Isomers: Different Compounds With The Same Molecular Formula Constitutional Isomers:

Isom ers Isomers: different compounds with the same molecular formula Constitutional isomers: isomers with a different connectivity Stereoisomers: isomers with the same molecular formula, the same connectivity but a different orientation of their atoms in space that cannot be interconverted by rotation about a single bond

1

Iso me ri sm → Constit uti ona l Iso me rs a nd S te reoi so me rs Ster eois omer s are is omer s wi th th e same mo le cul ar formu la an d same co nnect iv it y of at oms bu t di ffer en t ar ran ge men t of at oms in spa ce

2

St ereoc hem is try

is the chemistry of molecules in three dimension

3

Handed nes s Stereochemistry of organic molecules can be understood, if we understand the meaning of handedness the fundamental reason for this is that our hands are not identical, rather they are mirror images

4

Ch ira lity

The mirror image of a chiral object is different and will not superimpose on the original object.

Objects which are chiral have a sense of “handedness” and exist in two forms.

5

The reason for Handedness→ chirality • Although everything has a mirror image, mirror images may or may not be superimposable. • Some molecules are like hands. Left and right hands are mirror images, but they are not identical, or superimposable → chiral (property of handedness)

6

Mirr or I ma ge

7

Chiralit y a nd Non chir alit y Mirror image: the reflection of an object in a mirror Objects that are not superposable on their mirror images are said to be chiral, that is, they show handedness Objects that are superposable on their mirror images are said to be achiral, that is, they do not show handedness. An achiral object has at least one element of symmetry 8

Achiral Molecules • Do these molecules contain a Plane of Symmetry (Mirror Plane)?

9

Chiral Molecules • The molecule labeled A and its mirror image labeled B are not superimposable. No matter how you rotate A and B, all the atoms never align. Thus, CHBrClF is a chiral molecule, and A and B are different compounds. • A and B are stereoisomers—specifically, they are enantiomers. • A carbon atom with four different groups is a tetrahedral stereogenic center.

10

Chiral vs. Achiral • With one stereogenic center, a molecule will always be chiral. • With two or more stereogenic centers, a molecule may or may not be chiral, e.g. Meso compound (contains a plane of symmetry or a mirror plane)

11

Chiral vs . Ach ira l

Chiral: from the Greek, cheir, hand

an object that is not superposable on its mirror image

Achiral: an object that lacks chirality; one that lacks handedness an achiral object has at least one element of symmetry plane of symmetry: an imaginary plane passing through an object dividing it so that one half is the mirror image of the other half center of symmetry: a point so situated that identical components are located on opposite sides and equidistant from that point along the axis passing through it 12

Ele ments of Sy mme try Symmetry in objects

13

Plane of Symmetry or Mirror plane

14

TWO VIEWS OF THE PLANE OF SYMMETRY plane of symmetry

F Br

F Cl Br

Cl Cl

side view

F

Cl

Cl Br edge view

Pla ne of Sy mm et ry Symmetry plane

No symmetry plane

COOH H C H

CH3 H C OH

COOH

COOH

achiral

chiral

16

Eleme nts o f Sy mmetry Center of symmetry: a point so situated that identical components of the object are located equidistant on opposite sides and equidistant from the point along any axis passing through the point Br

H

Cl Cl H Br

center of   symmetry

17

Ch ira l Cen ter The mo st comm on ( but n ot the only) ca use of chi ra li ty i n orga ni c mol ecules is a tetr ah edra l atom , mo st comm on ly ca rb on, bond ed to f our di ff erent groups A ca rbon wi th four di ff erent group s bonded to it is cal led a chira l center al l ch ira l cen ter s ar e st ere ocen ter s, bu t no t all st er eocen ter s ar e chi ral cen ter s.

18

STEREOGENIC CARBON ATOMS

Stere og en ic Carb on At oms

Cl H

Thi s is on e ty pe of ….

stereocenter

…. others are possible

F Br

A stereogenic carbon is tetrahedral and has four different groups attached. 20

Stereogenic Centers • To locate a stereogenic center, examine the four groups —not the four atoms—bonded to each tetrahedral carbon atom in a molecule. • Omit from consideration all C atoms that cannot be tetrahedral stereogenic centers. These include • Methylene and methyl units, i. e. CH2 and CH3 groups respectively. • Any sp or sp2 hybridized Carbons, e.g. triple bonds, and double bonds in alkenes (C=C) and carbonyls (C=O).

21

Enantiomers 22

Enantiomers One of a pair of molecular species that are mirror images of each other and not superposable. They are mirror-image stereoisomers.

23

Drawing Enantiomers • To draw both enantiomers of a chiral compound such as 2-butanol, use the typical convention for depicting a tetrahedron: place two bonds in the plane, one in front of the plane on a wedge, and one behind the plane on a dash. Then, to form the first enantiomer, arbitrarily place the four groups—H, OH, CH3 and CH2CH3—on any bond to the stereogenic center. Then draw the mirror image.

24

Pairs of Enantiomers

25

Enantiomer s Cl H

Cl

F Br

F Br

Cl

this molecule is chiral

H

Br F

rotate

H note that the fluorine and bromine have been interchanged in the enantiomer 26

Enantiomer s Lactic acid

HO

C

O

O

C HO

C

OH

C H CH3

H H3 C

OH

27

Enantiom ers 3-Chlorocyclohexene Cl

Cl

28

Enantiom ers OH

1,2-propanediol OH

H3 C

C H

CH2 OH HOH2 C

CH3 CHCH2 OH

OH C

CH3

H

29

Enantiom ers A nitrogen chiral center +

N H3 C

CH2 CH3

+

N CH3 CH2 CH3

A pair of enantiomers

30

Enanti ome rs & Diaste reomers 31

En antiomers & Dia stereois om er Enantiomers: opposite configurations at all stereogenic centers. Diastereomers: Stereoisomers that are not mirror images of each other. Different configuration at some locations.

32

Two Stereocenters Cl Br H3C

H

H

Br Cl CH3

H3C

H

H

CH3

entaiomers

Cl Br H3C

H

Br Cl

H CH3

H H3C

H

CH3

d i a s t e r o m e r s

entaiomers 33

En antiomers & Dia ster eome rs For a molecule with 1 stereocenter, 2 stereoisomers are possible For a molecule with 2 stereocenters, a maximum of 4 stereoisomers are possible For a molecule with n stereocenters, a maximum of 2n stereoisomers are possible 2n-1 pairs of enantiomers

34

Dia ster eome rs 2,3,4-Trihydroxybutanal two chiral centers 22 = 4 stereoisomers exist; two pairs of enantiomers CHO

CHO

H

C

OH HO

C

H

H

C

OH HO

C

H

CH2 OH

CH2 OH

A pair of enantiomers (Erythreose)

CHO

CHO

H

C

OH HO

C

H

HO

C

H

C

OH

CH2 OH

H

CH2 OH

A pair of enantiomers (Threose)

Diastereomers: stereoisomers that are not mirror images refers to the relationship among two or more objects

35

Dia stereome rs 2,3-Dihydroxybutanedioic acid (tartaric acid) two chiral centers; 2n = 4, but only three stereoisomers exist COOH

COOH

H

C

OH HO

C

H

H

C

OH HO

C

H

COOH

COOH

A meso compound (plane of symmetry)

COOH

COOH

H

C

OH HO

C

H

HO

C

H

C

OH

COOH

H

COOH

A pair of enantiomers

Meso compound: an achiral compound possessing two or more chiral centers that also has chiral isomers 36

Enantiom ers & D ia stereom ers 2-Methylcyclopentanol CH3 OH

HO H3 C

H H H H cis­2­Methylcyclopentanol   (a pair of enantiomers) CH3 H

diastereomers

H H3 C

H OH H HO trans­2­Methylcyclopentanol     (a pair of enantiomers)

37

Dia stereome rs 1,2-Cyclopentanediol OH HO

OH HO

H H H H cis1,2-Cyclopentanediol (a meso compound) OH

H

H

diastereomers

HO

OH H H HO trans1,2-Cyclopentanediol (a pair of enantiomers)

38

Dia ster eome rs cis-3-Methylcyclohexanol H3 C

OH HO

CH3

39

Dia ster eome rs trans-3-Methylcyclohexanol H3 C

CH3 OH HO

40

Mes o comp ou nds Meso compounds are achiral by virtue of a symmetry plane, but contain a stereogenic center. plane of symmmetry

mirror

Cl Cl H3C

H

H

Cl Cl CH3

H3C

H

H

CH3

41

Mes o comp ou nds Meso compound: achiral despite the presence of stereogenic centers Not optically active Superposable on its mirror image Has a plane of symmetry

42

The Three Stereoisomers of 2,3-dibromobutane

• Because one stereoisomer of 2,3-dibromobutane is superimposable on its mirror image, there are only three stereoisomers, not four. 43

NUMBER OF STEREOISOMERS POSSIBLE

How Many Stereoisomers Are Possible? maximum number of stereoisomers n sometimes fewer = 2 , than this number will exist

where n = number of stereocenters (sterogenic carbons)

CH2OH CH3

OH

* C CH2 CH CH CH3 CH3

CH3

*

RR RS SR SS

22 = 4 stereoisomers

CH3

* * CH3

*

CH

OH CH3

RRR RRS RSR SRR

RSS SRS SSR SSS

23 = 8 stereoisomers

CONFIGURATION ABSOLUTE CONFIGURATION ( R / S )

CONFIGURATION The three dimensional arrangement of the groups attached to an atom

Stereoisomers differ in the configuration at one or more of their atoms.

CONFIGURATION → R,S convention

clockwise

1

2

2

C

C

4 view with substituent of lowest priority in back

1

4 3

R

3 (rectus)

S

(sinister)

counter clockwise

Rules for Labeling Stereogenic Centers with R or S • Since enantiomers are two different compounds, they need to be distinguished by name. This is done by adding the prefix R or S to the IUPAC name of the enantiomer. • Naming enantiomers with the prefixes R or S is called the Cahn-Ingold-Prelog system. • To designate enantiomers as R or S, priorities must be assigned to each group bonded to the stereogenic center, in order of decreasing atomic number. The atom of highest atomic number gets the highest priority (1).

50

Priority Rules for Naming Enantiomers (R or S) • If two atoms on a stereogenic center are the same, assign priority based on the atomic number of the atoms bonded to these atoms. One atom of higher priority determines the higher priority.

51

Priority of Isotopes on a Stereogenic Center • If two isotopes are bonded to the stereogenic center, assign priorities in order of decreasing mass number. Thus, in comparing the three isotopes of hydrogen, the order of priorities is:

52

Priority Rules for Multiple Bonds in (R or S) Labeling • To assign a priority to an atom that is part of a multiple bond, treat a multiply bonded atom as an equivalent number of singly bonded atoms. For example, the C of a C=O is considered to be bonded to two O atoms.

• Other common multiple bonds are drawn below:

53

Examples Assigning Priorities

54

Ca hn-Ingold -P relog S ys tem f or Na min g E nantiome rs R or S

55

R or S Enantiomers

56

Positioning the Molecule for R/S Assignment

57

R-enantiomer (Clockwise Rotation) S-enantiomer (Counterclockwise Rotation)

58

Manipulation of Chiral Molecules

59

The molecule is rotated to put the lowest priority group back If the groups descend in priority (a,b then c) in clockwise direction the enantiomer is R If the groups descend in priority in counterclockwise direction the enantiomer is S

60

R,S Con ven tion Priority rules (Cahn, Ingold, Prelog) Each atom bonded to the stereocenter is assigned a priority, based on atomic number. The higher the atomic number, the higher the priority 1 H

6 CH 3

7 NH 2

8

16

17

35

53

OH

SH

Cl

Br

I

Increasing Priority 61

R,S Con ven tion If priority cannot be assigned on the basis of the atoms bonded to the stereocenter, look to the next set of atoms. Priority is assigned at the first point of difference. 1 CH 2

H

6 CH 2 CH 3

7 CH 2 NH 2

8 CH 2 OH

Increasing Priority 62

R,S Con ven tion Atoms participating in a double or triple bond are considered to be bonded to an equivalent number of similar atoms by single bonds -CH=CH2 O -CH

is treated as is treated as

C

C

-CH-CH2 O C C

O

H C CH

is treated as

C C C C H C C

63

Priorit ie s -OH -COOH -CH3 -H

HO

H C

COOH

CH3 (R)-(-)-lactic acid

HOOC

H C

OH

CH3 (S)-(+)-lactic acid

64

Bromochlorofluoroiodomethane 1

1

I 4

I 4

C

F Cl

Br

2

C

F

3

Cl

Br

3

2

R

S Enantiomers

65

R and S Assignments in Compounds with Two or More Stereogenic Centers. • When a compound has more than one stereogenic center, the R and S configuration must be assigned to each of them.

One stereoisomer of 2,3-dibromopentane The complete name is (2S,3R)-2,3-dibromopentane

66

St ereois om eris m of Cyc li c Compo un ds 1,4-dimethylcyclohexane Neither the cis not trans isomers is optically active Each has a plane of symmetry

67

1,3-dimethylcyclohexane The trans and cis compounds each have two stereogenic centers The cis compound has a plane of symmetry and is meso The trans compound exists as a pair of enantiomers

68

Prop ert ies of St ereois om ers

69

Prop ert ies of Stere oiso mers Enantiomers have identical physical and chemical properties in achiral environments Diastereomers are different compounds and have different physical and chemical properties meso tartaric acid, for example, has different physical and chemical properties from its enantiomers (see Table 3.1) 70

Pla ne-P olarized L ig ht Ordinary light: light vibrating in all planes perpendicular to its direction of propagation Plane-polarized light: light vibrating only in parallel planes Optically active: refers to a compound that rotates the plane of plane-polarized light 71

Pla ne-P olarized L ig ht plane-polarized light is the vector sum of left and right circularly polarized light circularly polarized light reacts one way with an R chiral center, and the opposite way with its enantiomer the result of interaction of plane-polarized light with a chiral compound is rotation of the plane of polarization

72

Pla ne-P olarized L ig ht Polarimeter: a device for measuring the extent of rotation of plane-polarized light

73

Optica l Act iv it y ob serv ed rotation : th e num ber of deg re es , α, th rou gh which a comp ou nd rotate s th e plan e of pol ariz ed li ght dex tro rota tor y (+) : refers to a comp ou nd that rotates the pl ane of polari zed li ght to the ri gh t levorotatory (-): re fers to a comp ou nd that rota tes of the pl ane of polari zed li ght to the lef t specif ic rotati on: ob serv ed rotation when a pure samp le is pl ac ed in a tu be 1.0 dm in l eng th and con ce ntration in g/mL ( den sity); for a sol uti on, con ce ntration is ex pres sed in g/ 100 mL COOH C

H H3 C OH (S)­(+)­Lactic acid 21 [α]D = +2.6°

COOH H C CH3 HO (R)­(­)­Lactatic acid 21 [α]D = ­2.6°

74

Opti cal Purit y Optical purity: a way of describing the composition of a mixture of enantiomers Percent optical purity =

[α ]sam ple

[α ]pure enantio mer

x 100

Enantiomeric excess: the difference between the percentage of two enantiomers in a mixture [R] ­ [S] x 100 = %R ­ %S Enantiomeric excess (ee) = [R] + [S]

optical purity is numerically equal to enantiomeric excess, but is experimentally determined 75

Res olu ti on Racemic mixture: an equimolar mixture of two enantiomers because a racemic mixture contains equal numbers of dextrorotatory and levorotatory molecules, its specific rotation is zero

Resolution: the separation of a racemic mixture into its enantiomers

76

Racemates • An equal amount of two enantiomers is called a racemate or a racemic mixture. A racemic mixture is optically inactive. Because two enantiomers rotate plane-polarized light to an equal extent but in opposite directions, the rotations cancel, and no rotation is observed.

77

Specific Rotation • Specific rotation is a standardized physical constant for the amount that a chiral compound rotates planepolarized light. Specific rotation is denoted by the symbol [α] and defined using a specific sample tube length (l, in dm), concentration (c in g/mL), temperature (25 0C) and wavelength (589 nm).

78

Dis cov er y o f E nantiome rs “There is no doubt that in dextro tartaric acid there exists an assymetric arrangement having a nonsuperimposible image.”

-

COO Na H

C

HO C

+

OH H -

COO Na

+

79

OH OH HOOC

meso COOH

Tartaric Acid

H

H

OH OH HOOC

H

OH OH

H COOH

(+)-tartaric acid

H HOOC

enantiomers

OH OH HOOC

H

H

meso COOH

meso -tartaric acid

OH OH

H

COOH

(-)-tartaric acid

ALSO FOUND (as a minor component)

[α ]D = 0 more about this compound later

OH OH

80

Diastereoisomer Stereoisomers that are not mirror images of each other. Different configuration at some locations.

COOH NH 2 H C H

C

OH

CH 3

COOH H2N C H H

C

OH CH3

81

Diastereomers Threonine: 2 pairs of enantiomers

COOH NH2 H C H

2R,3R 2S,3S 2R,3S 2S,3R

2S,3S 2R,3R 2S,3R 2R,3S

2R,3S & 2S,3R 2R,3S & 2S,3R 2R,3R & 2S,3S 2R,3R & 2S,3S

C

OH

CH3

2R, 3R COOH H C NH2 C

COOH H H 2N C C

HO H H3C 2S, 3S COOH H 2N C H C

HO H H3C

H

OH CH3

2R, 3S

2S, 3R 82

Enantiomers & Diastereomers For tartaric acid, the three possible stereoisomers are one meso compound and a pair of enantiomers. Meso compound: an achiral compound possessing two or more stereocenters.

83

Symmetry Plane 2R, 3S and 2S, 3R are identical Molecule has a plane of symmetry perpendicular to C-C and is therefore achira

COOH H C OH HO

C

H COOH 2R, 3R

COOH H C OH H

C

OH COOH

2R, 3S

COOH H HO C H

C

OH COOH 2S, 3S

COOH H HO C HO

C

H COOH 2S, 3R 84

Symmetry Plane 2R, 3S and 2S, 3R are identical Molecule has a plane of symmetry perpendicular to C-C and is therefore achira One meso compound and a pair of enantiomers

COOH H C OH HO

C

H COOH 2R, 3R

COOH H C OH H

C

OH COOH

2R, 3S

COOH H HO C H

C

OH COOH 2S, 3S

COOH Mirror H HO Cimage is Cidentical HO H COOH 2S, 3R 85

CH3CHCHCH3 Cl Br

2-Bromo-3-chlorobutane mirror

Cl Br S

CH3

H

R

H

CH3

CH3

S

R

H

H

CH3

enantiomers 1

diastereomers

CH3

Br Cl

Cl Br S

H

Br Cl

S

H CH3

R

H CH3

R

H

CH3

enantiomers 2 86

CH3CHCHCH3 Cl Cl

2,3-Dichlorobutane Cl Cl CH3

S

R

H

H

diastereomers

CH3

Cl Cl CH3

mirror image CH3 is identical CH3

meso

H

Cl Cl S

H

H

Cl Cl

S

H CH3

R

H CH3

R

H

CH3

enantiomers

87

Tartaric Acid (-) - tartaric acid [α ]D = -12.0o mp 168 - 170o solubility of 1 g 0.75 mL H2O 1.7 mL methanol 250 mL ether insoluble CHCl3 d = 1.758 g/mL

(+) - tartaric acid [α ]D = +12.0o mp 168 - 170o solubility of 1 g 0.75 mL H2O 1.7 mL methanol 250 mL ether insoluble CHCl3 d = 1.758 g/mL

meso - tartaric acid [α ]D = 0o solubility of 1 g mp 140o H 2O

0.94 mL 88

Fische r Pr ojectio ns

89

CH3 H

Fis ch er Pr oject ion s

OH CH2 CH3

Fischer projection: a two-dimensional representation showing the configuration of a stereocenter horizontal lines represent bonds projecting forward vertical lines represent bonds projecting to the rear the only atom in the plane of the paper is the stereocenter 90

Fis ch er Pr oject ion s

COOH

COOH

OH H C H CH3 OH CH3 (R)-lactic acid

How?

91

Fisc her Pro ject ion s

COOH C H H OH CH3

COOH OH CH3 92

Fis ch er Pr oject ion s

COOH

COOH OH

OH H

H CH3

CH3 93

Fis ch er Pr oject ion s 



Orient the stereocenter so that bonds projecting away from you are vertical and bonds projecting toward you are horizontal Flatten it to two dimensions OH

H CH3 CH2

CH3 (1)

C CH3

(S)­2­Butanol  (3­D formula)

H

C

CH3 OH (2)

CH2 CH3

H

OH

CH2 CH3      (S)­2­Butanol  (Fischer projection) 94

Assigning R,S Configuration Lowest priority group goes to the top. View rest of projection. A curved arrow from highest to lowest priority groups. Clockwise - R (rectus) Counterclockwise - S (sinister)

95

Assigning R,S Configuration 4

H 3

2

H 3C

COOH OH 1

s-lactic acid 96

Rules of Motion  Can rotate 180°, but not 90° because 90° disobeys the Fischer projection. Same groups go in and out of plane

COOH H OH CH3

COOH =H

OH CH3

180

CH 3 HO

H COOH

=

CH3 HO H COOH

97

Rules of Motion  Can rotate 180°, but not 90° because 90° disobeys the Fischer projection. Different groups go in and out of plane This generates an enantiomeric structure COOH H OH CH3

COOH =H

OH CH3

(R)-lactic acid

90

H

H COOH =

H3C

H3C

OH

COOH OH

(S)-lactic acid 98

Rules of Motion  One group can be held steady and the others rotated. COOH H

OH CH3

COOH same as

HO

CH3 H

99

Rules of Motion To determine if two Fischer projections represent the same enantiomer carry out allowed motions. C 2H 5

H H 3C

C 2H 5 OH A

HO

H CH3 B

OH H

CH3 C2H 5 C 100

C2H 5

H H 3C

HO

C2H 5

H

OH H

CH 3

OH

Rules of Motion A

CH3 C2H 5 C

B

By performing two allowed movements on B, we are able to generate projection A. Therefore, they are identical. CH2CH 3 H

HO

CH 3 B

CH3

HO H

CH2CH3 CH 3

CH3CH2

H CH3

CH 2CH3 HO A 101

C2H 5

H H 3C

C2H 5

HO

H

A

H

CH 3

OH

Rules of Motion

OH CH3 C2H 5 C

B

Perform one of the two allowed motions to place the group with lowest priority at the top of the Fischer projection.

OH H

CH 2CH3 CH 3

CH 2CH3 C

180

H

H 3C OH

H OH 90

CH 3

CH 2CH OH 102 not A

Priorities HOOC

NH2 COOH CH3

H 2N

CH3

H

H HOOC

NH2 CH3

CH3

H H HOOC

HOOC

H NH2

HOOC

CH3 S - stereochemistry

NH2 CH3

H 2N

H CH3 103

1-Bromo-2-chlorocyclohexane Br

Cl

Cl

Br

cis

Br

tran s

enantiomers

diastereomers Br Cl

Cl

enantiomers 104

1-Bromo-2-chlorocyclopropane Br R

diastereomers Br

S

Cl

Cl R

S

Br

cis

enantiomers R

R

S

S

Br

tra ns Cl

Cl

enantiomers 105

1,2-Dibromocyclopropane mirror image identical

Br

Br

Br

Br ci s

diastereomers

meso

Br

Br

tra ns

Br

Br

enantiomers

106

Biol ogi cal Signif ic ance of St ereois om ers Structure Stereochemistry

causes

Properties Biological effects

Example •Pasteur’s plant mold metabolized (+)-tartaric acid but not (-)-tartaric acid

107

Bio logi ca l Si gn ifi canc e of Stereois om ers

Th alido mi de

•Marketed in 50 countries 1956-1962 Sedative for “hysterical” pregnant women Antiemetic to combat morning sickness •Caused thousands of birth defects

O

N N O

Teratogen: causes fetal abnormalities

O

O

H

One stereocenter

•Sold as racemic mixture: 1:1 mixture of enantiomers R enantiomer = antiemetic (not teratogenic) S enantiomer = teratogenic (not antiemetic) •Single-enantiomer drug not useful: quickly racemizes in body

108

Biol ogi cal Si gn ific ance of St ereois om ers

Another Biological Effect: Odor O

O

enantiomers H

(R)-(-)-carvone smells like spearmint

H

(S)-(+)-carvone smells like caraway

Mirror image molecules do not have “mirror image effects” 109

Biologi cal S igni fica nce of Stereo isom ers Of Han ds, Gl ov es, and B iol ogy

Why do stereoisomers have different biological properties? •Many biological effects involve interaction with a cavity in enzyme or receptor •Good fit to cavity (i.e., strong binding) triggers enzyme or receptor R

•Enzymes and receptors are proteins; built from amino acids:

H

OH H2N O

•Most amino acids are chiral, so protein cavity is also chiral •Metaphor: Stereoisomer = left hand or right hand Protein hole = left glove or right glove Left hand fits left glove but not right glove Left hand triggers “left protein” but not “right protein” •(R)-carvone triggers spearmint smell receptor but not caraway smell receptor

110

111