Grade by Grade
B. Biochemistry · Biochemistry

The Chemistry Biology Runs On: Bonds, Water and Functional Groups

B3.3 B2.1 B2.3 A1.12About 70 minutes
Learning goals
  • I can compare covalent bonds, ionic bonds, hydrogen bonds and hydrophobic interactions and explain where each matters in a cell.
  • I can explain how water's polarity makes molecules hydrophilic or hydrophobic.
  • I can identify the hydroxyl, carbonyl, carboxyl, amino, phosphate, sulfhydryl and methyl groups in a structural formula.
  • I can explain how each functional group contributes to a molecule's properties and function.

Words to know

covalent bond
A bond in which two atoms share a pair of electrons. It is polar if the atoms have different electronegativities, non-polar if they are about equal.
ionic bond
An attraction between oppositely charged ions. In cells, it often forms between charged groups such as –COO⁻ and –NH₃⁺.
hydrogen bond
A weak attraction between a δ+ hydrogen (bonded to O or N) and a δ− oxygen or nitrogen on another molecule or another part of the same molecule.
hydrophilic
"Water-loving": polar or charged, so it dissolves in or attracts water.
hydrophobic
"Water-fearing": non-polar, so it does not dissolve in water and clusters with other non-polar molecules.
functional group
A specific group of atoms attached to a carbon skeleton that gives a molecule characteristic chemical properties.
organic molecule
A molecule built on a carbon skeleton, usually with hydrogen. All four classes of biological macromolecules are organic.
isomers
Molecules with the same molecular formula but different arrangements of atoms, and so different properties (glucose and fructose are both C₆H₁₂O₆).

Same atoms, different jobs

Glucose, the sugar in your blood, is C₆H₁₂O₆. Fructose, the sugar in honey and fruit, is also C₆H₁₂O₆. Yet they taste different, behave differently in your cells, and give different results in some lab tests. The difference is how the atoms are arranged, and especially which functional groups they form.

This lesson is the chemistry toolkit for the rest of the unit: the bonds that hold biological molecules together and shape them, and the small groups of atoms that decide how a molecule behaves.

Remember from Grade 11 Chemistry

If you took SCH3U, you learned electronegativity (EN), how to classify bonds with ΔEN (about 0 to 0.4 non-polar covalent; 0.5 to 1.7 polar covalent; more than 1.7 ionic), and why water is a polar, bent molecule that forms hydrogen bonds. If you didn't take it, the short version is below. Useful EN values: H 2.2, C 2.6, N 3.0, O 3.4, P 2.2, S 2.6.

Carbon: the backbone

Carbon has four valence electrons, so it forms four covalent bonds. It can bond to other carbons in long chains, branches and rings, and to H, O, N, P and S. That makes an almost unlimited number of shapes possible. A carbon chain with only hydrogens attached (a hydrocarbon part) is non-polar, because C–H bonds have ΔEN = 2.6 − 2.2 = 0.4.

Four kinds of attraction in biological molecules

  1. Covalent bonds hold each molecule together. They are strong: in a cell, they are broken and made only with the help of enzymes.
  2. Ionic bonds form between charged groups, such as a negative carboxylate (–COO⁻) and a positive amino group (–NH₃⁺) in different parts of a protein. In water they are much weaker than in a dry salt crystal, because water molecules surround the ions.
  3. Hydrogen bonds form when a hydrogen attached to O or N (δ+) is attracted to a lone pair on another O or N (δ−). Each one is weak, but thousands of them hold the two strands of DNA together and shape every protein.
  4. Hydrophobic interactions and van der Waals attractions: non-polar parts of molecules are pushed together by the surrounding water (water molecules hydrogen-bond to each other and "squeeze out" non-polar groups). This is why oil forms droplets, and why cell membranes form at all.

It is a useful rule: covalent bonds make a molecule; the weak attractions give it its 3-D shape and let it interact with other molecules. Weak bonds can form and break quickly at body temperature, which is exactly what an enzyme binding its substrate or a hormone binding a receptor needs.

Strongestcovalent bondshared electron pairC–C, C–H, O–H, peptide bondionic bondattraction of + and − ions–COO⁻ ··· ⁺H₃N–hydrogen bondδ+ H to δ− O or Nbetween water molecules; DNA base pairshydrophobic effect / van der Waalsnon-polar parts clusterfatty-acid tails in a membraneWeakest (but there are millions of them)bar length: relative strength (not to scale)
The four kinds of attraction, from strongest to weakest. Covalent bonds build molecules; the weaker attractions shape them and let them bind to each other quickly and reversibly.

Water decides what is hydrophilic

Water is polar and forms hydrogen bonds. So:

  • Hydrophilic substances (ions, and molecules with polar groups such as –OH, –COOH or –NH₂) attract water molecules and dissolve. Glucose has five –OH groups, so it is very soluble.
  • Hydrophobic substances (long hydrocarbon chains, such as the tails of fats) cannot hydrogen-bond with water. Water molecules bond to each other instead, and the non-polar molecules are pushed together.
  • Amphipathic molecules have both: a hydrophilic "head" and a hydrophobic "tail". Phospholipids and soaps are amphipathic. You will see why that matters in the lessons on lipids and membranes.

The seven functional groups to know

A functional group is a group of atoms that behaves in a predictable way no matter which molecule it is attached to. Biochemists write the rest of the molecule as R. Learn each group's structure, its property, and where you will meet it:

  • Hydroxyl (–OH). Polar; forms hydrogen bonds; makes molecules water-soluble. Found in all sugars and in alcohols such as ethanol and glycerol. (Don't confuse it with the hydroxide ion, OH⁻: a hydroxyl group is covalently bonded and does not make a solution basic.)
  • Carbonyl (C=O). Polar. At the end of a carbon chain it is an aldehyde (–CHO); in the middle it is a ketone (C–CO–C). Glucose is an aldehyde sugar (an aldose); fructose is a ketone sugar (a ketose). That is the difference between them.
  • Carboxyl (–COOH). A carbonyl and a hydroxyl on the same carbon. It is acidic: it gives up H⁺, so at cell pH it is usually –COO⁻ (negative). Found in amino acids and fatty acids ("-ic acid" names: lactic, citric, palmitic).
  • Amino (–NH₂). Basic: it picks up H⁺, so at cell pH it is usually –NH₃⁺ (positive). Found in all amino acids.
  • Phosphate (–OPO₃²⁻). Acidic and negatively charged. Links nucleotides in DNA and RNA, forms the head of phospholipids, and the bonds between the phosphates of ATP transfer energy. Adding a phosphate (phosphorylation) is a common way to switch a protein on or off.
  • Sulfhydryl (–SH). Two –SH groups can join into a disulfide bridge (–S–S–), a covalent link that holds parts of a protein together. Found in the amino acid cysteine. (Hair "perms" work by breaking and re-forming these bridges in hair keratin.)
  • Methyl (–CH₃). Non-polar. Makes a region hydrophobic. Adding methyl groups to DNA (methylation) can switch genes off, a topic in Molecular Genetics.
hydroxylR–OHpolar; forms H bondssugars, alcoholscarbonylR–CHO or R–CO–R′polar; aldehyde or ketoneglucose, fructosecarboxylR–COOH ⇌ R–COO⁻ + H⁺acidic; negative at pH 7amino acids, fatty acidsaminoR–NH₂ + H⁺ ⇌ R–NH₃⁺basic; positive at pH 7amino acidsphosphateR–O–PO₃²⁻acidic; negative chargeATP, DNA, phospholipidssulfhydrylR–SHtwo can form S–S bridgescysteine in proteinsmethylR–CH₃non-polar; hydrophobicfatty acids, some amino acidsR =rest of the moleculeR′ = another carbon chaingroups set the properties
Functional group cards: the group, its formula, its key property, and where you will meet it. R stands for the rest of the molecule. Green cards are polar but neutral groups, blue cards can carry a charge at cell pH, the unfilled methyl card is non-polar, and the yellow card is the key to R.
Worked example

Example: Reading functional groups in a structural formula

Lactic acid builds up in muscles during hard exercise. Its structural formula is shown below. (a) Identify its functional groups. (b) Predict whether it dissolves in water. (c) What charge does it carry at pH 7?

  1. Find the carbons: there are three in a chain.
  2. Carbon 1 has three H atoms: a methyl group (non-polar).
  3. Carbon 2 has an –OH: a hydroxyl group (polar).
  4. Carbon 3 has a C=O and an –OH on the same carbon: a carboxyl group (acidic).
  5. (b) It has two polar groups and only one small non-polar group, so it is hydrophilic and dissolves in water.
  6. (c) The carboxyl group gives up H⁺ at pH 7, becoming –COO⁻. Lactic acid exists mostly as the lactate ion, with a 1− charge.

(a) methyl, hydroxyl, carboxyl; (b) soluble (hydrophilic); (c) mostly lactate, charge 1−. This is why biologists often say "lactate" rather than "lactic acid".

CCCHHHHOHOOHmethylhydroxylcarboxyllactic acidC₃H₆O₃
Lactic acid, C₃H₆O₃, with its three functional groups boxed: methyl (non-polar), hydroxyl (polar) and carboxyl (acidic).

Isomers: why arrangement matters

  • Structural isomers have the same formula but a different skeleton or different groups: glucose (aldehyde) and fructose (ketone) are both C₆H₁₂O₆.
  • Stereoisomers have the same bonds but a different 3-D arrangement. When a carbon is bonded to four different groups, two mirror-image forms are possible, like your left and right hands. Cells are very picky: the proteins in your body are built almost entirely from L-amino acids, and the enzymes that digest starch cannot digest cellulose, even though both are made only of glucose (you will see why in Carbohydrates).

Building 3-D models (B2.3)

Structural formulas on paper are flat, but molecules are not. Around a carbon with four single bonds, the bonds point to the corners of a tetrahedron (about 109.5° apart). A model kit (or gumdrops and toothpicks) shows this much better than a drawing. Throughout this unit you will build and draw 3-D models of a sugar, a fat, an amino acid chain and a nucleotide.

Just for fun

Biochemists say "R" stands for "the rest of the molecule". It's the most useful way ever invented of saying "and so on".

Hands-on activity

Gumdrop molecules: build in 3-D

You need: a bag of gumdrops or mini marshmallows in at least 4 colours (or modelling clay), about 40 toothpicks, and a marker and paper for a colour key. Safety: toothpicks are sharp; use them carefully and don't eat the model after it has been handled.

Colour key (write it down): black or dark = carbon (4 toothpicks), white = hydrogen (1), red = oxygen (2), any other colour = nitrogen (3). Use two toothpicks side by side for a double bond.

  1. Build methane (CH₄). Push the four toothpicks into the carbon so they point as far apart as possible. Notice the shape: a tetrahedron, not a flat cross.
  2. Build ethanol, CH₃–CH₂–OH. Circle (in your drawing) the hydroxyl group and the methyl group.
  3. Build glycine, H₂N–CH₂–COOH (the simplest amino acid). Label the amino and carboxyl groups.
  4. Build lactic acid from the example. Then rearrange the H and OH on the middle carbon to make its mirror image. Try to stack the two models on top of each other: they don't match, just like your hands.
  5. Draw each model as a structural formula and label every functional group.

What to look for: every carbon has exactly 4 bonds, oxygen 2, nitrogen 3 and hydrogen 1. The two lactic-acid models are mirror images that cannot be superimposed (stereoisomers).

Your turn

1

Name the functional group: (a) –NH₂ (b) –COOH (c) –OH (d) –SH (e) –CH₃

2

Which two functional groups usually carry a negative charge at cell pH, and which one usually carries a positive charge?

3

What is the difference between an aldehyde and a ketone?

4

Explain why glucose dissolves in water but a long fatty-acid tail does not.

5

Rank from strongest to weakest: hydrogen bond, covalent bond, hydrophobic interaction.

6

Which functional group can form a covalent bridge between two parts of a protein? What is the bridge called?

More practice: warm-up

1

How many covalent bonds does a carbon atom form?

2

What does "hydrophobic" mean?

3

Which functional group is in all sugars many times over?

4

Which functional group is found in ATP and DNA?

5

What are isomers?

More practice: on your own

1

Glycerol is HOCH₂–CH(OH)–CH₂OH. Name its functional groups and predict its solubility in water.

2

An amino acid has both a carboxyl and an amino group. At pH 7, what charges do they have, and what is the overall charge of glycine?

3

A phospholipid has a phosphate group at one end and two long hydrocarbon tails. Use the words hydrophilic, hydrophobic and amphipathic to describe it.

4

Why are hydrogen bonds, rather than covalent bonds, useful for holding the two strands of DNA together?

5

C–O has ΔEN = 3.4 − 2.6 = 0.8. Is the C–O bond polar? Which atom is δ−?

Challenge

1

Acetic acid (CH₃COOH, in vinegar) and ethanol (CH₃CH₂OH) both have an –OH. Explain why acetic acid is acidic but ethanol is not.

2

A protein is placed in a solution of urea, which forms hydrogen bonds with the protein's groups. The protein unfolds, but its sequence of amino acids is unchanged. Explain using bond types.

3

Draw (describe) the structure of the amino acid serine, HOCH₂–CH(NH₂)–COOH, and explain which of its groups would interact with water and how.

Check your understanding

Quiz

1.

Which functional group makes amino acids and fatty acids acidic?

2.

Glucose and fructose have the same formula, C₆H₁₂O₆, but glucose has an aldehyde group and fructose a ketone group. They are:

3.

Which attraction is mainly responsible for oil forming droplets in water?

4.

Two cysteine side chains can form a disulfide bridge using which group?

5.

At pH 7, an amino group is usually:

6.

A molecule with a charged head and long non-polar tails is best described as:

For parents and teachers

Big idea: This lesson covers B3.3 (functional groups and how they contribute to a molecule's function), B2.1 vocabulary (covalent and ionic bonds), and starts B2.3 (3-D molecular models).

How to help: Make a set of flashcards with the formula on one side and the name, property and example on the other. Quiz in both directions. The gumdrop models are worth doing: seeing that a carbon's bonds point in 3-D helps with every later lesson.

Common difficulties:

  • Confusing the hydroxyl group (–OH, covalent, neutral) with the hydroxide ion (OH⁻, basic).
  • Forgetting that carboxyl and phosphate groups are usually charged in cells.
  • Thinking hydrogen bonds are the bonds to hydrogen inside a molecule. They are attractions between a δ+ H and a δ− O or N.
  • If your teen did not take Grade 11 Chemistry, the electronegativity tip box gives everything needed for this course.