± 0,31
LCPL 75 2,50 ± 0,35
Unpolarized 54 0,30 ± 0,33
Flores, J. J.; Bonner, W. A.; Massey, G. A.; J. Am. Chem. Soc. 1977, 99, 3622
Assymmetric Photosynthesis
•Photocyclisation of alkenes in solution
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400nm (CPL)
I2, O2 about 20% ymax 2% ee
(UV light)
R
R
R
R
R
R
Bernstein, W. J.; Calvin, M.; Bechardt, O. J. Am. Chem. Soc. 1973, 95, 527
Circularly Polarized Light (CPL)
• Sunlight is polarized linearly (LPL) and non-assymmetric
• Right or left CPL is a result of natural (LPL) sunlight reflexion at the earth’s surface and earth’s magnetic field (0,1%)
• Sunlight is considered insufficient for enantioselective photochemistry.
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Circular Polarization in Space
• Strong IR circular polarisation resulting from dust scattering in Orion OMC-1 star-formation region
Baileys, J. and al. Science 1998, 281, 672
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Extraterestrial A.A. Meteorite
•Meteorite : Murchinson Autralia in 1970•Issue of terrestrial contamination…•5 α-Me A.A. (extremely rare or
unreported)CO2
-+H3N
Me Et
e.e. 15.2% S
CO2-
+H3N
Me Pr
e.e. 2.8% S
CO2-
+H3N
Me iPr
e.e. 2.8% S
CO2-
+H3N
Me
e.e. 7% S (3S)
CO2-
+H3N
Me
e.e. 9.1% S (3R)Et
MeMeEt
Cronin, J. R. ; Pizzarello, S. Science 1997, 275, 951.
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Strecker Synthesis in Space
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Silicate grains of sub-micrometer diameter coated with ice layer
Contains H2O, CO2, CO, CH3OH, NH3
Subsequent aggregation = formation of comets !
Strecker Synthesis in Space
Interstellar conditions in the lab :•Vaccum (10-7 mbar)•Low temperature (12K)•Mixture : H2O, NH3, CH3OH, CO, CO2•Irradiation with UV light for 24h•Warmed slowly up to room temperature. •Photochemically formed radicals are assumed to recombine in order to form oligomers and polymers
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Caro, M. and co. Chem Eur J 2005, 11, 4895
GC-MS Analysis• 16 amino acids were formed• 5/20 protein-constituent• Glycine = most abundant
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R H
O1. NH3, HCN H2N
R
OH
O
2. H+, H2O
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Magnetochiral Photochemistry•0.2M aq. solution Cr(III)tris-oxalato complex •Dissociation and reassociation of the ligands•Laser (unpolarized) around 696 nm (vis
rouge)•Magnetic field (B) at 7,5T
CrO
O O
O
O
O
OO
OO
O
O
33K
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Rikken, G. L. J. A.; E. Raupach E. Nature, 2000, 405, 932
Magnetochiral Photochemistry
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Enantioselectivity as a fct. of the magnetic field (B)
Enantioselectivity as a fct. of the wavelenght (λ)
CrO
O O
O
O
O
OO
OO
O
O
33K
Rikken, G. L. J. A.; E. Raupach E. Nature, 2000, 405, 932
Magnetochiral Photochemistry
• Does the magnetic field convert unpolarized light in CPL ?
• Earth’s magnetic field : 10-4 T … (vs 7.5 T)
Photoresolution time : 6minRacemization : 70min
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CrO
O O
O
O
O
OO
OO
O
O
33K
Rikken, G. L. J. A.; E. Raupach E. Nature, 2000, 405, 932
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Adsorption of Chiral Organic Molecules on Enantiomorphous Crystals•Quartz = most abondant mineral on Earth•Can be helically chiral in the solid form•1974 (Bonner) : preferential adsorption of
one a.a. enantiomer out of a racemate on the crystal▫Leads to enrichement of the solution in one enantiomer !
•Drawback : anhydrous conditions…
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Bonner, W. A. and al. Science 1974, 186, 143
Amplification Reaction - Saoi
•Discovered in 1995•Autocatalytic reaction
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N
N
H
O
iPr2Zn, PhMe0oC, 40h
N
N
OH
0,2 eq (99% ee)
N
N
OZn(iPr)HCl/H2O
N
N
OH
93% ee
in solution
Saoi on Crystals
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N
N
H
O
N
N
OZn(iPr)
N
N
OH
tBu
tBu
tBu
Zn
N
N
OZn(iPr)
tBu
N
N
OH
tBu
small ee small ee
N
N
H
O
tBu
N
N
H
O
tBu
Zn Zn
high eehigh ee
CD(+) CD(-)
Saoi, K. and al. Orig Life Evol Biosph, 2010, 40, 65
Snail Shells
•Right-helical shells are stereoselectively preferred and dominant
•1 ‘racemic’ snail (Cuban tree)•Helically chiral CaCO3 ! •
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Prebiotic synthesis : Formose Reaction•Ribose (C5H10O5) is a formal pentamer of
formaldehyde (CH2O)
Northrup, A. B.; MacMillan, D. W. C., J.A.C.S. 2002, 124, 6798Breslow, R. Tetrahedron Letters 52 (2011) 2028–2032Breslow, R. Tetrahedron Lett. 1959, 21, 22.
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H H
O2 slow CHO
OHH
H
H H
O
Aldol
CHO
OHH
CH2OH
Glyceraldehyde
higher carbohydrates
(D)-Glyceraldehyde
NH
CO2H
(L)-Proline
H
O
Me
NH
CO2H
10 mol%
DMF, 4oCH
O
Me
OH
Me80% y4:1 syn/anti99% ee
A.A. as Asymmetric Catalysts• Alanine : most common in protein• Isovaline : most common in meteorite• Aldol condensation of glycoaldehyde in water
H2NOH
O
Me
(L)-Alanine
H2NOH
O
Et
(L)-isovaline
Me
Pizzarello, S.; Weber, A. L. Science 2004, 303, 1151
H
O
HO
H2N
Me
OH
O
pH 5.4, 50oC, H2O HOH
HN
Me
OH
O
H
O
HO
H2N
Me
OH
O
CHO
HHO
OHH
CH2OH
D-theose7% ee
100% ee
L-A.A. gives D-sugars !
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Amino acid Ratio (D/L)
L-Serine 50,3/49,7
L-Alanine 50,8/49,2
L-Phenylalanine 52,2/47,8
L-Valine 52,2/47,8
L-Leucine 54,4/45,6
L-Glutamic Acid 60,7/39,3
L-Proline 28,9/71,1
Enantioselective Formose Reaction
L-A.A. catalyze the formation of D-glyceraldehyde preferentially?
Breslow, R. Tetrahedron Letters 52 (2011) 2028–2032
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CHO
OHH
HH H
O
CHO
OHH
CH2OH
R
H2N
O
OH
H2NOH
O
(L)-glutamic acidO
OH
21% ee
Enantioselective Formose Reaction
Breslow, R. Tetrahedron Letters 52 (2011) 2028–2032
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• Only small ee was obtained … amplification by selective solubilisation▫D-glyceraldehyde = complete water solubility▫DL-glyceraldehyde = limited water solubility
• 61/39 (21% ee) can become 92/8 (84% ee) after slow water evaporation
CHO
OHH
H
H H
O
CHO
OHH
CH2OH
H2NOH
O
O
OH
21% ee
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Morowithz Treatment – A. A.
•Most A.A. form racemic compound crystals are less solubles (and higher m.p.) than L or D enantiomers
•Ex : 1% ee solution of D and L-A.A (in H2O)▫As the water evaporates the less soluble
crystals would precipitates leaving increased richness in one enantiomers
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Morowitz, H. J. Theor. Biol. 1969, 25, 491
Example • 500mg of phenylalanine with 1% ee • Dissolved in water• Slow evaporation until the bulk of the material had
crystallized (>400mg)• Solution is now 40% ee … repeat• Solution is now 90,9% ee• Recovered mass is 20mg
H2NOH
O
Bn(L)-Phenylalanine
Breslow, R.; Levine, M. S. PNAS 2006, 35, 12979
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Precipitation of A.A.
•2001 (Viedma)•D-tyrosine crystallized faster
than L-tyrosine•Parity non-conserving energy
•2006 (Scolnik): repeated experiment
•Same result !• ‘undetectable impurities’…
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H2NOH
O
(L)-tyrosineOH
Viedma, C. Orig Life Evol Biosphere 2001, 31, 501Scolnik, Y. and al. Phys Chem 2006, 8, 333
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Unidirectional Rotation of Earth
•Tornado have a ‘prefered’ rotation that are opposite from Northern and Southern hemisphere.
•Due to ‘not well understood’ amplification mechanism
46
Kovacs, K. L.; Keszthelyi, L. Origin of Life 1981, 11, 93
NaClO3
• 100g of NaClO3 in 120mL of H2O at 50oC• Induce precipitation = racemic
• Stirred solution • 99,7% ee in 32 differents crystallisations
▫18 (L) ; 14 (R) • Unpredicable and random
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Kondepudi, D. K. and al. Science 1990, 250, 975
Unidirectional Rotation of Earth
• 1981 : Clockwise stirring = preference for the incorporation
of D-isomers into the polymers and longer polymers• Not convincing enough to conclude unequivocally…
HN
OO
R
O
NCA
H2N
R
NH
O R
OH
O
n
CO2
*NaOMe (cat.)
Kovacs, K., L.; Keszthelyi, L.; Goldanskii, V. J.; Origin of Life 1981, 11, 93-103
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Aggregation of Disk-Shaped Porphyrins
• Stacks (electrostatic and H-bonding interactions)
• Small aggregates assemble into fiberlike structures with helical orientation▫ controlled by the direction
of the vortex motion
• Orientations detected by the absorption of circularly polarized light.
Ribo, J. M. et al. Science 2001, 292, 2063
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• How ? a particular handedness is imposed by the stirring direction
• 1st unequivocal demonstration of chiral selection induced by stirring.
• The supramolecular structure may act as a homochiral template for subsequent asymmetric reactions or may function as a chiral catalyst.
Aggregation of Disk-Shaped Porphyrins
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Ribo, J. M. et al. Science 2001, 292, 2063
Conclusion
•No hypothesis has been accepted yet•Terrestrial vs Extraterrestrial theory
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1. Difference in energy of enantiomers : Parity violation
2. Chirality form polarized light : Selective degradation
3. Chiral field : Magnetism4. Amplification and transfert of chirality5. Crystallization6. Unidirectional rotation of Earth