Introduction and Historical Background

1.1 Introduction

Chirality, or handedness, in molecules related to living organisms has fascinated scientists ever since the phenomenon was first observed, and it remains a fundamental question still not fully explained. Of the two possible series of enantiomeric molecules, why did Nature choose the L-amino acids and D-sugars when creating the structures of life? Why not the other way round? Indeed, why not both, which is at first sight the most likely chemical outcome?

For some scientists this is an encrypted clue provided by Nature to unveil its origins. For others it is much less than that, merely a matter of chance. We will describe in this book the most relevant pieces of information gathered by scientists over the past 150 years concerning this issue. Along the way we will explore some of the basic principles of the laws of Nature, principles which govern all the processes in the Universe, some of them so profound that they approach the limits of scientific knowledge, and which have influenced the nature of the Universe since its origin.

1.2 The Contribution of Pasteur

We are indebted to Louis Pasteur for the first theory on the origins of biomolecular homochirality — in fact we owe not only the initial theory to him but also our awareness of the problem itself. Most chemists are familiar with Pasteur's work on the resolution of tartaric acid (later known as racemic acid) into its enantiomers, a procedure which established the foundations of molecular stereochemistry (Figure 1.1). The historic chain of events which led in the middle of the nineteenth century to the development of molecular stereochemistry had its origins in the observation of chirality in compounds obtained from living organisms. Correlation of their crystallographic properties with those found in mineral samples — mineralogy being the better developed field at the time — provided the necessary understanding for this.

1.2.1 Quartz

Quartz had an important role to play. At the beginning of the nineteenth century, in 1801, the crystallographer R. H. Haüy observed that the apparent hexagonal symmetry of quartz crystals was in fact reduced in most cases by the presence of small faces called hemihedral facets (hemihedral meaning that only half the faces required for complete symmetry were exhibited) at alternate corners of the crystal. The presence of these hemihedral facets has a profound effect on symmetry. It eliminates the centre and planes of symmetry of the basic holohedral (holohedral indicating that it has the highest symmetry) hexagonal crystal, and gives rise to two non-superimposable mirror image forms of quartz, both chiral and enantiomorphic, which can be recognized by their outward aspect (further details are given in Section 8.2, Chiral Crystals and Faces on Crystals). Around the same time, the discovery of optical activity — a necessary tool in the study of chirality on the molecular scale — was attributed to the mathematician-physician, F. Arago in the early nineteenth century (1811), and it is equally related to the mineral quartz, since this was the first material in which optical rotation was observed. Soon afterwards the physicist, J.-B. Biot, discovered that natural quartz existed in two forms which rotated the plane of polarization in opposite directions, and he also established a linear relationship between the magnitude of the angle of rotation and the thickness of the slice of quartz (1812). In addition, he introduced and refined the polarimeter as a scientific tool. The two forms of quartz which Biot found to rotate in opposite senses in his polarimeter were subsequently identified by J. W. F. Herschel (1822) as the two hemihedral forms.

1.2.2 Tartaric Acid and the Tartrates

The wave theory of light was gaining acceptance at the time. Defended among others by the physicist A. J. Fresnel, the theory of transverse waves led to the conclusion around 1824 that linearly polarized light might be considered to be the superimposition of left- and right-circular polarized light. From this, it followed that the optical rotation was the consequence of the different refractive index of the two beams when passing through a chiral medium. Biot noticed that the effect of optical rotation in the plane of polarized light was not specific to crystals but was also found with certain natural products in the liquid state, including turpentine, aqueous solutions of sugar or tartaric acid (in 1832), and even vapors of such substances where they were volatile.

Later in the century (1843) Biot gave an intriguing account of certain anomalous relationships between two isomeric substances of formula C4H6O6, the naturally occurring (+)-tartaric acid and the optically inactive paratartaric acid, in relation to the law of isomorphism, discovered earlier by the mineralogist, E. Mitscherlich. This brought Louis Pasteur on to the scene, around 1847–48. Mitscherlich had compared the crystal forms of the corresponding salts of the two acids and found that they differed in crystal morphology, those obtained from (+)-tartaric acid being hemihedral and those derived from paratartaric acid holohedral racemic crystals (using current terminology), except in one instance. This was the case of sodium ammonium tartrate and paratartrate, in which the crystals appeared identical, and these salts displayed hemihedral morphology in both cases.

Pasteur decided the latter case required further study. Witnessed by Biot, Pasteur worked with tartaric acid, which Biot had shown to be optically active, and with paratartaric acid, which was chemically identical but optically inactive, and prepared crystals of the corresponding sodium ammonium salts. He showed that although both salts were indeed hemihedral, in the (+)-tartrate the hemihedral facets were all facing in the same direction, whereas in the paratartrate there were equal amounts of crystals with hemihedral facets having either this orientation or the opposite, forming a conglomerate of enantiomorphous crystals (for the definition of a conglomerate, see Section 5.6, Amplification of Scalemic Compounds: Eutectic Mixtures).

Figure 1.2 illustrates two actual enantiomorphous crystals of sodium ammonium tartrate, similar to those obtained by Pasteur in his work with racemic acid. In Figure 1.3b drawings of the two enantiomorphic crystals are shown, taken from Pasteur's original notes. These crystals are enantiomorphous, since they are mirror images and are not superimposable. Pasteur performed the first enantiomeric resolution of the crystals using tweezers and a magnifying...