Tokyo University of Science
Successful synthesis of a double-helical zinc complex capable of chirality switching ~ Chiral amplification via chiral transfer to an achiral ligand is also possible ~
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[Research summary and points]
We synthesized a zinc (Zn) mononuclear complex with a double helical structure and clarified that the left-right winding direction of the helix can be reversed depending on the properties of the solvent used. A heteroleptic complex (*2) consisting of a ligand with a chiral (*1) moiety and a ligand without a chiral moiety has the ability to reversely switch the helical structure, thereby causing chirality transmission and amplification. I found out that.
Further development of this research is expected to lead to
applications in chiral switching materials and artificial
supramolecular systems.
[Research overview]
Tokyo University of Science Graduate School of Science, Department of Chemistry, Mr. Torataro Matsumura (2nd year doctoral course, 2024), Mr. Keigo Kinjo (graduated master’s course, 2017), and Dr. Kotaro Tateno, Department of Comprehensive Chemistry, Graduate School of Comprehensive Chemistry (2017) The research group led by Professor Hidetoshi Kawai of the Department of Chemistry, Department of Chemistry, Faculty of Science, Tokyo University of Science (completed doctoral course), has a double helix structure, and by changing the solvent used, the direction of left and right winding of the helix can be reversed. We have succeeded in synthesizing a zinc mononuclear complex (double helical monometallofoldamer (*3)) that can We also elucidated the mechanism behind this inversion switching and found that the structural change of the introduced chiral moiety has a major effect. Furthermore, in heteroleptic complexes formed by mixing a ligand with a chiral moiety (chiral ligand) and a ligand without a chiral moiety (achiral ligand), a double helix is formed. We demonstrated that the helical winding direction and helical reversal switching properties are transmitted to the achiral ligand via the molecule, and chiral information is amplified.
In a double helix structure like DNA, the two strands carry out information retention, transmission, transcription, amplification, etc. Control of such double helix structures is extremely important for maintaining the basic functions of living organisms, accurately transmitting genetic information, and regulating cell functions, and at the same time for constructing excellent artificial molecular systems. . Although molecules with various helical structures have been developed in the past, there are currently very few examples of synthesizing double helical structures, especially double helical molecules and supramolecules in which the direction of the helix can be reversed and controlled. This time, our research group has synthesized a new zinc mononuclear complex (double helix monometallo foldamer) in which the left and right winding directions of the double helix structure can be reversed depending on the solvent used, and have detailed its structure and properties. I rated it.
In this study, we used a ligand 1a- which is a combination of two dibenzopyrrolo[1,2-a][1,8]naphthyridine units (hereinafter referred to as L-shaped units) with an “L”-shaped structure connected by 2,2′-bipyridine. c (3 types of ligands with different substituents at the 4,4′ position of the bipyridine moiety, 1a; no substituent, 1b; octyloxy group, 1c; (R)-2-methoxy-2-phenylethoxy group) A new Zn mononuclear complex (double helical monometallofoldamer) was synthesized using Zn(II) and Zn(II) cations.
Single-crystal X-ray structural analysis of [(1a)2Zn][OTf]2 reveals that a double helical structure is formed in the crystal by the π-π interaction (3.2-3.4A) between the L-shaped unit and the bipyridine moiety. It turns out that. Furthermore, when we investigated the structure of the [(1b)2Zn][OTf]2 complex in solution, we found that it preferentially forms a double helical structure at low temperatures, and an open structure with the ligands oriented outward at high temperatures. I found out that Furthermore, it was revealed that the helical winding direction of [(1c)2Zn][OTf]2, which has a chiral moiety, can be controlled by the Lewis basicity of the solvent. In the heteroleptic double helix complex [(1b)(1c)Zn][OTf]2 with 1b without a chiral moiety and 1c with a chiral moiety as ligands, the winding direction of the helix is changed through the double helix. We also found that the signal is transmitted to chains without chiral sites, resulting in amplification of chirality.
The results of this research are expected to provide design guidelines for switching chiral properties and controlling higher-order chiral structures, and promote the development of new chiral switching materials.
The results of this research were published online in the
international academic journal “Journal of the American Chemical Society” on July 19, 2024.
*Please note that the system does not allow the use of superscripts, subscripts, special characters, etc., so the notation may differ from the official notation. For the official notation, please refer to the Tokyo University of Science web page
(https://www.tus.ac.jp/today/archive/20240808_8023.html
[Image 1: Upper left of the figure: Reversal switching of left-handed (M) and right-handed (P) double-helix monometallo foldamers
Lower left of the figure (a) X-ray structure of double helical monometallo foldamer (ORTEP diagram)
Lower left of the figure (b) X-ray structure seen from the side (π-π interaction between ligands)
Diagram right: Image diagram of left-handed (blue) and right-handed (red) double helix monometallo foldamer
[Research background]
Foldamers, which have a helical folded structure, are attracting attention as stimuli-responsive switching molecules and chiral materials due to their chiral properties and conformational switching properties. In particular, double-helical foldamers exhibit more stable and stronger chiral properties than single-helical foldamers, and are also expected to be used for applications that utilize higher-order structural control, such as transmission and
transcription of chiral information. From the perspective of controlling chiral information, it is important to develop chiral inversion systems and establish design guidelines for chirality control for small molecules. In particular, it is attractive to reverse chirality by achiral stimulation without exchanging chiral moieties. On the other hand, it is extremely difficult to change the direction of helical winding in small molecules or double-helix foldamers, and it has not been possible to achieve both helical inversion switching and chirality amplification in double helices. This research group has previously demonstrated that a helical foldamer containing dibenzopyrrolo[1,2-a][1,8]naphthyridine (L-shaped unit) with the shape of the letter “L” was prepared in deuterated chloroform (CDCl3). found that it forms a spirally folded structure. Based on these results, we linked two L-shaped units with
2,2′-bipyridine to create three types of ligands 1a-1c ( 1a; no substituent, 1b; octyloxy group, 1c; (R)-2-methoxy-2-phenylethoxy group) were synthesized. By adding zinc trifluoromethanesulfonate [Zn(OTf)2] to each ligand, the desired Zn mononuclear complex ([(1a)2Zn][OTf]2, [(1b)2Zn ][OTf]2, [(1c)2Zn][OTf]2,
[(1b)(1c)Zn][OTf]2) were synthesized and their structures and properties were evaluated.
[Image 2: Figure Synthesis of Zn mononuclear complex (double helical monometalofoldamer) [Details of research results]
1. Structure of Zn mononuclear complex (double helical monometallofoldamer) First, we revealed the crystal structure of [(1a)2Zn][OTf]2 by single-crystal X-ray structural analysis. As a result, it was found that two bipyridines are coordinated to one Zn(II) cation, and the entire complex forms a double helical structure. The bipyridine moiety was sandwiched between two L-shaped units, and the double-helical structure was stabilized by π-π interactions. It was also discovered that in the crystal, there are left-handed double helices (hereinafter referred to as M-type) and right-handed double helices (hereinafter referred to as P-type), which are stacked alternately.
Next, we investigated the structure of the [(1b)2Zn][OTf]2 complex in CDCl3 by 1H NMR spectra. The results suggest that in solution, in addition to the double helical conformation similar to
[(1a)2Zn][OTf]2, there is an open conformation (a state in which at least one L-shaped unit is oriented outward). it was done.
Temperature-variable 1H NMR spectra show that these two conformations are in equilibrium; at low temperatures, the double helix structure forming tight π-π interactions is enthalpically favored, while at high temperatures, the L-shaped unit It was found that an open type with a high degree of freedom is advantageous in terms of entropy, and the structure can be controlled by temperature.
2. Right-handed and left-handed switching in double helix structure The helical winding direction of the double helical
monometallofoldamer [(1c)2Zn][OTf]2, which consists of 1c and has a chiral moiety, was investigated in detail using 1H NMR spectra and CD spectra (*4).
As a result, it was found that the winding direction of the helix changes depending on the solvent. Specifically, for CDCl3, M type: P type = 39: 21 (40% open type), the difference is small, but for acetone-d6, M type: P type = 15: 61 (24% open type), P type. It was found that in toluene-d8, the M type is predominant, with M type: P type = ~ 71: 0 (29% open type). Further investigation revealed that the M type is preferentially used in nonpolar solvents (hexane, cyclohexane, benzene, toluene, diethyl ether, methyl tert-butyl ether, etc.), and the P type is preferentially used in Lewis base solvents (acetone, dimethyl sulfoxide, etc.). It became clear that it was formed.
3. Consideration regarding chiral amplification
In order to evaluate the chiral transfer and amplification properties in the double-helical monometallofolder, we investigated the heteroleptic complex [(1b)(1c)Zn][OTf]2 consisting of 1b without a chiral moiety and 1c with a chiral moiety. We investigated the winding direction of the spiral. As a result, the Cotton effect (*5) was not observed with [(1b)2Zn][OTf]2 alone, but with the addition of ligand 1c, the heteroleptic complex [(1b)(1c)Zn][ OTf]2 was formed, and it was found that the P type was predominant in acetone and the M type was predominant in toluene. These results imply that the helical inversion property of the chiral site is transferred to the chain without the chiral site via the double helix, and that the chirality is amplified.
In fact, this research group has found that by adding an excess amount of 1b to 1 equivalent of 1c to form a complex with Zn(II), chirality is amplified compared to when complexing with 1c alone. It’s proven.
[Image 3: Figure Heteroleptic complex [(1b)(1c)Zn][OTf]2
Mr. Matsumura, who conducted this research, said, “I started this research with the desire to develop an advanced chiral information control and transmission system that takes advantage of the unique properties of helical structures such as dynamic properties, chirality, and cooperativity. The results of this research have the potential to be applied to new chiral switching materials that output small stimuli as various chiral physical properties.In addition, by transmitting and amplifying the excellent chiral physical properties, it can be applied to materials that can be seen in nature. We hope that this will lead to the development of artificial supramolecular systems that can lead to deracemization, information transmission, replication, and amplification.”
*This research was supported by Grants-in-Aid for Scientific Research (JP20K05478, JP24K08385, JP16J08668) from the Japan Society for the Promotion of Science (JSPS) and the Challenging Research Program for Next Generation Researchers (SPRING, JPMJSP2151) from the Japan Science and Technology Agency (JST). This is what I did.
【term】
*1 Chirality: Chirality refers to the property that an object has a three-dimensional structure that is different from its mirror image and cannot be perfectly superimposed. Compounds that exhibit these properties are called chiral. Conversely, compounds whose mirror image can be exactly superimposed on the object are called achiral. *2 Heteroleptic complex: A complex formed by multiple different ligands. A complex formed from a single ligand is called a homoleptic complex.
*3 Double-helical monometallofoldamer: A mononuclear metal
complex-type foldamer with a double-helical structure. Foldamers are artificial molecules that can be sterically folded into sheet or helical structures under specific conditions.
*4 CD spectrum (circular dichroism spectrum): A method of obtaining information about the three-dimensional structure by measuring the absorption difference when a sample is irradiated with right-handed and left-handed circularly polarized light. It is often used to evaluate chiral substances that have optical rotation.
*5 Cotton effect: Refers to the property of a specific substance to absorb left-rotated and right-rotated light at different wavelengths and to different degrees.
[Paper information]
Magazine name: Journal of the American Chemical Society
Paper title: M/P Helicity Switching and Chiral Amplification in Double-Helical Monometallofoldamers
Author: Kotaro Matsumura, Keigo Kinjo, Kotaro Tateno, Kosuke Ono, Yoshitaka Tsuchido, and Hidetoshi Kawai
DOI: 10.1021/jacs.4c06560
URL: https://doi.org/10.1021/jacs.4c06560