Functionalization of Polyethyleneimine with Hollow Cyclotriveratrylene and Its Subsequent Supramolecular Interaction with Doxorubicin

Abstract

In this paper, a modified Cyclotriveratrylene was synthesized and linked to a branched Polyethylenimine, and this unique polymeric material was subsequently examined as a potential supramolecular carrier for Doxorubicin. Spectroscopic analysis in different solvents had shown that Doxorubicin was coordinated within the hollow-shaped unit of the armed Cyclotriveratrylene, and the nature of the host–guest complex revealed intrinsic Van der Waals interactions and hydrogen bonding between the host and guest. The strongest interaction was detected in water because of the hydrophobic effect shared between the aromatic groups of the Doxorubicin and Cyclotriveratrylene unit. Density functional theory calculations had also confirmed that in the most stable coordination of Doxorubicin with the cross-linked polymer, the aromatic rings of the Doxorubicin were localized toward the Cyclotriveratrylene core, while its aliphatic chains aligned closer with amino groups, thus forming a compact supramolecular assembly that may confer a shielding effect on Doxorubicin. These observations had emphasized the importance of supramolecular considerations when designing a novel drug delivery platform.

Synthesis and Coordination Properties of a Water-Soluble Material by Cross-Linking Low Molecular Weight Polyethyleneimine with Armed Cyclotriveratrilene

“…The cross-linked polymer Cross-PEI-800 was prepared as shown in Scheme 1 . Precursor 2a was obtained by reacting vanillyl alcohol with 1,4-dibromobutane, as reported in the literature [ 18 , 66 , 67 , 68 ]. The oligomerization of compound 2a with scandium triflate in CH 3 CN afforded Armed-CTV [ 18 ].…”

“…Precursor 2a was obtained by reacting vanillyl alcohol with 1,4-dibromobutane, as reported in the literature [ 18 , 66 , 67 , 68 ]. The oligomerization of compound 2a with scandium triflate in CH 3 CN afforded Armed-CTV [ 18 ]. The PEI-800 was cross-linked with Armed-CTV in DMSO overnight to obtain the highly water-soluble product Cross-PEI-800 .…”

“…For instance, doxorubicin (DOX) can be linked to PEI through covalent connection or coordinated through supramolecular interactions for drug-delivery applications [ 16 , 17 ]. Our group previously also reported the coordination of doxorubicin with PEI-25k cross-linked cyclotriveratrylene (CTV) [ 18 ].…”

Supermolecule—Drug Conjugates Based on Acid-Degradable Polyrotaxanes for pH-Dependent Intracellular Release of Doxorubicin

“…The DOX-HPR peaks detected by UV and RI appeared at similar retention times, suggesting that DOX molecules were chemically conjugated with HPR. In the 1 H NMR spectrum of DOX-HPR, peaks assignable to the anthraquinone ring of DOX appeared at 7.63, 7.71, and 7.97 ppm ( Figure 3 B) [ 37 ]. In accordance with these results, we concluded that DOX-HPR was successfully prepared without contamination with free DOX.…”