DNA binding cationic bolasomes with delocalized charge center - A structure-activity relationship study

Bolaamphiphilic dicationic quinolinium derivatives are being explored by us for the development of mitochondria-specific drug and DNA delivery systems . In this structure-activity relationship study, defined connections betwee n the structure of the bolaamphiphiles and their ability to form cationic v esicles (bolasomes) and to bind DNA are established. Nine quinolinium deriv atives with varying polar head groups and hydrophobic tail segments were sy nthesized according to published procedures. Their self-assembly behavior w as determined by photon correlation spectroscopy and their affinity to DNA was measured using the fluorescence dye SYBR Green I. The introduction of a DNA binding capacity allows the quantitative comparison between the quinol inium derivatives and Lipofectin regarding their ability to form lipoplexes . It is demonstrated that the primary 4-amino group at the quinolinium ring system plays an important role in DNA binding. The presence of a bulky ali phatic residue at the aromatic ring system favors the self-assembly of thes e bolaamphiphiles into bolasomes.