Homochirality

The Origin and Importance of Biomolecular Homochirality: 

The Origin and Importance of Biomolecular Homochirality Doug Archer Astrobiology Journal Club May 26, 2006

What is Chirality?: 

What is Chirality? Chirality is handedness [Mason, 1984] http://web99.arc.nasa.gov/~astrochm/aachiral.html

Examples of Chirality: 

Examples of Chirality Limonene Thalidomide Oranges Lemon http://www.rlc.dcccd.edu/MATHSCI/reynolds/thalidomide/chemistry/chemistry.htm http://www.popularmechanics.com/science/medicine/1281051.html

Definitions: 

Definitions Chiral – intrinsic handedness Achiral – no intrinsic handedness Enantiomer – a molecule of a particular handedness Homochiral – one chirality Racemic – both enantiomers present in equal amounts Polymer – molecule formed of smaller molecular units (monomers) Peptide – two or more amino acids joined by a peptide bond Polypeptide – more than 2 amino acids joined together. Another name for a protein Steric – related to shape

History: 

History Discovered in 1848 by Louis Pasteur while studying the optical activity of natural products in the crystal state. Pasteur called it dyssymetrie Kelvin used the term chirality (from Greek cheir, meaning hand)

Chirality and Life: 

Chirality and Life Chirality is intrinsic to complex molecules What was surprising was that all life uses L-Amino Acids (read proteins) and D-Sugars (DNA and RNA) Huge implications for origins of life

First Big Question: 

First Big Question Does life require homochirality to initiate or does life produce homochirality?

Problems with proteins: 

Problems with proteins No thermodynamic advantage to forming chains of a single chirality However, heterochiral polymers with random enantiomeric distribution have strong steric hindrances Protein function depends on shape Therefore, can’t have protein-initiated biology from a racemic solution

Slide9: 

CDK2 protein – important to melanoma growth http://imglib.lbl.gov/cgi-bin/ImgLib/displaytag/BERKELEY-LAB/RESEARCH-1991-PRESENT/LIFE-SCIENCES/tags/1993Highlights_pg10_image?both

Slide10: 

Peptide bonds are not energetically favored in aqueous solutions of moderate temperature The equilibrium constant of the condensation of alanine and glycine to form the dipeptide alanyl-glycine in water at 37º C and at pH 7 is 10-3 and the free energy requirement is 4.13 Kcal/mol. The equilibrium concentration of the dipeptide for 1 M solutions of the free amino acids is just above 10-5 M. The concentration of a 12,000 Dalton chain of amino acids at equilibrium is 10-99 M. The volume of solution required to produce just one molecule of this protein is 1050 times the volume of the entire earth [Brack et al., 2001].

Slide11: 

Formation of polypeptides, from energetic considerations alone, is rare. Probability of forming a long chain, homochiral polypeptide is vanishingly small

RNA Troubles: 

RNA Troubles Work by G.F. Joyce (1984) with template-directed RNA replication Template, not enzymatically driven Proceeds fine in homochiral solution Inhibited in the racemic case Opposite chirality monomer added acts as a chain terminator Also prevents complementarity (binding to opposite strand)

Slide13: 

From G.F. Joyce 1984

Preliminary Answer: 

Preliminary Answer Life seems to require homochirality Must be a mechanism that either Naturally selects for a certain chirality Produces a homochiral solution

Three primary mechanisms: 

Three primary mechanisms Parity violating energy differences (PVEDs) Enantio-specific destruction by circularly polarized light (CPL) in the interstellar medium (ISM) Mineral-mediated chiral selectivity

Parity: 

Parity The principle of parity states the laws of Nature are invariant upon reflection of rotation in space. Parity is violated, or symmetry is broken, when an unexplained excess of one chirality is found. Homochirality represents a symmetry break

PVED cont’d: 

PVED theory says that molecules of opposite chirality are not true enantiomers as they are only space-inverted structures True enantiomeric degeneracy requires one molecule to be made of antimatter Since this is not true of chiral enantiomers, different chiralities can have different energy states PVED cont’d

Two Chirally Selective Sources: 

Two Chirally Selective Sources Parity is not conserved in the weak nuclear interaction Asymmetric decay can preferentially destroy a certain chirality (never observed) Weak Neutral Current gives rise to a parity violating energy shift L-amino acids are more stable than the D form by about 2 x 10^-14 J/mol/amino acid residue. Thermodynamically, this corresponds to an L-enantiomer excess of ~10^6 per mole Sign and energy difference for sugars remains unknown

Problems with PVED: 

Problems with PVED Has been tested for over 40 years and there has never been any experimental confirmation of theory compared to temperature, pressure, and pH considerations, differences are so small that they should hardly make any difference in the outcome of isomerization kinetics Those supportive of the PVED theory have worked almost exclusively with chiral molecules in the crystal state, whereas life almost certainly evolved by aqueous means. (Bonner 2000)

The Nail in the Coffin: 

The Nail in the Coffin Others working on the PVED problem from different basic assumptions state that earlier conclusions and the energy numbers of amino acids “are uncertain even with respect to sign” and “must be viewed with considerable skepticism” [Backasov et al., 1998]

CPL: 

CPL Circularly polarized light (CPL) has been shown to exhibit enantio-selective photodesctruction in the lab [Bernstein et al., 2002] astronomical sources such as electromagnetic radiation from magnetic white dwarfs and white dwarfs binaries can be circular up to 12% CPL could also be produced by reflection off of dust grains aligned in a magnetic field of star forming regions [Meierhenrich et al., 2001].

Location, Location, Location: 

Location, Location, Location According to this theory, the only factor that determines L-amino acids and D-sugars or vice versa, is physical location in the galaxy.

Meteoritic Evidence: 

Meteoritic Evidence Studies of the Murchison Meteorite have shown that L-alanine is twice as abundant as the D-form and the L-glutamic acid was three times as abundant [Clark, 1999; Engel and Macko, 1997]

The problem step: 

The problem step Both of these chirally selective mechanisms require an additional step: enantiomeric amplification Essentially, the idea is that once an excess of one enantiomer reaches a certain, undefined level, an unknown and never observed process kicks in to start a positive feedback mechanism

Why is this a problem?: 

Why is this a problem? It, to my knowledge, has never been observed. In fact, experimental results show that kinetic processes in aqueous solution lead to racemization in a relatively short amount of time For a diluted aqueous solution of a simple triose, the time it takes the solution to racemize in an alkaline solution at 70-100º C is on the order of a day

Mineral-mediated Chirality: 

Mineral-mediated Chirality Macromolecular crystal structures have a chiral morphology that can depend on molecular handedness of constituent molecules This theory is very preliminary and current results only report a small enantiomeric excess on different crystal surfaces may only work for some amino acids Solid State organic production represents a novel way of chiral selection that has not yet been addressed false positive detection problem

Origin of Life theories: 

Origin of Life theories Current origin of life theories essentially ignore homochirality as a constraint on location (temp, pH, etc.) Shallow Pools – maybe Panspermia – avoids the issue, not instructive Hydrothermal vents – hard to imagine

References: 

References Avetisov, V.V., and V.I. Goldanskii, Homochirality and stereospecific activity: evolutionary aspects, Biosystems, 25 (3), 141, 1991. Backasov, A., T. Ha, and M. Quack, Ab initio calculations of molecular energies including parity violating interactions, J Chem Phys, 109, 7263-7285, 1998. Bernstein, M.P., J.P. Dworkin, S.A. Sandford, G.W. Cooper, and L.J. Allamandola, Racemic amino acids from the ultraviolet photolysis of interstellar ice analogues, Nature, 416, 401-403, 2002. Bonner, W.A., Parity violation and the evolution of biomolecular homochirality, Chirality, 12 (3), 114-126, 2000. Bonner, W.A., J. Mayo Greenberg, and E. Rubenstein, The Extraterrestrial Origin of the Homochirality of Biomolecules - Rebuttal to a Critique, Origins of Life and Evolution of the Biosphere, 29, 215-219, 1999. Brack, A., B. Barbier, M. Bertrand-Urbaniak, F. Boillot, A. Chabin, R. Jacquet, and U. Meierhenrich, Life in the solar system: chemical origin, chirality, life on Mars, in ESA SP-496: Exo-/Astro-Biology, pp. 49-54, 2001. Clark, S., Polarized starlight and the handedness of life, American Scientist, 87 (14), 336-338, 1999. Cody, G.D., N.Z. Boctor, R.M. Hazen, J.H. Scott, A. Sharma, and H.S. Yoder, Hydrothermal Origins of Biochemical Organosynthesis: A Red Herring or the Geochemical Roots of Life? in Eleventh Annual V. M. Goldschmidt Conference, pp. 3760, 2001.

Slide29: 

Avetisov, V.V., and V.I. Goldanskii, Homochirality and stereospecific activity: evolutionary aspects, Biosystems, 25 (3), 141, 1991. Backasov, A., T. Ha, and M. Quack, Ab initio calculations of molecular energies including parity violating interactions, J Chem Phys, 109, 7263-7285, 1998. Bernstein, M.P., J.P. Dworkin, S.A. Sandford, G.W. Cooper, and L.J. Allamandola, Racemic amino acids from the ultraviolet photolysis of interstellar ice analogues, Nature, 416, 401-403, 2002. Bonner, W.A., Parity violation and the evolution of biomolecular homochirality, Chirality, 12 (3), 114-126, 2000. Bonner, W.A., J. Mayo Greenberg, and E. Rubenstein, The Extraterrestrial Origin of the Homochirality of Biomolecules - Rebuttal to a Critique, Origins of Life and Evolution of the Biosphere, 29, 215-219, 1999. Brack, A., B. Barbier, M. Bertrand-Urbaniak, F. Boillot, A. Chabin, R. Jacquet, and U. Meierhenrich, Life in the solar system: chemical origin, chirality, life on Mars, in ESA SP-496: Exo-/Astro-Biology, pp. 49-54, 2001. Clark, S., Polarized starlight and the handedness of life, American Scientist, 87 (14), 336-338, 1999. Cody, G.D., N.Z. Boctor, R.M. Hazen, J.H. Scott, A. Sharma, and H.S. Yoder, Hydrothermal Origins of Biochemical Organosynthesis: A Red Herring or the Geochemical Roots of Life? in Eleventh Annual V. M. Goldschmidt Conference, pp. 3760, 2001. Engel, M.H., and S.A. Macko, Isotopic evidence for extraterrestrial nonracemic amino acids in the Murchison meteorite, Nature, 389, 265-268, 1997. Flynn, G.J., The Delivery of Organic Matter From Asteroids and Comets to the Early Surface of Mars, Earth, Moon, and Planets, 72, 469-474, 1996. Hazen, R.M., T.R. Filley, and G.A. Goodfriend, Selective adsorption of L- and D-amino acids on calcite: Implications for biochemical homochirality, PNAS, 98 (10), 5487-5490, 2001. Joyce, G.F., G.M. Visser, C.A.A. van Boeckel, J.H. van Boom, L.E. Orgel, and J. van Westrenen, Chiral selection in poly(C)-directed synthesis of oligo(G), Nature, 310 (5978), 602, 1984. Mason, S.F., Origins of biomolecular handedness, Nature, 311 (5981), 19, 1984. Meierhenrich, U., B. Barbier, R. Jacquet, A. Chabin, C. Alcaraz, L. Nahon, and A. Brack, Photochemical origin of biomolecular asymmetry, in ESA SP-496: Exo-/Astro-Biology, pp. 167-170, 2001. Sandars, P.G.H., A Toy Model for the Generation of Homochirality during Polymerization, Origins of Life and Evolution of the Biosphere, 33, 575-587, 2003. Toxvaerd, S., Origin of homochirality in biological systems, International Journal of Astrobiology, 4, 43-48, 2005. Tranter, G.E., Parity violation and the origins of biomolecular handedness, Biosystems, 20 (1), 37, 1987.