Theoretical study on the inclusion interaction of β-cyclodextrin with gabapentin and its stability

Abstract

In this paper, dispersion corrected density functional theory (DFT-D3) with the B3LYP method and the 6-31G(d) basis set is used to study the inclusion processes of gabapentin with β-cyclodextrin and the effect of inclusion on the dehydration condensation reaction of gaba­pentin. The calculation results show that β-cyclodextrin and gabapentin can form stable inclusion complexes in both vacuum and water. B-β-CDs is the most stable one of four inclusion complexes. After inclusion, the dehydration condensation potential barrier of gabapentin in the β-cyclodextrin cavity is significantly increased. Notably, the reaction barrier of gabapentin in the B-β-CDs complex (a protonated active group of gabapentin with a small mouth of β-cyclo­dextrin and its hexatomic ring in the cavity of cyclodextrin) even reaches 331.353 kJ/mol in vacuum and 283.538 kJ/mol in water, respectively. There are two obvious increases of 223.574 kJ/mol in vacuum and 193.932 kJ/mol in water after inclusion. Thus, the inclusion complex of β-cyclodextrin with gabapentin, especially B-β-CDs, inhibits the dehydration condensation side-reaction of gabapentin most effectively.