Rings, Hexagons, Petals, and Dipolar Moment Sink-Sources: The Fanciful Behavior of Water around Cyclodextrin Complexes

Abstract

The basket-like geometry of cyclodextrins (CDs), with a cavity able to host hydrophobic groups, makes these molecules well suited for a large number of fundamental and industrial applications. Most of the established CD-based applications rely on trial and error studies, often ignoring key information at the atomic level that could be employed to design new products and to optimize their use. Computational simulations are well suited to fill this gap, especially in the case of CD systems due to their low number of degrees of freedom compared with typical macromolecular systems. Thus, the design and validation of solid and efficient methods to simulate and analyze CD-based systems is key to contribute to this field. The behavior of supramolecular complexes critically depends on the media where they are embedded, so the detailed characterization of the solvent is required to fully understand these systems. In the present work, we use the inclusion complex formed by two α-CDs and one sodium dodecyl sulfate molecule to test eight different parameterizations of the GROMOS and AMBER force fields, including several methods aimed to increase the conformational sampling in computational molecular dynamics simulation trajectories. The system proved to be extremely sensitive to the employed force field, as well as to the presence of a water/air interface. In agreement with previous experiments and in contrast to the results obtained with AMBER, the analysis of the simulations using GROMOS showed a quick adsorption of the complex to the interface as well as an extremely exotic behavior of the water molecules surrounding the structure both in the bulk aqueous solution and at the water surface. The chirality of the CD molecule seems to play an important role in this behavior. All together, these results are expected to be useful to better understand the behavior of CD-based supramolecular complexes such as adsorption or aggregation driving forces, as well as to introduce new methods able to speed up general MD simulations.

Remdesivir interactions with sulphobutylether-β-cyclodextrins: A case study using selected substitution patterns

“…The simulation parameters are similar to those employed in previous works for similar systems [25,26]. All the simulations were performed using the GROMOS 54a7 force field [27] (Schmid, et al 2011) with SPC water molecules [28] and the GROMACS 2020 engine [29,30].…”

Comparative bioavailability study following a single dose intravenous and buccal administration of remdesivir in rabbits

“…The role of SBECD is to improve both the solubility and stability of remdesivir via inclusion complex formation ( Pipkin et al, 2020 ). Molecular dynamic study proved the interaction between remdesivir and SBECD of various DS ( Garrido et al, 2020 ; Piñeiro et al, 2021 , Piñeiro et al, 2022 ). Recent NMR investigations suggested that the protonation state of the aminopyrrolo-triazine moiety of remdesivir can play a key role in the cyclodextrin-remdesivir interaction ( Várnai et al, 2022 ).…”

Peering into the Kaleidoscope of Cyclodextrins

“…Less explored even is the effect of such interactions on the properties and distribution of water molecules—the main component of said emulsions. In the work of Garrido et al, the behavior of water molecules around (α-CD) 2 ·SDS (SDS denotes sodium dodecyl sulfate) was simulated, showing fast dynamics of hydrogen bonding [ 2 ]. Water molecules are distributed around the units of the complex in symmetric choreographies, as if the water molecules themselves were synchronized swimmers: they form a hexagon around the apolar water-exclusion area of the mid-transversal section of the α-CD ring, and, at the rims, hexasymmetric, flowerlike contact areas with the host.…”