Difficulty: Intermediate | Prerequisites: General Chemistry acid-base basics, Lewis structures, VSEPR, orbital hybridization (Chem 210 Lectures 1 through 10).
Acid-base chemistry is the backbone of reactivity in organic chemistry. Every reaction mechanism you will encounter in Chem 210 (and beyond) begins with identifying an electron-pair donor and an electron-pair acceptor. This lecture closes out the acid-base unit by connecting two frameworks, Lewis and Br\u00f8nsted, and showing how the pKa table lets you predict which way a reaction goes without memorising hundreds of individual reactions. If you skipped the earlier lectures on Lewis structures, resonance and hybridisation, go back: the five structural factors that determine acid strength all depend on concepts from those weeks.
Acids donate protons (Br\u00f8nsted) or accept electron pairs (Lewis); bases do the reverse. The pKa value tells you how strong an acid is: lower pKa means stronger acid. You can predict whether a reaction favours products or reactants by comparing pKa values on each side, and you can work out whether a molecule is protonated or deprotonated at a given pH by comparing the pH to each site's pKa.
Br\u00f8nsted acid
A proton (H+) donor. In simple terms, it is any species that can hand off a hydrogen ion to something else.
Br\u00f8nsted base
A proton (H+) acceptor. Think of it as the molecule that grabs the hydrogen the acid is giving up.
Lewis acid
An electron-pair acceptor (also called an electrophile in organic chemistry). It has an empty or electron-poor orbital ready to receive a pair of electrons.
Lewis base
An electron-pair donor (also called a nucleophile). It has a lone pair or a bond it can share with an electron-deficient partner.
Conjugate base
The species that remains after an acid loses its proton. If HA is the acid, A- is the conjugate base.
Conjugate acid
The species formed when a base gains a proton. If B is the base, BH+ is the conjugate acid.
pKa
The negative base-10 logarithm of the acid dissociation constant Ka, measured against water as the reference base. A lower pKa means a stronger acid. Think of it as a ranking number: the more negative, the more eager the acid is to lose its proton.
Keq (equilibrium constant)
The ratio of product concentrations to reactant concentrations at equilibrium. For acid-base reactions, Keq = 10^(pKa of product acid minus pKa of reactant acid). Keq > 1 means products are favoured.
Electrophile
A Lewis acid in the context of organic reaction mechanisms. Literally "electron-loving" -- it seeks out electron density.
Nucleophile
A Lewis base in the context of organic reaction mechanisms. Literally "nucleus-loving" -- it attacks electron-poor centres.
The Br\u00f8nsted definition focuses on proton transfer. In every Br\u00f8nsted acid-base reaction, one species donates H+ (the acid) and the other accepts it (the base). The products are the conjugate base of the acid and the conjugate acid of the base.
The Lewis definition is broader. A Lewis acid accepts an electron pair; a Lewis base donates one. Every Br\u00f8nsted acid-base reaction is also a Lewis acid-base reaction, but Lewis chemistry also covers complexation reactions where no proton moves at all (for example, BF3 accepting a lone pair from NH3).
Key link between the two: in organic chemistry, "electrophile" is essentially another word for Lewis acid, and "nucleophile" for Lewis base.
The general form is:
AH + B \u2192 A- + BH+
AH is the acid, B is the base.
A- is the conjugate base, BH+ is the conjugate acid.
The stronger acid always produces the weaker conjugate base. If it did not, the reverse reaction would be more favourable and the equilibrium would lie the other way.
The pKa value is the standard measure of acid strength, defined relative to water as the reference base:
pKa = -log(Ka), where Ka = [A-][H3O+] / [HA] (with [H2O] set to 1 because it is the solvent).
Lower pKa = stronger acid. An acid with pKa -12 (such as protonated HCN) is far stronger than one with pKa 49 (methane, the weakest acid on the Chem 210 table).
The pKa table provided in lecture ranks common organic functional groups from strongest acid (top) to weakest acid (bottom). The conjugate bases run from weakest base (top) to strongest base (bottom).
When your exact structure is not in the table, find the closest structural analogue. Keep the comparison fair: try to match hybridisation and delocalisation between the compound you know and the one you are estimating, because differences in those two features cause the largest errors in pKa estimates.
For any acid-base reaction, you can calculate the equilibrium constant from the pKa values of the two acids involved:
Keq = 10^(pKa of product acid - pKa of reactant acid)
Keq > 1: products are favoured (reaction goes to the right).
Keq = 1: neither side is favoured.
Keq < 1: reactants are favoured (reaction stays to the left).
A difference of 3 pKa units gives Keq = 10^3 = 1000, which is generally enough to say the reaction goes "to completion" in one direction.
For any ionisable group in a molecule:
pH = pKa: the protonated form [HA] and the deprotonated form [A-] are present in equal amounts (1:1 ratio).
pH > pKa: the deprotonated form dominates. Each unit above pKa shifts the ratio by a factor of 10 (at pH = pKa + 3, the ratio is 1000:1 in favour of A-).
pH < pKa: the protonated form dominates. Each unit below pKa shifts the ratio by a factor of 10 in favour of HA.
When a molecule has several ionisable groups (as amino acids do), compare the pH to each group's pKa independently to decide which groups are protonated and which are not. The result is the "major species" at that pH.
Ka = [A-][H3O+] / [HA][H2O], with [H2O] treated as 1.
pKa = -log(Ka)
Keq = 10^(pKa of product acid - pKa of reactant acid)
pH = pKa means [A-] = [HA] (the Henderson-Hasselbalch crossover point).
pH = pKa + n means [A-]/[HA] = 10^n (so at pH = pKa + 3, A- outnumbers HA by 1000 to 1).
Drug design relies heavily on pKa. Pharmaceutical chemists adjust the protonation state of a drug molecule at physiological pH (about 7.4) to control whether it crosses cell membranes (neutral forms pass more easily) or stays dissolved in the bloodstream (charged forms are more water-soluble). The aminophenylalanine example from this lecture is a direct analogue of how medicinal chemists think about amino acid-based drugs.
Buffer systems in blood maintain pH near 7.4 using the carbonic acid/bicarbonate equilibrium, which is simply the pKa vs. pH logic applied at a biological scale.
Students often think a lower pKa means a weaker acid. It is the opposite: lower pKa = stronger acid. The negative log inverts the scale.
Confusing Lewis and Br\u00f8nsted definitions in the middle of a problem. A Lewis acid does not have to donate a proton; it just needs to accept an electron pair. BF3 is a Lewis acid but has no proton to give.
Assuming you can always compare pKa values directly between two very different structures. If the two compounds differ in hybridisation or delocalisation, a simple pKa comparison can give misleading results. The lecture stresses: keep your comparisons within the same structural family when possible.
Forgetting that acid-base equilibria always favour the weaker acid and weaker base side. If you predict products that are stronger than the reactants, the equilibrium lies the other way.
\u26a0\ufe0f You will be expected to use the pKa table to predict which direction an acid-base equilibrium favours. Know the Keq formula cold.
\u26a0\ufe0f Identifying the most acidic proton in a complex molecule (multiple functional groups) is a recurring exam question. Compare each site's pKa using the table.
\u26a0\ufe0f "Draw the major species at pH = X" questions require you to compare pH against each ionisable group's pKa independently, then assemble the correct protonation state.
\u26a0\ufe0f The five structural factors that influence conjugate base stability (electronegativity, charge, atomic size, hybridisation, resonance) are tested both as short-answer explanations and as ranking questions.
\u26a0\ufe0f Lewis acid-base complexation (no proton transfer) can appear alongside Br\u00f8nsted problems. The exam study guide explicitly lists both.
True or false: A pKa of 4.6 indicates a stronger acid than a pKa of 10.6. (True.)
Fill in the blank: Keq = 10^(pKa of ______ acid minus pKa of ______ acid). (Product, reactant.)
True or false: At pH 7, a group with pKa 4.8 is mostly in its protonated (HA) form. (False. pH > pKa, so the deprotonated form A- dominates.)
Fill in the blank: A Lewis acid is an electron-pair ______. (Acceptor.)
True or false: Acid-base equilibria always favour the formation of the stronger acid and stronger base. (False. They favour the weaker acid and weaker base.)
Q: An acid HA has pKa = 38. A base B- has a conjugate acid BH with pKa = 43. Will B- completely deprotonate HA? Show your reasoning.
A: Keq = 10^(43 - 38) = 10^5. Because Keq >> 1 (and specifically >= 10^3, the threshold for "complete" reaction), B- will completely deprotonate HA.
Q: Aminophenylalanine has three ionisable groups with pKa values of 2.15, 6.10 and 10.60. What is the major species at pH 7.10?
A: Compare pH 7.10 to each pKa. pH > 2.15, so the carboxylic acid is deprotonated (COO-). pH > 6.10, so the alkylammonium (NH3+) is deprotonated to NH2 at that site. pH < 10.60, so the arylammonium (ArNH3+) remains protonated. The major species carries a deprotonated carboxylate, a free alkylamine, and a protonated arylamine.
Q: Why does the equilibrium in an acid-base reaction always favour the weaker acid and weaker base?
A: The stronger acid gives up its proton more readily, forming a more stable (weaker) conjugate base. The stronger base grabs that proton more readily, forming a more stable (weaker) conjugate acid. The products are therefore lower in energy, so the equilibrium lies on that side.
Q: Using the pKa table, predict whether HF (pKa 3.2) will protonate pyridine (conjugate acid pKa 5.2).
A: Keq = 10^(5.2 - 3.2) = 10^2 = 100. The equilibrium favours products (protonated pyridine + fluoride), though the reaction does not go fully to completion since Keq < 10^3.
This material connects directly to nucleophilic substitution and elimination reactions (SN1, SN2, E1, E2), which are the next major unit in Chem 210. Identifying the nucleophile (Lewis base) and electrophile (Lewis acid) is the first step in every mechanism you will draw.
Resonance and hybridisation, covered in earlier lectures, feed into the five structural factors for predicting pKa. If those concepts are not solid, the pKa reasoning here will feel like memorisation rather than logic.
The protonation-state analysis (pH vs. pKa) reappears in biochemistry when discussing amino acid charge states, enzyme active sites and drug-receptor binding.
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