Stereochemistry | Research & Encyclopedia Articles

Stereochemistry

Stereochemistry is the study of the three dimensional shape of molecules and the effects of shape upon the properties of molecules.

Dutch chemist Jacobus Hendricus van't Hoff—, the winner of the first Nobel Prize in Chemistry in 1901, pioneered the study of molecular structure and stereochemistry. Van't Hoff's ideas were not readily accepted by the scientific community in the late 1800s. His original paper was only 13 pages long, including one page of diagrams. This brief paper, however, gave rise to a powerful explanation of how molecules are structured and how they react with other molecules. 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.

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 is also a 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. With the proper enzymes present, biological temperatures suffice to allow reactions to proceed. This leaves the stereochemistry of molecules as a 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 an atom depends upon the number of bonds to other atoms and the presence or absence of lone pairs of electrons associated with the atom.

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 spatially superimposable.

Enantiomers are stereoisomers that are mirror images, that is, they cannot 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 contain equal amounts of the two enantiomers.

Symmetry is a term used to describes molecules made of equivalent 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 are excellent examples of the concept of handedness. The right and left hands are normally mirror images of each other. The single major difference between them is 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 that are mirror images of each other, alike in every way except for their handedness, are called enantiomers.

Handedness can have profound implications. Some medicines are vastly more effective in their left-handed configuration than in their right-handed configuration. In most cases biological systems make only one of the forms. Usually, 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 dissymmetric (or asymmetric), or chiral. 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 form four bonds about the central carbon atom. When the central carbon bonds with differing atoms or groups of atoms the carbon is termed a stereogenic 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, and it exists in the two enantiomeric forms.

Stereogenic carbon atoms may be described as cooresponding to either a R and S designation. Although the rules for determining this designation can be complex, for simple molecules and compounds 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 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 stereogenic carbon 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 carbon configuration is assigned as sinister (S). If the path from highest to lowest priority groups is clockwise, then the carbon is assigned as rectus (R).

The rectus (R) and sinister (S) descriptor relates to the structure of an individual carbon. In contrast, dextro (+) and levo (-) properties are based on the collective property of a large ensemble of the molecules.

A molecule can have more than one stereogenic carbon. The number of stereoisomers can be determined by the 2n rule, where n equals the number of stereogenic carbons. Thus, if one stereogenic carbon is present there are two possible stereoisomers, with two stereogenic 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.

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, 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. If the atoms are connected in the same order, but do not spatially superimpose, 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, or diastereomers. 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. Diastereoisomers 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.

Sometimes 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.

This is the complete article, containing 1,615 words (approx. 5 pages at 300 words per page).