Reflect and Apply Aspirin is an acid with a \(\mathrm{p} K_{\mathrm{a}}\) of \(3.5 ;\) its structure includes a carboxyl group. To be absorbed into the bloodstream, it must pass through the membrane lining the stomach and the small intestine. Electrically neutral molecules can pass through a membrane more easily than can charged molecules. Would you expect more aspirin to be absorbed in the stomach, where the pH of gastric juice is about \(1,\) or in the small intestine, where the \(\mathrm{pH}\) is about \(6 ?\) Explain your answer.

Understanding the relationship between pH and pKa is crucial when studying the absorption of drugs like aspirin. The pKa is a constant specific to each substance and represents the pH at which half of the molecules of that substance are ionized, and half are in their protonated form. This balance shifts depending on the pH of the surrounding environment. If the pH is lower than the pKa, most of the substance will remain in its protonated form because the environment is more acidic, making it more likely to keep hydrogen ions attached to molecules. Conversely, if the pH is higher than the pKa, the substance will lose hydrogen ions, leading to more molecules being in their ionized form. This critical concept helps explain why certain drugs are more readily absorbed in specific parts of the gastrointestinal tract.

To grasp how aspirin is absorbed, we need to understand the difference between protonated and ionized forms of molecules. Aspirin has a \(\textrm{pKa}\) of 3.5 and contains a carboxyl group that can donate a proton. When aspirin is in an environment where the pH is less than 3.5, it tends to keep its proton and remain neutral. This is its protonated form. On the other hand, when the pH is higher than its pKa, aspirin loses a proton, becoming negatively charged or ionized. The protonated form of aspirin is neutral, meaning it does not carry any electrical charge. This neutral form can easily pass through cell membranes. However, the ionized form, being charged, has more difficulty crossing the lipid barriers of cell membranes. This distinction is essential because it determines where in the body aspirin will be most effectively absorbed.

The pH of different parts of the digestive system plays a crucial role in the absorption of medications. In the stomach, the pH of gastric juice is about 1, which is highly acidic. This low pH means that aspirin will mostly be in its protonated (neutral) form in the stomach. Since neutral molecules can pass through cell membranes more easily, aspirin will be more readily absorbed in the stomach. On the other hand, the pH in the small intestine is about 6, much less acidic compared to the stomach. Here, aspirin will primarily be in its ionized (charged) form because the pH is higher than the pKa of aspirin. Ionized molecules face more difficulty passing through the cell membrane. Thus, the environment in the stomach is more favorable for the absorption of aspirin due to the high prevalence of its protonated form in such an acidic setting. This difference in pH between the stomach and the small intestine significantly influences how and where aspirin is absorbed into the bloodstream.