The activity of nitrogen heterocyclics present in biomacromolecules and its suitable sorbent from the dioctahedral smectite family is investigated using a range of reactivity index using density functional theory (DFT). For the first time, a novel function A has been defined for quantitative description of weak adsorption cases, which was so far qualitative inside the domain of DFT. From the values of the local softness, it is concluded that the local acidities of the inorganic material systems are dependent on several characteristics, which are of importance within the framework of the hard and soft acids and bases (HSAB) principle. We first rationalized an understanding of the electronic structures of a range of nitrogen heterocyclics ranging from indole, imidazole, pyrrole, and pyridine, followed by the local softness calculation to locate its active site. We compared its activity with that of the OH group of isomorphously substituted (Fe3+, Mg2+, Fe2+ and Li+) dioctahedral smectite family. Two types of interactions were identified between heterocyclics and smectite. The ordering for best sorption follows the order Mg2+ > Fe2+ > Fe3+ > Li+, whereas the order for best sorbent is imidazole > pyridine > pyrrole > indole. The results rationalize the experimental observation.