Interaction of testosterone-based compounds with dodecyl sulphate monolayers at the air–water interface

Abstract

A series of atomistic molecular dynamics simulations were performed for investigating the interactions between three different testosterone-based compounds (testosterone (T), testosterone propionate (TP) and testosterone enanthate (TE)) and sodium dodecyl sulphate (SDS) and ammonium dodecyl sulphate (ADS) monolayers, which vary only in the sodium or ammonium counterions used to neutralise the sulphate headgroup. These simulations were used to investigate how the structural and interfacial properties of the monolayer were affected by changing the number of drug molecules present per monolayer, and the chemical nature of the surfactant counterions and the testosterone-based compounds. Our results show that the structure of the interfacial water layer is affected by the change of the counterion but not the chemistry of the drug molecules. As a result of the difference in their chemical structure, the T, TP and TE drug molecules prefer different locations and orientations within the monolayers. Finally, we observed that the hydration of the drug molecules encapsulated within the ADS monolayers is significantly less than when they are encapsulated within the SDS monolayers. Understanding the role that the counterion and the chemistry of the drug molecules play in these systems provides us with a detailed description of the interactions that cause ADS micelles to encapsulate significantly less drug molecules than SDS micelles, which we have recently observed experimentally.

Structure and Dynamics of Nanoconfined Water Between Surfactant Monolayers

“…We then observe multiple local maxima in the region z < 0 (the larger of those at z ≈ −4 Å, with another at z ≈ −6 Å). This shows that water molecules are able to permeate past the monolayer headgroups, as has been previously observed for SDS monolayers. − , This behavior is not seen at the air–water interface, where the water intrinsic density decays monotonically, as shown in Figure S5c,d here. A hard confinement matrix, such as graphite or kaolinite, does not allow permeation of water through the interface to yield the secondary peak.…”

“…This shows that water molecules are able to permeate past the monolayer headgroups, as has been previously observed for SDS monolayers. [54][55][56]58 This behavior is not seen at the air−water interface, where the water intrinsic density decays monotonically, 2 as shown in Figure S5c,d here. A hard confinement matrix, such as graphite 4 or kaolinite, 8 does not allow permeation of water through the interface to yield the secondary peak. The permeation of water past the monolayer headgroups is probably aided by the bulky CTAB headgroups, whose mutually repulsive Coulombic interactions require mediation by water and counterions to form a stable monolayer.…”

“…This shows that water molecules are able to permeate past the monolayer headgroups, as has been previously observed for SDS monolayers. [55][56][57]59 This behavior is not seen at the air-water interface, where the water intrinsic density decays monotonically, 2 as shown in SI Figure 5 interface, which suggests that water molecules are unlikely to interact strongly with a neutral substrate, as in the experiments of Dhopatkar and co-workers. 9 We note that in a symmetric system, shown in Figure 2(a), the two intrinsic densities are identical.…”

“…This indicates that water molecules are highly ordered close to the interface due to attractive electrostatic interactions between the cationic monolayer headgroups and the polar water oxygen atoms. Numerous studies of hydrophilic sodium dodecyl sulfate (SDS) surfactant monolayers at the air/water interface have revealed multiple peaks in the intrinsic density of water. − Bekele and Tsige have recently shown that there are also multiple peaks in the density of water close to a polystyrene surface . While CTAB’s quaternary headgroup is cationic, its electrostatic interaction efficacy with water is somewhat negated by the presence of its three methyl groups, which sterically hinder the close association between water and the center of the polar headgroup.…”