[reaction: see text] The host cucurbit[7]uril (CB7) forms very stable inclusion complexes with simple 4,4'-bipyridinium (viologen) dication guests in aqueous solution. The binding constants were measured by electronic absorption spectroscopy and found to be as high as 1 x 10(5) L/mol. One-electron reduction of the viologen guest results in a modest 2-fold decrease of the binding constant. The rate of the heterogeneous electron-transfer reaction between the complexed viologen dication and cation radical remained fast in the voltammetric time scale.

The effects of the medium ionic composition on the apparent equilibrium association constant (K) for the formation of a 1:1 inclusion complex between the guest methyl viologen (MV(2+)) and the host cucurbit[7]uril (CB7) were studied in aqueous solutions. The K values were found to decrease with increasing ionic strength, with more pronounced effects for solutions containing divalent Ca(2+) ions than for solutions containing monovalent Na(+) ions. The competing ion-dipole interactions between Ca(2+) or Na(+) and MV(2+) ions appear to be responsible for the remarkable modulation of the K values observed in this work.

An exciting new direction in responsive liposome research is endogenous triggering of liposomal payload release by overexpressed enzyme activity in affected tissues and offers the unique possibility of active and site-specific release. Bringing to fruition the fully expected capabilities of this new class of triggered liposomal delivery system requires a collection of liposome systems that respond to different upregulated enzymes; however, a relatively small number currently exist. Here we show that stable, ~100 nm diameter liposomes can be made from previously unreported quinone-dioleoyl phosphatidylethanolamine (Q-DOPE) lipids, and complete payload release (quenched fluorescent dye) from Q-DOPE liposomes occurs upon their redox activation when the quinone headgroup possesses specific substituents. The key component of the triggerable, contents-releasing Q-DOPE liposomes is a “trimethyl-locked” quinone redox switch attached to the N-terminus of DOPE lipids that undergoes a cleavage event upon two-electron reduction. Payload release by aggregation and leakage of “uncapped” Q-DOPE liposomes is supported by results from liposomes wherein deliberate alteration of the “trimethyl-locked” switch completely deactivates the redox-destructible phenomena (liposome opening). We expect that Q-DOPE liposomes and their variants will be important in treatment of diseases with associated tissues that overexpress quinone reductases, such as cancers and inflammatory diseases, because the quinone redox switch is a known substrate for this group of reductases.

Ferrocenium and cobaltocenium form highly stable 1:1 inclusion complexes with the host cucurbit[7]uril. From electronic absorption spectroscopic data the association equilibrium constants for both complexes were found to be larger than 106 L/mol. The electrochemical reduction of either guest leads to a modest loss in binding affinity.

A new procedure for the modification of gold nanospheres (2-7 nm diameter) with thiolated cyclodextrin receptors is described. The resulting monolayer-protected nanoparticles behave as multisite hosts in aqueous media, engaging in host-guest interactions with guest molecules in the solution.

The preparation and characterization of gold nanoparticles (approximately 3 nm in diameter) capped with thiolated alpha- and beta-cyclodextrins (alpha and beta-CD) is described. The CD-capped nanoparticles are hydrophilic and bind ferrocene derivatives as evidenced by electrochemical and (1)H NMR spectroscopic measurements. The binding interactions of the CD-capped nanoparticles with a series of five alkyldimethyl(ferrocenylmethyl)ammonium ions (the alkyl group is propyl for compound 1, heptyl for 2, dodecyl for 3, hexadecyl for 4, and docosyl for 5) can be utilized for the phase transfer of the hydrophilic, CD-capped nanoparticles into a nonpolar chloroform phase. Only 3, 4, and 5 act as effective phase transfer agents, since 1 and 2 do not have enough amphiphilic character. The structure of the aggregates formed upon transfer of the CD-capped nanoparticles to the chloroform solution is postulated to resemble that of reverse micelles, as the nanoparticles template the peripheral arrangement of the cationic ferrocene amphiphiles, counterions and water molecules around their surfaces.

Water-soluble gold nanoparticles (3.2 nm diameter) capped with thiolated γ-cyclodextrin hosts form large network aggregates (∼300 nm) in the presence of C60 fullerene molecules. This aggregation phenomenon is driven by the formation of inclusion complexes between two cyclodextrinsattached to different nanoparticlesand one molecule of C60.

These preclinical data support using MPP technology to engineer topical formulations to deliver therapeutic drug levels to the back of the eye and could provide major advancements in managing sight-threatening diseases.