**Core Concept**
The concept of drug side effects arises from the interactions of a drug with non-target molecules, leading to unwanted effects. This is known as the "receptor occupancy" principle, where the drug binds to unintended receptors, causing side effects.

**Why the Correct Answer is Right**
The correct answer is related to the concept of "therapeutic index" (TI), which is a measure of a drug's safety. A high therapeutic index indicates that a drug has a wide margin between its effective dose and toxic dose, thereby minimizing side effects. This is achieved by reducing the interaction of the drug with non-target molecules. The therapeutic index is often expressed as a ratio of the dose that produces a toxic effect (TD50) to the dose that produces an effective effect (ED50).

**Why Each Wrong Option is Incorrect**
**Option A:** High potency is not directly related to minimizing side effects, although it may increase the risk of toxicity at higher doses.
**Option B:** High lipid solubility can increase the distribution of a drug to non-target sites, potentially increasing side effects.
**Option C:** High water solubility may reduce the absorption of a drug, but it does not directly minimize side effects.

**Clinical Pearl / High-Yield Fact**
A high therapeutic index is a desirable property of a drug, indicating its safety and efficacy. It is often determined by comparing the dose-response curves of a drug in animals and humans.

**Correct Answer: D. High therapeutic index.