1.2: Chemical Foundations

Search Fundamentals of Biochemistry

Learning Goals (ChatGPT o3-mini)

1. Fundamental Concepts in Organic Chemistry

   • Define what constitutes an organic molecule and distinguish it from inorganic compounds.
   • Explain the significance of carbon’s versatility in forming millions of unique compounds.

2. Understanding Functional Groups

   • Identify and describe common functional groups (e.g., hydroxyl, carbonyl, carboxyl, amine, phosphate, etc.) and their characteristic bonding patterns.
   • Predict the reactivity of a molecule based on the presence and arrangement of its functional groups.

3. Classification of Hydrocarbons

   • Differentiate between alkanes, alkenes, alkynes, and aromatics in terms of structure and reactivity.
   • Explain the concepts of saturation versus unsaturation and the implications for chemical behavior.

4. Reactivity and Structural Diversity

   • Illustrate how similar functional groups in different molecules lead to predictable reactivity patterns.
   • Analyze examples (such as capsaicin) to identify multiple functional groups within a single compound and discuss their collective impact on molecular behavior.

5. Specialized Functional Group Classes

   • Distinguish between closely related groups such as alcohols, phenols, and thiols, as well as ethers versus sulfides.
   • Understand the classification (primary, secondary, tertiary) of both alcohols and amines, noting how definitions differ between these groups.

6. Organic Phosphates and Carbonyl Compounds

   • Explain the structural and functional roles of organic phosphates in biomolecules.
   • Compare and contrast aldehydes, ketones, and carboxylic acids along with their derivatives, focusing on their reactivity in biological contexts.

7. Linking Organic Chemistry to Biochemistry

   • Demonstrate how functional groups participate in dehydration synthesis reactions that form major macromolecules (proteins, nucleic acids, carbohydrates, and lipids).
   • Recognize the importance of functional group activation in the synthesis of complex biomolecules.

8. Primary Metabolites and Cellular Function

   • Define primary metabolites and explain their role in fundamental cellular processes such as energy production, growth, and signaling.
   • Relate the chemical principles of organic reactions to the formation and function of cellular structures (e.g., membranes, cell walls, cytoskeleton).

By achieving these goals, students will deepen their understanding of the structure, reactivity, and biological significance of organic molecules and functional groups, laying a strong foundation for exploring more complex biochemical processes.

Organic Molecules

On Earth, all carbon-containing molecules have originated from biological, living organisms and are called organic compounds. The number of known organic compounds is quite large. There are many times more organic compounds known than all the other (inorganic) compounds discovered, about 7 million organic compounds. Fortunately, organic chemicals consist of relatively few similar parts combined differently. 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 with specific bonding patterns and atoms most commonly found in organic molecules (C, H, O, N, S, and P). Identifying functional groups and predicting 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, contains oxygen with attached hydrogen. 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 occur in the functional group, so learning about the reactivities of functional groups will prepare you to understand many other aspects of biochemistry.

Functional groups are structural units within organic compounds defined by specific bonding arrangements between specific atoms. The structure of capsaicin, the fiery compound found in hot peppers, has several functional groups, labeled in the figure below and explained throughout this section.

As we progress in the study of biochemistry, it will become extremely important to recognize the most common functional groups. These are the key structural elements that define how organic molecules react. Below is a brief introduction to the major organic functional groups.

Alkanes

The ‘default’ in organic chemistry (the lack of functional groups) is given the term alkane, characterized by single bonds between carbon and carbon or 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 bananas' ripening process)). 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.

Aromatics

The aromatic group is exemplified by benzene 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 the delocalization of the pi electrons, these groups are widespread.

Alkyl Halides

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 valuable 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. Still, 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 halide 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). All alcohols can be classified as primary, secondary, or tertiary. In primary alcohols, the carbon bonded to the OH group is also bonded to only one other carbon. The carbon is bonded to two or three other carbons in secondary and tertiary alcohols. 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, oxygen is bonded to two carbons. Below is the structure of diethyl ether, a common laboratory solvent and one of the first compounds to be used as an anesthetic during operations. The sulfur analog of ether is called a thioether or sulfide.

Amines

Amines contain 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 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.

Organic Phosphates

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

Many functional groups 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 similarly. 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 hydrogen and on the other side to 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. 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. Except for acid chlorides and acid anhydrides, carboxylic acid derivatives are very common in biological molecules and/or metabolic pathways and will be discussed in further detail in a later chapter.

Practice Recognizing Functional Groups in Molecules

A single compound often contains several functional groups, particularly in biological organic chemistry. For example, the six-carbon sugar molecules glucose and fructose contain aldehyde and ketone groups, respectively, containing 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 a complete list, this section covers the most important functional groups we will encounter in biochemistry. Table 1.7 provides a summary of all the groups listed in this section.

Table 1.7 Common Organic Functional Groups

Exercise \(\PageIndex{1}\)

Identify the functional groups (other than alkanes) in the following organic compounds. State whether alcohols and amines are primary, secondary, or tertiary.

Exercise \(\PageIndex{2}\)

Draw one example of each compound 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 check your structures with your instructor or tutor.

1. a compound with molecular formula C₆H₁₁NO that includes alkene, secondary amine, and primary alcohol functional groups.
2. an ion with molecular formula C₃H₅O₆P^2- that includes aldehyde, secondary alcohol, and phosphate functional groups.
3. A compound with molecular formula C₆H₉NO that has an amide functional group and does not have an alkene group.

Primary metabolites

Primary metabolites are components of basic metabolic pathways required for life. They are associated with essential cellular functions such as nutrient assimilation, energy production, and growth/development.  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).

Large polymers are made from repeating smaller monomer units (Fig. 1.28). The nucleotides are the monomer units for building nucleic acids, DNA, and RNA. In contrast, the monomers for proteins are amino acids, carbohydrates are sugar residues, and 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 combining repeating monomer subunits through dehydration synthesis. Interestingly, the organic functional units used in the dehydration synthesis processes for each major macromolecule type have similarities. Thus, it is helpful 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 these reactions, there is a functional group that contains two electron-withdrawing groups (the carboxylic acid, phosphoric acid, and the hemiacetal, each having 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 the electronegative oxygen or nitrogen can attack 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, which will be detailed in later chapters.

Primary metabolites involved with energy production include numerous enzymes that break down 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. Cells 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, comprise nucleic acid primary metabolites. Primary metabolites also also involved in cellular signaling, communication, and transport molecules. The structure and function of primary metabolites are key components of this text. These reactions will be detailed in the following chapters.

Summary

This chapter introduces the essential concepts of organic chemistry as they apply to biochemistry, highlighting the central role that carbon-containing compounds play in all life on Earth. It emphasizes that, despite the enormous diversity of organic compounds—numbering in the millions—they are composed of a limited number of recurring structural units known as functional groups. Understanding these groups is fundamental because their predictable reactivity patterns allow us to infer the chemical behavior of unfamiliar compounds.

The chapter begins by discussing the origins of organic molecules and explains how the unique bonding capabilities of carbon allow for the formation of complex and diverse molecular architectures. It outlines how functional groups such as hydroxyl, carbonyl, carboxyl, amine, phosphate, and others serve as the "building blocks" that determine the reactivity and interactions of organic molecules. This foundational knowledge is critical for predicting reaction outcomes in both synthetic organic chemistry and biological systems.

A significant portion of the chapter is dedicated to classifying organic compounds based on their structural features. It covers simple hydrocarbons, distinguishing between alkanes (saturated hydrocarbons), alkenes and alkynes (unsaturated hydrocarbons with double and triple bonds, respectively), and aromatic compounds known for their stable, conjugated ring structures. In addition, the chapter explores various derivatives formed when functional groups are introduced, such as alkyl halides, alcohols, phenols, thiols, ethers, and amines—each with its own characteristic reactivity and role in biological systems.

Further, the chapter connects these organic chemistry principles to biochemistry by explaining how dehydration synthesis reactions link monomers into macromolecules. It details the construction of proteins, nucleic acids, carbohydrates, and lipids from their respective monomer units and discusses the importance of functional group activation during these biosynthetic processes. The section on primary metabolites ties together the concept of organic reactivity with cellular function, underscoring the essential roles of these molecules in energy production, cell structure, and signaling.

Lastly, exercises included in the chapter challenge students to apply their understanding by identifying functional groups in complex molecules and designing compounds that meet specific structural criteria. This active learning component reinforces the practical importance of functional groups in predicting and controlling chemical reactivity in biological contexts.

Overall, the chapter equips students with a robust framework for understanding the structure and reactivity of organic molecules, laying the groundwork for more advanced studies in biochemistry and molecular biology.