Quantifying alkyl chain disorder in crystalline models of lipid bilayers using Raman spectroscopy

Abstract

Crystalline bis‐N‐alkyl‐chlorotriazines 2–6 can be considered multilayers of lipid bilayers comprising a rigid hydrogen‐bonded tape in the polar layer separated by a lipid region of small to medium‐length alkyl chains. The persistent ordering of these tapes acts as a scaffold in the solid state enabling measurement of temperature‐induced conformational changes in the “lipid phase” using X‐ray crystallography. The alkyl chains in these structures are loosely packed but generally ordered at low temperature, undergoing a slow transition to a disordered structure clearly observed in the Raman spectrum. The longer‐chain derivatives 4–6 show a distinct Raman spectrum for the ordered and disordered crystallographic phases enabling a least squares fitting at each temperature point. Calibration of the Raman fit values for 5 and 6 using powder X‐ray diffraction allows a quantification of each phase and highlights the unique response of each derivative with temperature. This approach for quantifying the onset of disorder and structural phase transitions should be relevant to a wide range of lipid‐based systems.

Thorough investigation on the high-temperature polymorphism of dipentyl-perylenediimide: thermal expansion vs polymorphic transition.

“…These motions are mainly represented by bending/breathing modes characteristic of the PDIs structure as confirmed from reported computed spectrum 42 . Lastly, the region between 500 and 600 cm -1 shows an isolated peak belonging to the bending of the lateral alkyl chains which has been reported to be very sensitive to change in phase with temperature 43 as we will also demonstrate later.…”

Synthetic Bilayers on Mica from Self-Assembly of Hydrogen-Bonded Triazines

“…Pole figure measurements using XRD confirm that the (001) reflection is out of plane, while the pole figure for the (021), (101), and (1–11) reflections suggests that there is a slight orientation of the ab -plane imposed by the mica (Figure S3, Supporting Information). The Raman spectra of thin multilayers on mica in Figure e show the same peaks expected from the bulk crystal, including the hydrogen-bonded NH peak and a disordered CH stretching profile . Surface analysis using the XPS spectra in Figure f shows the C, N, and Cl peaks from C5 , along with the K, Si, and O from the mica substrate.…”

“…Compound C2 was commercially available (Alfa Aesar, U.K.), while compounds C3 – C6 were synthesized according to standard methods . Crystallography of these compounds has been reported previously. ,, …”

“…Layer thickness in these crystals is proportional to the length of the alkyl chain . As with lipid bilayers found at interfaces and in biological systems, the alkyl chains in these systems are fully ordered at low temperatures but develop nanoscale disordered domains in the layer with increasing temperature, a process that can be measured and quantified using a combination of Raman spectroscopy and powder X-ray diffraction (PXRD) …”

Recent advances in linear and nonlinear Raman spectroscopy. Part XIV

“…They claim their method represents a complete spectroscopic tool capable of identifying biomarkers in a noninvasive, simple, and economical way, thereby eliminating the subjective interpretation of results and contributing to objective and more reliable diagnoses. Rich et al [ 55 ] used Raman to quantify alkyl chain disorder in crystalline models of lipid bilayers. They state that their approach for quantifying the onset of disorder and structural phase transitions should be relevant to a wide range of lipid‐based systems.…”