Phospholipid conjugates: formation of the intramolecular π-cation complex.

Phospholipid conjugates consist of functionally different classes of molecules: phospholipid drug conjugates, fluorescent lipid probes and lipid molecular motors. All these conjugates are molecules that bear a functional group- a drug, a fluorophore or a molecular motor attached to the phospholipid. The conjugation is needed to incorporate a functional group into the lipid bilayer of liposome or lipid nanoparticle and thus, either modulate the effect of the drug or bring a new function to the liposome. Here, using NMR spectroscopy and quantum chemistry calculations, we show that phospholipid conjugates can form intramolecular π-cation complexes between quaternary ammonium group of the phosphatidylcholine and aromatic ring of the conjugated moiety. We also report on how to avoid the π-cation complex formation. If the linker between the aromatic moiety and the choline group is long enough the formation of π-cation complex is not observed.