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

Regioselective Molecularly Imprinted Reaction Field for [4 + 4] Photocyclodimerization of 2‑Anthracenecarboxylic Acid

Molecularly imprinted cavities have functioned as a regioselective reaction field for the [4 + 4] photocyclodimerization of 2-anthracenecarboxylic acid (2-AC). Molecularly imprinted polymers were prepared by precipitation polymerization of <i>N</i>-methacryloyl-4-aminobenzamidine as a functional monomer to form a complex with template 2-AC and ethylene glycol dimethacrylate as a crosslinking monomer. The 2-AC-imprinted cavities thus constructed preferentially bound 2-AC with an affinity greater than that toward structurally related 9-anthracenecarboxylic acid, 2-aminoanthracene, and unsubstituted anthracene. Moreover, from the four possible regioisomeric cyclodimers, they mediated the [4 + 4] photocyclodimerization of 2-AC specifically to the <i>anti</i>-head-to-tail (<i>anti</i>-HT) isomer. This indicates that the imprinted cavities accommodate two 2-AC molecules in an <i>anti</i>-HT manner, thereby facilitating the subsequent regioselective photocyclodimerization

pH-Independent Charge Resonance Mechanism for UV Protective Functions of Shinorine and Related Mycosporine-like Amino Acids

The UV-protective ability of mycosporine-like amino acids (MAAs) has been well documented and is believed to serve as a protecting agent for marine organisms from solar radiation. However, the effective UV absorption by MAAs has not been well correlated to MAA (neutral) structures. In this study, the origin of UV-protecting ability of MAAs was elucidated by experimental and theoretical spectroscopic investigations. The absorption maxima of mycosporine–glycine and shinorine in the UVA region were practically unaffected over a wide range of pH 4–10 and only slightly blue-shifted at pH 1–2. It was revealed that the zwitterionic nature of the amino acid residue facilitates the protonation to the chromophoric 3-aminocyclohexenone and 1-amino-3-iminocyclohexene moieties and the operation of the charge resonance in the protonated species well accounts for their allowed low-energy transitions in the UVA region. The RI-CC2/TZVP calculations on model systems in their protonated forms well reproduced the observed transition energies and oscillator strengths of MAAs, only with insignificant systematic overestimations of the both values. The slight hypsochromic shifts at pH 1–2 were explained by (partial) protonation to a carboxylate anion in the amino acid residue, as confirmed by theory. Fluorescence spectral investigations of shinorine were also performed for the first time in water to confirm the effective nonradiative deactivation. Consequently, this study unequivocally demonstrated that the 3-aminocyclohexenone as well as 1-amino-3-iminocyclohexene moieties, which are readily protonated at a wide range of pH, are responsible for the UV-protective ability of aqueous solution of MAAs

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 (ee’s) 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 <i>re/si</i> 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 <i>re/si</i> complexes revealed that the product’s ee is critically controlled not only by the relative abundance of the <i>re/si</i> 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 ee’s. Finally, some practical strategies for enhancing the enantioselectivity in chiral template-mediated photochirogenesis have been proposed

Enantiodifferentiating Photocyclodimerization of 2‑Anthracenecarboxylic Acid via Competitive Binary/Ternary Hydrogen-Bonded Complexes with 4‑Benzamidoprolinol

Circular dichroism (CD) spectral examinations at various host/guest ratios revealed that 2-anthracenecarboxylic acid (AC) forms not only 1:1 but also novel 2:1 hydrogen-bonded/π-stacked complexes with a chiral 4-benzamidoprolinol template (TKS159). The 2:1 complexation is a minor process but causes significant CD spectral changes as a consequence of the exciton coupling interaction of two AC chromophores and greatly accelerates the head-to-head photocyclodimerization to significantly affect the stereochemical outcomes

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 (<i>M</i>)-<i>anti</i> head-to-head cyclo­dimer in 64% ee in aqueous methanol at −70 °C but the anti­podal (<i>P</i>)-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

Supramolecular Photochirogenesis with a Higher-Order Complex: Highly Accelerated Exclusively Head-to-Head Photocyclodimerization of 2‑Anthracenecarboxylic Acid via 2:2 Complexation with Prolinol

An unprecedented 2:2 complex was shown to intervene in the enantiodifferentiating photocyclodimerization of 2-anthracenecarboxylic acid (<b>A</b>) mediated by a hydrogen-bonding template l-prolinol (<b>P</b>) to accelerate the formation of chiral <i>anti-head-to-head</i> and achiral <i>syn-head-to-head</i> cyclodimers in >99% combined yield with enhanced enantioselectivities of up to 72% ee for the former. The supramolecular complexation and photochirogenic behaviors, as well as the plausible structures, of intervening <b>A</b>_<i>m</i>·<b>P</b>_<i>n</i> complexes (<i>m</i>, <i>n</i> = 1 or 2) were elucidated by combined theoretical and experimental spectroscopic, photophysical, and photochemical studies. Furthermore, the photochemical chiral amplification was achieved for the first time by utilizing the preferential 2:2 complexation of <b>A</b> with homochiral <b>P</b> to give normalized product enantioselectivities higher than those of the template used. The present strategy based on the higher-order hydrogen-bonding motif, which is potentially applicable to a variety of carboxylic acids and β-aminoalcohols, is not only conceptually new and expandable to other (photo)­chirogenic and sensing systems but also may serve as a versatile tool for achieving photochemical asymmetric amplification and constructing chiral functional supramolecular architectures

Supramolecular Photochirogenesis Driven by Higher-Order Complexation: Enantiodifferentiating Photocyclodimerization of 2‑Anthracenecarboxylate to Slipped Cyclodimers via a 2:2 Complex with β‑Cyclodextrin

Chiral slipped 5,8:9′,10′-cyclodimers were preferentially produced over classical 9,10:9′,10′-cyclodimers upon supramolecular photocyclodimerization of 2-anthracenecarboxylate (AC) mediated by β-cyclodextrin (β-CD). This photochirogenic route to the slipped cyclodimers, exclusively head-to-tail (HT) and highly enantioselective, has long been overlooked in foregoing studies but is dominant in reality and is absolutely supramolecularly activated by 2:2 complexation of AC with β-CD. The intricate structural and photophysical aspects of this higher-order complexation-triggered process have been comprehensively elucidated, while the absolute configurations of the slipped cyclodimers have been unambiguously assigned by comparing the experimental and theoretical circular dichroism spectra. In the 2:2 complex, two ACs packed in a dual β-CD capsule are not fully overlapped with each other but are only partially stacked in a slipped <i>anti</i>- or <i>syn</i>-HT manner. Hence, they do not spontaneously cyclodimerize upon photoexcitation but instead emit long-lived excimer fluorescence at wavelengths slightly longer than the monomer fluorescence, indicating that the slipped excimer is neither extremely reactive nor completely relaxed in conformation and energy. Because of the slipped conformation of the AC pair in the soft capsule, the subsequent photocyclodimerization becomes manipulable by various internal or external factors, such as temperature, pressure, added salt, and host modification, enabling us to exclusively obtain the slipped cyclodimers with high regio- and enantioselectivities. In this supramolecularly driven photochirogenesis, the dual β-CD capsule functions as a chiral organophotocatalyst to trigger and accelerate the nonclassical photochirogenic route to slipped cyclodimers by preorganizing the conformation of the encapsulated AC pair, formally mimicking a catalytic antibody

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

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