Page - (000022) - in Biomedical Chemistry: Current Trends and Developments

Scheme 1.1.2: Example of a proton transfer reaction. This specific reaction explains why it is difficult for condensations to happen directly between an amine and a carboxylic acid, as the non-ionic forms of these molecules are more reactive (Chapter 1.1.4.5). Acids can differ in their ability to donate protons, being classified as strong or weak according to the extent of deprotonation. A strong acid will have a stable conjugate base (or weak conjugate base), resulting in ready donation of a proton. Table 1.1.3 lists the acidity of some typical functional groups (water and ammonium acidity are also given for comparison). The acidity is measured by the acidity constant, Ka or by its pKa (Scheme 1.1.3), where a stronger acid has a smaller pKa and a weaker acid has a larger pKa. The same approach can be applied to bases and their strength. Scheme 1.1.3: Acidity constant and pKa. The problem with the Brönsted/Lowry definition is that it only covers the compounds that donate or accept protons. The more general and widely used model is the Lewis definition. A Lewis acid is a molecule that accepts a pair of electrons and a Lewis base is a molecule that donates a pair of electrons. To accept electrons, a Lewis acid must have a vacant low-energy orbital. As a consequence, many species, including H+ itself, metal cations such as Mg2+ and Zn2+, and neutral species such as boron trifluoride (BF3) and carbon dioxide (CO2) are Lewis acids. Lewis acids and bases are involved in many biological reactions, such as the transformation of carbon dioxide into hydrogen carbonate (Scheme 1.1.4). Lewis bases use unshared electrons to form new bonds with other atoms and are usually referred as nucleophiles (“nucleus- loving”, versus Lewis acids as electrophiles, “electron-loving”). The terms “electrophile” and “nucleophile” are commonly used in organic