Stereochemistry
Stereochemistry
Fundamentals of stereochemistry
Determination of stereochemical properties
The importance of stereochemistry
Stereochemistry is the study of the three dimensional shape of molecules and the effects of shape upon the properties of molecules. The term stereo–chemistry is derived from the Greek word stereos, which means solid.
Historical development
Dutch chemist Jacobus Hendricus van’t Hoff (1852–1911), the winner of the first Nobel Prize in chemistry (1901), pioneered the study of molecular structure and stereochemistry. Van’t Hoff proposed that the concept of an asymmetrical carbon atom explained the existence of numerous isomers that had baffled chemists of the day. Van’t Hoff’s work gave eventual rise to stereochemistry when he correctly described the existence of a relationship between a molecule’s optical properties and the presence of an asymmetrical carbon atom.
The stereochemistry of carbon is important in all biological processes. Stereochemistry is also important in geology, especially mineralogy, with dealing with silicon based geochemistry.
Fundamentals of stereochemistry
Assuming that the all reactants are present, inorganic reactions are chiefly governed by temperature. In biological reactions, however, the shape of the molecules becomes the critical factor. Small changes in the shape or alignment of molecules can determine whether or not a reaction will proceed. In fact, one of the critical roles of enzymes in biochemistry is to lower the temperature requirements for chemical reactions. Assuming the proper enzymes are present, biological temperatures are usually sufficient to allow reactions to proceed. This leaves the stereochemistry of molecules as the controlling factor in biological and organic reactions (reactions with molecules and compounds containing Carbon) reactions. Assuming all the reactants are present, the shape and alignment of the reacting molecules is usually controlling with regard to the speed of reactions.
The molecular geometry around any atom depends upon the number of bonds to other atoms and the presence or absence of lone pairs of electrons associated with the atom.
The chemical formula of a molecule is only a simple representation of the order of arrangement of atoms. It does not show the three–dimensional structure of the molecule. It is usually left up to the reader to translate the chemical formula into its geometric arrangement. For example, the chemical formula for methane is CH4. This formula indicates that a central carbon atom is bonded to four hydrogen atoms (C–H). In order to convert this formula into the three dimensional molecular array for methane, one must know that when a carbon atom has four single bonds to four atoms, each of the bonds points towards a different corner of a tetrahedron, as shown in Figure 1. In the figure, the solid wedge shaped bonds are coming out of the paper and the dotted wedges are going into the paper.
Stereoisomers
Some compounds differ only in their shape or orientation in space. Compounds that have the same molecular formula are called isomers. Stereoisomers are isomers (i.e., they have the same molecular weight and formula) but that differ in their orientation in
space. No matter how a stereoisomer is rotated it presents a different picture than its stereoisomer counterpart. Most importantly, stereoisomers are not superimposable.
Enantiomers are stereoisomers that are mirror images, that is, they can map onto one another (if the molecules were two dimensional we would say that the molecules, just like human hands, could not be laid on top or superimposed upon each other.
Stereoisomers that rotate polarized light are called optical isomers. With the help of an instrument called a polarimeter, molecules are assigned a sign or rotation, either (+) for dextrorotatory molecules that rotate a plane of polarized light to the right, or (–) for levorotatory molecules that rotate a plane of polarized light to the left. Enantiomers differ in the direction that they rotate a plane of polarized light and in the rate that they react with other chiral molecules. Racemic mixtures of compounds contain equal amounts of enantiomers.
Symmetry and handedness
Symmetry is a term used to describes molecules with equal parts. When a molecule is symmetrical it has portions that correspond in shape, size, and structure so that they could be mapped or transposed on one another. Bilateral symmetry means that a molecule can be divided into two corresponding parts. Radial symmetry means that if a molecule is rotated about an axis a certain number of degrees rotation (always less than 360°) it looks identical to the molecule prior to rotation.
A molecule is said to be symmetrical if it can be divided into equal mirror image parts by a line or a plane. Humans are roughly bilaterally symmetrical. Draw a line down the middle of the human body and the line divides the body into two mirror image halves. If a blob of ink were placed on a piece of paper, and then the paper was folded over and then unfolded again, you would find two ink spots—the original and the image—symmetrical about the fold in the paper. Molecules and complexes can have more than just two planes of symmetry.
Human hands provide an excellent example of the concept of molecular handedness. The right and left hands are normally mirror images of each other, the only major difference between them being in the direction one takes to go from the thumb to the fingers. This sense of direction is termed handedness, that is, whether a molecule or complex has a left and right orientation. Two molecules can be mirror images of each other, alike in every way except for their handedness.
Handedness can have profound implications. Some medicines are vastly more effective in their left–handed configuration than in their right–handed configuration. In some cases biological systems make only one of the forms. In some cases only one of the forms is effective in cellular chemical reactions.
A molecule that is not symmetric, that is, a molecule without a plane of symmetry, is termed an asymmetric molecule. Asymmetric molecules can have another property termed chirality.
Chiral molecules
A molecule is said to be chiral if it lacks symmetry and its mirror images are not superimposable. To be chiral a molecule must lack symmetry, that is, a chiral molecule can not have any type of symmetry.
Carbon atoms with four sp3 hybridized orbitals can enter into up to four different bonds about the central carbon atom. When the central carbon bonds with differing atoms or groups of atoms the carbon is termedan asymmetric carbon atom. Bromochlorofluoromethane is an example of such a molecule. The central carbon, with four sp3 bonds oriented (pointing) to the corners of a tetrahedron, is bonded to bromine, chlorine, fluorine, and methane atoms. There is no symmetry to this molecule.
Chiral carbon atoms are also assigned an R and S designation. Although the rules for determining this designation can be complex, for simple molecules and compounds with chiral carbons the determination is easily accomplished with the help of a model of the molecule. The four different bonded groups are assigned a priority. When assigning priority to groups, atoms that are directly bonded to the central chiral carbon atom have their priority based upon their atomic number. The atom with the highest atomic number has highest priority and the atom with the lowest atomic number the lowest priority. As a result, hydrogen atoms bonded to the chiral molecule have the lowest priority. If isotopes are bonded then the isotope with the largest mass has the higher priority. The molecule is then turned so that the lowest priority group is farthest away from view. If one must take a counterclockwise path from the highest to lowest priority group the chiral configuration is said to be sinister (S). If the path from highest to lowest priority groups is clockwise then the chiral molecule is said to be rectus (R).
The compound carvone has two three–dimensional structures, one S and the other R (see Figure 4).
The compounds differ in their three–dimensional structure by the position of the indicated hydrogen atom. In S–Carvone, only the hydrogen atom is pointed into the paper, while in the R compound, the hydrogen atom is coming out of the paper. S–Carvone has a caraway flavor when tasted, whereas the R compound has the flavor of spearmint.
The rectus (R) and sinister (S) property relates to the structure of an individual molecule. In contrast, dextro (+) and levo (–) properties are based on the properties of a large collection of the molecules or complex.
Because a molecule can have more than one chiral carbon, the number of stereoisomers can be determined by the 2n rule, where n equals the number of chiral carbons. Thus, if one chiral carbon is present there are two possible stereoisomers, with two chiral carbons there are four possible stereoisomers. Any chemical reaction that yields predominantly one stereoisomer out of several stereoisomer possibilities is said to be a stereoselective reaction.
Determination of stereochemical properties
Sometimes it is difficult to tell whether or not two molecules or complexes will exhibit stereochemical properties. If two molecules or complexes have the same molecular formula they are candidates for stereo–chemical analysis. The first step is to determine if the two molecules or complexes are superimposable. If they are then they are identical structures and will not exhibit stereochemical properties. The second step is to determine if the atoms are connected to each other in the same order. If the atoms are not connected in the same order then the molecules or complexes are constitutional isomers and will not exhibit stereochemical properties. If the atoms are connected in the same order then they are stereoisomers. The next step is to see if the stereoisomers can be made identical by rotating them around a single bond in the molecule or complex, in which case they are called conformational isomers. Stereoisomers that can not be so rotated are called configurational isomers. The last step is to analyze the configurational isomers to determine whether they are enantiomers, diastereomers, or cis–trans isomers. Those that are mirror images are enantiomers. Those stereoisomers that are not mirror images of each other are diastereomers (the prefix dia indicated opposite or across from as in diagonal) or cis–trans isomers. Stereoisomers can also be characterized as cis (Latin for “on this side”) or trans (Latin for “across”) when they differ in the positions of atoms or groups relative to a reference plane. They are cis–isomers if the atoms are on the same side of the plane or trans–isomers if they are on opposite sides of the reference plane.
If the molecule has a double bond in its chemical formula—for example, formaldehyde, O=CH2—then the three–dimensional structure of the molecule is somewhat different. To translate formaldehyde into its geometric structure, one must know its chemical
formula indicates a central carbon atom that has a double bond to an oxygen atom (C=O) and two single bonds to hydrogen atoms (C–H). In the geometric arrangement of a carbon atom that has a double bond to another atom, there is a 120° angle between any two bonds, and each bond points away from the central carbon atom. If the bonded atoms are connected by imaginary lines, they represent the corners of an equilateral triangle (see Figure 2). In molecules that contain two carbon atoms connected by a double bond and each of which is bonded to a hydrogen atom and another atom, then the geometric isomer that has both hydrogen atoms on the same side is in a cis configuration. The molecule with the hydrogen atoms on opposite sides of the double bond is designated as the trans configuration. For example, cis–1, 2–dichloroethene has the hydrogen atoms on the same side of the double bond, where as trans–1,2–dichloroethene has them on opposite sides. Both of these compounds have the same chemical formula (ClHC=CHCl), but their geometric representations are different (see Figure 3).
The only other type of bond a carbon atom can have is a triple bond—that is, three bonds to the same atom. Acetylene (HCCH) is a molecule that contains a triple bond between the two carbon atoms, and each carbon atom is bonded to a hydrogen atom (C–H). A carbon atom with a triple bond to another atom is geometrically straight or linear.
H—C≡C—H
The importance of stereochemistry
The three–dimensional structure of a molecule determines its physical properties, such as the temperature at which it turns from a liquid to a gas (boiling point) and the temperature at which it changes from a solid to a liquid (melting point). The geometric structure of a molecule is also responsible for its chemical properties, such as its strengthasanacidorbase. Thecompound trans–1,2–dichloroethene becomes a gas at a much higher
KEY TERMS
Cis —The geometric isomer of a molecule that contains a double bond between two carbon atoms and has both hydrogen atoms on the same side of the double bond.
Trans —The geometric isomer of a molecule that contains a double bond between two carbon atoms and has both hydrogen atoms on opposite sides of the double bond.
temperature than the structurally similar cis–1,2–dichloroethene. The compound cis–3–phenylpropenoic acid is a stronger acid than trans–3–phenylpropenoic acid only because the hydrogen atoms are connected to the doubly bonded carbon atoms differently.
The geometric structure of a molecule can also have a dramatic effect on how that molecule tastes or how it functions as a drug. The antibacterial drug chloramphenicol is commercially produced as a mixture of the two compounds in Figure 5. One three–dimensional arrangement of atoms is an active drug, the other geometric structure is ineffective as an antibacterial agent.
In most cases the energy of a molecule or a compound, that is, the particular energy level of its electrons depends upon the relative geometry of the atoms comprising the molecule or compound. Nuclear geometry means the geometrical or spatial relationships between the nucleus of the atoms in a compound or molecule (e.g., the balls in a ball and stick model). When a molecule or compound’s energy is related to its shape this is termed a stereoelectronic property.
Stereoelectronic effects arise from the different alignment of electronic orbitals with different arrangements of nuclear geometry. It is possible to control the rate or products of some chemical reactions by controlling the stereoelectronic properties of the reactants.
See also Chemical bond; Formula, chemical; Formula, structural.
Resources
BOOKS
Anslyn, E.V. and D.A. Dougherty. Modern Physical Organic Chemistry. Herndon, Virginia: University Science Books, 2005.
Jensen, F. Introduction to Computational Chemistry. New York: Wiley, 2006.
Andrew J. Poss
K. Lee Lerner
Stereochemistry
Stereochemistry
Stereochemistry is the study of the three dimensional shape of molecules and the effects of shape upon the properties of molecules. The term stereochemistry is derived from the Greek word stereos, which means solid.
Historical development
Dutch chemist Jacobus Hendricus van't Hoff (1852–1911), the winner of the first Nobel Prize in chemistry (1901), pioneered the study of molecular structure and stereochemistry. Van't Hoff proposed that the concept of an asymmetrical carbon atom explained the existence of numerous isomers that had baffled the chemists of the day. Van't Hoff's work gave eventual rise to stereochemistry when he correctly described the existence of a relationship between a molecule's optical properties and the presence of an asymmetrical carbon atom.
The stereochemistry of carbon is important in all biological processes. Stereochemistry is also important in geology , especially mineralogy , with dealing with silicon based geochemistry .
Fundamentals of stereochemistry
Assuming that the all reactants are present, inorganic reactions are chiefly governed by temperature , that is, temperature is critical to determining whether or not a particular reaction will proceed. In biological reactions, however, the shape of the molecules becomes the critical factor. Small changes in the shape or alignment of molecules can determine whether or not a reaction will proceed. In fact, one of the critical roles of enzymes in biochemistry is to lower the temperature requirements for chemical reactions . Assuming the proper enzymes are present, biological temperatures are usually sufficient to allow reactions to proceed. This leaves the stereochemistry of molecules as the controlling factor in biological and organic (molecules and compounds with Carbon) reactions (assuming all the reactants are present) is the shape and alignment of the reacting molecules.
The molecular geometry around any atom is depends upon the number of bonds to other atoms and the presence or absence of lone pairs of electrons associated with the atom.
The chemical formula of a molecule is only a simple representation of the order of arrangement of atoms. It does not show the three-dimensional structure of the molecule. It is usually left up to the reader to translate the chemical formula into its geometric arrangement. For example, the chemical formula for methane is CH4. This formula indicates that a central carbon atom is bonded to four hydrogen atoms (C-H). In order to convert this formula into the three dimensional molecular array for methane, one must know that when a carbon atom has four single bonds to four atoms, each of the bonds points towards a different corner of a tetrahedron , as shown in Figure 1. In the figure, the solid wedge shaped bonds are coming out of the paper and the dotted wedges are going into the paper.
Another way to visualize a carbon atom with four single bonds is to consider the central carbon atom at the center of a pyramid , also shown in Figure 1. At each point in the pyramid is located a hydrogen atom that is bonded to you. One hydrogen or pyramid point is directly above your head. One is in front of you, one point is behind you to your right, and another behind you to your left. These three hydrogen atoms or points are all on a level below the one you are on. The three dimensional arrangement of each carbon atom with four single bonds is always the same and the angle between any two bonds is 109.5°.
Stereoisomers
Some compounds differ only in their shape or orientation in space . Compounds that have the same molecular formula are called isomers. Stereoisomers are isomers (i.e., they have the same molecular weight and formula) but that differ in their orientation in space. No matter how a stereoisomer is rotated it presents a different picture than its stereoisomer counterpart. Most importantly, stereoisomers are not superimposable.
Enantiomers are stereoisomers that are mirror images, that is, they can map onto one another (if the molecules were two dimensional we would say that the molecules, just like human hands, could not be laid on top or superimposed upon each other.
Stereoisomers that rotate polarized light are called optical isomers. With the help of an instrument called a polarimeter, molecules are assigned a sign or rotation , either (+) for dextrorotatory molecules that rotate a plane of polarized light to the right, or (-) for levorotatory molecules that rotate a plane of polarized light to the left. Enantiomers differ in the direction that they rotate a plane of polarized light and in the rate that they react with other chiral molecules. Racemic mixtures of compounds contain equal amounts of enantiomers.
Symmetry and handedness
Symmetry is a term used to describes molecules with equal parts. When a molecule is symmetrical it has portions that correspond in shape, size, and structure so
that they could be mapped or transposed on one another. Bilateral symmetry means that a molecule can be divided into two corresponding parts. Radial symmetry means that if a molecule is rotated about an axis that a certain number of degrees rotation (always less than 360°) it looks identical to the molecule prior to rotation.
A molecule is said to be symmetrical if it can be divided into equal mirror image parts by a line or a plane. Humans are roughly bilaterally symmetrical. Draw a line down the middle of the human body and the line divides the body into two mirror image halves. If a blob of ink were placed on a piece of paper, and then the paper was folded over and then unfolded again, you would find two ink spots—the original and the image—symmetrical about the fold in the paper. Molecules and complexes can have more than just two planes of symmetry.
Human hands provide an excellent example of the concept of molecular handedness. The right and left hands are normally mirror images of each other, the only major difference between them being in the direction one takes to go from the thumb to the fingers. This sense of direction is termed handedness, that is, whether a molecule or complex has a left and right orientation. Two molecules can be mirror images of each other, alike in every way except for their handedness.
Handedness can have profound implications. Some medicines are vastly more effective in their left-handed configuration than in their right-handed configuration. In some cases biological systems make only one of the forms. In some cases only one of the forms is effective in cellular chemical reactions.
A molecule that is not symmetric, that is, a molecule without a plane of symmetry, is termed an asymmetric molecule. Asymmetric molecules can have another property termed chirality.
Chiral molecules
A molecule is said to be chiral if it lacks symmetry and its mirror images are not superimposable. To be chiral a molecule must lack symmetry, that is, a chiral molecule can not have any type or symmetry.
Carbon atoms with four sp3 hybridized orbitals can enter into up to four different bonds about the central carbon atom. When the central carbon bonds with differing atoms or groups of atoms the carbon is termed an asymmetric carbon atom. Bromochlorofluoromethane is an example of such a molecule. The central carbon, with four sp3 bonds oriented (pointing) to the corners of a tetrahedron, is bonded to a bromine, chlorine , fluorine and methane atoms. There is no symmetry to this molecule.
Chiral carbon atoms are also assigned an R and S designation. Although the rules for determining this designation can be complex, for simple molecules and compounds with chiral carbons the determination is easily accomplished with the help of a model of the molecule. The four different bonded groups are assigned a priority. When assigning priority to groups, atoms that are directly bonded to the central chiral carbon atom have their priority based upon their atomic number . The atom with the highest atomic number has highest priority and atom with the lowest atomic number the lowest priority. As a result, hydrogen atoms bonded to the chiral molecule have the lowest priority. If isotopes are bonded then the isotope with the largest mass has the higher priority. The molecule is then turned so that the lowest priority group is farthest away from view. If one must take a counterclockwise path from the highest to lowest priority group the chiral configuration is said to be sinister (S). If the path from highest to lowest priority groups is clockwise then the chiral molecule is said to be rectus (R).
The compound carvone has two three-dimensional structures, one S and the other R (see Figure 4).
The compounds differ in their three-dimensional structure by the position of the indicated hydrogen atom. In S-Carvone, only the hydrogen atom is pointed into the paper, while in the R compound, the hydrogen atom is coming out of the paper. S-Carvone has a caraway flavor when tasted, whereas the R compound has the flavor of spearmint.
The rectus (R) and sinister (S) property relates to the structure of an individual molecule. In contrast, dextro (+) and levo (-) properties are based on the properties of a large collection of the molecules or complex.
Because a molecule can have more than one chiral carbon. The number of stereoisomers can be determined by the 2n rule, where n = the number of chiral carbons. Thus, if one chiral carbon is present there are two possible stereoisomers, with two chiral carbons there are four possible stereoisomers. Any chemical reaction that yields predominantly one stereoisomer out of several stereoisomer possibilities is said to be a stereoselective reaction.
Determination of stereochemical properties
Sometimes it is difficult to tell whether or not two molecules or complexes will exhibit stereochemical properties. If two molecules or complexes have the same molecular formula they are candidates for stereochemical analysis. The first step is to determine if the two molecules or complexes are superimposable. If they are then are identical structures and will not exhibit stereochemical properties. The second step is to determine if the atoms are connected to each other in the same order. If the atoms are not connected in the same order then the molecules or complexes are constitutional isomers and will not exhibit stereochemical properties. If the atoms are connected in the same order then they are stereoisomers. The next step is to see if the stereoisomers can be made identical by rotating them around a single bond in the molecule or complex then they are called conformational isomers. Stereoisomers that can not be so rotated are called configurational isomers. The last step is to analyze the configurational isomers to determine whether they are enantiomers, diastereomers, or cis-trans isomers. Those that are mirror images are enantiomers. Those stereoisomers that are not mirror images of each other are diastereomers (the prefix dia indicated opposite or across from as in diagonal) or cis-trans isomers. Stereoisomers can also be characterized as cis (Latin for "on this side") or trans (Latin for "across") when they differ in the positions of atoms or groups relative to a reference plane. They are cis-isomers if the atoms are on the same side of the plane or trans-isomers if they are on opposite sides of the reference plane.
If the molecule has a double bond in its chemical for mula—for example, formaldehyde, O=CH2—then the three-dimensional structure of the molecule is somewhat different. To translate formaldehyde into its geometric structure, one must know its chemical formula indicates a central carbon atom that has a double bond to an oxygen atom (C=O) and two single bonds to hydrogen atoms (CH). In the geometric arrangement of a carbon atom that has a double bond to another atom, there is a 120° angle between any two bonds, and each bond points away from the central carbon atom. If the bonded atoms are connected by imaginary lines, they represent the corners of an equilateral triangle (see Figure 2). In molecules that contain two carbon atoms connected by a double bond and each of which is bonded to a hydrogen atom and another atom, then the geometric isomer that has both hydrogen atoms on the same side is in a cis configuration. The molecule with the hydrogen atoms on opposite sides of the double bond is designated as the trans configuration. For example, cis-1,2-dichloroethene has the hydrogen atoms on the same side of the double bond, where as trans-1,2-dichloroethene has them on opposite sides. Both of these compounds have the same chemical formula (ClHC=CHCl), but their geometric representations are different (see Figure 3).
The only other type of bond a carbon atom can have is a triple bond—that is, three bonds to the same atom. Acetylene (HCCH) is a molecule that contains a triple bond between the two carbon atoms, and each carbon atom is bonded to a hydrogen atom (C-H). A carbon atom with a triple bond to another atom is geometrically straight or linear.
The importance of stereochemistry
The three-dimensional structure of a molecule determines its physical properties, such as the temperature at which it turns from a liquid to a gas (boiling point ) and the temperature at which it changes from a solid to a liquid (melting point). The geometric structure of a molecule is also responsible for its chemical properties, such as its strength as an acid or base. The compound trans-1,2-dichloroethene becomes a gas at a much higher temperature than the structurally similar cis-1,2-dichloroethene. The compound cis-3-phenylpropenoic acid is a stronger acid than trans-3-phenylpropenoic acid only because the hydrogen atoms are connected to the doubly bonded carbon atoms differently.
The geometric structure of a molecule can also have a dramatic effect on how that molecule tastes or how it functions as a drug. The antibacterial drug chloramphenicol is commercially produced as a mixture of the two compounds in Figure 5. One three-dimensional arrangement of atoms is an active drug, the other geometric structure is ineffective as an antibacterial agent.
In most cases the energy of a molecule or a compound, that is, the particular energy level of its electrons depends upon the relative geometry of the atoms comprising the molecule or compound. Nuclear geometry means the geometrical or spatial relationships between the nucleus of the atoms in a compound or molecule (e.g., the balls in a ball and stick model). When a molecule or compound's energy is related to its shape this is termed a stereoelectronic property.
Stereoelectronic effects arise from the different alignment of electronic orbitals with different arrangements of nuclear geometry. It is possible to control the rate or products of some chemical reactions by controlling the stereoelectronic properties of the reactants.
See also Chemical bond; Formula, chemical; Formula, structural.
Resources
books
Boyer, Rodney. Concepts in Biochemistry. Pacific Grove, CA: Brooks/Cole Publishing Company, 1999.
Carroll, Felix A. Perspectives on Structure and Mechanism inOrganic Chemistry. Pacific Grove, CA: Brooks/Cole Publishing Company, 1998.
Mislow, Kurt M. Introduction to Stereochemistry. Dover Publications, 2002.
Morris, David G. Stereochemistry. John Wiley & Sons, 2002.
Andrew J. Poss
K. Lee Lerner
KEY TERMS
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .- Cis
—The geometric isomer of a molecule that contains a double bond between two carbon atoms and has both hydrogen atoms on the same side of the double bond.
- Trans
—The geometric isomer of a molecule that contains a double bond between two carbon atoms and has both hydrogen atoms on opposite sides of the double bond.
stereochemistry
ster·e·o·chem·is·try / ˌsterē-ōˈkeməstrē; ˌsti(ə)r-/ • n. the branch of chemistry concerned with the three-dimensional arrangement of atoms and molecules and the effect of this on chemical reactions.DERIVATIVES: ster·e·o·chem·i·cal / -ˈkemikəl/ adj.ster·e·o·chem·i·cal·ly adv.