Solubility and permeation of hydrogen sulfide in lipid membranes

Abstract

Hydrogen sulfide (H(2)S) is mainly known for its toxicity but has recently been shown to be produced endogenously in mammalian tissues and to be associated with physiological regulatory functions. To better understand the role of biomembranes in modulating its biological distribution and effects; we measured the partition coefficient of H(2)S in models of biological membranes. The partition coefficients were found to be 2.1±0.2, 1.9±0.5 and 2.0±0.6 in n-octanol, hexane and dilauroylphosphatidylcholine liposome membranes relative to water, respectively (25°C). This two-fold higher concentration of H(2)S in the membrane translates into a rapid membrane permeability, P(m) = 3 cm s(-1). We used a mathematical model in three dimensions to gain insight into the diffusion of total sulfide in tissues. This model shows that the sphere of action of sulfide produced by a single cell expands to involve more than 200 neighboring cells, and that the resistance imposed by lipid membranes has a significant effect on the diffusional spread of sulfide at pH 7.4, increasing local concentrations. These results support the role of hydrogen sulfide as a paracrine signaling molecule and reveal advantageous pharmacokinetic properties for its therapeutic applications.

Figure 1. Modeling three-dimensional diffusion from a single cell.

A) The model consists of a single spherical cell producing H₂S at a constant rate. We interrogate how the concentration of total sulfide (H₂S+HS⁻) changes as a function of time and distance from the source cell with or without surrounding cells. The sphere of action is defined by the distance from the source cell at which the concentration of total sulfide is 10.0 arbitrary units. B) Expansion 1s after formation starts, with membranes at acidic pH (green), with membranes at pH 7.4 (red), with membranes at pH 6.5 (gray) and without membrane resistance (blue) C) Expansion of the sphere of action as a function of time, without membrane resistance (blue), with membranes at acidic pH (green), with membranes at pH 7.4 (red) and at pH 6.5 (gray). Plots are derived from Equation 2. The resistance imposed by the membranes was weighed into the aqueous diffusion coefficient (Equation 5) so that 20 membranes would cause the apparent diffusion coefficient of H₂S to decrease from D_w = 2.32×10⁻⁵ cm² s⁻¹ (H₂S in water, blue line) to 2.02×10⁻⁵ cm² s⁻¹ (green line). Considering ionization to HS⁻, the apparent diffusion coefficient of H₂S/HS⁻ drops to 1.51×10⁻⁵ cm² s⁻¹ at pH 7.4 (red line) and to 1.94×10⁻⁵ cm² s⁻¹ at pH 6.5 (gray line).