Adaptive Chirality of an Achiral Cage: Chirality Transfer, Induction, and Circularly Polarized Luminescence through Aqueous Host–Guest Complexation
Lin Cheng, Kai Liu, Yanjuan Duan, Honghong Duan, Yawen Li, Meng Gao, Liping Cao
Abstract
Open AccessCCS ChemistryRESEARCH ARTICLE1 Nov 2021Adaptive Chirality of an Achiral Cage: Chirality Transfer, Induction, and Circularly Polarized Luminescence through Aqueous Host–Guest Complexation Lin Cheng†, Kai Liu†, Yanjuan Duan, Honghong Duan, Yawen Li, Meng Gao and Liping Cao Lin Cheng† Key Laboratory of Synthetic and Natural Functional Molecule of the Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi'an 710069 , Kai Liu† Institute of Marine Drugs, Guangxi University of Chinese Medicine, Nanning 530200 , Yanjuan Duan Key Laboratory of Synthetic and Natural Functional Molecule of the Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi'an 710069 , Honghong Duan Key Laboratory of Synthetic and Natural Functional Molecule of the Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi'an 710069 , Yawen Li Key Laboratory of Synthetic and Natural Functional Molecule of the Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi'an 710069 , Meng Gao State Key Laboratory of Luminescent Materials and Devices, South China University of Technology, Guangzhou 510640 Guangdong Provincial Key Laboratory of Luminescence from Molecular Aggregates, South China University of Technology, Guangzhou 510640 The AIE Institute, Center for Aggregation-Induced Emission, National Engineering Research Center for Tissue Restoration and Reconstruction, Key Laboratory of Biomedical Engineering of Guangdong Province, Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education, Innovation Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou 510006 and Liping Cao *Corresponding author: E-mail Address: [email protected] Key Laboratory of Synthetic and Natural Functional Molecule of the Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi'an 710069 State Key Laboratory of Luminescent Materials and Devices, South China University of Technology, Guangzhou 510640 Guangdong Provincial Key Laboratory of Luminescence from Molecular Aggregates, South China University of Technology, Guangzhou 510640 https://doi.org/10.31635/ccschem.020.202000509 SectionsSupplemental MaterialAboutAbstractPDF ToolsAdd to favoritesDownload CitationsTrack Citations ShareFacebookTwitterLinked InEmail Chirality transfer, induction, and circularly polarized luminescence (CPL) using supramolecular hosts, such as macrocycles and cages, have been explored for wide-ranging applications in chiral recognition, sensing, catalysis, and chiroptical functional materials. Herein, we report the adaptive chirality of an achiral tetraphenylethene (TPE)-based octacationic cage ( 1) induced by binding with enantiopure deoxynucleotides ( A, T, C, and G) through host–guest (H–G) complexation in water. The hydrophobic cavity of the cage efficiently stabilizes the hydrogen-bonded dimerization of deoxynucleotides ( A2, T2, C2, and G2) to form H–G complexes in 1∶2 ratios. Given the photophysical properties and dynamic rotational conformation of the TPE units of the cage, cage⊃deoxynucleotide complexes exhibited excellent chiroptical properties based on chirality transfer and induction from the chiral guest to the achiral host. For this supramolecular system, the cage showed a unique adaptive chirality of the double clockwise-typed (PP) rotational conformation of the two TPE units, which was induced by chiral guests (e.g., A2, T2, C2, and G2) through H–G complexation in water. Furthermore, the adaptive chirality of the cage⊃deoxynucleotide complexes successfully induced CPL signals in homogeneous aqueous solutions. This study provides insights for the construction of adaptive chirality from an achiral TPE-based octacationic cage with dynamic conformational nature, and might facilitate further design of chiral functional materials for several applications, such as chiral recognition, sensing, displays, catalysis, and other chiral fluorescent supramolecular systems based on aqueous H–G complexation. Download figure Download PowerPoint Introduction Chirality is a key aspect in the expression, preservation, and inheritance of biologically genetic information and is vital to life.1,2 Depending on their chirality, amino acids, carbohydrates, proteins, RNA, and DNA play critical roles as carriers, expressers, and users of molecular chirality in biological processes, such as catalysis, energy transfer, replication, transcription, and translation.3 Therefore, understanding the mechanisms and structure–activity relationships between chirality and biological function are crucial to sustain life. Scientific approaches, such as NMR and high performance liquid chromatography (HPLC), aided by chiral reagents, are conventionally employed to uncover and characterize chiral information.4–7 Notably, spectroscopic features of molecular chirality, such as circular dichroism (CD)8 and circularly polarized luminescence (CPL),9–13 have also been utilized to obtain chiral information in convenient and straightforward approaches that do not require chiral auxiliaries or tedious chiral syntheses. While CD relies on the optical rotation feature of chiral molecules in their ground state, CPL is an expression of the chiral structure in the excited state. Recently, CPL has attracted significant attention as a chiral fluorescence technology for developing advanced applications, such as three-dimensional (3D) display,14–16 smart information storage,17,18 and chiral optical devices for sensing and catalysis.19,20 The combination of CD and CPL can provide further information about the stereochemistry, conformation, and 3D-assembled structure of chiral molecules or systems, and even the chirality relationship between their ground and excited states. Therefore, these advanced technologies aid the in-depth understanding of structure–functionality relationships, which guide the development of new chiral functional materials.14,19,21–25 However, most natural chiral molecules do not exhibit strong optical rotational effects or fluorescent groups. For examples, amino acids, carbohydrates, and nucleotides cannot be easily detected by CD or CPL due to their weak Cotton effect.26 To address these problems, supramolecular chemists, inspired by natural systems, have developed supramolecular chirality27 based on the self-assembly of chiral/achiral molecules through noncovalent interactions, including H–G interactions, hydrogen bonding, π–π interactions, ion–dipole interactions, and electrostatic interactions. These supramolecular strategies involving highly ordered and selective assembly are efficient and convenient approaches to the generation, induction, transfer, and amplification of the supramolecular system's chirality on self-assembled morphologies, CD/CPL signals, and/or even enantioselective activities (e.g., recognition, sensing, and catalysis) in the solution, gel, and solid states.27–53 Among these, the H–G strategy is a supramolecular approach that affords good controllability and designability, and has been used to achieve supramolecular chirality in several applications, such as chiral recognition, sensing, and catalysis.31–48 In this strategy, the H–G complexation between macrocycles or cages as hosts and enantiomers as guests is enantioselective and induces distinct changes in the electrical, magnetic, and/or optical properties of the system. For examples, chiral hosts, such as cyclodextrins36,37 or chiral crown ethers/calixarenes,38–42 with their chiral interior cavities or chiral functional groups exhibit excellent chiral recognition for enantiomeric guests and form chiral H–G complexes (Scheme 1a). Furthermore, some achiral hosts, such as cucurbit[6]uril,43 have also achieved chiral recognition and sensing with amplification of the CD signals to produce diastereomeric H–G complexes in the presence of other additional chiral guests (Scheme 1a). In these cases, the intrinsic chirality of the host is a crucial factor, which determines the selectivity of the recognition for enantiomeric guests. On the other hand, some achiral hosts comprising dynamic clockwise (P) or anticlockwise (M) rotational units are transformed into chiral hosts with homodirectional rotation upon binding with chiral guests (e.g., pillararenes with planar chirality).27,44–48 Herein, we present the dynamically conformational chirality of an H–G system, also called adaptive chirality. In this novel system, the selectively conformational chirality of an achiral host is induced by chiral guests via efficient through-space chirality transfer49 to form chiral H–G complexes (Scheme 1b). The formation of the chiral H–G complex affords chirality transfer and induction of the CD and CPL signals via H–G complexation. This H–G recognition is an adaptive recognition which depends on the chirality of the guests.27,50–53 For example, when an enantiomeric molecule is encapsulated in the cavity of an achiral host, the chiral guest creates an asymmetric interior environment to induce selective homodirectional rotation of the rotatable units on the host, which results in effective chirality transfer and induction from the inner chiral guest to the outer host. Scheme 1 | (a and b) H–G strategies for chiral recognition: (1) H–G complexation; (2) enantioselective recognition; (3) adaptive recognition. Download figure Download PowerPoint Tetraphenylethene (TPE) and its derivatives are well-known molecular building blocks with multiple structural advantages, such as the propeller-like P/M rotational conformation of their four phenyl rings, angles of 60° and 120°, between the two adjacent p-substituted phenyl rings, and excellent photophysical property like aggregation-induced emission (AIE),54–59 which offer an expansive scope for the design and synthesis of various supramolecular hosts, including macrocycles,60–71 cages,72–81 and frameworks.82–102 Given their fluorescence with high emitting efficiency and typical AIE properties in aggregated states (e.g., gel or solid), chiral groups covalently attached to TPEs have been widely studied for their CPL properties.103–107 Therefore, TPE molecules with both propeller-like P/M rotational conformations and AIE properties are ideal building blocks for exploring conformational chirality with dynamic nature for achieving chirality transfer, induction, and CPL function in the H–G systems. Although conformational chirality is common in biological systems,108–110 such as α-helix and β-sheet in the secondary structure of proteins, and in some artificial supramolecular systems,111,112 the P/M rotational conformation of TPE has rarely been utilized for chiral applications, because of the absence of an energy barrier between the P and M conformations in unrestricted TPE structures. Rare examples have shown that propeller-like P/M rotational conformation of TPE units can be restricted and stabilized in confined structures such as tetracycles or cages with mutually interlinked structures for producing chiroptical properties including both CD and CPL in the solution state.113–116 Recently, we reported that a TBE-based octacationic cage ( 1) possesses excellent fluorescence properties and H–G recognition ability with polycyclic aromatic hydrocarbons such as coronene and water-soluble dyes (e.g., sulforhodamine 101) in solution.81 In its crystal structure, the two TPE units of the cage simultaneously adopt a propeller-like conformation with P and M rotation, which resulted in the cage molecule being mesomeric (Figure 1a). Given its H–G recognition ability, photophysical properties, and dynamical rotational conformation of TPEs, this achiral TPE-based cage can be transformed into a chiral cage with homodirectional rotation (PP or MM) of the two TPE units upon binding with chiral guests, which thereby confers chiroptical properties (e.g., CD and CPL). Figure 1 | Chemical structures of (a) 1, (b) deoxynucleotides (A, T, G, and C), and (c) possible structures of hydrogen-bonded dimers (A2, T2, C2, and G2) based on X-ray structure analysis from the Cambridge Structural Database (see the Supporting Information). PF6– is the counter ions in cage's X-ray structure and Na+ for all guests. Download figure Download PowerPoint Herein, we report the adaptive chirality of an achiral TBE-based octacationic cage ( 1). The cage acts as a host for enantiopure deoxynucleotides such as 5′-adenosine monophosphate ( A), 5′-thymidine monophosphate ( T), 5′-cytidine monophosphate ( C), and 5′-guanosine monophosphate ( G) (Figure 1b) through H–G complexation in water. Specifically, deoxynucleotide guests can form hydrogen-bonded dimers ( A2, T2, C2, and G2, Figure 1c) in the cavity of the cage to successfully transfer the point chirality of the D-ribodesose units to the induced propeller-like planar chirality (PP rotational conformation) of the two TPE units on the cage with dual CD and CPL signals. In these H–G complexes, the two TPE units of the cage can adopt a PP rotational conformation with new negative (300–450 nm) Cotton effects (gabs ≈ −10−4) for PP- 1⊃A2/ T2/ C2, and new positive (300–416 nm) and negative (416–450 nm) Cotton effects (gabs ≈ −10−4) for PP- 1⊃G2 on the CD spectra. Furthermore, cage⊃deoxynucleotide complexes exhibited right-handed CPL signals centered at 550 nm with dissymmetric factors (glum ≈ −10−4) in water. Experimental Methods Starting materials were purchased from commercial suppliers and used without further purification. NMR spectra were recorded on a Bruker ascend spectrometer operating at 400 MHz. Electronspray-ionization (ESI) mass spectra were acquired with a Bruker micrOTOF-Q II electrospray instrument. UV–vis spectra were generated on an Agilent Cary-100 spectrometer. Fluorescence spectra were performed using a Horiba Fluorolog-3 spectrometer. Isothermal titration calorimetry (ITC) was carried out using a VP-ITC (Malvern, Worcestershire, United Kingdom) at 25 °C, and computer fitting of the data was performed using the VP-ITC analyze software. The CD spectra were recorded on a J-1500 spectropolarimeter, using a 1 cm quartz cuvette. CPL spectra were measured on JASCO CPL-200 spectrophotometers. Cage 1 was synthesized through a modified synthetic procedure. Results and Discussion Host–guest complexation We prepared the water-soluble TPE-based octacationic cage 1 with eight Cl– counter ions for each cage molecule, which has good water solubility of ∼22 mM ( Supporting Information Figure S1). A modified synthetic procedure was used for the preparation and afforded a higher yield (∼22%) compared with our previously reported yield (∼5%).81 With eight electron-deficient pyridinium rings on its two TPE units, cage 1 exhibited excellent H–G recognition ability for electron-rich molecules with π-conjugated moieties and negatively charged groups. Therefore, the chiral deoxynucleotides with adenine, thymine, guanine, or cytosine units as the CH–π/π–π binding sites and the monophosphate group as the electrostatic binding site were chosen for testing the adaptive recognition abilities of the cage (Figure 1b). The H–G complexation between 1 and them was investigated by employing 1H NMR, ITC, and ESI time-of-flight mass spectrometry (ESI-TOF-MS). Initially, 1H NMR titration experiments of 1 with four deoxynucleotides were employed to investigate the binding interaction and location between the cage and the guests in D2O (Figure 2). The 1H NMR titration of 1 with A showed the following changes for the proton resonances of the cage and the guest (Figure 2b): (1) Due to rapid exchange and broadening effect117 upon complexation between the cage and A at room temperature (298 K), the 1H NMR spectra of the H–G complexes showed broad peaks for 1 and the peaks corresponding to A disappeared, indicating that molecule A was entirely located within the cage and shielded by the cavity of 1. When excess A was added, clear proton resonances were observed, which were the averages of the resonances of the free A and bound A due to their rapid exchange. Furthermore, the proton resonances of adenine (H1′–H2′), ribodesose units (H3′–H6′), and bridging CH2 (H7′) proton resonances shifted upfield, strongly confirming that A molecules are completely encapsulated inside the cavity of the cage by H–G complex formation. (2) The phenyl (Ha′–Hb′) and pyridinium (Hc′) proton resonances from the central portion of the cage's TPE units showed large upfield shifts (ΔHa′ = −0.41 ppm, ΔHb′ = −0.20 ppm, and ΔHc′ = −0.05 ppm at the ratio of 1∶ A = 1∶2) caused by the π-electron shielding of the adenine units of A. The shielding effects gradually decreased from the center to the edge of the TPE units, which indicates that the adenine units of A are located at the center of the cavity in cage. (3) In contrast, the resonances of the pyridinium proton (Hd′), CH2 groups (He′), and p-xylylene moieties (Hf′) displayed slight downfield shifts (ΔHd′ = 0.08 ppm, ΔHe′ = 0.04 ppm, and ΔHf′ = 0.11 ppm at a ratio of 1: A = 1∶2), because these hydrogen atoms were located in the deshielding region of the adenine groups of A and also influenced by the electrostatic interactions between the phosphate groups of A and the pyridinium cationic units near the p-xylylene rings in the cage.66 Figure 2 | (a) Schematic representation of the formation of 1⊃A2. (b) 1H NMR titration (400 MHz, 298 K, D2O) of 1 (0.40 mM) with A (0–10 equiv). Primes (′) denote the resonances within the H–G complex. Download figure Download PowerPoint Furthermore, the titration process showed an obvious two-step binding process between the cage and two molecules of A. For example, proton Ha at 7.23 ppm, which is located at the center of the TPE units, showed the largest upshift to 6.75 ppm (ΔH = −0.84 ppm) when 1.0 equiv of A was added. However, when 2.0 equiv of A was added, the chemical shift of Ha shifted back slightly to the downfield region (6.81 ppm, ΔH = 0.06 ppm). This is because the formation of the hydrogen bonds between the two molecules of A can enhance the delocalization of the conjugated electrons between the two adenine units, which could decrease their electron-cloud density, thus weakening the shielding effect experienced by the TPE units from the adenine units. 1H–1H nuclear Overhauser effect spectroscopy (NOESY) conformed spatial correlation between cage and A, which revealed some sets of clear intermolecular NOEs (H3′–H4′ with Ha′–Hc′, and H6′–H7′ with Hc′ and Hf′) ( Supporting Information Figure S2). These NOEs also indicated that adenosine groups were located at the center portion of the cavity, and monophosphate groups were located at the edge portion of the cavity, which are favorable for the formation of hydrogen bonds between two molecules A in the hydrophobic cavity of the cage. The Job plot by NMR measurements confirmed the 1∶2 stoichiometry of the 1⊃ A2 complex ( Supporting Information Figure S4). It is well known that mononucleotides cannot form stable hydrogen-bonded base pairs in water due to the interference of strong hydrogen bonds with water molecules. However, the hydrophobic cavity of the cage offers an ideal shelter for promoting the formation of the hydrogen-bonded base pairs of A2 (Figure 1b) in the 1⊃ A2 complex.118,119 ITC experiments in water further confirmed that the cage could simultaneously encapsulate two molecules of A with a moderate binding constant (Ka) of (5.15 ± 0.69) × 104 M−1 ( Supporting Information Figure S7 and Table S1). ESI-TOF-MS also showed one set of peaks with continuous charge states at m/z 588.9633 and 487.3646, which corresponded to the +4 to +5 charge states of 1⊃ A2 ( Supporting Information Figure S9).These results indicate that the formation and stabilization of the dimer A2 are possible through the hydrogen bonding between the two adenine units under the hydrophobic environment inside the cavity of the cage, which led to the formation of the 1⊃ A2 ternary complex (Figure 2a). The H–G recognition behaviors were also observed in the case of 1 with T and C. 1H NMR titrations of 1 with T and C showed similar chemical shifts, indicating the formation of 1⊃ T2 and 1⊃ C2, respectively (Figures 1b and Supporting Information Figures S5 and S6). All proton resonances of the guests showed obvious upfield shifts, strongly confirming that the entire T and C molecules were encapsulated inside the cavity of the cage by forming H–G In these NMR excess T or C could not the obvious indicating the 1∶2 stoichiometry of 1⊃ T2 and 1⊃ C2, which was further confirmed by the Job ( Supporting Information Figure S4). ITC indicated the 1∶2 stoichiometry between 1 and C with the binding of ± × M−1 for 1⊃ T2 and ± × M−1 for 1⊃ in ( Supporting Information Figure ESI-TOF-MS indicated the of 1⊃ T2 and 1⊃ ( Supporting Information Figure In the 1H NMR titration of 1 with G, the proton resonances of the cage shifted 2.0 equiv of was added, indicating that the H–G complexes between 1 and could a 1⊃ complex (Figures 1b and a ratio of 1∶ = the resonances of the phenyl (Ha′–Hb′) located in the central portion of the cage's TPE units showed large upfield shifts (ΔHa′ = ppm and ΔHb′ = −0.20 ppm) caused by the π-electron shielding of the hydrogen-bonded in (Figure that the two units were located at the central portion of the cage's In contrast, the resonances of the pyridinium proton the CH2 groups (He′), and the p-xylylene moieties (Hf′) displayed slight downfield shifts = ppm, = 0.11 ppm, ΔHe′ = ppm, and ΔHf′ = because these hydrogen atoms are located at the deshielding region of the groups of and are influenced by the electrostatic interactions between the phosphate groups at the of and the pyridinium cationic units near the p-xylylene rings in the cage.66 In the titration all of the proton resonances of showed obvious upfield shifts, strongly confirming that the molecules were completely encapsulated inside the cavity of the cage by forming H–G In revealed some sets of clear intermolecular NOEs (H3′–H4′ with and H6′–H7′ with between the cage and G, indicating that that groups were located at the center portion of the cavity and monophosphate groups were located at the edge portion of the cavity ( Supporting Information Figure ESI-TOF-MS confirmed the formation of a 1⊃ complex ( Supporting Information Figure On the other hand, the 1∶2 H–G stoichiometry and binding constant of ± × M−1 were further by ITC (Figure Figure | (a) Schematic representation of the formation of (b) 1H NMR titration (400 MHz, 298 K, D2O) of 1 (0.40 mM) with (0–10 equiv). (c) ITC of 1 mM) with mM) at 298 in water. Primes (′) denote the resonances within the H–G complex. Download figure Download PowerPoint The formation of all H–G complexes with a ratio of 1∶2 indicates that the cavity of the cage can offer a hydrophobic to efficiently the intermolecular hydrogen bonds of the base dimer via hydrophobic effects in aqueous Although the results of NMR, ITC, and the 1∶2 stoichiometry of cage⊃deoxynucleotide complexes, the hydrogen-bonded of the base dimers in the cavity of the cage are of the structures adenine, thymine, guanine, or cytosine units from the Cambridge Structural Database revealed that each deoxynucleotide could have two or of possible hydrogen-bonded in with the or to form hydrogen-bonded dimers with or hydrogen-bonded (Figure and Supporting Information Figure Therefore, the hydrogen-bonded dimers ( A2, T2, C and G2) could adopt hydrogen-bonded inside the cage cavity ( Supporting Information properties at the region nm) and emission due to the of conjugated groups. However, the TPE-based cage the H–G complex of the cage and deoxynucleotides with distinct photophysical properties, including UV–vis nm) and fluorescence emission which are for exploring their chiroptical properties, such as CD and In UV–vis titration experiments of 1 with deoxynucleotides in the of the host was slightly with two corresponding to the interactions between the cage and guests in the cage⊃deoxynucleotide complexes (Figures and and Supporting Information Figure the fluorescence titration between 1 and deoxynucleotides in water showed an in the of the emission of 1 centered at by the of A, T, or C (Figure and Supporting Information Figure In contrast, the of induced obvious fluorescence of this H–G (Figure These two fluorescence changes of 1 upon binding with C and indicate that the formation process of the cage⊃deoxynucleotide complex between the fluorescence of the of rotation and the of the transfer (1) When guests are into the cavity of 1, the H–G complexes the free rotation of the TPE units in 1, which could the fluorescence based on the (2) the the formation of H–G complexes also the interaction between the cage and the guests, which could decrease the fluorescence based on the Therefore, in the of A, T, or C, the a the in the case of to the higher of to electrons for fluorescence compared with the other ( Supporting Information Table Figure | and fluorescence titration of 1 with guests in (a and b) A and and Fluorescence of 1 and under nm) in water. = = 2 of or fluorescence the equiv of guests, is fluorescence Download figure Download PowerPoint properties CD is the approach for the chiroptical properties of chiral molecules or supramolecular systems. However, biological chiral such as amino and have weak to completely CD signals, or CD signals that are due to their location in the region It is that the cage exhibited in the region from to Given the photophysical properties of CD was employed to the chiroptical properties of these H–G It is that when the H–G complexes are between 1 and the chiral the chirality of the deoxynucleotides could transfer to 1, which could induce homodirectional rotation of the TPE units to achieve a CD in from the mesomeric rotation of the cage's two TPE units in the state, 1 not exhibit obvious Cotton effects at and in indicating that the two TPE units in 1 adopt a mesomeric rotational conformation in the solution and that their rotational conformation (PP or MM) cannot be easily induced and stabilized at the or under temperature ( Supporting Information Figures and However, when deoxynucleotides are into the solution of 1 in CD signals from a new Cotton effect corresponding to the of 1 at nm was strongly confirming that the chiral nature