Induced Circular Dichroism of Achiral Cyclic Bisurea via Hydrogen Bonds with Chiral Carboxylates

Abstract

Chiral induction properties of achiral bisurea derivatives by binding tetrabutylammonium salts of N-acetylated chiral carboxylates (Ac-AlaO–, Ac-ValO–, Ac-LeuO–, and Ac-PheO–) was studied. Ultraviolet–visible titrations showed 1:1 complex formation between the bisureas and the carboxylates. The calculated association constants of cyclic bisurea (1a) were 5–10 times larger than those of the acyclic derivative (2), and 1a showed the highest binding affinity for Ac-LeuO–. While circular dichroism (CD) of both 1a and 2 was induced upon the addition of chiral carboxylates, the CD intensity of 1a was greater than that of 2. Especially, the intensity induced by chiral Ac-LeuO– was the greatest. 1H nuclear magnetic resonance titrations and density functional theory (DFT) calculations showed the cooperative hydrogen bonds of four urea N–Hs and the carboxylate group and the CH−π interactions between a naphthyl unit of 1a and the methyl moieties of Ac-LeuO–. Furthermore, DFT calculations suggested that the twisted anticlockwise conformation of 1a would be dominantly induced by Ac-d-LeuO–. The CD intensity changes of 1a showed a good linear relationship with the enantiomeric excess (ee) values of Ac-LeuO–; therefore, 1a could be utilized as a stereodynamic chiral probe for determining the ee of chiral anions.

Circular Dichroism Based Chirality Sensing with Supramolecular Host–Guest Chemistry

“…The hexaurea cage developed by Davis and co‐workers ( 23 , Figure 10c) [60] can not only selectively and effectively bind glucose in water, but also can work as a chirality sensor for this monosaccharide, [61] and could be used for the continuous monitoring of glucose concentration in blood. A bisurea macrocycle ( 24 , Figure 10d) [62] was used for the chiroptical sensing of chiral carboxylates in nonpolar solvents through hydrogen bonding and C−H⋅⋅⋅π interactions. DFT calculations reveal that a twisted conformation is induced after binding to chiral carboxylates.…”

Advances in Chirality Sensing with Macrocyclic Molecules

“…Kondo et al reported [17] the synthesis of a bisurea-based macrocycle 6 and an acyclic bisurea analog for the purpose of chirality sensing of chiral carboxylic acid anions (Figure 4). These bisureas form a 1:1 complex with chiral carboxylates through hydrogen-bonding interaction in MeCN with high binding affinity up to 10 7 M −1 .…”

Quantitative Kinetic Modeling in Photoresponsive Supramolecular Chemistry: The Case of Water-Soluble Azobenzene/Cyclodextrin Complexes

“…Different spectroscopic techniques such as NMR, UV-visible absorption, or circular dichroism have traditionally been used to demonstrate supramolecular complexation. We have used three complementary techniques: circular dichroism to determine whether the complex was formed or not, NMR for the stoichiometry elucidation and UV-visible spectrophotometry 18 to obtain the association equilibrium constant and the spectra of the supramolecular complexes.…”