Chemists claim to be able to make any molecule … …

2. 化学家能告诉我们 生命的起源在哪里吗? What Can Chemists Tell Us About the Origin of Life? Richard N. Zare Department of Chemistry Stanford University Stanford, CA 94305-5080 USA Chemists claim to be able to make any molecule … … OK -- if chemists are so smart, then why don’t they make a living system?

3. What Do We Mean By Life? Respond to stimuli Capacity to grow Capacity to reproduce Driven by chemical energy

4. How Did Life Begin on Earth? • 1. Supernatural Explanations: • “Creation myths” • 2. Spontaneous Generation: • “Nonlife  Life” is a natural • process • Panspermia: “It all started • somewhere else.”

5. Primordial Broth? 1871 -- Darwin suggests that simple chemicals in “warm little ponds” might spontaneously form organic compounds in the presence of energy from heat, light, or electricity from lightning strikes. These organic compounds could then have replicated and evolved to create more complex forms. 1953 – Miller and Urey synthesize amino acids by passing sparks (lightning) through a gas mixture of ammonia, methane, above a pool of water.

6. The RNA World? 1980’s -- Thomas Cech and Sidney Altman showed that some RNA molecules can act as enzyme-like catalysts. RNA was assembled by chance, and was then able to fill twin roles as both enzyme and hereditary molecule in the runup to life.

7. “Networks of synthetic pathways that are recursive and self-catalyzing are widely known in organic chemistry, but they are notorious for generating side products, which may disrupt the reaction system or simply dilute the reactants, preventing them from accumulating within a pathway. The important feature necessary for chemical selection in such a network, which remains to be demonstrated, is feedback-driven self-pruning of side reactions, resulting in a limited suite of pathways capable of concentrating reagents as metabolism does.” James Trefil, Harold Morowitz, and Eric Smith, American Scientist 97, 206 (2009).

8. How To Search For Origins Consider the automotive transportation system in China. If you wanted to explain this system in all of its complexity, you would not ask whether cars led to roads or roads led to cars. It would be more productive to consider the state of transport in preindustrial China and ask how primitive foot and horse trails that must certainly have existed had developed into paved roads and so on. We need to look for multi-step processes with feedback, which may have occurred in the past.

9. Setting The Stage The story of life begins with the origin of the Solar System.

10. Scenario for Star and Planet Formation outflow n~105-108 cm-3 T~10-300 K n~104-105 cm-3 T~10 K 0.1 pc infall Factor 100 smaller Cloud collapse t=0 Protostar with disk t~105 yr 100 AU Planet formation t~106-107 yr Solar system t>108 yr 1 AU = Sun – Earth distance ; 1 pc ~ 2x105 AU ~3x1018 cm

11. Geologic Time

13. D. W. Deamer, “The First Livings Systems: A Bioenergetic Perspective,” Microbiology and Molecular Biology Reviews, 61, 239 (1997).

14. How Did Life on Earth Begin? The details of the beginning of life on Earth remain obscure. All that scientists can say with certainty from the geological record in Precambrian rocks is somewhere between the origin of the Earth around 4600 million years ago and the appearance of the first simple fossils about 3450 million years ago the crucial steps from nonliving to living matter happened and cells began to populate the Earth. Scientists also believe that all life has a common origin.

15. Three-Dimensional Architechture of Molecules Chirality = Handedness

16. What Are the Facts of Life? Life as we know it requires homochiral biopolymers: RNA DNA Proteins Polysaccharides

17. …from P. Frank, W. A. Bonner, and R. N. Zare, “On One Hand, but not the Other,” in Chemistry for the 21st Century, eds. E. Keinan and I. Schechter, Wiley-VCH, Weinheim, 2001, pp. 173-208.

18. Two Problems:  Establishing an initial enantiomeric excess (e.e.)  Amplifying a small e.e. into a dominant e.e.

19. Origin of an Initial e.e. on Earth Is it Intrinsic?  Is it Fluctuational?  Is it Extrinsic?

20. Is Chirality Intrinsic? • In 1966 Yamagata argued that parity violation energy differences (PVED) would account for the asymmetric appearance of biomolecules on Earth. • PVED is on the order of 10-18 to 10-15 kJ/mol for molecules composed of light elements, which should be compared to RT at room temperature (2 kJ/mol).

21. Is Chirality From Chance? Testing a Fluctuational Origin

22. Left-Handed and Right-Handed Quartz Crystals

23. Quartz: An Experimental Test of FluctuationalChirality The distribution of chirality among quartz crystals within the Earth is extremely close to 50:50. For example, in the largest study to date, of 27,053 naturally occurring quartz crystals, 49.83% of them (13,481) were found to be left-handed, and 50.17% (13,572) were found to be right-handed.

24. The most appealing fluctuation hypothesis seems to be that the cells all of one handedness ate those of the opposite handedness.

25. Experiments on Chiral Induction Testing an Extrinsic Origin

26. A Twist of Fate? Left and right circularly polarized light (CPL) is not absorbed equally by any two enantiomers. Hence, CPL from an external source is able to engender asymmetric stereoselection thereby leading to a small e.e.

27. A Twist of Fate? On Earth, light from the sun can exhibit weak (ca. 0.2%) left circular polarization at sunrise and right circular polarization at sunset. These differences would sum to zero over a completely flat Earth. Where the terrain is tilted, however, a net circular polarization of light could result. Such an explanation cannot be ruled out but does sound like special pleading.

28. A Twist of Fate? Cronin and Pizzarello found a chiral excess of L-amino acids could be extracted from the Murchison meteorite. These include nonbiogenic L,L-2-amino-2,3-dimethyl pentanoic acid, which has two chiral centers.

29. Chiral Amplification Many ways are possible! Example: Autoamplification by polymerization 1957 -- Wald proposes that the secondary -helix structure of a polypeptide chain should bias the selection of amino acid enantiomers toward homochirality as polymerization progresses. Soon thereafter, abundant verification of this suggestion follows. 1997 – Eschenmoser elaboration

30. Chiral Amplification Another example: Autoamplification by partial hydrolysis Partial hydrolysis of mixtures of nonhomochiralleucine peptides cause the preferential hydrolysis of those components of the mixtures that were enantiomerically more random. Bonner (1991) proposed that partial polymerization - partial hydrolysis steps, driven by environmental dry and wet cycles, lead to homochiral biopolymers on early Earth.

31. Chiral Amplification

32. Chiral Amplification R. Breslow and M. S. Levine, “Amplification of enantiomeric concentrations under credible prebiotic conditions,” Proc. Natl. Acad. Science USA 103, 12979-12990 (2006). Solutions with as little as 1% enantiomeric excess (ee) of D- or L-phenylalanine are amplified to 90% ee (a 95/5 ratio) by two successive evaporations to precipitate the racemate.

33. Sequestration of Chirality Once chirality is induced and amplified by some mechanism, the excess must be preserved.

34. J. V. Smith and co-workers have suggested the uptake of organic molecules within the micron-sized, three-dimensional, cross-linked network of pores found to exist within the top 50 microns, or so, of weathered feldspar surfaces. A 2.5 km2 granite reef is estimated to contain possibly 1018"catalytic microreactors, open by diffusion to the dynamic reservoir of organic molecules ... but protected from the dispersive effects of flow and convection" as well as protected from the high flux of ultraviolet radiation impinging on the early Earth.

35. SEM images of weathered (001) surfaces of alkali feldspar fragments (Scale bar 5 µm.) (a) Fragment from gravel, showing the beginning of formation of etch pits; (b) a highly weathered Shap feldspar from a peat soil, inhabited by at least three varieties of rod and disc-shaped bacteria. (a) (b)

36. Plutonic Love? 1981, F. Westheimer stresses the important and universal role of phosphorus in biochemistry. This fact hints at the origination of life as Life on the Rocks!

37. Hydrothermal Deep-Sea Vents Marine scientists (late 1970’s) discover ecosystems, the energy source of which is chemical synthesis by bacteria. Associated with the midoceanic ridge and rift systems where the thin plates of the earth's crust are spreading, creating vents. Seawater seeps through. The resulting plume is often black because mineral particles precipitate when hot vent fluid and cold seawater mix.

38. Hydrothermal Deep-Sea Vents

39. The Rocky Road to Life? A hydrothermal origination of life within porous weathered granitic materials potentially solves an apparent contradiction. Polyphosphates in biochemistry are ubiquitous as contrasted both to the relative rarity of crustal phosphate and to the insolubility of native calcium phosphate (apatite: Ca5(PO4)3X, (X=F,Cl)) and consequent low average concentration (ca. 2 µM) of dissolved oceanic phosphate.

40. Does Life Require a Volcanic Eruption? Most phosphate in the primordial crust must have been sequestered in nearly insoluble calcium phosphates or basalts and weathering produced only dissolved monomeric phosphate. But volatile P4O10 is known to be a component of volcanic gases. P4O10 hydrolyzes to polyphosphates and trimetaphosphate. Moreover, aqueous phosphoric acid is known to efficiently polymerize into polyphosphates under conditions of temperature (250 - 350 C) well within those attained within hydrothermal vent systems.

41. A Possible Synthesis: Life starts in weathered granite reefs near hydrothermal vents using organics from Earth and from space. This hypothesis solves problems of: (1) early Earth atmosphere composed of CO2 and N2; (2) hostile surface bombardment and UV irradiation; (3) capture and concentration of dilute organics and capture by vesicles; (4) locale for catalytic synthesis and polymerization; (5) scarcity of phosphorus in a usable form; (6) source of energy to drive biogenic chemistry; (7) need for multitude of microreactors to promote a rich evolutionary biogenesis.

42. What This Talk Was NOT About: Past, Present, Future?

43. Concluding Remarks I: The universe appears to be self-organizing across all length scales. Evidence of self-organization is obvious in the self-assembly of atoms from quarks and leptons, in the building up of the periodic table by the organization of electrons in shells and subshells, and even in the life cycles of stars. The origin of life has been regarded as emerging from chemical self-organization of one type or another. To find an answer to the question "What is life?” it is imperative to answer the question: "From whence life?"

44. Concluding Remarks II: • At the heart of life, as we know it, are homochiral biopolymers. • This lecture has considered three questions: • how an initiatingenantiomeric excess was generated on Earth, • (2) what sort of amplification mechanisms might have • been able to transform that small enantiomeric • excess into the homochiral arrays found in • contemporary biomolecules, • (3) how such biopolymers might survive to become • incorporated into living systems.

45. Concluding Remarks III: In the course of exploring this question, I have outlined what might have happened. I hope this outline might inspire a series of experiments and eventually evolve into a workable model for this process. The question of the origin of life is among the most profound questions asked by human minds. I dare to imagine that during the 21st century a more complete answer to this question will be found to this great mystery.

46. Closing Thoughts: If you feed someone, you have less food for yourself. If you give someone knowledge, you gain knowledge for yourself! Science is not a zero-sum game. Everyone wins!