Theoretical studies on inclusion complexes of cyclodextrins

Abstract

Quantum chemical calculations and molecular dynamics simulations are carried out to study the host−guest inclusion complexes of cyclodextrins (α-, β-, and γ-CDs) with small guest molecules such as H²O, NH³, NH⁴⁺, C₆H₆, and bisimidazolyl compounds. The uptake ability of the CDs to accommodate the small molecules inside the cavity is examined by the sequential addition of 10 molecules of water or ammonia using the semiempirical (PM3) method. In the case of benzene, this was done up to six molecules. PM3 calculations indicate that α-, β-, and γ-CD can accommodate three, seven, and nine water molecules, respectively. In the case of NH3 as guest molecule, α-, β-, and γ-CDs can accommodate up to two, five, and six molecules, respectively. Semiempirical calculations indicate that two benzene molecules can be accommodated in the α-CD cavity, whereas β- and γ-CD cavities adopt three and four benzene molecules, respectively. Molecular dynamics simulations were carried out for 1.0 ns on benzene and bisimidazolyl complexes of CDs in explicit solvent (TIP3P water model). The interaction energies calculated by the MM/PBSA method reveal that ligand 1,6-bis(imidazol-l-lyl) hexane (B) and 1,4-bis(imidazol-l-lylmethyl) benzene (C) molecules prefer to form 1:1 complexes with α-, β-, and γ-CDs. However, C preferentially forms 1:2 complexes with α-CDs. Ligands 1,10-bis(imidazol-l-lyl) decane (A) and 4,4′-(bis(imidazol-l-ylmethylene))biphenyl (D) form 1:2 complexes with α-, β-, and γ-CDs in head-to-head (HH) orientation of CDs. The stability of inclusion compounds depends on the type of CD and the physicochemical properties of the involved guest. Both of these methods (semiempirical and MD simulations) reveal that β-CDs form more stable complexes compared with α- and γ-CDs with C, D, NH⁴⁺, and C₆H₆, whereas α-CD forms more stable complexes with A and B.