Solitary and Synergistic Effects of Different Hydrophilic and Hydrophobic Phospholipid Moieties on Rat Behaviors.

Glycerophospholipids have hydrophobic and hydrophilic moieties. Previous studies suggest that phospholipids with different moieties have different effects on rodent behavior; however, the relationship between chemical structures and behavioral effects remains unclear. To clarify the functions of phospholipid moieties, we injected male rats with phospholipids with different moieties and conducted behavioral tests. Exploratory activity was reduced by phosphatidylethanolamine (PE)(18:0/22:6) but not PE(18:0/18:0) or PE(18:0/20:4). Conversely, exploratory activity was increased by plasmanyl PE(16:0/22:6), which harbors an alkyl-ether linkage, but not by phosphatidylcholine (PC)(16:0/22:6) or plasmanyl PC(16:0/22:6). Docosahexaenoic acid (DHA)(22:6) and an alkyl-ether linkage in PE were thus postulated to be involved in exploratory activity. Anxiety-like behavior was reduced by plasmenyl PC(18:0/20:4), which harbors a vinyl-ether linkage, but not by PC(18:0/20:4) or plasmanyl PC(18:0/20:4), suggesting the anxiolytic effects of vinyl-ether linkage. The activation of social interaction was suppressed by PE(18:0/18:0), PE(18:0/22:6), PC(16:0/22:6), plasmanyl PE(16:0/22:6), and plasmanyl PC(16:0/22:6) but not by PE(18:0/20:4), plasmenyl PE(18:0/20:4), or plasmanyl PC(18:0/22:6). DHA may suppress social interaction, whereas arachidonic acid(20:4) or a combination of alkyl-ether linkage and stearic acid(18:0) may restore social deficits. Our findings indicate the characteristic effects of different phospholipid moieties on rat behavior, and may help to elucidate patterns between chemical structures and their effects.

A Chiral Metal-Organic 1D-Coordination Polymer Upon Complexation of Phenylene-Bridged Bipyrrole and Palladium (II) Ion.

Metal-organic 1D-coordination polymers, having unique electronic and optical properties, are expected to be a novel advanced functional material capable of fabricating smart plastics, films, and fibers. In this study, we have synthesized a novel metal-organic 1D-coordination polymer composed of a phenylene-bridged bipyrrole bearing N-alkylimino groups (BPI) and palladium(II) ion. The BPI and Pd(II) form square planar bis(bidentate) complex to form a metal coordinated π-conjugation polymer (Poly-BPI/Pd). It is stable in solutions at room temperature, and allowed measurement of its average molecular weight in SEC (M w = 106,000 and M n = 18,000, M w/M n = 5.88). It also provided a reversible multi redox profile in cyclic voltammetry, most likely originating from strong π-electronic interactions between the BPI components via Pd ion. A variety of substituent groups can be attached to the imino-nitrogens of BPI. A coordination polymer composed of a BPI derivative bearing chiral alkyl chains and Pd(II) showed strong circular dichroism (CD) in the solution due to the unidirectional chiral conformation of the BPI components in the polymer backbone.

Preferential Tumor Accumulation of Polyglycerol Functionalized Nanodiamond Conjugated with Cyanine Dye Leading to Near-Infrared Fluorescence In Vivo Tumor Imaging.

Preferential accumulation of nanoparticles in a tumor is realized commonly by combined effects of active and passive targeting. However, passive targeting based on an enhanced permeation and retention (EPR) effect is not sufficient to observe clear tumor fluorescence images in most of the in vivo experiments using tumor-bearing mice. Herein, polyglycerol-functionalized nanodiamonds (ND-PG) conjugated with cyanine dye (Cy7) are synthesized and it is found that the resulting ND-PG-Cy7 is preferentially accumulated in the tumor, giving clear fluorescence in in vivo and ex vivo fluorescence images. One of the plausible reasons is the longer in vivo blood circulation time of ND-PG-Cy7 (half-life: 58 h determined by the pharmacokinetic analysis) than that of other nanoparticles (half-life: <20 h in most of the previous reports). In a typical example, the fluorescence intensity of tumors increases due to continuous tumor accumulation of ND-PG-Cy7, even more than one week postinjection. This may be owing to the stealth effect of PG that was reported previously, avoiding recognition and excretion by reticuloendothelial cells, which are abundant in liver and spleen. In fact, the fluorescence intensities from the liver and spleen is similar to those from other organs, while the tumor exhibits much stronger fluorescence in the ex vivo image.

Spiroborate-Based Double-Stranded Helicates: Meso-to- Racemo Isomerization and Ion-Triggered Springlike Motion of the Racemo-Helicate.

A one-handed double-stranded spiroborate helicate exhibits a unique reversible extension-contraction motion coupled with a twisting motion in one direction triggered by binding and release of a Na+ ion while retaining its handedness. Here we report that an extended meso-helicate was also produced together with the racemo-helicate, and the meso-helicate was readily converted to the racemo-helicate assisted by a Na+ ion as a template in the presence of water. The thermodynamic analyses of the ion-triggered springlike motion of the racemo-helicate using a series of monovalent cations with different sizes revealed that the association constants of the extended racemo-helicate decreased in the following order: Li+ > Na+ > NH4+ > Ag+ ≥ K+ > Cs+ > Rb+, which roughly agrees with the reverse order of their ionic radii except for the NH4+ ion due to the more elongated contracted helicates when complexed with larger cations as supported by the crystal and DFT calculated structures. The one-handed contracted helicates showed characteristic CD spectra depending on the cation species due to the differences in their contracted helical structures, and its absolute handedness of the spiroborate helicate was determined by X-ray crystallography. The kinetic studies of the springlike motions of the racemo-helicate showed that the exchange rate between the extended and contracted helicates tend to increase in the following order: Li+ < Na+ < K+ ≤ NH4+ < Rb+ < Cs+ < Ag+ as anticipated from the association constants, being in good agreement with the order of the cation sizes except for Ag+.

Supramolecular Organogels Formed through Complementary Double-Helix Formation.

Optically active amidine ((R)-1) and achiral carboxylic acid (2) dimers with a m-terphenyl backbone linked by a 1,4-phenylene diacetylene unit form a double helix, (R)-1⋅2, through complementary amidinium-carboxylate salt bridges in THF. Upon the addition of poor solvents, such as n-hexane, the duplex forms an organogel as a result of supramolecular polymerization of the duplex by intermolecular rearrangement of the salt bridges. In sharp contrast, an analogous racemic duplex composed of achiral amidine residues and an optically active duplex linked by a shorter diacetylene unit with a higher binding affinity than that of (R)-1⋅2 does not show any gelation. The supramolecular fluorescent gels exhibit reversible thermo- and chemoresponsive behavior. The chiroptical properties of the gels, the mechanism of gelation, and the amplification of helical chirality during the gelation of (R)-1⋅2 in the absence and presence of its enantiomeric counterpart, (S)-1⋅2, and a racemic duplex, consisting of achiral amidine and carboxylic acid dimers, were investigated by following changes in the absorption and circular dichroism spectra.

Synthesis of helically twisted [1 + 1]macrocycles assisted by amidinium-carboxylate salt bridges and control of their chiroptical properties.

A series of optically active, helically twisted [1 + 1]macrocycles connected via o-, m-, and p-linkages (o-, m-, and p-) was prepared from the corresponding linear duplexes stabilized by complementary amidinium-carboxylate salt bridges bearing two arms with terminal vinyl groups at both ends through the ring-closing metathesis reaction in the good yields of 67, 92, and 96%, respectively. The chiroptical properties of the macrocycles were dependent on the linker geometries and could be controlled by acid-base interactions and zinc coordination, the changes in which were detected by their CD and absorption spectral changes and fluorescence colors.

Thermodynamic and kinetic stabilities of complementary double helices utilizing amidinium-carboxylate salt bridges.

A series of dimer strands consisting of m-terphenyl backbones bearing complementary chiral or achiral amidines and achiral carboxylic acid residues connected by various types of linkers, such as diacetylene, Pt(II)-acetylide, and p-diethynylbenzene linkages, were synthesized by a modular strategy, and their chiroptical properties on the complementary double helix formations were investigated by absorption, circular dichroism (CD), and (1)H NMR spectroscopies. The thermodynamic and kinetic stabilities of the complementary double helices assisted by amidinium-carboxylate salt bridges are highly dependent on their linkages, and the thermodynamic analyses of the dimer duplexes revealed that the association constants increased in the order: Pt(II)-acetylide linker < p-diethynylbenzene linker < diacetylene linker, which is in agreement with the reverse order of their bulkiness. The substituents on the amidine groups were also found to affect the stabilities on the duplexes and the association constants increased in the order: isopropyl < (R)-1-phenylethyl < cyclohexyl. In addition, the introduction of electron-donating and/or electron-withdrawing substituents at the phenyl groups of the p-diethynylbenzene linkers connecting the amidine and carboxylic acid units, respectively, tends to stabilize the complementary double helices, especially in polar solvents, such as DMSO, due to the attractive charge-transfer interactions between the aromatic linkers, although the salt bridge formation is hampered in DMSO. Furthermore, the kinetic analyses of the chain exchange reactions for the duplexes bearing diacetylene and p-diethynylbenzene linkages showed that these were slow processes with negative ΔS([symbol: see text]) values, meaning that the chain exchange reactions proceed via direct exchange pathways. In contrast, those for the duplexes bearing Pt(II)-acetylide linkages were fast processes supported by positive ΔS([symbol: see text]) values, suggesting that the chain exchange reactions proceed via dissociation-exchange ones. The helix-inversion kinetics investigated for the racemic dimer duplexes composed of achiral amidines based on variable-temperature (1)H NMR measurements indicated that the barriers for the helix-inversion increased in the order: Pt(II)-acetylide linker, p-diethynylbenzene linker < diacetylene linker.

Diastereoselective imine-bond formation through complementary double-helix formation.

Optically active amidine dimer strands having a variety of chiral and achiral linkers with different stereostructures are synthesized and used as templates for diastereoselective imine-bond formations between two achiral carboxylic acid monomers bearing a terminal aldehyde group and racemic 1,2-cyclohexanediamine, resulting in a preferred-handed double helix stabilized by complementary salt bridges. The diastereoselectivity of the racemic amine is significantly affected by the chirality of the amidine residues along with the rigidity and/or chirality of the linkers in the templates. NMR and kinetic studies reveal that the present imine-bond formation involves a two-step reversible reaction. The second step involves formation of a preferred-handed complementary double helix assisted by the chiral amidine templates and determines the overall reaction rate and diastereoselectivity of the amine.

Synthesis and optical resolution of a Cu(I) double-stranded helicate with ketimine-bridged tris(bipyridine) ligands.

A tetranuclear Cu(I) double-stranded helicate was synthesized from ketimine-bridged tris(bipyridine) ligands and Cu(I) ions, and the racemate was successfully resolved by diastereomeric salt formation using an optically pure phosphate anion followed by anion exchange with NaPF(6) without racemization.

Synthesis and function of double-stranded helical polymers and oligomers.

The design and synthesis of artificial helical polymers and oligomers has attracted much interest, in connection with fascinating biological helices and their sophisticated functions as well as possible applications in novel chiral materials. The last half-century has seen a significant advancement in the synthesis of single-stranded helical polymers and oligomers, since the discovery of the helical structure of isotactic polypropylene. In contrast, the chemistry of double-stranded helical counterparts is still premature. This paper highlights our recent achievements in the synthesis, structures, and functions of double-stranded helical polymers and oligomers, stressing an important role of supramolecular chemistry in the design and synthesis of double helices with a controlled helical sense.

Synthesis of complementary double-stranded helical oligomers through chiral and achiral amidinium-carboxylate salt bridges and chiral amplification in their double-helix formation.

A series of complementary molecular strands from 2-mer to 5-mer that are composed of m-terphenyl units bearing chiral/achiral amidine or achiral carboxyl groups linked via Pt(II) acetylide complexes were synthesized by sequential stepwise reactions, and their chiroptical properties on the double-helix formation were investigated by circular dichroism (CD) and (1)H NMR spectroscopies. In CHCl(3), the "all-chiral" amidine strands consisting of (R)- or (S)-amidine units formed preferred-handed double helices with the complementary achiral carboxylic acid strands through the amidinium-carboxylate salt bridges, resulting in characteristic induced CDs in the Pt(II) acetylide complex regions, indicating that the chiral substituents on the amidine units biased a helical sense preference. The Cotton effect patterns and intensities were highly dependent on the molecular lengths. The complementary double-helix formation was also explored using the chiral/achiral amidine strands with different sequences in which a chiral amidine unit was introduced at the center (center-chiral) or a terminus (edge-chiral) of the amidine strands. The effect of the sequences of the chiral and achiral amidine units on the amplification of chirality (the "sergeants and soldiers" effect) in the double-helix formation was investigated by comparing the CD intensities with those of the corresponding all-chiral amidine double helices with the same molecular lengths. Variable-temperature CD experiments of the all-chiral and chiral/achiral amidine duplexes demonstrated that the Pt(II)-linked complementary duplexes are dynamic and their chiroptical properties including the chirality transfer from the chiral amidine unit to the achiral amidine ones are significantly affected by the molecular lengths, sequences, and temperatures. On the basis of the above results together with molecular dynamics simulation results, key structural features of the Pt(II)-linked oligomer duplexes and the effect of the chiral/achiral amidine sequences on the amplification of chirality are discussed.

A hetero-stranded double helix composed of m-diethynylbenzene-based complementary molecular strands stabilized by amidinium-carboxylate salt bridges.

A hetero-stranded double helix with a controlled helix sense was designed and synthesized from an optically active dimeric amidine and its complementary achiral dicarboxylic acid strand with conjugated m-diethynylbenzene backbones, being stabilized by the salt bridges.

Ion-triggered spring-like motion of a double helicate accompanied by anisotropic twisting.

Molecules that extend and contract under external stimuli are used to build molecular machines with nanomechanical functions. But although common in biological systems, such extension and contraction motions with helical molecules have rarely been accompanied by unidirectional twisting in synthetic systems. Here we show that sodium ions can trigger the reversible anisotropic twisting of an enantiomeric double-stranded helicate, without racemization. An optically active helicate consisting of two tetraphenol strands bridged by two spiroborate groups sandwiches a sodium ion. On removal of the central sodium-through addition of a cryptand [2.2.1] in solution-the double helicate extends. Crystallographic and nuclear magnetic resonance studies reveal that the extended helicate is over twice as long as the initial molecule, and is twisted in the right-handed direction. Circular dichroism analysis suggests that the twisting doesn't affect the helicate's handedness. This anisotropic extension-contraction process is reversibly triggered by the successive addition and removal of sodium ions in solution.

Complementary double helix formation through template synthesis.

The dimerization of carboxylic acid derivatives bearing an amino or a formyl group at one end was significantly enhanced in benzene in the presence of an optically active amidine dimer to afford a complementary double helix stabilized with salt bridges.

Axle length effect on photoinduced electron transfer in triad rotaxane with porphyrin, [60]fullerene, and triphenylamine.

Photoinduced multiple electron-transfer processes of a newly synthesized rotaxane with one acceptor and two donors are studied with the time-resolved fluorescence and absorption methods. In this rotaxane, zinc porphyrin (ZnP) with a crown-ether necklace is employed as a photosensitized electron donor; through the crown-ether, a short axle with C(60) and triphenylamine (TPA) at both terminals is penetrating as an electron acceptor and a hole-shift, respectively (abbreviated as (ZnP;C(60)-(A(S))-TPA)(Rot)). The time-resolved fluorescence and transient absorption measurements reveal that the through-space electron-transfer processes take place via the excited states of the ZnP unit to the spatially arranged C(60) moiety, giving the radical ion pair (ZnP(*+);C(60)(*-)-(A(S))-TPA)(Rot) in polar solvents. Consecutively, (ZnP;C(60)(*-)-(A(S))-TPA(*+))(Rot) is also generated by the through-space hole-shift between ZnP and TPA, in addition to the through-bond charge separation via the excited state of the C(60) moiety. Both radial ion pairs have lifetimes of 320-420 ns, which are longer than those of the previously reported similar rotaxane with cationic longer axle (150-170 ns).

Successive catalytic reactions specific to Pd-based rotaxane complexes as a result of wheel translation along the axle.

Rotaxane-structure-specific Pd-catalyzed rearrangement of propargyl or allyl urethane groups to oxazolidinone moieties proceeded efficiently. The conversion took place successively by the translation of the wheel along the axle, thus providing a novel macrocyclic catalytic system.