Enantiomer separation of 2-halomandelic acids via diastereomeric salt formation with chiral N-substituted 2-amino-2-phenylethanols.

Chiral N-substituted secondary 1,2-aminoalcohols have been developed for the enantioseparation of ortho-halomandelic acids (o-X-MAs) via diastereomeric salt formation. Two structural isomers, N-methyl-2-amino-1,2-diphenylethanol and N-benzyl-2-amino-2-phenylethanol, showed high separation abilities for o-X-MAs (X = Cl, Br, I). The chiral recognition mechanism was elucidated by crystallographic analysis of the less-soluble salts. The substituents on the nitrogen atom of the resolving agents and the inclusion of the crystallization solvent stabilized the salt and enhanced their separation ability.

Chemical Storage of Ammonia through Dynamic Structural Transformation of a Hybrid Perovskite Compound.

Toward renewable energy for global leveling, compounds that can store ammonia (NH3), a carbon-free energy carrier of hydrogen, will be of great value. Here, we report an organic-inorganic halide perovskite compound that can chemically store NH3 through dynamic structural transformation. Upon NH3 uptake, a chemical structure change occurs from a one-dimensional columnar structure to a two-dimensional layered structure by addition reaction. NH3 uptake is estimated to be 10.2 mmol g-1 at 1 bar and 25 °C. In addition, NH3 extraction can be performed by a condensation reaction at 50 °C under vacuum. X-ray diffraction analysis reveals that reversible NH3 uptake/extraction originates from a cation/anion exchange reaction. This structural transformation shows the potential to integrate efficient uptake and extraction in a hybrid perovskite compound through chemical reaction. These findings will pave the way for further exploration of dynamic, reversible, and functionally useful compounds for chemical storage of NH3.

Development of Low-Molecular-Weight Organogelators from Cyclic ß-Amino Acid: Effect of Stereochemistry and their Application on Visual Chiral Recognition of Amines.

This study reports the formation of low-molecular-weight gelators based on carboxylic acids derived from chiral cyclicß-amino acids. The effect of their stereochemistry on the gelation of organic solvents was investigated, and their assemblies with the intermolecular interactions in the xerogels were proposed via infrared spectroscopy, X-ray diffraction, scanning electron microscopy, and crystallographic details of the related model compounds. The effect of the alkyl chain length on the gelators was studied, and they were applied to the chiral recognition of amines. Only one diastereomeric salt with amines afforded gels, whereas the others resulted in precipitates. Chiral recognition was also achieved in the gel state, and the appearance of the as-prepared gel changed upon the addition of each amine enantiomer, thus enabling the visual detection of their chirality.

Enantioseparation of 3-Hydroxycarboxylic Acids via Diastereomeric Salt Formation by 2-Amino-1,2-diphenylethanol (ADPE) and Cinchonidine.

Enantioseparation of 3-hydroxycarboxylic acids via diastereomeric salt formation was demonstrated using 2-amino-1,2-diphenylethanol (ADPE) and cinchonidine as the resolving agents. Racemic 3-hydroxy-4-phenylbutanoic acid (rac-1), 3-hydroxy-4-(4-chlorophenyl)butanoic acid (rac-2), and 3-hydroxy-5-phenylpentanoic acid (rac-3) were efficiently resolved using these resolving agents. Moreover, the successive crystallization of the less-soluble diastereomeric salt of 1 and cinchonidine using EtOH yielded pure (R)-1 · cinchonidine salt in a high yield. The crystal structures of less-soluble diastereomeric salts were elucidated and it was revealed that hydrogen bonding and CH/π interactions play an important role in reinforcing the structure of the less-soluble diastereomeric salts.

Tubular Network Formation by Mixing Amphiphilic Polypeptides with Differing Hydrophilic Blocks.

Artificial tubular networks are promising structures for biomaterial applications because of their large surface areas. A tubular network was formed by co-assembling two different amphiphilic polypeptides, poly(ethylene glycol)-b-(l-Leu-Aib)6 (PL12) and polysarcosine-b-(l-Leu-Aib)6 (SL12). They both have the same hydrophobic 12-mer helical block (l-Leu-Aib)6 but different hydrophilic chains, poly(ethylene glycol) and polysarcosine. In water, both polypeptides self-assembled into a tubular structure having a uniform 80 nm diameter that was formed by packing among the hydrophobic L12 blocks. The SL12 nanotubes were short (200 nm), straight, and robust. PL12 formed long (>1 µm), bendable, and fusogenic nanotubes. The amphiphiles were then co-assembled with various mixing ratios to form tubular networks. Higher concentrations of PL12 made the nanotubes more bendable and fusogenic between open tube ends, which produced branching junctions under heat treatment.

Phosphorogenic and spontaneous formation of tris(bipyridine)ruthenium in peptide scaffolds.

Redox-active ruthenium complexes have been widely used in various fields; however, the harsh conditions required for their synthesis are not always conducive to their subsequent use in biological applications. In this study, we demonstrate the spontaneous formation of a derivative of tris(bipyridine)ruthenium at 37°C through the coordination of three bipyridyl ligands incorporated into a peptide to a ruthenium ion. Specifically, we synthesized six bipyridyl-functionalized peptides with randomly chosen sequences. The six peptides bound to ruthenium ions and exhibited similar spectroscopic and electrochemical features to tris(bipyridine)ruthenium, indicating the formation of ruthenium complexes as we anticipated. The photo-excited triplet state of the ruthenium complex formed in the peptides exhibited an approximately 1.6-fold longer lifetime than that of tris(bipyridine)ruthenium. We also found that the photo-excited state of the ruthenium complexes was able to transfer an electron to methyl viologen, indicating that the ruthenium complexes formed in the peptides had the same ability to transfer charge as tris(bipyridine)ruthenium. We believe that this strategy of producing ruthenium complexes in peptides under mild conditions will pave the way for developing new metallopeptides and metalloproteins containing functional metal-complexes.

Spontaneous Formation of Gating Lipid Domain in Uniform-Size Peptide Vesicles for Controlled Release.

Hybrid assemblies composed of phospholipids and amphiphilic polymers have been investigated previously as a biomimetic model of biological cells. However, these studies focused on the functions of polymers in a sea of membrane lipids. Here, we prepared a highly stable peptide-lipid hybrid vesicle from a combination of an amphiphilic polypeptide and the phospholipid, 1,2-dimyristoyl- sn-glycero-3-phosphocholine, with a mixing molar ratio of 1:1. The phase-separated structure of the hybrid vesicle was demonstrated by fluorescence resonance energy transfer analysis. The lipid domain of the hybrid vesicle had a phase-transition temperature of 38 °C and allowed the permeation of a hydrophilic molecule, fluorescein isothiocyanate-labeled polyethylene glycol ( Mw: 2000), above 38 °C. The designed peptide-lipid hybrid vesicle and a "lipidic gate" are a promising tool for smart drug delivery.

Photocatalytic CO2 Reduction by Trigonal-Bipyramidal Cobalt(II) Polypyridyl Complexes: The Nature of Cobalt(I) and Cobalt(0) Complexes upon Their Reactions with CO2, CO, or Proton.

The cobalt complexes CoIIL1(PF6)2 (1; L1 = 2,6-bis[2-(2,2'-bipyridin-6'-yl)ethyl]pyridine) and CoIIL2(PF6)2 (2; L2 = 2,6-bis[2-(4-methoxy-2,2'-bipyridin-6'-yl)ethyl]pyridine) were synthesized and used for photocatalytic CO2 reduction in acetonitrile. X-ray structures of complexes 1 and 2 reveal distorted trigonal-bipyramidal geometries with all nitrogen atoms of the ligand coordinated to the Co(II) center, in contrast to the common six-coordinate cobalt complexes with pentadentate polypyridine ligands, where a monodentate solvent completes the coordination sphere. Under electrochemical conditions, the catalytic current for CO2 reduction was observed near the Co(I/0) redox couple for both complexes 1 and 2 at E1/2 = -1.77 and -1.85 V versus Ag/AgNO3 (or -1.86 and -1.94 V vs Fc+/0), respectively. Under photochemical conditions with 2 as the catalyst, [Ru(bpy)3]2+ as a photosensitizer, tri- p-tolylamine (TTA) as a reversible quencher, and triethylamine (TEA) as a sacrificial electron donor, CO and H2 were produced under visible-light irradiation, despite the endergonic reduction of Co(I) to Co(0) by the photogenerated [Ru(bpy)3]+. However, bulk electrolysis in a wet CH3CN solution resulted in the generation of formate as the major product, indicating the facile production of Co(0) and [Co-H] n+ ( n = 1 and 0) under electrochemical conditions. The one-electron-reduced complex 2 reacts with CO to produce [Co0L2(CO)] with νCO = 1894 cm-1 together with [CoIIL2]2+ through a disproportionation reaction in acetonitrile, based on the spectroscopic and electrochemical data. Electrochemistry and time-resolved UV-vis spectroscopy indicate a slow CO binding rate with the [CoIL2]+ species, consistent with density functional theory calculations with CoL1 complexes, which predict a large structural change from trigonal-bipyramidal to distorted tetragonal geometry. The reduction of CO2 is much slower than the photochemical formation of [Ru(bpy)3]+ because of the large structural changes, spin flipping in the cobalt catalytic intermediates, and an uphill reaction for the reduction to Co(0) by the photoproduced [Ru(bpy)3]+.

Fluorogenic Enhancement of an in Vitro-Selected Peptide Ligand by Replacement of a Fluorescent Group.

To prepare a fluorogenic peptide ligand which binds to an arbitrary target, we previously succeeded in seeking a fluorogenic ligand to calmodulin using in vitro selection. In this study the environment-sensitive fluorescent group in the selected peptide ligand was replaced with other fluorescent groups to find the possibility to increase the fluorogenic activity. Surface plasmon resonance measurement exhibited that the binding affinity was held even after the replacement. However, the replacement significantly affected the fluorogenic activity. It depended on the kind of incorporated fluorophors and linker length. As a result, the incorporation of 4-N,N-dimethylamino-1,8-naphthalimide enhanced the fluorescence intensity over 100-fold in the presence of target calcium-bound calmodulin. This study demonstrated that the functionality of in vitro selected peptide can be tuned with keeping the binding affinity.

Enantioseparation via Chiral Supramolecular Gels Comprising Ambidextrous Gelators Based on ß-Peptide-type Primary Amines.

While ß-peptides have been paid attention due to their diverse secondary structures, their application to the design of low-molecular-weight gelators (LMWGs) is less explored. In this work, chiral cyclic ß-amino acid-based ß-peptides were developed as ambidextrous LMWGs, wherein multiple hydrogen bonds between the amide moieties led to high gelation ability. Their molecular assembly was elucidated using spectroscopies, microscopy, and X-ray analysis. Further, the supramolecular gel was used as a platform for the enantioselective extraction of (S)-naproxen from its racemate under optimized conditions. These findings have expanded the utility of ß-peptides and shown the potential of supramolecular gels as a distinct dynamic medium for enantiomer separation.

Solvent-induced reversed stereoselectivity in reciprocal resolutions of mandelic acid and erythro-2-amino-1,2-diphenylethanol.

Solvent-induced chirality switching in reciprocal optical resolution between mandelic acid (1) and erythro-2-amino-1,2-diphenylethanol (2) has been demonstrated. The stereochemistry of the deposited salts was controlled by changing the crystallization solvent from 1-PrOH or 1-BuOH to 1,4-dioxane. It was revealed from (1)H NMR spectra, thermogravimetric analysis, and X-ray crystallography of the salts that an equimolar amount of the crystallization solvent was incorporated in each diastereomeric salt. On the basis of the crystal structures, it was found that both the hydrogen-bonding ability and the size of the solvent molecule played an important role. Differences in the formed hydrogen-bonding networks (columnar or sheetlike structure) and their packing manner were found to be crucial for the reversed stereoselectivity. Furthermore, pseudopolymorphic salt crystals that incorporated 1,4-dioxane were obtained during the enantioseparation of racemic 2, and their solid-state properties were examined by measurement of their IR spectra. This solvent-induced dual stereocontrol technique was successfully applied to the successive resolution process, eliminating the need to change the resolving agent for access to both enantiomers of 1 and 2.

Thermoreversible helical fibers from photoreactive triphenylene-derived liquid crystals in liquid paraffin.

Liquid crystalline triphenylene derivatives, TPC1p-n (n = 6, 12, 14, 16) were prepared using p-alkoxycinnamate as the [2+2] photo-cyclization site. TPC1p-n (n = 12, 14, 16) showed Colr phase and gave crescent-shaped or helical fibers after UV-irradiated in liquid paraffin solutions at 90 and 110 °C in the Colr temperature range. The apparent photoreaction products were shown to be thermally reversible, i.e. they dissolved in liquid paraffin at high temperatures and reappeared on cooling, indicating that they were aggregates of oligomerized TPC1p-n. The reaction mechanism was discussed in terms of the structure of the liquid crystalline phase.

Highly efficient D2 generation by dehydrogenation of formic acid in D2O through H+/D+ exchange on an iridium catalyst: application to the synthesis of deuterated compounds by transfer deuterogenation.

Deuterated compounds have received increasing attention in both academia and industrial fields. However, preparations of these compounds are limited for both economic and practical reasons. Herein, convenient generation of deuterium gas (D(2)) and the preparation of deuterated compounds on a laboratory scale are demonstrated by using a half-sandwich iridium complex with 4,4'-dihydroxy-2,2'-bipyridine. The "umpolung" (i.e., reversal of polarity) of a hydrogen atom of water was achieved in consecutive reactions, that is, a cationic H(+)/D(+) exchange reaction and anionic hydride or deuteride transfer, under mild conditions. Selective D(2) evolution (purity up to 89 %) was achieved by using HCO(2)H as an electron source and D(2)O as a deuterium source; a rhodium analogue provided HD gas (98 %) under similar conditions. Furthermore, pressurized D(2) (98 %) without CO gas was generated by using DCO(2)D in D(2)O in a glass autoclave. Transfer deuterogenation of ketones gave α-deuterated alcohols with almost quantitative yields and high deuterium content by using HCO(2)H in D(2)O. Mechanistic studies show that the H(+)/D(+) exchange reaction in the iridium hydride complex was much faster than ß-elimination and hydride (deuteride) transfer.

Cyanative self-condensation of aromatic aldehydes promoted by VO(O(i)Pr)(3)-Lewis base as a cooperative catalyst.

Self-condensation of aromatic aldehydes with trimethylsilyl cyanide proceeded by the cooperative catalytic effect of VO(O(i)Pr)(3) and a Lewis base to give the corresponding O-acylated cyanohydrins. The reaction conversion and selectivity were strongly dependent on the solvent used, the Lewis base, and the presence of oxygen. All the nine kinds of aromatic aldehydes considered herein afforded the O-acylated cyanohydrins with excellent selectivity under an O(2) atmosphere.

Enantioseparation of 1-arylethanols via a supramolecular chiral host consisting of N-(2-naphthoyl)-L-aspartic acid and an achiral diamine.

A supramolecular chiral host consisting of N-(2-naphthoyl)-L-aspartic acid (L-1) and meso-1,2-diphenylethylenediamine (2) is effective in enantioseparation of 1-arylethanols (up to 96% ee with 100% inclusion ratio). Here we report three different methods to prepare the inclusion crystals and discuss the chiral recognition mechanism on the basis of X-ray crystallography results.

Construction of hydrogen-bonded ternary organic crystals derived from L-tartaric acid and their application to enantioseparation of secondary alcohols.

Ternary organic crystals consisting of an L-tartaric acid-derived dicarboxylic acid, a commercially available achiral diamine, and a chiral secondary alcohol have been developed and characterized by X-ray crystallography. 1D, 2D, and 3D hydrogen-bonded supramolecular networks were constructed, depending on the structure of the diamine used. Benzylic and aliphatic secondary alcohols were enantioselectively incorporated into the crystal and were successfully enantioseparated with up to 86 and 79% enantiomeric excess (ee), respectively. Selective incorporation of one enantiomer of 2-butanol, which is a small chiral aliphatic alcohol, was achieved by the cooperative effects of hydrogen bonds, CH···π interactions, and van der Waals interactions between the guest and host molecules, with the aid of two water molecules. The high host potential of the binary supramolecular system is mainly attributed to the skewed conformation of two rigid aromatic groups of tartaric acid derivatives, which prevents dense packing of the molecules and enhances the formation of multicomponent inclusion crystals.

Synthesis of chiral 1,3-diamines derived from cis-2-benzamidocyclohexanecarboxylic acid and their application in the Cu-catalyzed enantioselective Henry reaction.

In this study, 13 different chiral 1,3-diamines were synthesized from (-)-cis-2-benzamidocyclohexanecarboxylic acid. They were successfully applied as ligands in the Cu-catalyzed asymmetric Henry reaction between benzaldehyde and nitromethane. It was confirmed that the enantioselectivity of the product could be controlled by the substituents on the two amino groups. A time-course study revealed a decrease in product enantioselectivity caused by spontaneous retro-Henry reaction, which was suppressed by conducting the reaction at 0 °C. This versatile reaction afforded various ß-nitroalcohols in excellent yields and enantioselectivities (up to 98% yield, 91% enantiomeric excess) under the optimized reaction conditions. The chiral induction mechanism was explained on the basis of a previously proposed transition-state model.

Switching of enantioselectivity in the catalytic addition of diethylzinc to aldehydes by regioisomeric chiral 1,3-amino sulfonamide ligands.

Twenty chiral 1,3-amino sulfonamides of two classes (2a-i and 3a-k) have been prepared from (-)-cis-2-benzamidocyclohexanecarboxylic acid (1) and studied as ligands for catalytic enantioselective addition of Et(2)Zn to a variety of aromatic and aliphatic aldehydes. The ligands 2 and 3 are regioisomers in which the position of the amine and sulfonamide groups is exchanged. Each class of ligands with the same chirality was shown to afford sec-alcohols with the opposite stereochemistry. Structural surveys revealed that the combination of tertiary amino and p-toluenesufonylamido groups works most effectively for the reaction. Through optimization of the structural and reaction conditions, the best ligands quantitatively provided both enantiomeric secondary alcohols in good to excellent enantioselectivity of up to 94% and 98% ee for (S)- and (R)-enantiomers, respectively.

Solvent-induced chirality control in the enantioseparation of 1-phenylethylamine via diastereomeric salt formation.

Solvent-induced chirality control in the enantioseparation of 1-phenylethylamine 1 by N-(p-toluenesulfonyl)-(S)-phenylalanine 2 via diastereomeric salt formation was studied. (S)-1·(S)-2 was preferentially crystallized as a less-soluble salt from aqueous alcohol, while (R)-1·(S)-2 salt was mainly obtained by addition of solvents with a six-membered ring such as dioxane, cyclohexane, tetrahydropyran, and cyclohexene to 2-propanol. Further investigations were carried out from the viewpoints of molecular structures, optical rotation measurement, and X-ray crystallographic analyses. Crystallographic analyses have revealed that incorporation of the six-membered ring solvent molecule in (R)-1·(S)-2 without hydrogen bonds changed the molecular conformation of (S)-2 to stabilize the salt, which changed the selectivity of 1 in the enantioseparation.

Direct enantioseparation of axially chiral 1,1'-biaryl-2,2'-diols using amidine-based resolving agents.

Amidine-based optically active resolving agents for enantiomer separation of axially chiral 1,1'-biaryl-2,2'-diols have been developed. A strongly basic amidine bearing no substituents on its nitrogen atoms enables the formation of their diastereomeric salts upon being mixed with weakly acidic phenol derivatives. Enantiopure 1,1'-biaryl-2,2'-diols can be obtained in high yields after only one crystallization of their salts with the chiral amidine derived from dehydroabietic acid. X-ray crystallography revealed that the amidine moiety forms a salt with the phenol group and additional intermolecular NH/π interactions contribute to the efficient chiral recognition process.