Gaku Fukuhara

Explaining the highly enantiomeric photocyclodimerization of 2-anthracenecarboxylate bound to human serum albumin using time-resolved anisotropy studies.

The mechanism for the high enantiomeric excess (ee) (80-90%) observed in the photocyclodimerization of 2-anthracenecarboxylate (AC) in the chiral binding sites of human serum albumin (HSA) was studied using fluorescence anisotropy. A long rotational correlation time of 36 ns was observed for the excited states of the ACs bound to the HSA site responsible for the high ee, suggesting that the ACs have restricted rotational mobility in this site. The ACs in this site have the same prochiral face protected by the protein, and this protection is responsible for the high ee observed. These insights provide a strategy for the rational design of supramolecular photochirogenic systems.

Highly Selective Oligosaccharide Sensing by a Curdlan−Polythiophene Hybrid

An in situ hybrid complex of Curdlan with water-soluble polythiophene functioned as a highly sensitive and selective saccharide chemosensor in aqueous media, enabling us to discriminate tetrasaccharide acarbose at 1 μM from 24 mono-, di-, tri-, tetra-, and pentasaccharides.

Ammonia-Driven Chirality Inversion and Enhancement in Enantiodifferentiating Photocyclodimerization of 2-Anthracenecarboxylate Mediated by Diguanidino-γ-cyclodextrin

In the supramolecular photocyclodimerization of 2-anthracenecarboxylate mediated by 6(A),6(D)-diguanidino-γ-cyclodextrin (CD), the chiral sense and enantiomeric excess of the photoproduct were dynamic functions of temperature and cosolvent to afford the (M)-anti head-to-head cyclodimer in 64% ee in aqueous methanol at -70 °C but the antipodal (P)-isomer in 86% ee in aqueous ammonia at -85 °C, while the corresponding diamino-γ-CD host did not show such unusual photochirogenic behaviors. The ee landscape was very steep against the temperature and sign-inverted against the ammonia content to reveal the opposite temperature dependence at low and high ammonia contents, for which an altered solvent structure and/or guanidinium-carboxylate interaction mode would be responsible.

Phase-controlled supramolecular photochirogenesis in cyclodextrin nanosponges

Pyromellitate-bridged cyclodextrin nanosponges (CDNSs) evolved from sol into gel state upon gradual increase of the concentration from 0.2 to 2000 mg mL(-1) in water. The enantiodifferentiating geometrical photoisomerizations of (Z)-cyclooctene and (Z,Z)-1,3-cyclooctadiene sensitized by CDNS at various concentrations were critically affected by the phase transition of CDNS to afford the corresponding (E)- and (E,Z)-isomers in the highest enantiomeric excesses in the gel state.

Chirality‐Sensing Binaphthocrown Ether–Polythiophene Conjugate

An enantiomeric binaphthyl unit was tethered to adjacent thiophenes with oxyethylene linkers to give a chiral polythiophene with binaphthocrown ether cavities. Upon inclusion of a chiral cationic guest in the cavity of the chiral crown ether-polythiophene conjugate, the bithiophene unit was twisted to shorten the effective conjugation length of polythiophene backbone, enabling us to sense the guest binding by reading out the amplified optical signal gains arising from the backbone structure change. This strategy allowed us to discriminate the guest chirality without using chiroptical signals or a circular dichroism spectrometer to achieve the highest enantioselectivity of 7.3 for valine methyl ester with a 40-fold enhanced sensitivity compared with the corresponding monomeric sensor.

Inherently Chiral Azonia[6]helicene-Modified β-Cyclodextrin: Synthesis, Characterization, and Chirality Sensing of Underivatized Amino Acids in Water

The (P)- and (M)-3-azonia[6]helicenyl β-cyclodextrins exhibit L/D selectivities of up to 12.4 and P/M preferences of up to 28.2 upon complexation with underivatized proteinogenic amino acids in aqueous solution at pH 7.3.

Cyclodextrin nanosponge-sensitized enantiodifferentiating photoisomerization of cyclooctene and 1,3-cyclooctadiene

Summary Enantiodifferentiating geometrical photoisomerizations of (Z)-cyclooctene and (Z,Z)-1,3-cyclooctadiene were performed by using the pyromellitate-linked cyclodextrin network polymer, termed “cyclodextrin nanosponge (CDNS)”, as a supramolecular sensitizing host. The photochirogenic behavior of the nanosponges incorporating β- or γ-cyclodextrin was significantly different from that reported for the conventional sensitizer-appended monomeric cyclodextrins, affording chiral (E)-cyclooctene and (E,Z)-cyclooctadiene in enantiomeric excesses critically dependent on the solution pH and solvent composition employed, revealing the active roles of chiral void spaces of CDNS in the photochirogenic reaction.

Bio-supramolecular photochirogenesis with molecular chaperone: enantiodifferentiating photocyclodimerization of 2-anthracenecarboxylate mediated by prefoldin

Photocyclodimerization of 2-anthracenecarboxylate mediated by molecular chaperone protein was performed for the first time to afford chiral syn-head-to-tail and anti-head-to-head dimers (2 and 3) in 10% and 16% enantiomeric excess, respectively, with enhanced yields of sterically and electrostatically less-favored head-to-head dimers (3 and 4).

Photochirogenesis in chiral ionic liquid: enantiodifferentiating [4+4] photocyclodimerization of 2-anthracenecarboxylic acid in (R)-1-methyl-3-(2,3-dihydroxypropyl)imidazolium bistriflimide

Enantiodifferentiating photocyclodimerization of 2-anthracenecarboxylic acid and its alkali metal salts performed in a chiral ionic liquid gave chiral cyclodimers in good enantiomeric excesses of up to 41%, which is the highest ever reported for a photochirogenic reaction in chiral media.

Cross- versus Homo-Photocyclodimerization of Anthracene and 2-Anthracenecarboxylic Acid Mediated by a Chiral Hydrogen-Bonding Template. Factors Controlling the Cross-/Homo-Selectivity and Enantioselectivity

Competitive cross-/homo-photocyclodimerization of anthracene (AN) and 2-anthracenecarboxylic acid (AC) mediated by a chiral hydrogen-bonding template (TKS) was investigated under various conditions. The cross-photocyclodimerization was favored by a factor of 4-5 at all temperatures and wavelengths examined to afford the AC-AN cross-dimer in 80-84% yield even at AN/AC = 1 and in 98% yield at AN/AC = 10. The enantiomeric excesses (ees) obtained were 27-47% for the homo-dimers and 21-24% for the cross-dimer. The absolute configuration of the cross-dimer was determined by comparing the experimental and theoretical circular dichroism spectra and further correlated with the re/si enantiotopic-face selectivity upon AC-TKS complexation in the ground state. Detailed analyses of the complexation behavior and the fluorescence lifetime and cyclodimerization rate of excited re/si complexes revealed that the products ee is critically controlled not only by the relative abundance of the re/si complexes in the ground and excited states but also by their relative photocyclodimerization rate. Crucially, the ground-state thermodynamics and the excited-state kinetics are not synergistic but offsetting in enantiotopic-face selectivity, and the latter overwhelms the former to give the homo- and cross-dimers in modest ees. Finally, some practical strategies for enhancing the enantioselectivity in chiral template-mediated photochirogenesis have been proposed.