On the Earth, all carbon containing molecules have originated from biological, living organisms causing them to be termed organic compounds. The number of known organic compounds is a quite large. In fact, there are many times more organic compounds known than all the other (inorganic) compounds discovered so far, about 7 million organic compounds in total. Fortunately, organic chemicals consist of a relatively few similar parts, combined in different ways. These structural similarities allow us to predict how a compound we have never seen before may react, if we know how other molecules containing the same types of parts are known to react.
These parts of organic molecules are called functional groups and are made up from specific bonding patterns with the atoms most commonly found in organic molecules (C, H, O, N, S, and P). The identification of functional groups and the ability to predict reactivity based on functional group properties is one of the cornerstones of organic chemistry.
Functional groups are specific atoms, ions, or groups of atoms having consistent properties. A functional group makes up part of a larger molecule.
For example, -OH, the hydroxyl group that characterizes alcohols, is an oxygen with a hydrogen attached. It could be found on any number of different molecules.
Just as elements have distinctive properties, functional groups have characteristic chemistries. An -OH functional group on one molecule will tend to react similarly, although perhaps not identically, to an -OH on another molecule.
Organic reactions usually take place at the functional group, so learning about the reactivities of functional groups will prepare you to understand many other aspects about biochemistry.
Functional groups are structural units within organic compounds that are defined by specific bonding arrangements between specific atoms. The structure of capsaicin, the fiery compound found in hot peppers, incorporates several functional groups, labeled in the figure below and explained throughout this section.
As we progress in our study of biochemistry, it will become extremely important to be able to quickly recognize the most common functional groups, because they are the key structural elements that define how organic molecules react. Below is a brief introduction to the major organic functional groups.
The ‘default’ in organic chemistry (essentially, the lack of any functional groups) is given the term alkane, characterized by single bonds between carbon and carbon, or between carbon and hydrogen. Methane, CH4, is the natural gas you may burn in your furnace. Octane, C8H18, is a component of gasoline.
Alkenes and Alkynes
Alkenes (sometimes called olefins) have carbon-carbon double bonds, and alkynes have carbon-carbon triple bonds. Ethene, the simplest alkene example, is a gas that serves as a cellular signal in fruits to stimulate ripening. (If you want bananas to ripen quickly, put them in a paper bag along with an apple – the apple emits ethene gas (also called ethylene), setting off the ripening process in the bananas). Ethyne, commonly called acetylene, is used as a fuel in welding blow torches.
Many alkenes can take two geometric forms: cis or trans. The cis and trans forms of a given alkene are different isomers with different physical properties because there is a very high energy barrier to rotation about a double bond. In the example below, the difference between cis and trans alkenes is readily apparent. Biochemists don't usually use the E (entgegen) and Z (zusammen) labels for groups attached to double bonds (using IUPAC priority numbering).
Alkanes, alkenes, and alkynes are all classified as hydrocarbons, because they are composed solely of carbon and hydrogen atoms. Alkanes are said to be saturated hydrocarbons, because the carbons are bonded to the maximum possible number of hydrogens – in other words, they are ‘saturated’ with hydrogen atoms. The double and triple-bonded carbons in alkenes and alkynes have fewer hydrogen atoms bonded to them – they are thus referred to as unsaturated hydrocarbons.
The aromatic group is exemplified by benzene (which used to be a commonly used solvent on the organic lab, but which was shown to be carcinogenic), and naphthalene, a compound with a distinctive ‘mothball’ smell. Aromatic groups are planar (flat) ring structures, with conjugated pi bonding with 4n+2 pi electrons. Given the stability of aromatic groups due to delocalization of the pi electrons, these groups are widespread in nature.
When the carbon of an alkane is bonded to one or more halogens, the group is referred to as an alkyl halide or haloalkane. Chloroform is a useful solvent in the laboratory, and was one of the earlier anesthetic drugs used in surgery. Chlorodifluoromethane was used as a refrigerant and in aerosol sprays until the late twentieth century, but its use was discontinued after it was found to have harmful effects on the ozone layer. Bromoethane is a simple alkyl halide often used in organic synthesis. Alkyl halides groups are quite rare in biomolecules.
Alcohols, Phenols, and Thiols
In the alcohol functional group, a carbon is single-bonded to an OH group (the OH group, when it is part of a larger molecule, is referred to as a hydroxyl group). Except for methanol, all alcohols can be classified as primary, secondary, or tertiary. In a primary alcohol, the carbon bonded to the OH group is also bonded to only one other carbon. In a secondary alcohol and tertiary alcohol, the carbon is bonded to two or three other carbons, respectively. When the hydroxyl group is directly attached to an aromatic ring, the resulting group is called a phenol. The sulfur analog of an alcohol is called a thiol (from the Greek thio, for sulfur).
Note that the definition of a phenol states that the hydroxyl oxygen must be directly attached to one of the carbons of the aromatic ring. The compound below, therefore, is not a phenol – it is a primary alcohol.
The distinction is important, because there is a significant difference in the reactivity of alcohols and phenols
Ethers and Sulfides
In an ether functional group, an oxygen is bonded to two carbons. Below is the structure of diethyl ether, a common laboratory solvent and also one of the first compounds to be used as an anesthetic during operations. The sulfur analog of an ether is called a thioether or sulfide.
Amines are characterized by nitrogen atoms with single bonds to hydrogen and carbon. Just as there are primary, secondary, and tertiary alcohols, there are primary, secondary, and tertiary amines. Ammonia is a special case with no carbon atoms.
One of the most important properties of amines is that they are basic, and are readily protonated to form ammonium cations. In the case where a nitrogen has four bonds to carbon (which is somewhat unusual in biomolecules), it is called a quaternary ammonium ion.
Note: Do not be confused by how the terms ‘primary’, ‘secondary’, and ‘tertiary’ are applied to alcohols and amines – the definitions are different. In alcohols, what matters is how many other carbons the alcohol carbon is bonded to, while in amines, what matters is how many carbons the nitrogen is bonded to.
Phosphate and its derivative functional groups are ubiquitous in biomolecules. Phosphate linked to a single organic group is called a phosphate ester; when it has two links to organic groups it is called a phosphate diester. A linkage between two phosphates creates a phosphate anhydride.
Aldehydes and Ketones
There are a number of functional groups that contain a carbon-oxygen double bond, which is commonly referred to as a carbonyl. Ketones and aldehydes are two closely related carbonyl-based functional groups that react in very similar ways. In a ketone, the carbon atom of a carbonyl is bonded to two other carbons. In an aldehyde, the carbonyl carbon is bonded on one side to a hydrogen, and on the other side to a carbon. The exception to this definition is formaldehyde, in which the carbonyl carbon has bonds to two hydrogens.
Carboxylic Acids and Their Derivatives
When a carbonyl carbon is bonded on one side to a carbon (or hydrogen) and on the other side to an oxygen, nitrogen, or sulfur, the functional group is considered to be one of the ‘carboxylic acid derivatives’, a designation that describes a set of related functional groups. The main member of this family is the carboxylic acid functional group, in which the carbonyl is bonded to a hydroxyl group. The carboxylate ion form has donated the H+ to the solution. Other derivatives are carboxylic esters(usually just called ‘esters’), thioesters, amides, acyl phosphates, acid chlorides, and acid anhydrides. With the exception of acid chlorides and acid anhydrides, the carboxylic acid derivatives are very common in biological molecules and/or metabolic pathways and will be discussed in further details in a later chapter.
Practice Recognizing Functional Groups in Molecules
A single compound often contains several functional groups, particularly in biological organic chemistry. The six-carbon sugar molecules glucose and fructose, for example, contain aldehyde and ketone groups, respectively, and both contain five alcohol groups. A compound with several alcohol groups is often referred to as a ‘polyol’.
The hormone testosterone, the amino acid phenylalanine, and the glycolysis metabolite dihydroxyacetone phosphate all contain multiple functional groups, as labeled below.
While not in any way a complete list, this section has covered most of the important functional groups that we will encounter in biochemistry. Table 1.7 provides a summary of all of the groups listed in this section.
Table 1.7 Common Organic Functional Groups
Identify the functional groups (other than alkanes) in the following organic compounds. State whether alcohols and amines are primary, secondary, or tertiary.
Draw one example each of compounds fitting the descriptions below, using line structures. Be sure to designate the location of all non-zero formal charges. All atoms should have complete octets (phosphorus may exceed the octet rule). There are many possible correct answers for these, so be sure to check your structures with your instructor or tutor.
a) a compound with molecular formula C6H11NO that includes alkene, secondary amine, and primary alcohol functional groups
b) an ion with molecular formula C3H5O6P2- that includes aldehyde, secondary alcohol, and phosphate functional groups.
c) A compound with molecular formula C6H9NO that has an amide functional group, and does not have an alkene group.
Primary metabolites are components of basic metabolic pathways that are required for life. They are associated with essential cellular functions such as nutrient assimilation, energy production, and growth/development. They have a wide species distribution that span many phyla and frequently more than one kingdom. Primary metabolites include the building blocks required to make the four major macromolecules within the body: carbohydrates, lipids, proteins, and nucleic acids (DNA and RNA).
These are large polymers of the body that are built up from repeating smaller monomer units (Fig. 6.1). The monomer units for building the nucleic acids, DNA and RNA, are the nucleotide bases, whereas the monomers for proteins are amino acids, for carbohydrates are sugar residues, and for lipids are fatty acids or acetyl groups.
Figure 1.28 The Molecular building blocks of life are made from organic compounds. Modified from: Boghog
Reactions forming the Major Macromolecules
The major macromolecules are built by putting together repeating monomer subunits through the process of dehydration synthesis. Interestingly, the organic functional units used in the dehydration synthesis processes for each of the major types of macromolecules have similarities with one another. Thus, it is useful to look at the reactions together (Figure 1.29)
Figure 1.29 Dehydration Synthesis Reactions Involved in Macromolecule Formation. The major organic reactions required for the biosynthesis of lipids, nucleic acids (DNA/RNA), proteins, and carbohydrates are shown. Note that in all of the reactions, there is a functional group that contains two electron withdrawing groups (the carboxylic acid, phosphoric acid and the hemiacetal each have two oxygen atoms attached to a central carbon or phosphorus atom). This forms a reactive partially positive center atom (carbon in the case of the carboxylic acid and hemiacetal, or phosphorus in the case of the phosphoric acid) that can be attacked by the electronegative oxygen or nitrogen from an alcohol or amine functional group. Within biological systems, many functional groups, such as carboxylic acids, require activation before they can be utilized in synthesis reactions and will be detailed in later chapters.
Primary metabolites that are involved with energy production include numerous enzymes that breakdown food molecules, such as carbohydrates and lipids, and capture the energy released during the hydrolysis of adenosine triphosphate (ATP). Enzymes are biological catalysts that speed up the rate of chemical reactions. Typically they are proteins, which are composed of amino acid building blocks. The basic structure of cells and of organisms are also composed of primary metabolites. These include cell membranes (e.g. phospholipids), cell walls (e.g. peptidoglycan, chitin), and cytoskeletons (proteins). DNA and RNA which store and transmit genetic information are composed of nucleic acid primary metabolites. Primary metabolites also include molecules involved in cellular signaling, communication and transport. The structure and function of primary metabolites are a key component of this text. These reactions will be detailed in the following chapters.
Inorganic Ions and Complexes
to be added