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 (alpha-, beta-, and gamma-CDs) with small guest molecules such as H(2)O, NH(3), NH(4)(+), C(6)H(6), 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 alpha-, beta-, and gamma-CD can accommodate three, seven, and nine water molecules, respectively. In the case of NH(3) as guest molecule, alpha-, beta-, and gamma-CDs can accommodate up to two, five, and six molecules, respectively. Semiempirical calculations indicate that two benzene molecules can be accommodated in the alpha-CD cavity, whereas beta- and gamma-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 alpha-, beta-, and gamma-CDs. However, C preferentially forms 1:2 complexes with alpha-CDs. Ligands 1,10-bis(imidazol-l-lyl) decane (A) and 4,4'-(bis(imidazol-l-ylmethylene))biphenyl (D) form 1:2 complexes with alpha-, beta-, and gamma-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 beta-CDs form more stable complexes compared with alpha- and gamma-CDs with C, D, NH(4)(+), and C(6)H(6), whereas alpha-CD forms more stable complexes with A and B.

Analysis of Molecular Interaction of Drugs within β-Cyclodextrin Cavity by Solution-State NMR Relaxation

“…Several analytical techniques, viz., fluorescence, ,, UV–vis, , differential scanning calorimetry, , Fourier transform infrared, X-ray diffraction, , scanning electron microscopy, , and NMR − spectroscopy have been employed for this purpose. Besides these experimental methods, CD inclusion complexes have also been extensively studied by quantum chemical calculations and molecular dynamics simulations to understand the host–guest interactions. − …”

Molecular Basis of Binding and Stability of Curcumin in Diamide-Linked γ-Cyclodextrin Dimers

“…Molecular dynamics simulations of curcumin in the past have focused on its interaction with DNA, metalloenzymes, beta-amyloid fibrils, and a range of other targets. Similarly, simulations of cyclodextrins have focused on their role as host molecules to encapsulate smaller guest molecules − or on structural differences between α-, β-, and γ-CDs in water . The binding energies of CDs with various guest molecules have been investigated in several studies. − The self-interaction of CDs in the formation of dimers or larger molecular structures has been examined in other studies. − This work is the first to simulate diamide-linked γ-CDs and their interactions with curcumin and elucidates the relationships between the properties of the diamide linker and the binding constant and stabilization of curcumin.…”

Host–guest complex of cypermethrin with β-cyclodextrin: A spectroscopy and theoretical investigation

“…The size and conformal flexibility of CDs make the geometrical optimization very expensive and difficult precluding the use of more sophisticated ab initio methods, such as Møller-Plesset perturbation theory (MP2, MP3 or MP4). Instead, some research works are based on molecular dynamics (MD) [23][24][25][26], semi-empirical quantum mechanics (QM) methods [27][28][29], Hartree-Fock method [30] and Density functional theory with appropriate basis set [31][32][33][34]. Among these works, the combining distinct theoretical methodologies, such as semi-empirical and DFT, are able to obtain reliable structures and interaction energies of CD's systems [27][28][29].…”