Carbon - What Makes It Special

Basically, carbon is incredibly versatile. It can form 4 bonds because of its half-full (or half-empty depending on your worldview) valence shell. This also means that it can form single, double, or triple covalent bonds. And it isn't too attached to its electrons, so it might form nonpolar or polar covalent bonds depending on how hard its neighbors play tug-of-war.

But here's the real magic: not only can carbon bond with 4 atoms, like in methane (CH4), it can also bond with itself. So it can form really long chains, rings, and just about any shape you can imagine by bonding with lots of other carbons in conjunction with other atoms. Some of these shapes will become very important when we talk about macromolecules next. Below are some examples of what these shapes may look like at a molecular level, but keep in mind - this is just the tip of the iceberg. There are technically infinite shapes that organic (carbon-containing) molecules can take. Don't bother memorizing the names or shapes of these structures, just take a quick glance at them and note some similarities and differences.

Organic chemistry is the study of compounds that contain carbon.  Organic compounds range from simple molecules to colossal ones.  Most organic compounds contain hydrogen atoms in addition to carbon atoms

Organic Molecules and the Origin of Life on Earth

•  Stanley Miller’s classic experiment demonstrated the abiotic synthesis of organic compounds
  

• Experiments support the idea that abiotic synthesis of organic compounds, perhaps near volcanoes, could have been a stage in the origin of life

Hydrocarbon structures and isomers

Even though you likely see gasoline-powered vehicles everyday, you rarely see what gasoline itself looks like! To the naked eye, gasoline is a pretty uninteresting yellowish-brown liquid. At the molecular level, though, gasoline is actually made up of a striking range of different molecules, most of them hydrocarbons (molecules containing only hydrogen and carbon atoms).

Some of the hydrocarbons in gasoline are small and contain just four carbon atoms, while others are much larger and have up to twelve carbons. Some hydrocarbons form straight lines, while others have a branched structure; some have only single bonds, while others have double bonds; and still others contain rings. While the different hydrocarbons in gasoline often have very different properties, such as melting point and boiling point, they all produce energy when they’re burned in an engine.

Hydrocarbons are diverse!

As the gasoline example shows, hydrocarbons come in many different forms. They may differ in length, be branched or unbranched, form linear or ring shapes (or both), and include various combinations of single, double and triple carbon-carbon bonds. Even if two hydrocarbons have the same molecular formula, their atoms may be connected or oriented in different ways, making them isomers of one another (and sometimes giving the two molecules very different properties).

Each of these structural features can influence the three-dimensional shape, or molecular geometry, of a hydrocarbon molecule. In the context of large biological molecules such as DNA, proteins, and carbohydrates, structural differences in the carbon skeleton often affect how the molecule functions.

Branching, multiple bonds, and rings in hydrocarbons

Hydrocarbon chains are formed by a series of bonds between carbon atoms. These chains may be long or short: for instance, ethane contains just two carbons in a row, while decane contains ten. Not all hydrocarbons are straight chains. For example, while decane’s ten carbon atoms are lined up in a row, other hydrocarbons with the same molecular formula (C10 H22)  have shorter primary chains with various side branches. (In fact, there are 75 possible structures for  C10H22

Hydrocarbons may contain various combinations of single, double, and triple carbon-carbon bonds. The hydrocarbons ethane, ethene, and ethyne provide an example of how each type of bond can affect the geometry of a molecule:

• Ethane (C2H6) with a single bond between the two carbons, adopts a two-tetrahedron shape (one tetrahedron about each carbon). Importantly, rotation occurs freely about the carbon-carbon bond.

• In contrast, Ethene (C2H4), with a double bond between the two carbons, is planer (all of its atoms lie in the same plane). Furthermore, rotation about the carbon-carbon double bond is restricted. This is a general feature of carbon-carbon double bonds, so anytime you see one of these in a molecule, remember that the portion of the molecule containing the double bond will be planar and unable to rotate.

• Finally, Ethyne (C2H2), with a triple bond between the two carbons, is both planar and linear. As with the double bond, rotation is completely restricted about the carbon-carbon triple bond

An additional structural feature that is possible in hydrocarbons is a ring of carbon atoms. Rings of various sizes may be found in hydrocarbons, and these rings may also bear branches or include double bonds. Certain planar rings with conjugated atoms, like the benzene ring shown below, are exceptionally stable. These rings, called aromatic rings, are found in some amino acids as well as in hormones like testosterone and estrogens (the primary male and female sex hormones, respectively).

Isomers

• The molecular geometries of hydrocarbons are directly related to the physical and chemical properties of these molecules. Molecules that have the same molecular formula but different molecular geometries are called isomers.  

• Structural isomers have different covalent arrangements of their atoms

• Cis-trans isomers  (Geometric) have the same covalent bonds but differ in spatial arrangements

• Enantiomers are isomers that are mirror images of each other

C. Enantiomers 

Enantiomers are stereoisomers that are non-superimposable mirror images of each other (“non-superimposable” means that the two molecules cannot be perfectly aligned one on top of the other in space). Enantiomerism is often seen in molecules containing one or more asymmetric carbons, which are carbon atoms that are attached to four different atoms or groups. Enantiomers are molecules that share the same chemical structure and chemical bonds but differ in the three-dimensional placement of atoms so that they are mirror images. 

Why do we eat glucose D and not glucose L?

L-Glucose does not occur naturally in living organisms, but can be synthesized in the laboratory. L-Glucose is indistinguishable in taste from d-glucose, but cannot be used by living organisms as a source of energy because it cannot be phosphorylated by hexokinase, the first enzyme in the glycolysis pathway.

Enantiomers are important in the pharmaceutical industry

•  Two enantiomers of a drug may have different effects
  

•  Usually, only one isomer is biologically active
  

•  Differing effects of enantiomers demonstrate that organisms are sensitive to even subtle variations in molecules
   

Most Famous Example.  Thalidomide

Thalidomide exists in two mirror-image forms: it is a racemic mixture of (R)- and (S)-enantiomers. The (R)-enantiomer, shown in the figure, has sedative effects, whereas the (S)-isomer is teratogenic.

Thalidomide is a drug that was developed in the 1950s by the West German pharmaceutical company Chemie Grünenthal GmbH. It was originally intended as a sedative or tranquiliser, but was soon used for treating a wide range of other conditions, including colds, flu, nausea and morning sickness in pregnant women. 

During early testing, researchers at the company found that it was virtually impossible to give test animals a lethal dose of the drug (based on the LD50 test). Largely based on this, the drug was deemed to be harmless to humans. Thalidomide was licensed in July 1956 for over-the-counter sale (no doctor’s prescription was needed) in Germany.  

The drug was prescribed for a range of conditions including pneumonia, colds and flu and for relieving the symptom of nausea often experienced in early pregnancy.

One country that did not approve thalidomide for marketing and distribution was the USA, where it was rejected by the Food and Drug Administration.

Pharmacologist Frances Oldham Kelsey turned down several requests from the distributing company who did not provided clinical evidence to refute reports of patients who developed nerve damage in their limbs after long-term thalidomide use. This prevented the drug thalidomide from ever being used in the United States. 

THALIDOMIDE AND PREGNANCY

In the 1950s, scientists did not know that the effects of a drug could be passed through the placental barrier and harm a fetus in the womb, so the use of medications during pregnancy was not strictly controlled. And in the case of thalidomide, no tests were done involving pregnant women.

As the drug was traded under so many different names in 49 countries, it took five years for the connection between thalidomide taken by pregnant women and the impact on their children to be made. A UK Government warning was not issued until May 1962.

One reason why researchers and doctors were slow to make this connection was due to the wide range of changes to fetal development. Limbs, internal organs including the brain, eyesight and hearing could all be affected.

Later, they found that the impact on development was linked to when during pregnancy the drug was taken, and effects only occurred between  20 and 37 days after conception. After that, thalidomide had no effect on the fetus.  

Another reason why it took so long to establish the link to thalidomide was that some of the damage caused by the drug was very similar to certain genetic conditions that affect the upper or lower limbs. 

THE THALIDOMIDE SCANDAL

The first time the link between thalidomide and its impact on development was made public was in a letter published in The Lancet from an Australian doctor William McBride, in 1961.

The drug was formally withdrawn by Chemie Grünenthal on 26 November 1961 and a few days later, on 2 December 1961, the UK distributors followed suit. However, it remained in many medicine cabinets under many different names.

In the few short years that thalidomide was available, it's estimated that over 10,000 babies were affected by the drug worldwide. Around half died within months of being born. The thalidomide babies who survived and their families live with the effects of the drug.  

THE CONSEQUENCES OF THALIDOMIDE

Thalidomide forced governments and medical authorities to review their pharmaceutical licensing policies. As a result, changes were made to the way drugs were marketed, tested and approved both in the UK and across the world.

One key change was that drugs intended for human use could no longer be approved purely on the basis of animal testing. And drug trials for substances marketed to pregnant women also had to provide evidence that they were safe for use in pregnancy.

The easy, over-the-counter access to thalidomide prompted many countries to improve their classification and control of medicines. In the UK the 1968 Medicines Act, passed as a result of the thalidomide scandal, made distinctions between prescription drugs, drugs only available in pharmacies and drugs available for general sale.

The Yellow Card Scheme was set up for doctors to share previously unknown side effects of medications they prescribed. The Scheme has now widened so anyone can report a side effect.

In the UK thalidomide is only prescribed by a doctor under strict controls. Women taking thalidomide are required to use two forms of birth control and regular pregnancy tests. Men are required to use contraception when taking thalidomide. People who are prescribed thalidomide undergo counseling and are talked through the risks. 

USES OF THALIDOMIDE TODAY

This was not the end of the thalidomide story. In 1964 a leprosy patient at Jerusalem’s Hadassah University Hospital was given thalidomide when other tranquilizers and painkillers could not help him. His doctor, Jacob Sheskin, noticed the drug had an effect on the patient’s leprosy symptoms. 

Within three days leprosy (Hansen's disease) had gone and skin lesions healed. When the patient stopped taking the thalidomide the leprosy returned. The drug seemed to be able to suppress the disease, although it was not a cure.

As a result, the WHO  ran a clinical trial on the use of thalidomide for leprosy in 1967. And after more positive results, thalidomide was used as a treatment for leprosy in many countries. 

More recently, it has been used successfully to control some AIDS-related conditions, and as a targeted cancer drug for treating cancers such as multiple myeloma.

But the renewed use of thalidomide remains controversial because of its past history.