1.2 The Chemical Foundations

• Four covalent bonds — carbon forms chain, branched and ring skeletons; single and double bonds create further variety
• Rotation — C–C single bonds rotate; double bonds are restricted by the π bond, shaping flexibility, planarity and accessibility
• Functional groups — hydroxyl, carbonyl, carboxyl, amino, sulfhydryl, phosphate, methyl and amide groups set polarity, charge and reactivity
• Several groups at once — glycine carries amino and carboxyl; glucose carries hydroxyls and a carbonyl and is mainly cyclic in solution
• Zwitterions — in biological solutions amino acids usually carry both NH₃⁺ and COO⁻
• pH dependence — above its pKa a carboxyl group is deprotonated; an amino group loses its proton as pH rises

• Monosaccharides and sugar phosphates — carbon and energy supply, nucleic acid precursors
• Amino acids — protein synthesis and nitrogen metabolism
• Nucleotides — nucleic acid synthesis, phosphate transfer, signalling
• Organic acids and intermediates — linking carbon skeletons between pathways
• Fatty acids and lipid precursors — membrane and storage lipids
• Cofactors and coenzymes — NAD⁺/NADH, FAD, coenzyme A carrying electrons and groups
• Inorganic ions — Mg²⁺, K⁺, Ca²⁺, Fe²⁺/Fe³⁺ for charge balance, catalysis, signalling and electron transfer

• Molecular mass — the mass of one molecule, in kg or Da
• Relative molecular mass (Mr) — the ratio to the atomic mass unit; dimensionless
• Molar mass — mass divided by amount of substance, g/mol
• Dalton — 1 Da = 1 u = 1/12 the mass of a ¹²C atom
• Example A — glucose C₆H₁₂O₆ gives Mr = 180.156, so one molecule ≈ 180.156 Da and one mole ≈ 180.156 g
• Example B — a 50 kDa protein has a molar mass of 50,000 g/mol; 0.10 μmol weighs 5.0 mg
• Example C — Gly-Gly: 2 × 75.07 − 18.015 = 132.125 g/mol; n residues form n−1 bonds

• Proteins — amino acids joined by peptide (amide) bonds; N-terminal to C-terminal sequence
• Polysaccharides — monosaccharides joined by glycosidic bonds; α/β linkage and branching change the material
• Nucleic acids — nucleotides joined by 3′–5′ phosphodiester bonds with 5′→3′ directionality
• Lipids — phospholipids, triglycerides and steroids differ too much for one repeating monomer
• Condensation and hydrolysis — the overall stoichiometry; real synthesis needs activated precursors, tRNA and ribosomes
• Beyond the sum of parts — sequence constrains folding, base complementarity stores information, branching separates starch, glycogen and cellulose
• Levels of protein structure — primary, secondary, tertiary and quaternary; flexible and disordered regions exist

• Configuration — spatial difference not removed by rotation about a single bond: enantiomers, E/Z isomers
• Conformation — arrangement changed by rotation about single bonds or by folding
• Chirality — not superimposable on its mirror image; a carbon with four different substituents is a chiral centre, but not every chiral molecule has one
• Enantiomers — identical in achiral environments, opposite in optical rotation and different in chiral recognition
• D/L, R/S, (+)/(−) — relative configuration, absolute configuration by CIP priority, and observed rotation are three different systems
• Conformational energy — eclipsed and staggered arrangements differ; rotation is possible but not free of energy cost

• Observation — tartrate crystals of identical composition differed in optical activity
• Classification — two mirror-image crystal forms were identified in paratartrate samples
• Separation and measurement — individual crystals were picked apart and each solution rotated polarised light in the opposite direction
• Interpretation — equal amounts of both enantiomers cancel, leaving no apparent activity
• Measurement — α = [α]_λ,T · l · c; sucrose [α]_D,20 ≈ +66.5°·mL·g⁻¹·dm⁻¹, so 10 % (w/v) in a 10 cm cell gives about +6.65°
• Legacy — the basis of enzyme stereospecificity, biomolecular chirality and enantiomeric drugs
• Caution — zero rotation does not prove achirality: a racemic mixture also reads zero

• Chiral active site — proteins built from L-amino acids create a chiral pocket, so enantiomers make different contacts
• Stereospecific — a difference in substrate configuration leads to a different outcome or pathway
• Stereoselective — one of several possible stereoisomeric products predominates
• Beyond lock and key — induced fit and selection among pre-existing conformations; substrate orientation changes the activation barrier
• Chiral choices of life — proteins use L-α-amino acids, nucleic acids use D-sugars, yet D-amino acids occur in some bacterial cell walls

• Carbon and functional groups — the skeleton sets shape; the groups set reactivity, charge and solubility
• Groups and pH — protonation follows pKa and the surrounding environment
• Small molecules — sugars, amino acids, nucleotides and cofactors feed connected reactions
• Mass units — Da, g/mol and a dimensionless Mr are not interchangeable
• Macromolecule classes — proteins, polysaccharides and nucleic acids are polymers; lipids are not uniformly so
• Configuration and conformation — two different descriptions of spatial structure
• Chirality — recognition differs in chiral environments

Data tables for this section, shown on click and printed in the appendix.