Supramolecular dissociation

Keywords CD mobility, Gene delivery, Multivalent interaction, Saccharide/protein interaction, Supramolecular dissociation... 

Supramolecular dissociation of the polyrotaxanes into constituent molecules such as a-CD and PEG was quite a new image as a mode of biodegradation in a living body. This insight was the first step to initiate our studies on polyrotaxanes as biomaterials 15 years ago [6],... 

Fig. 11 Polyplex formation and pDNA release accompanied by the supramolecular dissociation of DMAEC-SS-polyrotaxanes...

The finding as observed above is likely due to the mobile motion of a-CDs in the necklace-like structure of the polyrotaxane. The pDNA dissociation of the polyplex occurred through the SS cleavage in the polyrotaxane and the subsequent interexchange with polyanions. This is presumably due to a reduction on the potency of the multivalent interaction between the cationic polyrotaxane and the anionic pDNA through the supramolecular dissociation. A rapid endosomal escape and pDNA delivery to the nucleus using such cytocleavable polyrotaxanes can be achieved through systematic analyses of polyrotaxane structures. 

Figure 2. Proposed two functions of the polyrotaxancs (a) supramolecular dissociation by terminal hydrolysis and (b) sliding of CDs along the liner polymeric chain.

Drug Release from Biodegradable Polyrotaxanes via Supramolecular Dissociation and its Relation to Solution Properties... 

Figure 8. Delay-time of the supramolecular dissociation as a function of the degree of acetylation.

In this review, CPOs constructed by covalent bonds are mainly focused on however, stable coordination bonds comparable to the stability of the covalent bonds have potential for future enhanced molecular design of novel CPOs. One representative is the bond between pyridine-type nitrogen and metal, which is widely used in supramolecular chemistry, that is, the cyclic supramolecular formation reaction between pyridine-substituted porphyrin and metal salts (Fig. 6d) [27,28]. Palladium salts are frequently used as the metal salts. From the viewpoint of the hard and soft acid and base theory (HSAB), this N-Pd coordination bond is a well-balanced combination, because the bonds between nitrogen and other group X metals, N-Ni and Ni-Pt coordination bonds, are too weak and too strong to obtain the desired CPOs, respectively. For the former, the supramolecular architectures tend to dissociate into pieces in the solution state, and for the latter. 

A supramolecular assembly of macromolecules bearing antenna dendron has been reported. Pyrazole-anchored PBE dendrons were synthesized to examine the coordination behavior to transition-metal cations (Cu, Au, Ag) [31]. Self-assembled metallacycles were found. The Cu-metallacycle further formed luminescent fibers about 1 pm in diameter. The luminescence (605 nm) occurred by the excitation of the dendron (280 nm) and the excitation spectrum was coincident with the absorption spectrum of the dendron, suggesting the antenna effect. Interestingly, the luminescence of the Cu-metallacycle fiber disappeared when the fiber was dissociated into the individual metallacycles in C2H2. 

The dynamics of a supramolecular system are defined by the association and dissociation rate constants of the various components of the system. The time-scale for the dynamic events is influenced by the size (length-scale) and by the complexity of the system. The fastest time for an event to occur in solution is limited by the diffusion of the various components to form encounter complexes. This diffusion limit provides an estimate for the shortest time scale required for kinetic measurements. The diffusion of a small molecule in water over a distance of 1 nm, which is the length-scale for the size of small host systems such as CDs or calixarenes, is 3 ns at room temperature. In general terms, one can define that mobility within host systems can occur on time scales shorter than nanoseconds, while the association/dissociation processes are expected to occur in nanoseconds or on longer time scales. The complexity of a system also influences its dynamics, since various kinetic events can occur over different time scales. An increase in complexity can be related to an increase in the number of building blocks within the system, or complexity can be related to the presence of more than one binding site. 

Figure 3.4 Relationship between the equihbrium association constant ( Teq) and the rate constants for supramolecular association and dissociation.

Figure 3.5 Pincer-hgand motifs that provide independent control of supramolecular asso-ciation/dissociation kinetics relative to thermodynamics.

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