Chiral Asymmetry of Organic Compounds and Biological Homochirality

As we know now, in fact, a common and most interesting case of chirality is that displayed by the compounds of carbon (C). This element has four binding valences and the spatial distribution of its bonds is such that a C in a molecule can be visualized as a regular tethrahedron with C at its center and the four bonded groups at the vertices (Fig. 7.1C,D). When all these groups differ, the C becomes asymmetric (C*) and the molecules that contain such a carbon atom are chiral, i.e., they can exist in two "handed" forms called enantiomers. The enantiomers of a chiral molecule have matching chemical properties and will interact equally with nonchiral molecules and structures. However, they do not have identical physicochemical properties, because ofthe different spatial distribution (configuration) ofthe chiral carbon substituents groups and the different polarizability of its electrons that this difference entails. For example, solutions of the two enantiomers of a chiral molecule will rotate polarized light in opposite directions and it is only when they are present in equal amounts and compensate each other's effect that solutions become optically inactive (this equal mixture of enantiomers is called racemic, as the synthetic tartaric acid Pasteur analyzed). Figure 7.1D, gives the Fisher projection formula of glyceraldehyde, which is the simplest chiral sugar whose enantiomers are designated by convention as d- and L-, from being dextro-rotatory and levo-rotatory for polarized light, respectively. Glyceraldehyde is also the reference compound in the designation of other sugar and amino acid enantiomers.

One difference between enantiomers, which derives from the above properties and is most important to biochemistry, is that they will interact differently with other chiral molecules. Even for the same compound, enantiomers will behave differently upon encountering enantiomers of the same or opposite configuration, for example, the interaction/reaction of an L-amino acid with its l- or d- enantiomer will differ and the interacting DD and DL complexes will have different energies.

*Sandra Pizzarello—Department of Chemistry and Biochemistry, Arizona State University, Tempe Arizona 85287-1604 USA. Email: [email protected]

Figure 7.1. Chirality.

Figure 7.3. "Right" and "Wrong" handshakes.

Again, an analogy with the hands may be helpful. Disregarding their common difference in strength, the left and right hand will pick up a symmetrical object such as a ball equally. However, when confronted with a chiral object, another hand (Fig. 7.3) or a rotary valve for example, they will act with different ease towards the two forms of this object depending on their spatial match.

Essentially, therefore, chirality is an interactive property of molecules as well as ofobjects and it is as such that it becomes a prerequisite of life's molecules. Because extant life is based on carbon chemistry", many among the myriads of organic compounds that make up the biosphere and are a result of the unique ability of carbon to bond to itself and other atoms have at least one asymmetric carbon. It also happens, as discovered by Pasteur, that extant life makes a precise use of chiral compounds by building its polymers such as proteins, RNA, DNA, polysaccharides with monomers of only one handedness, L-amino acids and D-sugars. Many metabolic activities are also dependent on precise chiral interactions, with the result that chiral configuration determines many of the chemical communications within our body and also with the environment. The latter include the effect of medications, of which there are innumerable examples that vary from the tragic, when only one enantiomer of the drug thalidomide taken by pregnant women caused birth defects in the early '60s, to the amusing as in the case of the compound limonene that smells like lemon-orange in the R- and pine in the S-enantiomer configuration (only sugar and amino acid enantiomers take the D- and

L-notations, whereas all other organic compounds are indicated by R- and S- from the Latin rectus and sinisterb).

This chiral homogeneity of biomolecules, called homochiral-ity, appears essential to life as we know it. If we stipulate that life depends on the function of its polymers (see Chapter 6), it is easy to understand this essential role. Since the activity of a biopolymer is dependent on its spatial structure, the functional specificity ofits superstructure is determined by the homochirality ofthe monomeric constituent molecules. The helices ofproteins and DNA, the sheets into which proteins may organize and the precise lock-key combinations of substrate and enzyme of extant life are achieved thanks to one-handed monomers. Could life function with a different chiral organization of biopolymers—for example, could protein enzymes be built with d- and L-amino acids instead ofbeing homochiral ?2 As long as protein sequences are dictated in a precise and reproducible way, as L-amino acids are in contemporary enzymes, we may assume that D- and L-monomers could also yield some exact and appropriate spatial structure, with a matching active site for the targeted molecule on which they perform their function. Such structures may turn out to be less economically built than extant homochiral ones, but there seems to be no reason to believe that they would be disruptive to a life system. However, this is not always the case, with DNA offering the primary example (Scheme 7.1). This biopolymer is formed by double stranded molecules twisted into a helix, with each strand comprised of a D-sugar-phosphate repeat-backbone to which the four bases of adenine, thymine, cytosine and guanine are attached in precise complimentarity. The bases face and exchange H-bonds with each other across the strands and maintain the integrity ofthe helix. Changing the chirality ofany ofthe sugars along the strands would disrupt this regular ordering and complimentarity, making the double helical structure impossible. Because the fundamental biological processes involving DNA, such as transcription and replication, rely upon the maintenance ofthis specific structure, any alteration of its structure would also impede its function. For life as we know it, therefore, we have to conclude that homochirality is an essential trait of terrestrial biomolecules.

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