Synthesis of a New Cationic Pyropheophorbide Derivative and Studies of its Aggregation Process in Aqueous Solution

Abstract— A new water-soluble cationic pyropheophorbide was prepared from pyropheophorbide a by a Curtius rearrangement. The self-aggregation process of this chlorhydrate of aminopyropheophorbide was investigated from the changes observed in its spectroscopic properties when passing from ethanol to aqueous solutions. The formation of aggregates was characterized in the absorption spectrum by a broadening of the Qy band, which is slightly shifted to the red, a significant increase in signals of circular dichroism and a drastic quenching of the fluorescence intensity at 674 nm. Analysis of the nonlinear variation of the fluorescence intensity with the dye concentration in Tris-buffered solutions shows that dimerization is the dominant aggregation process. The dimerization equilibrium constant(at 25_AoC, pH 7.5 in 5 m M Tris buffer, 10 m M NaCl) was determined to be 3.10₆ M _-l. NMR measurements performed in DMSO at various dye concentrations showed that only the chemical shifts of some atoms are affected by these changes, indicating the part of the ring involved in the overlap of the two molecules in the dimer.A molecular modeling study of the packing arrangement of the aminopyropheophorbide molecules in aggregates performed by both semi-empirical quantum chemical PM3 and force field MM2 methods provided a structure consistent with these spectroscopic data.