Adressing "orgin of life" problem in terms of origin of homochirality

1. Manoj Kumar Sahoo

2. Part-I: ChiralityPart-I: Chirality
(History, chiral technologies e.g. asymmetric synthesis,(History, chiral technologies e.g. asymmetric synthesis,
absolute configuration, enantiomeric excess)absolute configuration, enantiomeric excess)
Part-II: Origin of lifePart-II: Origin of life
(Origin of homochirality, physical and chemical models)(Origin of homochirality, physical and chemical models)

3. Part.I
CHIRALITY

4. The term Chirality was first used by Lord Kelvin in 1884
Chirality Ξ Handedness
Ξ Non-superimposable mirror image
Objects which are chiral have a sense of handednessObjects which are chiral have a sense of handedness

5. Mirror Image Asymmetry

6. Refers to molecules that interact with plane polarised lightRefers to molecules that interact with plane polarised light
Optical ActivityOptical Activity

7. Louis Pasteur Separated these &Louis Pasteur Separated these &
Gave them to BIOT to measureGave them to BIOT to measure
Pasteur’s DiscoveryPasteur’s Discovery

9. Diastereomer: Stereoisomers that are not mirror images

10. Enantiomers:
Identical physical and chemical properties in an achiral environment
Diastereomers:
Different physical and chemical properties
Different physical properies crystalinity, solubility & polarity allows them to be separated

11. Absolute Configuration (R/S)Absolute Configuration (R/S)
(CAHN-INGOLD-PRELOG CONVENTION)
R/S Nomenclature not synonymous with D/L nomenclatureR/S Nomenclature not synonymous with D/L nomenclature

12. Synthesis of Chiral MoleculesSynthesis of Chiral Molecules
Synthesizing a single enantiomer selectively
Normal reactions produce both enantiomers (50:50), so needs separation or resolution
ResolutionResolution
AsymmetricAsymmetric
SynthesisSynthesis
SingleSingle
EnantiomerEnantiomer
NormalNormal
SynthesisSynthesis
RacemicRacemic
MixtureMixture

13. Enzymatic resolutionEnzymatic resolution
Enzymes are very useful for the resolution of certain compounds • Frequently they
display very high selectivity • There can be limitations due to solubility, normally
only one enantiomer exists and can be too substrate specific

14. Stereoselective(Asymmetric) SynthesisStereoselective(Asymmetric) Synthesis
Diastereoselective or enantioselective synthesis or the synthesis of chiral molecules
Use enantiomerically pure starting material and stereospecific reactions
Good - if a cheap, readily available source of chirality exists
Problems - often results in long, tortuous syntheses .......................
suitable material not always available
A. Chiral PoolA. Chiral Pool

15.  Chiral auxiliary - allows enantioselective synthesis via diastereoselective reaction
 Add chiral unit to substrate to control stereoselective reaction
 Can act as a built in resolving agent (if reaction not diastereoselective)
 Problems - need point of attachment, adds additional steps, cleavage conditions must
not damage product!
B. Chiral AuxillaryB. Chiral Auxillary

16.  Chiral reagent - stereochemistry initially resides on the reagent
 Advantages - No coupling / cleavage steps required
 Often override substrate control
 Can be far milder than chiral auxiliaries
 Disadvantages - Need a stoichiometric quantity (not atom economic)
.................Frequently expensive ..........Problematic work-ups
C. Chiral ReagentC. Chiral Reagent

17. Chiral catalysis - ideally a reagent that accelerates a reaction (without being
destroyed) in a chiral environment thus permitting one chiral molecule to generate
millions of new chiral molecules.
D. Chiral CatalystD. Chiral Catalyst

18. ((Enantiomeric Excess (ee)Enantiomeric Excess (ee)))
Measuring ChiralityMeasuring Chirality
• Optical purity:Optical purity: a way of describing the composition of
a mixture of enantiomers
• Enantiomeric excess:Enantiomeric excess: the difference between the
percentage of two enantiomers in a mixture
optical purity is numerically equal to enantiomeric
excess, but is experimentally determined
x 100
[α]sample
Percent optical purity =
[α]pure enantiomer
x 100
[R] + [S]
[R] - [S]
Enantiomeric excess (ee) = = %R - %S

19. 1. Chiral chromatography1. Chiral chromatography
 Normally HPLC or GC
 Chiral stationary phase
 Rapid & reversible diastereotopic interaction with stationary phase

21. 2. Chiral Shift reagents (NMR)2. Chiral Shift reagents (NMR)

23. 3. Chiral Derivatizing agents3. Chiral Derivatizing agents
A good chiral derivatising agent should:
• Be enantiomerically pure (or it is pointless)
• Coupling reaction of both enantiomers must reach 100% (if you are measuring ee)
• Coupling conditions should not racemise stereogenic centre
• Enantiomers must contain point of attachment
• Above list probably influenced depending whether you are measuring %ee or
preparatively separating enantiomers

24. Derivatizing Agents: Mosher’s acid
 Popular derivatising agent for alcohols and amines :
α-methoxy-α- trifluoromethylphenylacetic acid or Mosher’s acid
 Difference in nmr signals between diastereoisomers (above):
1
H nmr Δδ = 0.08 (Me) 19
F nmr Δδ = 0.17 (CF3)
 No α-hydrogen so configurationally stable
 Diastereoisomers can frequently be separated

25. Chiral Derivatising AgentsChiral Derivatising Agents

26. Chiral Solvating Agents (CSA)Chiral Solvating Agents (CSA)
(NMR)(NMR)
IbuprofenIbuprofen

27. Determining Absolute ConfigurationDetermining Absolute Configuration
 Single crystal X-ray
 Chiroptical methods:
Circular Dichroism(CD), Optical rotatory dispersion (ORD), Specific Rotation
Infrared Vibrational CD (VCD), Vibrational raman optical activity (ROA)
 Nuclear Magnetic Resonance (NMR)

28. Manoj Kumar Sahoo

29. Part.II
Origin of life
(The homochirality problem)

30. "Deducing the mechanism of the origin of life on earth has always
remained a fascinating but unsolved puzzle. Some have even
considered it too difficult for scientific study, because the direct
evidence is long gone, and we can only work by plausible
inference."
-R.H. Crabtree, Science, 1997, 276, 222
"Biogenesis, as a problem of science, is lastly going to be a problem
of synthesis. The origin of life cannot be 'discovered', it has to be
re-invented."
-A. Eschenmoser, Tetrahedron, 2007, 63, 12821-12844.

31. Living or not?Living or not?
Seven life processes:- from bacteria to plants to animals
1 Nutrition/feeding.
2 Growth.
3 Movement.
4 Respiration/breathing.
5 Reproduction.
6 Sensitivity.
7 Excretion

32. Primordial Soup TheoryPrimordial Soup Theory
(Soviet biologist Alexander Oparin, 1924)
1. Early Earth had a chemically reducing atmosphere.
2. This atmosphere, exposed to energy in various forms, produced
simple organic compounds ("monomers").
3. These compounds accumulated in a "soup", which may have been
concentrated at various locations (shorelines, oceanic vents etc.).
4. By further transformation, more complex organic polymers and
ultimately life – developed in the soup.

33. Miller-Urey ExperimentMiller-Urey Experiment
Miller, Stanley L. Science, 1953, 117 (3046): 528–9
"Production of Amino Acids Under Possible Primitive Earth Conditions""Production of Amino Acids Under Possible Primitive Earth Conditions"

34. Homochirality is a term to describe a group of moleculesHomochirality is a term to describe a group of molecules
that possess the same sense of chiralitythat possess the same sense of chirality
Origin of LifeOrigin of Life Origin of HomochiralityOrigin of Homochirality
Homochirality is precondition of lifeHomochirality is precondition of life
??? How did life choose its handedness?????? How did life choose its handedness???
??? How did enantiopurity arise from a racemic prebiotic world?????? How did enantiopurity arise from a racemic prebiotic world???

35. Conclusion from Part-IConclusion from Part-I
Chirality is created in presence of a chiral directing for
(Chiral pool, chiral auxillary, chiral catalyst,
chiral reagent, & circularly polarised light)
Absolute asymmetric synthesis
How the first chiral compound synthesized???

36. The Hypothesis for Homochirality
3. Chiral Transmission
1. Mirror Symmetry Breaking
Racemic
0% ee
2. Chiral Amplification
Homochiral
100% ee

37. Symmetry Breaking
Stastistical
Parity violation
Circular polarised light

38. 1.Franck’s Autocatalytic1.Franck’s Autocatalytic
ModelModel
Biochim. Biophys. Acta, 1953, 11, 459-463
Autocatalysis & mutual antagonism
“A laboratory demonstration may not be impossible”
Am
plification
M
echanism
Sigmoid variation of product
Concentration in autocatalytic reaction

39. 3L:2D (ee: 20%)
6L:4D (ee: 20%)
12L:8D (ee: 20%)
3L:2D
(ee: 20%)
4L:2D
(ee: 33.3%)
6L:2D
(ee: 50%)
10L:2D
(ee: 66.6%)
Simple autocatalytic Autocatalytic with
mutual antagonism Pair
selected
for
mutual
antagonism
Deactivated
enantiomers

40. Am
plification
M
echanism

41. Noyori Vs Kagan modelNoyori Vs Kagan modelAm
plification
M
echanism

42. Am
plification
M
echanism

43. Soai’s Autocatalytic ReactionSoai’s Autocatalytic Reaction
K. Soai et.al. Nature, 1995, 378, 767-768
Am
plification
M
echanism

44. Kenso Soai et.al. Science, 2009, 24,492-495
Kenso Soai et.al. Angew. Chem. Int. Ed., 2004, 43,4490; Kenso Soai et.al. Angew. Chem. Int. Ed., 2003, 43,315
Soai Reactions with Outstanding AmplificationSoai Reactions with Outstanding AmplificationAm
plification
M
echanism

45. Blackmonds Model for Soai ReactionBlackmonds Model for Soai Reaction
J. Am. Chem. Soc. 2001, 123, 10103-10104
Am
plification
M
echanism

46. 2. Chiral Amnesia Model2. Chiral Amnesia Model
(Solid phase homochirality)(Solid phase homochirality)
C. Videma, Astrobiology, 2007, 7, 312-319
Am
plification
M
echanism

47. Chiral Amnesia ModelChiral Amnesia Model
(Organic Solid Phase Homochirality)(Organic Solid Phase Homochirality)Am
plification
M
echanism

48. Gradient heating to 1600
Isothermal @ 900
Chiral Amnesia ModelChiral Amnesia Model
(Organic Solid Phase Homochirality)(Organic Solid Phase Homochirality)Am
plification
M
echanism

49. 3. Eutectic Model3. Eutectic Model
(Solution phase homochirality)(Solution phase homochirality)
Eutectic enantiomeric excess (ee eut
)
Klussmann et. Al., J. Am, Chem, Soc, 2007, 123, 7657.
Am
plification
M
echanism

50. Blackmond et.al. Chem. Commun., 2007, 3990
Eutectic ModelEutectic Model
(Solution phase homochirality)(Solution phase homochirality)Am
plification
M
echanism

51. ConclusionConclusion
1. Chemical models provide a plausible pathway for the evolution of
homochirality in nature
2. These investigations will be helpful in the new field of “Systems
Chemistry” which will uncover the chemical roots of biological
organization ultimately enable the engineering of novel biological
systems & functions
3. Building systems that can self-recognize & self assemble, process
information, transport material and energy impact future
technology in areas of material science, synthetic biology
and pharmaceuticals