Synthesis of specific deuterated derivatives of the long chained stratum corneum lipids [EOS] and [EOP] and characterization using neutron scattering

Abstract

The synthesis of specific deuterated derivatives of the long chained ceramides [EOS] and [EOP] is described. The structural differences with respect to the natural compounds are founded in the substitution of the 2 double bonds containing linoleic acid by a palmitic acid branched with a methyl group in 10-position. The specific deuteration is introduced both in the branched and in the terminal methyl group, which was realized by common methods of successive deuteration of carboxylic groups in 3 steps. These modified fatty acids resp. the corresponding ceramides [EOS] and [EOP] were prepared for neutron scattering investigations. First results of these investigations were presented in this manuscript showing that the deuterated compounds could be detected in the stratum corneum lipid model membranes. The deuterated ceramides [EOS] and [EOP] are valuable tools to investigate the influence of these long chained ceramide species on the nanostructure of stratum corneum lipid model membranes.

Investigation of a CER[NP]- and [AP]-Based Stratum Corneum Modeling Membrane System: Using Specifically Deuterated CER Together with a Neutron Diffraction Approach

“…Despite the only small chemical differences between the CER, different mixtures did show a wide variety of different structures and properties in the past. These include variable repeat distances, ,, in some cases also phase separation, and other distinct effects. As expected, the CERs that were used are two of the most abunant.…”

Investigating the Nanostructure of the Stratum Corneum Lipid Matrix: A Combined Neutron Diffraction & Molecular Dynamics Simulations Approach

“…If the deuteration profile shows, that the deuterated groups are in the same position (again also observable from the global minimum in the central region) and the repeat distance is decreased, the only possible arrangement to lead to this is a tilt of the chains either with a tilted hairpin or V-shaped arrangement (Figure 5). Also more complex lipids like the CER[EOS] analogue CER[EOS]-br can be located this way [38]. Like the CER molecules, other molecules can also be located very well by using deuterated molecules.…”

“…Its underlying principle is very similar to x-ray diffraction; however, it has the advantage of being suitable to distinguish different isotopes, particularly 1 H and 2 H/D (Deuterium). This provides the possibility to use specific deuteration of lipids as a means to generate distinguishable labels, to localize certain molecules or parts of molecules within the lamellar system without majorly changing their biophysical properties [36,38,42,43,44,45].…”

“…This complexity prevented the possibility to focus on the properties of single lipid species. Today, due to the advances in bio-organic chemistry, it is possible, to produce single CER species with defined properties synthetically [36,37,38,39]. This has led to creation of model systems consisting of only few lipid species with defined head group and chain length.…”

State of the Art in Stratum Corneum Research. Part II: Hypothetical Stratum Corneum Lipid Matrix Models

“…A swelling of native skin was shown to be a result of cellular swelling due to a water uptake hydrating the intracellular proteins and not by a change in lamellar structure [17]. Some studies also observe either a Vshaped or a tilted arrangement of the CERs which is influencing the lamellar thickness [56,92,[99][100][101][102]. While a small angle between the chains and/or a small proportion of V-shaped CERs would certainly be possible [56,102], an arrangement with mostly strongly V-shaped CERs would hardly be possible within the native LM.…”