Homochirality: A Trip Through The LookingGlass

1
Homochirality A Trip Through The Looking-Glass

• R. David Pace, Ph.D.

2
What is Homochirality?

• Immanuel Kant,
• 1783
• The glove of one hand cannot be used on the
  other

3
Celts (A.K.A. Rattlebacks)

• Chiral tools called Celts.
• Biased toward one direction of spin due to an
  ellipsoidally shaped bottom.
• Spin freely in one direction only.
• Any attempt to spin in the wrong direction
  results in the rattleback stopping and reversing
  its direction of spin.

4
Through The Looking-Glass (1872)

• Lewis Carroll
• Charles Lutwidge Dodgson
• His work may have been affected by Louis Pasteur
• Maybe Looking-glass milk isnt good to drink.
  Alice

5
On Which Side Of The Glass Are We?

• Or What came first, the chicken or the egg?
• Natural laws effective for explaining how the
  world functions.
• Natural laws tell us nothing of where the world
  comes from.

6
Jon Cohen, Science, 1995, 267 (5202), 1265-6.

• Why do sugar molecules in DNA and RNA twist to
  the right in all known organisms? Similarly, all
  of the amino acids from which proteins are formed
  twist to the left. The reason these molecules
  have such a uniform handedness, or chirality,
  is not known, but there is no shortage of
  theories on the subject. (yellow italics mine)

7
The Limit of Scientific Reliability

• Papers dealing with the origin of homochirality
  are unanimous in the use of phrases like
• We speculate
• It could have happened this way
• Maybe
• We envision

8
Chiral Gastropods

• Knobbed Whelk
• Almost always right handed
• 20,0001

http//www.assateague.com
9
Chiral Gastropods

• Lightning Whelk
• Almost always left handed

http//www.assateague.com
10
Crossbill Finch
http//www.fs.fed.us/r6/fremont/birds/recr.jpg
http//www.geocities.com/mules_hybrids/crossbill_c
rosses.htm
11
Fibonacci Series

• 1 1 2 3 5 8 13 21 34 55 89 144 233

http//www.branta.connectfree.co.uk/Thistle2.jpg
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Fundamentals of Stereochemistry

• Isomers

13
Chirality in One Dimension
Enantiomers
mirror point
reflection
14
Chirality in Two Dimensions
Enantiomers
mirror line
reflection
15
Chirality in Three Dimensions
Enantiomers
mirror plane
16
Crystals of Sodium Ammonium Tartrate
hemihedral faces

• Rare example of self-resolution
• Phenomenon occurs at lt23oC
• These are enantiomers

(-)
()
Biots results
17
Chirality in Three Dimensions

• Enantiomers - nonsuperimposable mirror images.
• Identical physical properties except one.
• Drastically different behaviors in living systems.

18
Bighorn Sheep and 3D Chirality
The horns are enantiomorphic
19
Three Types of Chiral Molecules
20
Chirality in Three Dimensions

• achiral chiral

21
Types of Enantiomeric Mixtures
Racemic Modification
22
Importance of Chirality
23
A Booming Business

• Worldwide growth in sales of chiral drugs in
  single enantiomer dosage forms is exponential

• 133 billion 2000 (actual)
• 200 billion 2008 (projected)

Chemical and Engineering News, 2003, 81(18),
45-55.
24
The Origin of Homo-chirality in Life

• Conference held in Santa Monica, CA
• 24 physicists, chemists, astronomers
• Feb. 15-17, 1995
• Conclusions

• No agreement on any model or theory
• Homochirality (total predominance) is necessary
  for present-day life

Cohen, J, Science, 1995, 267(5202), 1265-66
25
Two Camps
26
A Testable Prediction

• Synthesis of chiral compounds from achiral
  reagents always yields the racemic modification
  (red emphasis mine)
• Optically inactive reagents yield optically
  inactive products (red emphasis mine)
• The facts have always agreed!

Morrison and Boyd, Organic Chemistry, 6th Ed.,
Prentice Hall New Jersey, 1992, p. 152.
27
Thermodynamics Agrees

• DG 0

(R) (S)
D
-

/
RT
G
e
K
eq

\
1
K
eq
28
Six Popular Theories on the Origin of
Homochirality

• Magnetic Fields
• Parity Violation Energy Difference
• Circular Dichroism
• Magnetochiral Dichroism
• Extraterrestrial Seeding
• Homochiral Templates

29
Strong Magnetic Fields

• Magnetic fields of 1.2 2.1 Tesla
• 98 enantiomeric excess!

CH3MgBr
Zadel, G. Eisonbraun, C. Wolff, G.-J.
Breitmaier, E. Angew. Chem. Int. Ed. Engl. 1994,
33, 454.
Bradley, D. Science, 1994, 264, 908.
30
Organic Chemistrys Version of Cold Fusion
Zadel, G. Eisonbraun, C. Wolff, G.-J.
Breitmaier, E. Angew. Chem. Int. Ed. Engl. 1994,
33, 454.

• DuPont took lead.
• Incorrect NMR results reported.
• 20 international groups could repeat the work.
• It took six weeks.
• The original paper was withdrawn.

Clery, D. Bradley, D. Science, 1994, 265, 21.
31
The Standard Model
http//particleadventure.org/particleadventure/fra
meless/standard_model.html
32
CP Violation The Weak Force

• Physical symmetry-breaking in b-decay and weak
  forces
• The energy difference between enantiomers is
  vanishingly small (10-14J)

http//cc.oulu.fi/tumannin/hel1303.pdf
Pro Mason, S.F. Tranter, G.E. Proc. Royal Soc.
London, 1985, 397(1812), 45-65 Con Bada, J.L.
Nature, 1995, 374, 594-595.
33
CP Violation and L-Amino Acids
34
CP Violation and L-Amino Acids

• Only 106 excess L-alanines for every 6.0223x1023
  molecules of the racemate.
• Amino acid racemization is a rapid geochemical
  process 1,000 years at 50oC.
• At this rate only 1x1012 molecules per mole in 1
  billion years! (Cambrian Explosion?)
• Some chiral amplification process would have to
  be active what would that be?

35
Circular Dichroism and UV Light

• Circularly Polarized Light Two electromagnetic
  waves perpendicular to one another that are 90o
  out of phase.
• Homochiral molecules interact differently with
  left and right CPL.
• One of the best results Camphor

Belavoine, G. Moradpour, A. Kagan, H.B. J. Am.
Chem. Soc. 1974, 96, 5152-58.
36
Circular Dichroism and UV Light

• 20 ee after destruction of 99 of the racemic
  modification.
• 35.5 ee after destruction of 99.9 of the
  racemic modification.
• 100 optical purity is reached asymptotically
  where no material remains.

37
CPL and Nebula

• Recent discovery of CP visible light in nebula
  (0.03).
• The requisite CP UV light not present.
• CP light exhibits enantioselectivity over a very
  narrow range.
• According to the Kuhn-Condon rule the effect
  averages to zero over the whole spectrum and
  cannot select enantiomers in a racemic
  modification.

Bailey, J, et. al. Science, 1998, 281 (5377),
672-674.
38
Magnetochiral Dichroism

• MChD A chiral medium will absorb light
  traveling parallel to a magnetic field
  differently than light traveling antiparallel to
  the magnetic field.

39
Magnetochiral Dichroism
Anisotropic effect linking chirality and
magnetism
(Different magnetic properties at different
points in space)
40
Problems with MChD

• Monochromatic light required (695.5nm laser)
• The light must travel parallel to the magnetic
  field
• Magnetic fields up to 15T required
• Only 15mL sample irradiated at one time

Rikken, G.L.J.A. Raupach, E. Nature, 2000, 405,
932-5.
41
More Problems with MChD
(S)
(R)

• The best ees 0.016
• Solutions racemized when irradiation stopped.

Rikken, G.L.J.A. Raupach, E. Nature, 2000, 405,
932-5.
42
Rikkens and Raupachs Conclusion

• Clearly the question of the origin of the
  homochirality of life is far from answered.

But reviewers say something much different
Rikken, G.L.J.A. Raupach, E. Nature, 2000, 405,
932-5.
43
Laurence D. Barron, for Instance

• On both experimental and theoretical grounds, we
  now have to seriously consider magnetochiral
  photochemistry in discussions of the possible
  origins of biological homochirality.

Barron, L.D. Nature, 2000, 405, 895-6.
44
Extraterrestrial Seeding

• The Murchison Meteorite
• Small ee (4 - 8) of a few biologically
  important L-amino acids.
• Several others present as racemic modifications.

Engel, M.H. Macko, S.A. Nature, 1997, 398,
265-268. Cronin, J.R. Pizzarello, S. Science,
1997, 275 (5302), 951-5.
45
Extraterrestrial Seeding Problems

• Nanogram quantities detected
• Extreme possibility of contamination
• Sample size not representative
• Remember the three kinds of racemic modifications?

Astrobiology Mag 2003 www.astrobio.net/news/arti
cle375.html Bada, J. Nature, 1995, 374, 594-5.
46
Homochiral Templates

• Many variants to this proposition.
• Chiral molecules that act as templates or
  replicators.
• All involve the prebiotic presence of highly
  ordered, complex, and chiral molecules.
• Consider the so-called RNA World.

47
RNA World?
48
RNA World? Sugar Formation

• Formose Reaction

Orgel, L.E. Proc. Natl. Acad. Sci. 2000, 97,
12503-12507.
49
RNA World? Ribose Decomposition

Larralde, R. Robertson, M.P. Miller, S. L.
Proc. Natl. Acad. Sci. 1995, 92, 8158-8160.
50
RNA World? Cytosine Decomposition

t1/2 340 yr at 25 oC

• Cytosine not produced in spark experiments
• Uracil unstable in concentrations gt0.1M

Shapiro, R. Proc. Natl. Acad. Sci, 1999, 96,
4396-4401. Levy, M. Miller, S. L. Proc. Natl.
Acad. Sci. 1998, 95, 7933-8.
51
A Multiplicity of Other Issues

• Ca2 ions precipitate fatty acids and phosphate
• Amino acids are good chelation agents
• Origin of the DNA coding system for proteins
• Origin of the message encoded in DNA
• Origin of the code translation apparatus and
  replication machinery that are themselves encoded
• Stabilizing and preserving thermally sensitive
  molecules in a harsh geochemical environment

52
Ending Where We Started

Why do sugar molecules in DNA and RNA twist to
the right in all known organisms? Similarly, all
of the amino acids from which proteins are formed
twist to the left. The reason these molecules
have such a uniform handedness, or chirality,
is not known, but there is no shortage of
theories on the subject. (yellow italics mine)
Jon Cohen, Science, 1995, 267 (5202), 1265-6.
53
Summation A quote from the Masters

The Morrison and Boyd text, Organic Chemistry,
now in its 6th Edition, is nearly unanimously
recognized as the premiere undergraduate organic
chemistry text by the international chemical
community. Quote from page 159.