Computational insights into the chemical reactivity of Alzheimer’s therapeutics: a DFT-based study

In this research, the structural and electronic characteristics, as well as the chemical reactivity of several therapeutic compounds employed in the management of Alzheimer’s disease, were examined through Density Functional Theory (DFT) analysis. The molecular structures were optimized by applying the B3LYP functional together with the 6-31G(d,p) basis set. The obtained computational outcomes indicate that the analyzed molecules exhibit notable reactivity, especially in aqueous conditions, supporting their relevance for drug transport, considering the biological importance of water as a medium. To better understand the electronic nature of the molecules, atomic charge distributions were also evaluated, providing insight into their potential interactions with protein active sites. These findings help clarify the molecular basis of their inhibitory effects. Among all investigated agents, Donepezil demonstrated the highest level of chemical reactivity according to the calculated descriptors. Moreover, every compound assessed fulfilled Lipinski’s Rule of Five, indicating promising pharmacokinetic behavior and potential as orally active pharmaceutical candidates.