by Isaac Asimov
Just as the atom has furnished chief excitement in twentieth-century physics, so the molecule has been the subject of equally exciting discoveries in chemistry. Chemists have been able to work out detailed pictures of the structure of even very complex molecules, to identify the roles of specific molecules in living systems, to create elaborate new molecules, and to predict the behavior of a molecule of a given structure with amazing accuracy.
By the mid-twentieth century, the complex molecules that form the key units of living tissue, the proteins and nucleic acids, were being studied with all the techniques made possible by an advanced chemistry and physics. The two sciences biochemistry (the study of the chemical reactions going on in living tissue) and biophysics (the study of the physical forces and phenomena involved in living processes) merged to form a brand new discipline-molecular biology. Through the findings of molecular biology, modern science has in a single generation of effort all but wiped out the borderline between life and nonlife.
Yet less than a century and a half ago, the structure of not even the simplest molecule was understood. About all the chemists of the early nineteenth century could do was to separate all matter into two great categories. They had long been aware (even in the days of the alchemists) that substances fall into two sharply distinct classes with respect to their response to heat. One group—for example, salt, lead, water—remain basically unchanged after being heated. Salt might glow red hot when heated, lead might melt, water might vaporize—but when they are cooled back to the original temperature, they are restored to their original form, none the worse, apparently, for their experience. On the other hand, the second group of substances—for example, sugar, olive oil—are changed permanently by heat. Sugar becomes charred when heated and remains charred after being cooled again; olive oil is vaporized, and the vapor does not condense on cooling. Eventually the scientists noted that the heat-resisting substances generally came from the inanimate world of the air, ocean, and soil, while the combustible substances usually came from the world of life, either from living matter directly or from dead remains. In 1807, Berzelius, who invented the chemical symbols and was to prepare the first adequate list of atomic weights (see chapter 6) named the combustible substances organic (because they were derived, directly or indirectly, from the living organisms) and all the rest inorganic.
Early chemistry focused mainly on the inorganic substances. It was the study of the behavior of inorganic gases that led to the development of the atomic theory. Once that theory was established, it soon clarified the nature of inorganic molecules. Analysis showed that inorganic molecules generally consist of a small number of different atoms in definite proportions. The water molecule contains two atoms of hydrogen and one of oxygen; the salt molecule contains one atom of sodium and one of chlorine; sulfuric acid contains two atoms of hydrogen, one of sulfur, and four of oxygen; and so on.
When the chemists began to analyze organic substances, the picture seemed quite different. Two substances might have exactly the same composition and yet show distinctly different properties. (For instance, ethyl alcohol is composed of two carbon atoms, one oxygen atom, and six hydrogen atoms; so is dimethyl ether—yet one is a liquid at room temperature, while the other is a gas.) The organic molecules contained many more atoms than the simple inorganic ones, and there seemed to be no rhyme or reason in the way they were combined. Organic compounds simply could not be explained by the straightforward laws of chemistry that applied so beautifully to inorganic substances.
Berzelius decided that the chemistry of life was something apart which obeyed its own set of subtle rules. Only living tissue, he said, could make an organic compound. His point of view is an example of vitalism.
Then, in 1828, the German chemist Friedrich Wöhler, a student of Berzelius, produced an organic substance in the laboratory! He was heating a compound called ammonium cyanate, which was then generally considered inorganic. Wöhler was thunderstruck to discover that, on being heated, this material turned into a white substance identical in properties with urea, a component of urine. According to Berzelius’s views, only living tissue could form urea; and yet Wöhler had formed it from inorganic material merely by applying a little heat.
Wöhler repeated the experiment many times before he dared publish his discovery. When he finally did, Berzelius and others at first refused to believe it. But other chemists confirmed the results. Furthermore, they proceeded to synthesize many other organic compounds from inorganic precursors. The first to bring about the production of an organic compound from its elements was the German chemist Adolph Wilhelm Hermann Kolbe, who produced acetic acid (the substance that gives vinegar its taste) in this fashion in 1845. It was this work that really killed Berzelius’s version of vitalism. More and more it became clear that the same chemical laws applied to inorganic and organic molecules alike. Eventually the distinction between organic and inorganic substances was given a simple definition: all substances containing carbon (with the possible exceptions of a few simple compounds, such as carbon dioxide) are called organic; the rest are inorganic.
CHEMICAL STRUCTURE
To deal with the complex new chemistry, chemists needed a simple shorthand for representing compounds, and fortunately Berzelius had already suggested a convenient, rational system of symbols. The elements were designated by abbreviations of their Latin names. Thus C would stand for carbon, O for oxygen, H for hydrogen, N for nitrogen, S for sulfur, P for phosphorus, and so on. Where two elements began with the same letter, a second letter was used to distinguish them: for example, Ca for calcium, Cl for chlorine, Cd for cadmium, Co for cobalt, Cr for chromium, and so on. In only a comparatively few cases are the Latin or Latinized names (and initials) different from the English, thus: iron (ferrum) is Fe; silver (argentum), Ag; gold (aurum), Au; copper (cuprum), Cu; tin (stannum), Sn; mercury (hydragyrum) Hg; antimony (stibium), Sb; sodium (natrium), Na; and potassium (kalium), K.
With this system it is easy to symbolize the composition of a molecule. Water is written H2O (thus indicating the molecule to consist of two hydrogen atoms and one oxygen atom); salt, NaCl; sulfuric acid, H2SO4, and so on. This is the empirical formula of a compound; it tells what the compound is made of but says nothing about its structure—that is, the manner in which the atoms of a molecule are connected.
In 1831, Baron Justus von Liebig, a co-worker of Wöhler’s, went on to work out the composition of a number of organic chemicals, thus applying chemical analysis to the field of organic chemistry. He would carefully burn a small quantity of an organic substance and trap the gases formed (chiefly CO2 and water vapor, H2O) with appropriate chemicals. Then he would weigh the chemicals used to trap the combustion products to see how much weight had been added by the trapped products. From that weight he could determine the amount of carbon, hydrogen, and oxygen in the original substance. It was then an easy matter to calculate, from the atomic weights, the numbers of each type of atom in the molecule. In this way, for instance, he established that the molecule of ethyl alcohol had the formula C2H6O.
Liebig’s method could not measure the nitrogen present in organic compounds; but in 1833, the French chemist Jean Baptiste André Dumas devised a combustion method that did collect the gaseous nitrogen released from substances. He made use of his methods to analyze the gases of the atmosphere with unprecedented accuracy in 1841.
The methods of organic analysis were made more and more delicate until veritable prodigies of refinement were reached in the microanalytical methods of the Austrian chemist Fritz Pregl. He devised techniques, beginning in 1909, for the accurate analysis of quantities of organic compounds barely visible to the naked eye and received the Nobel Prize for chemistry in 1923 in consequence.
Unfortunately, determining only the empirical formulas of organic compounds was not very helpful in elucidating their chemistry. In contrast to inorganic compounds, which usually consist of two or three atoms or at most a dozen, the organic molecules are often huge. Liebig found that th
e formula of morphine was C17H19O3N, and of strychnine, C21H22O2N2.
Chemists were pretty much at a loss to deal with such large molecules or make head or tail of their formulas. Wöhler and Liebig tried to group atoms into smaller collections called radicals and to work out theories to show that various compounds were made up of specific radicals in different numbers and combinations. Some of the systems were most ingenious, but none really explained enough. It was particularly difficult to explain why two compounds with the same empirical formula, such as ethyl alcohol and dimethyl ether, should have different properties.
This phenomenon was first dragged into the light of day in the 1820s by Liebig and Wöhler. The former was studying a group of compounds called fulminates; the latter, a group called isocyanates—and the two turned out to have identical empirical formulas. The elements were present in equal parts, so to speak. Berzelius, the chemical dictator of the day, was told of this finding and was reluctant to believe it until, in 1830, he discovered some examples for himself. He named such compounds, with different properties but with elements present in equal parts, isomers (from Greek words meaning “equal parts”). The structure of organic molecules was indeed a puzzle in those days.
The chemists, lost in the jungle of organic chemistry, began to see daylight in the 1850s when they noted that each atom could combine with only a certain number of other atoms. For instance, the hydrogen atom apparently could attach itself to only one atom: it could form hydrogen chloride, HCl, but never HCl2. Likewise chlorine and sodium could each take only a single partner, so they formed NaCl. An oxygen atom, on the other hand, could take two atoms as partners—for instance, H2O. Nitrogen could take on three: for example, NH3 (ammonia). And carbon could combine with as many as four: for example, CCl4 (carbon tetrachloride).
In short, it looked as if each type of atom had a certain number of hooks by which it could hang on to other atoms. The English chemist Edward Frankland, in 1852, was the first to express this theory clearly, and he called these hooks valence bonds, from a Latin word meaning “power,” to signify the combining powers of the elements.
The German chemist Friedrich August Kekulé von Stradonitz saw that if carbon were given a valence of 4, and if it were assumed that carbon atoms could use those valences, in part at least, to join up in chains, then a map could be drawn through the organic jungle. His technique was made more visual by the suggestion of a Scottish chemist, Archibald Scott Couper, that these combining forces between atoms (bonds, as they are usually called) be pictured in the form of small dashes. In this way, organic molecules could be built up like so many “Tinkertoy” structures.
In 1861, Kekulé published a textbook with many examples of this system, which proved its convenience and value. The structural formula became the hallmark of the organic chemist.
For instance, the methane (CH4), ammonia (NH3), and water (H2O) molecules, respectively, can be pictured this way:
Organic molecules can be represented as chains of carbon atoms with hydrogen atoms attached along the sides. Thus, butane (C4H10) has the structure:
Oxygen or nitrogen might enter the chain in the following manner, picturing the compounds methyl alcohol (CH4O) and methylamine (CH5N), respectively:
An atom possessing more than one hook, such as carbon with its four, need not use each of them for a different atom: it might form a double or triple bond with one of its neighbors, as in ethylene (C2H4) or acetylene (C2H2):
Now it became easy to see how two molecules can have the same number of atoms of each element and still differ in properties. The two isomers must differ in the arrangement of those atoms. For instance, the structural formulas of ethyl alcohol and dimethyl ether, respectively, can be written:
The greater the number of atoms in a molecule, the greater the number of possible arrangements and the greater the number of isomers. For instance, heptane, a molecule made up of seven carbon atoms and sixteen hydrogen atoms, can be arranged in nine different ways; in other words, there can be nine different heptanes, each with its own properties. These nine isomers resemble one another fairly closely, but it is only a family resemblance. Chemists have prepared all nine of these isomers but have never found a tenth—good evidence in favor of the Kekulé system.
A compound containing forty carbon atoms and eighty-two hydrogen atoms can exist in some 62.5 trillion arrangements, or isomers. And organic molecules of this size are by no means uncommon.
Only carbon atoms can hook to one another to form long chains. Other atoms do well if they can form a chain as long as half a dozen or so. Hence, inorganic molecules are usually simple and rarely have isomers. The greater complexity of the organic molecule introduces so many possibilities of isomerism that millions of organic compounds are known, new ones are being formed daily, and a virtually limitless number await discovery.
Structural formulas are now universally used as indispensable guides to the nature of organic molecules. As a short cut, chemists often write the formula of a molecule in terms of the groups of atoms, or radicals, that make it up, such as the methyl (CH3) and methylene (CH2) radicals. Thus the formula for butane can be written as CH3CH2CH2CH3.
The Details of Structure
In the latter half of the nineteenth century, chemists discovered a particularly subtle kind of isomerism which was to prove very important in the chemistry of life. The discovery emerged from the oddly asymmetrical effect that certain organic compounds had on rays of light passing through them.
OPTICAL ACTIVITY
A cross section of a ray of ordinary light will show that the innumerable waves of which it consists undulate in all planes-up and down, from side to side, and obliquely. Such light is called unpolarized. But when light passes through a crystal of the transparent substance called Iceland spar, for instance, it is refracted in such a way as to emerge polarized. It is as if the array of atoms in the crystal allows only certain planes of undulation to pass through (just as the palings of a fence might allow a person moving sideways to squeeze through but not one coming up broadside to them). There are devices, such as the Nicol prism, invented by the Scottish physicist William Nicol in 1829, that let light through in only one plane (figure 11.1). This has now been replaced, for most purposes, by materials such as Polaroid (crystals of a complex of quinine sulfate and iodine, lined up with axes parallel and embedded in nitrocellulose), first produced in 1932 by Edwin Land.
Figure 11.1. The polarization of light. The waves of light normally oscillate in all planes (top). The Nicol prism (bottom) lets through the oscillations in only one plane, reflecting away the others. The transmitted light is plane-polarized.
Reflected light is often partly plane-polarized, as was first discovered in 1808 by the French physicist Etienne Louis Malus. (He invented the term polarization through the application of a remark of Newton’s about the poles of light particles—one occasion where Newton was wrong—but the name remains anyway.) The glare of reflected light from windows of buildings and cars and even from paved highways can therefore be cut to bearable levels by the use of Polaroid sunglasses.
In 1815, the French physicist Jean Baptiste Biot had discovered that when plane-polarized light passes through quartz crystals, the plane of polarization is twisted: that is, the light goes in undulating in one plane and comes out undulating in a different plane. A substance that performs thus is said to display optical activity. Some quartz crystals twist the plane clockwise (dextrorotation) and some counterclockwise (levorotation). Biot found that certain organic compounds, such as camphor and tartaric acid, do the same thing. He thought it likely that some kind of asymmetry in the arrangement of the atoms in the molecules was responsible for the twisting of light. But for several decades, this suggestion remained purely speculative.
In 1844, Louis Pasteur (only twenty-two at the time) took up this interesting question. He studied two substances: tartaric acid and racemic acid. Both had the same chemical composition, but tartaric acid rotated the plane of polarized light, whi
le racemic acid did not. Pasteur suspected that the crystals of salts of tartaric acid would prove to be asymmetric and those of racemic acid would be symmetric. Examining both sets of crystals under the microscope, he found to his surprise that both were asymmetric. But the racemate crystals had two versions of the asymmetry: half of them were the same shape as those of the tartrate, and the other half were mirror images. Half of the racemate crystals were left-handed and half right-handed, so to speak.
Pasteur painstakingly separated the left-handed racemate crystals from the right-handed and then dissolved each kind separately and sent light through each solution. Sure enough, the solution of the crystals possessing the same asymmetry as the tartrate crystals twisted the plane of polarized light just as the tartrate did, and by the same amount. Those crystals were tartrate. The other set twisted the plane of polarized light in the opposite direction, with the same amount of rotation. The reason the original racemate had shown no rotation of light, then, was that the two opposing tendencies canceled each other.
Pasteur next reconverted the two separated types of racemate salt to acid again by adding hydrogen ions to the respective solutions. (A salt, by the way, is a compound in which some hydrogen ions of the acid molecule are replaced by other positively charged ions, such as those of sodium or potassium.) He found that each of these racemic acids was now optically active—one rotating polarized light in the same direction as tartaric acid did (for it was tartaric acid), and the other in the opposite direction.
Other pairs of such mirror-image compounds (enantiomorphs, from Greek words meaning “opposite shapes”) were found. In 1863, the German chemist Johannes Wislicenus found that lactic acid (the acid of sour milk) forms such a pair. Furthermore, he showed the properties of the two forms to be identical except for the action on polarized light. This property has turned out to be generally true of enantiomorphs.
