Critical Role of Achiral Guest Molecules in Planar Chirality Inversion of Alanine-Appended Pillar[5]arenes.

Planar chirality inversion of pillar[5]arenes bearing d- or l-alanine substituents on both rims was investigated upon addition of guest molecules having pyridinium or imidazole moieties and long alkyl chains. The d- and l-alanine-substituted pillar[5]arenes exhibited pS and pR planar chirality, respectively. However, this planar chirality was inverted upon inclusion of certain achiral molecules, comprising pyridinium or imidazole moieties and long alkyl chains with terminal hydroxyl or methyl groups.

Peculiar Triarylamine-Based Co-assembled Supramolecular Polymers That Exhibit Two Transition Temperatures in the Formation of a Coiled Helical Bundle.

This paper describes the peculiar co-assembly supramolecular polymerization behavior of triphenylamine trisamide derivatives with d-alanine (T-ala) or glycine (T-gly) moieties. Concentration and temperature-dependent circular dichroism (CD) spectroscopy revealed that the heating curves of co-assemblies obtained at various molar ratios of T-ala to T-gly exhibited two distinct transition temperatures. The first transition was due to the transformation from coiled helical bundles to single helical fibers without handedness. The second was due to a change from typical elongation to nucleation. These phenomena were confirmed by solvent-dependent decoiling of coiled helical structures and concentration-dependent morphological analysis. The two transitioning temperatures were dependent on the concentration of T-ala in the co-assemblies, suggesting that T-ala concentration plays an important role in the formation of coiled helical bundles. Our study demonstrated the first observation of two distinct transition temperatures in supramolecular polymers.

Helicity Control of Triphenylamine-Based Supramolecular Polymers: Correlation between Solvent Properties and Helicity in Supramolecular Gels.

We describe the role of amide groups formed by achiral and chiral moieties to study supramolecular helicity at the molecular level and the correlation between helicity and solvent properties at the supramolecular level. Using circular dichroism (CD) spectroscopy, we observed the CD spectra of supramolecular gel 1, which comprised a triphenylamine (TPA) core, terpyridine, and alanine moieties, formed in various solvents. The strong positive CD signals of supramolecular gel 1 formed in organic solvents, such as chloroform, tetrahydrofuran (THF), and dichloromethane, which have low polarity and a low acceptor number, were observed at 350 nm, indicating right-handed helicity. In contrast, the negative CD signals of supramolecular gel 1 formed in mixed DMSO/water (5:1 v/v), methanol, ethanol, and n-propanol were obtained at 350 nm, indicating left-handed helicity. These findings suggest that the helicity of supramolecular gel 1 was strongly influenced by the solvent properties. Indeed, atomic force spectroscopy images showed the right- and left-handed helicity of supramolecular gel 1 formed in various organic solvents, which was pure helicity.

Self-Assembled Coumarin Nanoparticle in Aqueous Solution as Selective Mitochondrial-Targeting Drug Delivery System.

The development of specifically targeted nanoparticles for subcellular organelles modified with a low-molecular-weight organic compound as drug nanocarriers can bring about wide applications in cancer therapy. However, their utility has been hampered by low selectivity, poor biodistribution, and limited efficiency. Herein, we report the aggregation behavior of a triphenylphosphonium-appended coumarin probe (TPP-C) in an aqueous solution and its applications as a mitochondria-targeting probe, and drug delivery carrier, which is a rare example for a low molecular-weight organic compound. The TPP-C formed homogeneous nanoparticles with small diameters in water as well as in mixtures of organic solvents and water. In pure water, the homogeneous nanoparticles induced J-aggregation, whereas in mixed solvents, the homogeneous nanoparticles induced H-aggregation. The luminescence intensities of nanoparticles originated from the aggregation-induced emission (AIE) effect in pure water and also in mixtures of organic solvents and water. These findings indicate that the AIE effect of TPP-C was dependent on the solvent. More interestingly, the TPP-C nanoparticles selectively accumulated in mitochondria. The TPP-C nanoparticles alone exhibited noncytotoxicity toward cancer cells. However, with the encapsulation of the anticancer drug doxorubicin (DOX) into the TPP-C nanoparticles, the DOX was efficiently delivered to the mitochondria. These results indicated that the proposed system demonstrates promise as a platform for future clinical medication, particularly for specific suborganelle-targeted drug delivery systems for cancer therapy.

Non-peptidic guanidinium-functionalized silica nanoparticles as selective mitochondria-targeting drug nanocarriers.

We report on the design and fabrication of a Fe3O4 core-mesoporous silica nanoparticle shell (Fe3O4@MSNs)-based mitochondria-targeting drug nanocarrier. A guanidinium derivative (GA) was conjugated onto the Fe3O4@MSNs as the mitochondria-targeting ligand. The fabrication of the Fe3O4@MSNs and their functionalization with GA were carried out by the sol-gel polymerization of alkoxysilane groups. Doxorubicin (DOX), an anti-cancer drug, was loaded into the pores of a GA-attached Fe3O4@MSNs due to both its anti-cancer properties and to allow for the fluorescent visualization of the nanocarriers. The selective and efficient mitochondria-targeting ability of a DOX-loaded GA-Fe3O4@MSNs (DOX/GA-Fe3O4@MSNs) was demonstrated by a co-localization study, transmission electron microscopy, and a fluorometric analysis on isolated mitochondria. It was found that the DOX/GA-Fe3O4@MSNs selectively accumulated into mitochondria within only five minutes; to the best of our knowledge, this is the shortest accumulation time reported for mitochondria targeting systems. Moreover, 2.6 times higher amount of DOX was accumulated in mitochondria by DOX/GA-Fe3O4@MSNs than by DOX/TPP-Fe3O4@MSNs. A cell viability assay indicated that the DOX/GA-Fe3O4@MSNs have high cytotoxicity to cancer cells, whereas the GA-Fe3O4@MSNs without DOX are non-cytotoxic; this indicates that the DOX/GA-Fe3O4@MSNs have great potential for use as biocompatible and effective mitochondria-targeting nanocarriers for cancer therapy.

Origin of Both Right- and Left-Handed Helicities in a Supramolecular Gel with and without Ni2+ at the Supramolecular Level.

We demonstrate the different origins of helical directions in polymeric gels derived from a hydrazone reaction in the absence and presence of Ni2+. The right-handed helicity of polymeric gels without Ni2+ originates from the enantiomeric d-form alanine moiety embedded in the building block. However, the right-handed helicity is inverted to a left-handed helicity upon the addition of Ni2+, indicating that added Ni2+ greatly affects the conformation of the polymeric gel by overcoming the influence of the enantiomer embedded in the building block on the helicity at the supramolecular level. More interestingly, the ratio of the right-toleft-handed helical fibers varies with the concentration of Ni2+, which converts from 100% right-handed helical fiber to 90% left-handed helical fiber. In the presence of Ni2+, both right- and left-handed helical fibers coexist at the supramolecular level. Some fibers also exhibit both right- and left-handed helicities in a single fiber.

A duplex DNA-gold nanoparticle probe composed as a colorimetric biosensor for sequence-specific DNA-binding proteins.

Using duplex DNA-AuNP aggregates, a sequence-specific DNA-binding protein, SQUAMOSA Promoter-binding-Like protein 12 (SPL-12), was directly determined by SPL-12-duplex DNA interaction-based colorimetric actions of DNA-Au assemblies. In order to prepare duplex DNA-Au aggregates, thiol-modified DNA 1 and DNA 2 were attached onto the surface of AuNPs, respectively, by the salt-aging method and then the DNA-attached AuNPs were mixed. Duplex-DNA-Au aggregates having the average size of 160 nm diameter and the maximum absorption at 529 nm were able to recognize SPL-12 and reached the equivalent state by the addition of ∼30 equivalents of SPL-12 accompanying a color change from red to blue with a red shift of the maximum absorption at 570 nm. As a result, the aggregation size grew to about 247 nm. Also, at higher temperatures of the mixture of duplex-DNA-Au aggregate solution and SPL-12, the equivalent state was reached rapidly. On the contrary, in the control experiment using Bovine Serum Albumin (BSA), no absorption band shift of duplex-DNA-Au aggregates was observed.