Mass spectrometry enables the in-depth structural elucidation of membrane protein complexes, which is of great interest in structural biology and drug discovery. Recent breakthroughs in this field revealed the need for design rules that allow fine-tuning the properties of detergents in solution and gas phase. Desirable features include protein charge reduction, because it helps to preserve native features of protein complexes during transfer from solution into the vacuum of a mass spectrometer. Addressing this challenge, we here present the first systematic gas-phase study of azobenzene detergents. The utility of gas-phase techniques for monitoring light-driven changes of isomer ratios and molecular properties are investigated in detail. This leads to the first azobenzene detergent that enables the native mass spectrometry analysis of membrane proteins and whose charge-reducing properties can be tuned by irradiation with light. More broadly, the presented work outlines new avenues for the high-throughput characterization of supramolecular systems and opens a new design strategy for detergents in membrane protein research.
The ability to design amphiphiles with predictable solubility properties is of everlasting interest in supramolecular chemistry. Relevant structural parameters include the hydrophobic-hydrophilic balance and structural flexibility. In this work, we investigate the water solubility of azobenzene-based triglycerol bolaamphiphiles (TGBAs). In particular, we analyzed the structural effects of backbone hydrophobicity, flexibility, and cis/trans isomerization on the water solubility of a subset of five TGBAs. This leads to the first example of a non-ionic bolaamphiphile whose water solubility can be changed by irradiation with light. The underlying kinetics were monitored using liquid chromatography and a closer analysis of the underlying aggregation processes provides a mechanistic understanding of the light-driven dissolution process. We anticipate that the results obtained will help to engineer bolaamphiphiles with predictable solution properties in the future.
