Synthesis of Cross-Chain Bridging Cryptands and Induction of Molecular Chirality.

In this study, we synthesized two cryptands featuring entangled tri- and tetra(ethylene glycol) linkers. The cryptand bearing short linkers was chiral without any asymmetric carbon atoms. After chiral high-performance liquid chromatography was used to separate the enantiomers, the absolute configuration of each cryptand was determined through single-crystal X-ray and circular dichroism analyses. The racemization of the cryptand possessing long linkers proceeded at room temperature.

Four- and two-armed hetero porphyrin dimers: their specific recognition and self-sorting behaviours.

In this study we self-assembled the four-armed porphyrin hetero dimer capsule Cap4, stabilized through amidinium-carboxylate salt bridges, in CH2Cl2 and CHCl3. The dimer capsule Cap4 was kinetically and thermodynamically more stable than the corresponding two-armed dimer Cap2. The number of arms strongly influenced their recognition behaviour; guests possessing small aromatic faces (e.g., 1,3,5-trinitrobenzene) preferred residing in the cavity of the two-armed capsule Cap2, rather than in Cap4, both thermodynamically and kinetically; in contrast, large aromatic guests (e.g., 9,10-dibromoanthracene) were encapsulated predominantly by Cap4 because of favourable entropic effects. The number of arms enabled self-sorting behaviour of the dimer formation; complexation studies using an equimolar mixture of the four porphyrin constituents of the two capsules revealed the quantitative formation of the corresponding dimers Cap2 and Cap4. Furthermore, we examined the specific molecular recognition of Cap2 and Cap4; NMR experiments of mixtures of Cap2 and Cap4 in the presence of favourable guests for Cap2 and Cap4 revealed that these guest molecules were encapsulated selectively by their preferred hosts.

Synthesis of a Mechanically Planar Chiral and Axially Chiral [2]Rotaxane.

In this study, we synthesized a [2]rotaxane that was both mechanically planar chiral and axially chiral, comprising a symmetrical bis-crown ether featuring a biphenyl moiety (as the macrocyclic component) and a symmetrical bis-ammonium salt (as the dumbbell-shaped component).

A Chiral [3]Rotaxane Comprising Achiral Bis-macrocyclic and Dumbbell-Shaped Components.

In this study, we synthesized a molecularly chiral [3]rotaxane comprising a calix-bis-crown ether (as the macrocyclic component) and two unsymmetrical dialkylammonium salts (as dumbbell-shaped components) without any chirality in any of the individual components. Chiral high-performance liquid chromatography was used to separate the enantiomers, which were characterized by circular dichroism spectroscopy. Density functional theory calculations gave an insight into the absolute configuration of each [3]rotaxane.

Base-induced multi-state fluorescence of a trefoil-shaped salicylaldehyde azine derivative.

A trefoil-shaped salicylaldehyde azine derivative bearing multiple acidic protons displays base-induced multi-state luminescence. The azine was prepared through the reaction of 1,3,5-triformylphloroglucinol with 4-methoxysalicylaldehyde hydrazone. 1H NMR spectroscopy revealed that the azine existed in solution at room temperature as an equilibrium mixture of two geometric isomers. The three-step deprotonation (four-state change) of the azine in solution was confirmed using 1H NMR, UV-vis absorption, and emission spectroscopy.

Locking the Dynamic Axial Chirality of Biphenyl Crown Ethers through Threading.

This paper describes the syntheses of [2]rotaxanes comprising 23- and 26-membered biphenyl crown ethers as the macrocyclic components and secondary ammonium ions as the dumbbell-shaped components, and the locking of the dynamic axial chirality of the biphenyl moieties in these structures. Chiral high-performance liquid chromatography (HPLC) revealed that our [2]rotaxane featuring the 26-membered crown ether racemized at room temperature, but the racemization of the [2]rotaxane featuring the 23-membered crown ether did not proceed at room temperature over a period of three days. After separation of the enantiomers of the [2]rotaxane incorporating the 23-membered crown ether through chiral HPLC, we studied its racemization at elevated temperature. The rate of stereoinversion in dimethylsulfoxide (a polar solvent) was faster than that in o-dichlorobenzene (a nonpolar solvent), and herein we discuss these kinetic parameters.

A Five-layer π-Aromatic Structure Formed through Self-assembly of a Porphyrin Trimer and Two Aromatic Guests.

In this study we synthesized two- and four-armed porphyrins - bearing two carboxyl and four 2-aminoquinolino functionalities, respectively, at their meso positions - as a complementary hydrogen bonding pair for the self-assembly of a D2 -symmetric porphyrin trimer host. Two units of the two-armed porphyrin and one unit of the four-armed porphyrin self-assembled quantitatively into the D2 -symmetric porphyrin trimer, stabilized through ammidinium-carboxylate salt bridge formation, in CH2 Cl2 and CHCl3 . The porphyrin trimer host gradually bound two units of 1,3,5-trinitrobenzene between the pair of porphyrin units, forming a five-layer aromatic structure. At temperatures below -40 °C, the rates of association and dissociation of the complexes were slow on the NMR spectroscopic time scale, allowing the 1 : 1 and 1 : 2 complexes of the trimer host and trinitrobenzene guest(s) to be detected independently when using less than 2 eq of trinitrobenzene. Vis titration experiments revealed the values of K1 (2.1±0.4×105  M-1 ) and K2 (2.2±0.06×104  M-1 ) in CHCl3 at room temperature.

Emission Control by Molecular Manipulation of Double-Paddled Binuclear PtII Complexes at the Air-Water Interface.

Molecular functions depend on conformations and motions of the corresponding molecular species. An air-water interface is a suitable asymmetric field for the control of molecular conformations and motions under a small applied force. In this work, double-paddled binuclear PtII complexes containing pyrazole rings linked by alkyl spacers were synthesized and their orientations and emission properties dynamically manipulated at the air-water interface. The complexes emerge from water with concurrent variation of interface orientation of the planes of the PtII complexes from perpendicular to parallel during mechanical compression suggesting a unique 'submarine emission'. Phosphorescence of the complexes is quenched at the air-water interface prior to monolayer formation with intensities subsequently rapidly increasing during monolayer compression. These results indicate that asymmetric reactions and motions might be controlled by applying mechanical force at the air-water interface.

Efficacy and safety of a new topical formulation containing selamectin and sarolaner in the prevention of heartworm disease and the treatment of roundworm infection in cats presented as veterinary patients in Japan.

The efficacy and safety of a new topical formulation containing selamectin plus sarolaner (Revolution® Plus / Stronghold® Plus, Zoetis) was evaluated for the prevention of heartworm (Dirofilaria immitis) disease and the treatment of roundworm infection in cats enrolled as veterinary patients in two field studies conducted in Japan. In the heartworm field study, 91 cats negative for D. immitis antigen and anti-D. immitis antibody were enrolled and received 9 monthly topical treatments with selamectin plus sarolaner during the period of April to December 2015. Efficacy was assessed by testing post-treatment blood samples collected 8, 12, and 15 months after initiation of treatment for the presence of D. immitis antigen and anti-D. immitis antibody. Eighty-seven cats completed the entire study and were included in the determination of efficacy. No D. immitis antigen or anti-D. immitis antibody were detected in any of the post-treatment samples. In the roundworm field study, completed in the period from April to November 2015, 64 cats with ≥100 roundworm eggs per gram (EPG) of feces were enrolled and allocated randomly in a 1:1 ratio, to receive either selamectin plus sarolaner or emodepside plus praziquantel (Profender®, Bayer). Treatments were administered topically on Days 0 and 30, and efficacy was assessed by fecal EPG counts conducted on Days 14, 30, and 60. All cats completed the entire study. At enrollment, all cats were infected with Toxocara cati. Compared to pre-treatment, geometric mean T. cati EPG counts on Days 14, 30, and 60 were reduced by >99.9% in both treatment groups. There were no treatment-related adverse events in either study. Monthly topical administration of Revolution® Plus / Stronghold® Plus providing a minimum of 6 mg/kg selamectin and 1 mg/kg sarolaner was safe and effective in the prevention of heartworm disease and the treatment of roundworm infection in cats enrolled as veterinary patients in Japan.

Efficacy of a new topical formulation of selamectin plus sarolaner for the control of fleas and ticks infesting cats in Japan.

The efficacy of a single application of a new topical formulation containing selamectin plus sarolaner (Revolution® Plus / Stronghold® Plus, Zoetis) was evaluated against fleas and ticks infesting cats enrolled as veterinary patients in two field studies conducted in Japan and against Haemaphysalis longicornis ticks on cats in a laboratory study. In the laboratory study, sixteen cats were ranked based on pre-treatment tick counts and allocated randomly to treatment on Day 0 with either selamectin plus sarolaner or placebo. Cats were infested with adult H. longicornis on Days -2, 5, 12, 19, 26 and 33. Efficacy relative to placebo was based on live attached tick counts conducted 48 h after treatment and subsequent re-infestations. Selamectin plus sarolaner reduced live, attached H. longicornis counts by 96.4% within 48 h of treatment, and by ≥91.7% within 48 h of weekly re-infestation for 35 days, based on arithmetic means. In the field studies, 67 client-owned cats harboring six or more live fleas and 63 cats harboring four or more live attached ticks were enrolled to evaluate selamectin plus sarolaner for efficacy and safety compared with a registered product. Cats were allocated randomly to treatment with selamectin plus sarolaner or fipronil plus (S)-methoprene based on order of presentation. Treatment was administered once on Day 0 and efficacy was assessed by parasite counts conducted on Days 14 and 30 compared to the pre-treatment count. In the flea field study, live flea counts on Days 14 and 30 were reduced by 99.5% and 99.9% in the selamectin plus sarolaner group, and by 97.6% and 98.6% in the fipronil plus (S)-methoprene group, based on least squares mean percentage reductions. Clinical signs typically associated with flea allergy dermatitis improved following treatment. In the tick field study, live tick counts on Days 14 and 30 were reduced by 97.5% and 97.7% in the selamectin plus sarolaner group, and by 91.5% and 93.4% in the fipronil plus (S)-methoprene group, based on least squares mean percentage reductions. Selamectin plus sarolaner was determined to be non-inferior to fipronil plus (S)-methoprene in both field studies. There were no treatment-related adverse events in any study. A single topical dose of Revolution® Plus / Stronghold® Plus providing a minimum dosage of 6.0 mg/kg selamectin and 1.0 mg/kg sarolaner was confirmed to be effective against H. longicornis ticks on cats for one month and safe and effective in the treatment of fleas and ticks on cats enrolled as veterinary patients in Japan.

Heat-Resistant Properties in the Phosphorescence of trans-Bis[ß-(iminomethyl)aryloxy]platinum(II) Complexes: Effect of Aromaticity on d-π Conjugation Platforms.

The heat-resistant properties towards thermal emission quenching of trans-bis[(ß-iminomethyl)aryloxy]platinum(II) complexes bearing 3-iminomethyl-2-naphtholato- (1), 1-iminomethyl-2-naphtholato- (2), 2-iminomethyl-1-naphtholato- (3), and 2-iminomethyl-1-phenolato (4) moieties, and a mechanistic rationale of these properties, are described in this report. Complex 1 a, with N,N'-dipentyl groups, exhibits intense red emission in 2-methyl-2,3,4,5-tetrahydrofuran (2-MeTHF) at 298 K, whereas the analogues 2 a-4 a are less or non-emissive under the same measurement conditions. All four complexes are highly emissive at 77 K. The heat-resistant properties toward thermal emission quenching (Φ298 K /Φ77 K ) increase in the order 1 a (0.52)>2 a (0.09)>3 a (0.02)>>4 a (0.00). We investigated the emission decay and thermal-deactivation processes using density functional theory (DFT), time-dependent (TD) DFT, and double-hybrid density functional theory (DHDF) calculations of N,N'-diethyl forms 1 b-4 b, and discuss the results with a focus on the energy levels, molecular structures, and electronic configurations in the triplet excited states. The energy differences between the triplet metal-ligand charge transfer (3 MLCT) state and minimum-energy crossing point between the lowest triplet state and singlet ground state (MECP) increase in the order 1 a>2 a, 3 a>4 a, consistent with the experimental results for the heat-resistant properties of these complexes. The origin of the present structure dependence of the 3 MLCT-MECP energy gap is ascribed to the ease or difficulty of the high-lying dσ* orbital participating in the MECP upon thermal structural distortion. The structure dependence in energy gaps between the π* and dσ* orbitals, which is key for facilitating the thermal deactivation process, is rationally correlated with the extent of aromaticity on the coordination platforms (1 b>(2 b, 3 b)>4 b).

Control of Metal Arrays Based on Heterometallics Masquerading in Heterochiral Aggregations of Chiral Clothespin-Shaped Complexes.

Heterometal arrays in molecular aggregations were obtained by the spontaneous and ultrasound-induced gelation of organic liquids containing the chiral, clothespin-shaped trans-bis(salicylaldiminato) d8 transition-metal complexes 1. Heterometallic mixtures of complexes 1 a (Pd) and 1 b (Pt) underwent strict heterochiral aggregation entirely due to the organic shell structure of the clothespin shape, with no effect of the metal cores. This phenomenon provides an unprecedented means of generating highly controlled heterometallic arrangements such as alternating sequences [(+)-Pd(-)-Pt(+)-Pd(-)-Pt⋅⋅⋅] as well as a variety of single metal-enriched arrays (e.g., [(+)-Pt(-)-Pd(+)-Pd(-)-Pd(+)-Pd(-)-Pd⋅⋅⋅] and [(+)-Pd(-)-Pt(+)-Pt(-)-Pt(+)-Pt(-)-Pt⋅⋅⋅]) upon the introduction of an optically active masquerading unit with a different metal core in the heterochiral single-metal sequence. The present method can be applied to form various new aggregates with optically active Pd and Pt units, to allow 1) tuning of the gelation ultrasound sensitivity based on the different hearing abilities of the metal units; 2) aggregation-induced chirality transfer between heterometallic species; and 3) aggregation-induced chirality enhancement. A mechanistic rationale is proposed for these molecular aggregations based on the molecular structures of the units and the morphologies of the aggregates.

Binuclear trans-bis(ß-iminoaryloxy)palladium(II) complexes doubly linked with pentamethylene spacers: structure-dependent flapping motion and heterochiral association behavior of the clothespin-shaped molecules.

The synthesis, structure, and solution-state behavior of clothespin-shaped binuclear trans-bis(ß-iminoaryloxy)palladium(II) complexes doubly linked with pentamethylene spacers are described. Achiral syn and racemic anti isomers of complexes 1-3 were prepared by treating Pd(OAc)2 with the corresponding N,N'-bis(ß-hydroxyarylmethylene)-1,5-pentanediamine and then subjecting the mixture to chromatographic separation. Optically pure (100 % ee) complexes, (+)-anti-1, (+)-anti-2, and (+)-anti-3, were obtained from the racemic mixture by employing a preparative HPLC system with a chiral column. The trans coordination and clothespin-shaped structures with syn and anti conformations of these complexes have been unequivocally established by X-ray diffraction studies. (1)H NMR analysis showed that (±)-anti-1, (±)-anti-2, syn-2, and (±)-anti-3 display a flapping motion by consecutive stacking association/dissociation between cofacial coordination planes in [D8]toluene, whereas syn-1 and syn-3 are static under the same conditions. The activation parameters for the flapping motion (ΔH(≠) and ΔS(≠)) were determined from variable-temperature NMR analyses as 50.4 kJ mol(-1) and 60.1 J mol(-1) K(-1) for (±)-anti-1, 31.0 kJ mol(-1) and -22.7 J mol(-1) K(-1) for (±)-anti-2, 29.6 kJ mol(-1) and -57.7 J mol(-1) K(-1) for syn-2, and 35.0 kJ mol(-1) and 0.5 J mol(-1) K(-1) for (±)-anti-3, respectively. The molecular structure and kinetic parameters demonstrate that all of the anti complexes flap with a twisting motion in [D8]toluene, although (±)-anti-1 bearing dilated Z-shaped blades moves more dynamically than I-shaped (±)-anti-2 or the smaller (±)-anti-3. Highly symmetrical syn-2 displays a much more static flapping motion, that is, in a see-saw-like manner. In CDCl3, (±)-anti-1 exhibits an extraordinary upfield shift of the (1)H NMR signals with increasing concentration, whereas solutions of (+)-anti-1 and the other syn/anti analogues 2 and 3 exhibit negligible or slight changes in the chemical shifts under the same conditions, which indicates that anti-1 undergoes a specific heterochiral association in the solution state. Equilibrium constants for the dimerizations of (±)- and (+)-anti-1 in CDCl3 at 293 K were estimated by curve-fitting analysis of the (1)H NMR chemical shift dependences on concentration as 26 M(-1) [KD(racemic)] and 3.2 M(-1) [KD(homo)], respectively. The heterochiral association constant [KD(hetero)] was estimated as 98 M(-1), based on the relationship KD(racemic) = 1/2 KD(homo) +1/4 KD(hetero). An inward stacking motif of interpenetrative dimer association is postulated as the mechanistic rationale for this rare case of heterochiral association.

A clothes-peg-shaped binuclear trans-bis(2-aminotroponato)palladium(II) complex bearing pentamethylene spacers.

rac-Bis{µ-trans-2,2'-[pentane-1,5-diylbis(azanediyl)]ditroponato}dipalladium(II), [Pd2(C19H20N2O2)2], has been synthesized and fully characterized using single-crystal X-ray diffraction, (1)H NMR, FT-IR and mass spectroscopy. The trans coordination, vaulted structure and anti conformation have been unequivocally established from the X-ray diffraction studies. This is the first example of a bis(aminotroponato)palladium complex. In the crystalline state, the molecule has twofold symmetry and each molecular unit undergoes intermolecular offset π-stacking of the tropone rings to afford heterochiral interpenetrating dimers that are aligned in a lamellar manner with a herringbone packing motif.