Interaction of naphthalene derivatives with lipids in membranes studied by the 1H-nuclear Overhauser effect and molecular dynamics simulation

Abstract

The location, orientation, and dynamics of hydrophobic small molecules in lipid membranes are studied through combined use of solution-state (1)H-NMR and MD simulation. 1-Naphthol and 1-methylnaphthalene were adopted as the small molecules with or without hydrophilic groups. The nuclear Overhauser effect (NOE) measurement was performed for large unilamellar vesicles (100 nm in diameter) composed of dimyristoylphosphatidylcholine (DMPC) and the naphthalene derivative. The transient NOE-SE (spin-echo) scheme previously reported (J. Phys. Chem. B, 2011, 115, 9106-9115) was employed to quantitatively determine the NOE cross relaxation rate constant between DMPC and the naphthalene derivative. The observed NOE shows that both the naphthalene derivatives distribute over a wide domain across the normal of the essentially planar membrane ranging from the hydrophobic core to the hydrophilic headgroup. The experimental NOE information was further refined in combination with the analysis of time correlation functions in MD simulation. It was found that 1-naphthol exhibits a slight preference for pointing its OH group toward the hydrophilic domain of the membrane and that no definite preference can be concluded for the orientation of 1-methylnaphthalene. When 1-naphthol and 1-methylnaphthalene are compared, the NOE is stronger for 1-naphthol due to the restricted motion of the OH group. The slowdown of the 1-naphthol motion is also evidenced by the (1)H spectral line width.

Free-Energy Analysis of Peptide Binding in Lipid Membrane Using All-Atom Molecular Dynamics Simulation Combined with Theory of Solutions

“…It was then found that the solute–solvent interaction energy ⟨ u ⟩ becomes larger in magnitude in the outer region of membrane due to the growth of the water contribution. The variation of ⟨ u ⟩ with the binding depth z actually competes against the effect of excluded volume Δμ excl , leading to a mild dependence of Δμ on z and the diffuse distribution of a hydrophobic solute from the membrane center to the interfacial region, which is in agreement with experiment . This shows that the attractive interaction effect captured by ⟨ u ⟩ and the repulsive interaction effect represented by Δμ excl act similarly in membrane for the peptide treated in the present work and for the small, hydrophobic solutes examined in the previous work and that a common mechanism is operative for the solute’s stability toward the outer region of membrane.…”

Nanoparticle-Supported Lipid Bilayers as an In Situ Remediation Strategy for Hydrophobic Organic Contaminants in Soils

“…The ability of vesicles to incorporate large amounts of hydrophobic small molecules, lipophilic drugs, and cholesterol has previously been reported, and can result in a similar calorimetric signature, namely a shift and broadening of T m , as observed here for BaP. There is also evidence that lipids from humic acid/humin-fractionated extracts preferentially sorb PAHs …”

Transfer of Pollutants from Macrocystis pyrifera to Tetrapygus niger in a Highly Impacted Coastal Zone of Chile

“…The absence of other PAHs in both analyzed biological matrices could be due to biodegradation mechanisms or to the small size of NAF compared to other PAHs. As previously established [63], small molecules such as NAF can permeate phospholipid membranes, with diverse naphthalene derivatives exhibiting different preferences for the hydrophilic or hydrophobic domain of phospholipids. This mechanism may explain the high NAF levels observed in M. pyrifera.…”