Diffusivity of α-, β-, γ-cyclodextrin and the inclusion complex of β-cyclodextrin: Ibuprofen in aqueous solutions; A molecular dynamics simulation study

Abstract

Cyclodextrins (CDs) are widely used in drug delivery, catalysis, food and separation processes. In this work, a comprehensive simulation study on the diffusion of the native α -, β - and γ -CDs in aqueous solutions is carried out using Molecular Dynamics simulations. The effect of the system size on the computed self-diffusivity is investigated and it is found that the required correction can be as much as 75% of the final value. The effect of the water force field is examined and it is shown that the q4md-CD/TIP4P/2005 force field combination predicts the experimentally measured self-diffusion coefficients of CDs very accurately. The self-diffusion coefficients of the three native CDs were also computed in aqueous-NaCl solutions using the Joung and Cheatham (JC) and the Madrid-2019 force fields. It is found that Na ions have higher affinity towards the CDs when the JC force field is used and for this reason the predicted diffusivity of CDs is lower compared to simulations using the Madrid-2019 force field. As a model system for drug delivery and waste-water treatment applications, the diffusion of the β -CD:Ibuprofen inclusion complex in water is studied. In agreement with experiments for similar components, it is shown that the inclusion complex and the free β -CD have almost equal self-diffusion coefficients. Our analysis revealed that this is most likely caused by the almost full inclusion of the ibuprofen in the cavity of the β -CD. Our findings show that Molecular Dynamics simulation can be used to provide reasonable diffusivity predictions, and to obtain molecular-level understanding useful for industrial applications of CDs.

Chiral induction in a novel self-assembled supramolecular system composed of α-cyclodextrin porous liquids, chiral silver nanoparticles and planar conjugated molecules

“…46,47 Moreover, the substituted groups on a-CDPL may compete with the azobenzene group to be included into the cavity of a-CDPL. 48 Then the inclusion interaction between a-CDPL and the azobenzene group located at the surface of Azo-Ag NPs is weakened, which results in the decrease of the induced CD signal of methylene blue. What is more, chloride ions are likely to form precipitates with silver as the concentration of NaCl in the system increases, which affects the stability of silver nanoparticles, resulting in the weakening of the plasma absorption peak intensity of silver nanoparticles, 49 and the CD intensity of induced chirality decreases in turn.…”

Local Ion Densities can Influence Transition Paths of Molecular Binding

“…The role of ions along molecular binding pathways is much less understood. Ion distributions surrounding molecules such as double stranded DNA Kolesnikov et al (2021) and RNA Auffinger et al (2004) have been studied and it has been found that ion affinity for molecules such as cyclodextrins and DNA is dependent on the force field used Erdos et al (2021) as well as the water model employed Kolesnikov et al (2021) . A difference in unbinding rates has been found between implicit and explicit ions in simulation, with implicit ion representations overestimating unbinding rates across a broad range of ion concentrations Erbas et al (2018) .…”

Evaluating the Performance of Water Models with Host–Guest Force Fields in Binding Enthalpy Calculations for Cucurbit[7]uril–Guest Systems

“…Another recent work reports a comprehensive study of the diffusivity of α-, β-, γ-cyclodextrin in aqueous solutions using TIP3P, SPC/E,TIP4P/2005 and Bind3P water models. 32 Thus a significant amount of work has already been done in this area. However, a comparison of widely used methods for general force-field parametrization has not yet been presented.…”