A 02 Stereo notes and figs v5 renumb 54-78B Lecture 02 Stereo hmwk comb 79-8554STEREOCHEMISTRY OF BIOMOLECULES LECTURE # 2 R,S system 1. Overview of terms 2. Priorities of groups in cysteine and aspartic acid 3. Summary of R,S rules D,L system 4. Polarimeter : d vs l : whole molecule 5. Bio sugars : D at chiral carbon furthest from C=O 6. Chiral carbons : groups extend to infinity 7. Uniquely different chiral carbons : # forms = 2^n 8. Monosaccharides : aldoses 9. Monosaccharides : ketoses 10. Biological amino acids : L at backbone carbon 11. Protein amino acids : L, both R & S, both d & l Biological applications 12. Alpha helix : repetitive pattern 13. Right-handed helix : amino acids must be L 14. Stereospecific binding : three-point attachment 15. Stereoisomers : different tastes 16. Thalidomide - birth defects caused by wrong isomer 17. Asymmetry in plants and animals 18. Prebiotic chemical evolution : apparatus 19. Prebiotic chemical evolution : racemic mixtures 20. Symmetric and asymmetric catalysts 21. Discrimination between the Z groups in XYZZ 22. 3-d drawing of an enzyme-citrate complex55STEREOCHEMISTRY OF BIOMOLECULES : Lecture #2 R,S system 1. Overview of terms This figure includes a summary of terms used to describe geometries of carbon compounds. You are familiar with these from your first semester of organic chemistry. Examples of situations include constitutional isomers, different conformations of the same molecule, viewing the same molecule from different directions, and stereoisomers. Different conformations of a single molecule are obtained by twisting around single bonds. Constitutional isomers have the same overall molecular formula but have different sequences of connections between the atoms. In two related stereoisomers, the sequence of atoms will be the same but the arrangements in three-dimensional space will be different, and those arrangements can not be interconverted by rotations around single bonds. There are two types of cases. The first involves double bonds between carbon atoms, a situation which generates two forms called cis and trans configurations. The second case involves carbon atoms connected to four different molecular groups. Such carbons are called chiral carbons. The four groups may be arranged two different ways in three-dimensional space, called the R and S configurations. Panel A summarizes the terms that need to be learned. Panel B illustrates staggered and eclipsed forms of ethane, which can be converted to each other by rotation around the C-C single bond. Panel C illustrates 7 different possible arrangements of atoms in a molecule whose composition includes 5 C's, 1 O, and 12 H's. These arrangements comprise a set of constitutional isomers. Panel D illustrates cis and trans isomers of 1-chloro, 2-bromo ethylene. Rotation around the C=C double bond does not occur, since that would break the pi cloud formed by overlap of p orbitals, so the cis isomer can not be converted into the trans form unless covalent bonds are broken and atoms are reattached in new locations. The cis and trans forms are two related configurations. Panel E illustrates two stereoisomers of alanine, the amino acid with a CH3 sidechain. There are four different groups attached to the central carbon, which therefore is a chiral carbon. The two molecules represent a pair of related configurations, which are mirror images of each other. You can not convert one form into the other unless covalent bonds are broken and atoms are reattached at different locations. If any two of the four groups attached to the central carbon are swapped, then this inverts the symmetry and generates the mirror image. That can be seen here by swapping the H and NH2 groups. 2. Priorities of groups in cysteine and aspartic acid There are two systems for naming a pair of enantiomers. One system uses the names R and S. The other system names them D and L (note that these letters are upper case or "capital" D and L). The R vs S system is more modern and can be used for all organic chemicals, including those found in your body. The D vs L system originated earlier in history, but unfortunately is not easy to apply to most molecules. It has particular applications in biochemistry that are still in common use, so you need to learn it. We begin by reviewing the modern R,S system which is taught in organic chemistry courses. The four groups attached to an asymmetric carbon are given priorities 1, 2, 3 and 4, with #1 representing the highest priority and #4 representing the lowest priority. This figure reviews assignment of group priorities for the amino acids named "aspartic acid" and "cysteine". You will remember from organic chemistry that this system is based on atomic weights, not on the weights of whole groups. In the drawings of these amino acids, the backbone amino group is at the left, the56backbone carboxylic acid group is at the top, there is a hydrogen at the right, and the amino acid sidechain (which differs in these two examples) points to the bottom. Consider aspartic acid at the top. The central asymmetric carbon atom is attached to the four atoms N-15, C-12, C-12 and H-1, each enclosed in a small shaded box. Since the atomic weight of N (15) is highest and the atomic weight of H (1) is lowest, it is easy to assign priority #1 to the amino group and priority # 4 to the H. However both the backbone COOH group and the sidechain -CH2-COOH group are attached by carbon (C-12) atoms to the central asymmetric carbon. Thus we need to look further out in the group to break the tie. In the COOH group at the top, the highest atomic weight atom attached to the C is an oxygen (O-16), which is drawn as a large unshaded white box. In the CH2-COOH sidechain group at the bottom, the highest atomic weight atom attached to the -CH2 carbon atom is the carbon (C-12) in a large white box. Since O has a higher wt than C, the COOH group wins the tie, so the backbone carboxyl group is assigned priority #2 and the -CH2-COOH sidechain is as-signed priority #3. In the above example we only needed to examine (1) the four atoms (small shaded boxes) attached to the chiral carbon and (2) the highest atomic weight atoms (large white boxes) attached to the shaded carbons which were tied with each other.