Inclusion Complex Formation with Tetra-PEGylated Tetraphenylporphyrin and Face-to-Face Cyclodextrin Dimer through Unprecedented Molecular Threading

Herein, a host-guest inclusion complex formation between tetra-PEGylated tetraphenylporphyrin with a per-O-methylated cyclodextrin (CD) dimer through the molecular threading process that is physically unexpected to occur is described. Although the molecular size of the PEGylated porphyrin is much greater than that of the CD dimer, the sandwich-type porphyrin/CD dimer 1 : 1 inclusion complex was spontaneously formed in water. The ferrous porphyrin complex binds O₂ reversibly in aqueous solution, which functions as an artificial O₂ carrier in vivo. Pharmacokinetic study using rats revealed that the inclusion complex showed a long circulation in blood in contrast to the complex without PEG. We further demonstrate the unique host-guest exchange reaction from the PEGylated porphyrin/CD monomer 1/2 inclusion complex to the 1/1 complex with the CD dimer through the complete dissociation process of the CD monomers.