Up until now we’ve focused on which atoms share electrons, and the different ways that we can describe and represent these bonds. But in many bonds and molecules, the electrons are not distributed equally. Unequal electron distribution has a major impact on molecular properties and reactivity. In this section, we will examine bonding electrons more closely, focusing on how they are distributed within bonds and molecules. We will explore four key factors that affect the electronic distribution in a molecule: electronegativity, induction, atom size (polarizability), and resonance. We will use these factors to help us predict reactivity trends and how each of these factors affects the stability of a molecule. Using this information we’ll be able to predict the relative strengths of acids and bases in the next section.
Pharmaceutical drugs generally function by binding to a biological target, such as a receptor on a cell. In order to bind effectively, the drug molecule must be complementary to the target. For example, where the target molecule has an area of high electron density (i.e. negative charge), the drug should have an area of low electron density (i.e. positive charge) and vice versa. It's also important that the distances between these areas of high and/or low charge are similar on the drug and the target. Before synthesizing a new drug candidate, scientists sometimes use computational chemistry to calculate the predicted charges and distances between atoms. Once they find a drug design that matches the target well in theory, they will synthesize the drug and test how well it binds to the target in practice.
Another reason drug designers care about the overall polarity of a molecule is that it affects whether the drug can reach its target to begin with. If a drug is to be administered orally, it must be sufficiently polar to dissolve in water. However, to reach most targets, the drug will have to pass through multiple membranes in the body, which requires the drug to be relatively non-polar. Thus, it is important to strike a fine balance in polarity, or to design the molecule to change polarity as it passes through the body.