1. Chirality and Stereoisomers

2. Isomers and Stereoisomers
Isomer: different compound with same molecular formula
Structural or Constriutional Isomers: different structures
Propan-1-ol Propan-2-ol Methyl ethyl ether
Stereoisomers: same bonding structure, but different geometrical positioning
“Spatial” isomers
Divided into two classes
Enantiomers: non-superimposible mirror images
Diastereomers: NOT mirror image
Lactic acid

3. Two classes of Diastereomers Cis-trans isomers
Caused by rigid structure of molecule (double bond)
cis-but-2-ene trans-but-2-ene
Confomers or conformal isomers
Change form by rotation about a single bond
Energy Barrier to rotation
Molecule can get “locked” in one structural form
Also called “Rotamers”
Butane: Newman projection

4. “Chiral” molecule: one with non-superimposible mirror image:
An enantiomer
Usually due to an sp3 hybridized carbon (asymmetric carbon)
Four different groups attached
Only other atoms that are chiral: certain metals (octahedral complex)
Diastereomers: different physical and chemical properties
Enantiomers: very similar properties
Differ only in 1) how they rotate polarized light
Rotate in clockwise or counterclockwise directions
Also differ in 2) how they interact with other chiral molecules
Significant effect in biology

6. Properties of Enantiomers
Exhibit “optical activity”
Rotates plane of polarization of light
Not all compounds can do this, i.e. optically inactive
“Racemic” mixture of enantiomers also optically inactive
Racemic: same amounts of both isomers
(-) isomer rotates in counter-clockwise direction: levorotary
(+) iomer rotates in clockwise direction: dextrorotary
Separation of racemic mixtures
Only be done with other optically active compound
Enantiomeric excess or “ee”: measure of excess of one isomer vs. the other
40% ee in one isomer (R): 60% of mixture is racemic
Total amount of R is 70%

7. Nomenclature R and S designation Each of 4 groups given a priority
Group having atom of higher atomic number has higher priority
If tie, consider next atom from the stereocenter, then 3rd atom, etc.
Point lowest priority group away
If ordering is clockwise: R (latin: rectus)
If ordering is counter-clockwise: S (latin: sinister)
Not mapped into (+), (-) or L/D

8. (+) and (-) designation: optical characterization
If light traveling towards viewer, clockwise rotation is + or d
If light traveling towards viewer, counterclockwise is – or l
D/L designation: based on glyceraldehyde
Labeled according to which form of glyceraldehyde its derived
D-glyceraldehyde has + (dextrorotary) rotation
L-glyceraldehyde has - (levorotary) rotation
If molecule looks like D (L)-glyceraldehyde, then D (L) form
If amino acid, look at COOH, -R, NH2 and H
H atom pointed away, COOH, R, amine go clockwise: D
COOH, R, amine go counter-clockwise: L
Glyceraldehyde
L- Glyceraldehyde
L-alanine

9. D-glyceraldehyde
L-glyceraldehyde
L-alanine

10. Importance in Biology
Biological systems: amino acids exclusively L-form in Proteins
Sugars are exclusively D-form in RNA, DNA
Source of homochirality: UNKNOWN
Biological systems sense difference
Spearmint leaves contain L-carvone
Caraway seeds D-carvone
Caraway and spearmint taste differently
Left and Right-handed proteins: L and D amino acids
Enzymes have specific active sites
Molecule upon which an enzyme acts: substrate
Only one chiral form of substrate “fits”
Only one chiral form generated by enzyme
Muscle tissue converts pyruvic acid: (+)-lactic acid only

11. Active Site: cleft or pocket lined by amino acid residues
Pocket defined by hydrogen bonds, hydrophobic interactions,
temporary covalent interactions (van der Waals)
Amino acids recognize substrate and can participate in enzyme reaction
COOH
O=C
CH2
Pyruvic acid (+) lactic acid

12. Origin of Chirality in Biological Systems
Subject of great debate
Result of polarized light in interstellar space
Interaction of magnetic fields
Clay surfaces with pockets for reactions that favor R or S
Quantum mechanical basis ?
Where else are chiral compounds found ?
Cannot distinguish with molecular spectroscopy
Use polarized light or chemical analysis
Difficult for remote sensing
Have observed ee in meteorites
Compounds extracted from several
carbonaceous chondrites
ee found in 8 amino acids, one hydroxy acid (Pizzarello and Groy 2011)

13. L-lactic acid has highest
MN = Murchison
MY = Murray
OR = Orgiel
Excesses 3 –12%
L-lactic acid has highest

14. Is Technique Reliable ?
GCMS = Gas chromatography with Mass Spectroscopy
Inert carrier gas: helium, nitrogen
Inject liquid sample into gas
Gas carriers mixture through a packed column
Column heated: liquid remains in gas phase
Separation of compounds: detected with mass spectrometer

16. Source of EE in Meteorites ??
Asymmetric photolysis of amino acids by circularly-polarized UV light
Experiments show this possible, but much lower ee
Inorganic matrices in meteorite surface might favor one form
Synthesize a chiral compound in the lab: racemic mixture
Non-racemic mixtures will racemize over time
Measurements in meteorites only findings of ee outside biosphere
Suggest connection of life to interstellar space