Stereochemistry and the Origins of Life James H. Brewster
J. Chem. Educ. 1986.63:667. Downloaded from pubs.acs.org by UNIV OF LOUISIANA AT LAFAYETTE on 01/23/19. For personal use only.
Purdue University, West Lafayette, IN 47907
What is life? When and where and how did it begin? For the open, questing, and critical mind there can be no final answers. Not from philosophy and not from religion. Not even from science, although it offers us an increasingly clear and detailed picture of how life has developed since about 3.4 X 109 years ago (1), when single-celled entities appear to have existed in what is now Swaziland. Since the oldest surviving rocks (~3.8 X 109 years old (2)) are not much more ancient, geology may not be able to take us back to the very beginnings of life. But the earth itself is about 4.6 X 10® years old (2) so that, allowing time for it to cool from a molten state, there may be only a few hundred million years of life’s existence unaccounted for. For that period of time, the best that science can do is to offer us more and more sophisticated chemical scenarios for how life might have begun, based on familiar principles that can be demonstrated in the laboratory1 (4-8). The ultimate test of these scenarios will be their ability to suggest ways to create primitive life forms de novo in the laboratory. To do so would prove nothing historically but it would serve to demystify the subject of the origin of life and that is a legitimate goal of science.2 That much demystification remains to be done is shown by a recent “Provocative Opinion” in THIS JOURNAL by Gonzalez (9). He asserts that the monochirality of living organisms, known since the beginnings of organic stereochemistry (10,11), cannot be accounted for by modern concepts in that field and appears to contravene the second law of thermodynamics. This, he claims, casts doubt on the Theory of Evolution and, further, suggests that the prebiotic hands of some Great Resolver must have been involved at some point in the origin of life. Those assertions are wrong; the suggested supernatural intervention—which, of course, can This is an area with a rich and joyful literature, characterized by lively (and sometimes extravagant) speculation, ingenious (and often careful) experimentation, and enthusiastic (if occasionally premature) publication, of which the sobersides chemist may be unaware. For the latest segment of a running annual bibliography (entries 5287-5566) see ref 3. 2 To demystify is not to trivialize. Students of paleontology or molecular biology often end up more in awe of the glories and intricacies of life than have, e g., those men of God who have been capable of burning witches and sending young men into battle, to kill and die over differences in religious doctrine. 3 Chirality is only one of the attributes shared by modern forms of life. Others include: encapsulation of protoplasm by cell membranes, a nucleic acid-protein economy, a common genetic code, a common set of structural building blocks and metabolites, and related enzymatic processes. Taken together, these attributes suggest a common ancestry, but it is not required that any of them have been possessed by the most primitive life forms. We should not mistake the last common ancestor (LCA) for the first living entity (FLE). Studies of homologies in nucleic acids and proteins appear to be able, thanks to the conservative powers of natural selection, to allow the development of a detailed family tree back to the LCA and even to provide some picture of it (see, for example, refs 12, 13, 14). In this sense, the LCA is an historical entity which is accessible to scientific study. But it may well have been hundreds of millions of years more recent than the FLE; it may well have had many contemporaries, some related and some not, whose lines have died out leaving no trace in the genes of modern living beings. The FLE, on the other hand, has left no certain tracks. If life formed easily, early, and often, as some have suggested, the FLE may not even have been ancestral to the LCA. If it was silicate-based (8), there may have been no organic trace to be left. 1
be categorically ruled out—is not required to account for the monochirality of life. The matter deserves extended discussion because, as Gonzalez properly points out, there are important gaps in even the most carefully elaborated scenarios and because some of the chemical speculation in this area seems to be misdirected. But it is much too soon to say that science has struck out on this matter. Science has not exhausted the resources of its intellectual machinery, which has an innate capacity for self-correction and redirection. For only a little more than 40 years has it seriously addressed the hypothesis that life had a natural (and essentially chemical) origin. A great deal of progress has been made in that time and work on that hypothesis has made important contributions to our understanding of contemporary life processes; we can expect further progress. Give science a chance—after all, philosophy and religion have had thousands of years to work on their answers! The observable fact is that, with some highly specific exceptions, the principal and characteristic organic compounds of the terrestrial biota are not only chiral but (within limits of detection) almost always enantiomerically pure in their individual occurrences and of the same chiral sense in the various species.3 To an organic chemist familiar with difficult resolutions, easy racemizations, and low optical yields, this is at first an astonishing state of affairs (4,5,11), and it has prompted searches for physical phenomena that might have produced a pool of chiral compounds from which the first living entity (FLE) might form (15,16). But there is nothing extraordinary about organic reactions that give mixtures of products in proportions remote from what they would be at equilibrium. Such processes are said to be subject to kinetic, rather than thermodynamic, product control (17). It is only required that the factors controlling the relative free energies of the transition states be different from those controlling the relative free energies of the products and that the products not be brought into equilibrium. Thus, it is possible to convert an a, (1-unsatu rated ketone (more stable) to the /3, y isomer (less stable) via kinetically controlled protonation of the enolate (18) (eq 1). Selective catalysts favor one transition state more than another, sometimes facilitating formation of the less-stable stereoisomer, as in the hydrogenation of disubstituted acetylenes to cisolefins (19) (eq 2). Very high degrees of kinetically controlled asymmetric synthesis have been achieved in certain hydrogenations with chiral Wilkinson-type (homogeneous) catalysts, as in the course of a synthesis of DOPA (20) (eq 3). Clearly, then, the spontaneous formation of a system having a significant enantiomeric imbalance would be possible if the chiral product were, itself, an efficient, stereospecific catalyst for the process. The very first such entity formed will replicate itself rapidly; if the starting system is achiral, or racemic but labile, the entire sample could go over to one enantiomer. Examples of such spontaneous resolution (21) are important because they show that such processes are, indeed, thermodynamically feasible. never
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Volume 63
Number 8
August 1986
667
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