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Optical Resolution of the Water-soluble Ti4(embonate)6 Cages for Enantioselective Recognition of Chiral Drugs Yan-Ping He, Lv-Bing Yuan, Jin-Shuai Song, GuangHui Chen, Qipu Lin, Chunsen Li, Lei Zhang, and Jian Zhang Chem. Mater., Just Accepted Manuscript • DOI: 10.1021/acs.chemmater.8b03174 • Publication Date (Web): 24 Oct 2018 Downloaded from http://pubs.acs.org on October 25, 2018

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Chemistry of Materials

Optical Resolution of the Water-soluble Ti4(embonate)6 Cages for Enantioselective Recognition of Chiral Drugs Yan-Ping He#, Lv-Bing Yuan#, Jin-Shuai Song, Guang-Hui Chen, Qipu Lin, Chunsen Li, Lei Zhang* and Jian Zhang* State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 350002, P. R. China. ABSTRACT: Synergetic optical resolution and chiral amplification of tetrahedral Ti4L6 cages by enantiopure coordination cations have been realized in this work. Anionic ΔΔΔΔ-[Ti4L6] and ΛΛΛΛ-[Ti4L6] cages (L = embonate) have been completely resolved by enantiopure Λ-[Mn(1R,2R-DCH)3] and Δ-[Mn(1S,2S-DCH)3] cations, respectively. Accordingly, two homochiral compounds (PTC-108(Δ) and PTC-108(Λ)) with three-dimensional supramolecular architectures were formed, containing larger diamondoid cages. Such unusual resolution process clearly shows the stepwise transfer of homochirality from an enantiopure molecule to a resolved hydrogen-bonding aggregation and a final homochiral framework. Moreover, the separated homochiral Ti4L6 cage presents enantioselective recognition towards chiral organic and pharmaceutical molecules. This work opens a novel resolution-dependent homochiral framework construction approach, and it also takes the homochiral tetrahedral Ti4L6 cages with high solubility and stability into promising enantioselective application.

INTRODUCTION Inspired by the cage structure of enzymes, many metalorganic cages (MOCs) with various geometries have been designed and synthesized in the past decades.1-15 As enzyme has both cage structure and homochiral feature, one of the most challenging tasks on MOCs is to get homochirality and investigate the enantioselective process. Most homochiral MOCs prepared so far consist of enantiopure organic ligands as building units that impart homochirality to the resulting crystals.16-23 Among the MOCs, of particular interest is the tetrahedral M4L6 cage constructed from achiral bis-bidentate ligands and octahedral metal ions24-30, which form intrinsically chiral structure with all metal centers having the same chiral configuration (Λ or Δ). In the absence of enantiopure building units, such M4L6 cages usually exist as racemic mixtures in solution or in the solid-state, which limits their enantioselective applications. It is necessary to separate the racemates to obtain homochiral MOCs. Up to date, only several racemic M4L6 cages have been successfully resolved by enantiopure organic molecules or guest cations. 31-34 Usually, these resolving agents only help the formation of diastereomeric ion pairs with M4L6 cages to get simple enantiomers. None of them perform further effect on chiral amplification to generate new homochiral cages.

respectively (Scheme 1). Both homochiral crystals (PTC108(Δ) and PTC-108(Λ), Table 1) containing simple ΔΔΔΔ[Ti4L6] and ΛΛΛΛ-[Ti4L6] cages, respectively, have been synthesized successfully. For comparison, the expected achiral compound (PTC-107(Δ,Λ)) was also synthesized by using racemic [Mn(DCH)3] cations to assemble racemic Ti4L6 cages. Remarkably, PTC-108(Δ) (or PTC-108(Λ)) displays threedimensional supramolecular architecture with bigger diamondoid cages constructed from Ti4L6 cages and [Mn(DCH)3] units via N−H···O hydrogen bonds. Moreover, the separated homochiral Ti4L6 cage shows enantioselective recognition towards organic and pharmaceutical chiral molecules, including mandelic acid (Man) and naproxen (Nap). Scheme 1. Optical resolution of ΔΔΔΔ-[Ti4L6] (green) and ΛΛΛΛ[Ti4L6] (purple) cages by Λ-[Mn(1R,2R-DCH)3] and Δ[Mn(1S,2S-DCH)3] units.

In this work, we present the complete resolution and chiral amplification of tetrahedral Ti4L6 cages by enantiopure coordination compound, which lead to an unusual homochiral hydrogen-bonding framework with newly generated diamondoid cages. Through our methodology, the anionic ΔΔΔΔ-[Ti4L6] and ΛΛΛΛ-[Ti4L6] cages (L = embonate) can be completely resolved by enantiopure Λ-[Mn(1R,2R-DCH)3] and Δ-[Mn(1S,2S-DCH)3] cations (1R,2R- and 1S,2S-DCH = 1R,2R-(-)and (1S,2S)-(+)-1,2-Diaminocyclohexane),

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Table 1. Summary of the compositions and chiral characteristics of the obtained compounds. Complex

Composition

Space Group

Flack

R1 Value

PTC-107(Δ, Λ)

[(Ti4L6)2(Mn(DCH)3)7]

P21/c

------------

0.1175

PTC-108(Δ)

[(ΔΔΔΔ-Ti4L6)(Λ-Mn(1R,2R-DCH)3)2]

F4132

0.031(13)

0.0716

PTC-108(Λ)

[(ΛΛΛΛ-Ti4L6)(Δ-Mn(1S,2S-DCH)3)2]

F4132

0.044(17)

0.0907

EXPERIMENTAL SECTION Reagents were purchased commercially and used without further purification. PTC-101 as a starting material of Ti4L6 cages was massively synthesized by the method reported in our previous work.35 All syntheses were carried out in a 20 ml vial under autogenous pressure. Thermal stability studies were carried out on a NETSCHZ STA-449C thermoanalyzer with a heating rate of 10 °C/min under a nitrogen atmosphere. Elemental analyses (C, H, N) were performed on a Flash EA 2000 elemental analyzer. All Powder X-ray diffraction (PXRD) analyses were recorded on a Rigaku Dmax 2500 diffractometer with Cu Kα radiation (λ = 1.54056 Å) with a step size of 0.05°. The solid and liquid circular dichroism CD spectra were measured on a MOS-450 spectropolarimeter using KBr pellets and DMF as solvent, respectively. Synthesis of (Me2NH2)2[(Ti4L6)2(Mn(DCH)3)7]·80(H2O)·52 (DMF) (PTC-107(Δ,Λ)). PTC-101 (200 mg, 0.055 mmol), Mn(CH3COO)2·4H2O (12 mg, 0.065 mmol) and 1,2Diaminocyclohexane (DCH) (22 µL, 0.185 mmol) were added to 6 mL of DMF/H2O (2:1, v/v) and placed at room temperature (15 °C) for three days. Orange crystals of PTC107(Δ,Λ) were obtained. Yield: 86% based on PTC-101. Elemental analysis for C562H978N96O204Mn7Ti8, Calcd (%): C, 51.48; H, 7.51; N, 10.25. Found: C, 51.11; H, 7.61; N, 10.22.

Synthesis of (Me2NH2)4[(ΔΔΔΔ-Ti4L6)(Λ-Mn(1R,2RDCH)3)2]·32(H2O)·28(DMF) (PTC-108(Δ)). PTC-101 (200 mg, 0.055 mmol), Mn(CH3COO)2·4H2O (12 mg, 0.065 mmol) and (1R,2R)-(-)-1,2-Diaminocyclohexane (1R,2R-DCH) (22 µL, 0.185 mmol) were added to 6 mL of DMF/H2O (2:1, v/v) and placed at room temperature (15 °C) for three days. Orange crystals of PTC-108(Δ) were obtained. Yield: 45% based on PTC-101. Elemental analysis for C266H448N44O96Mn2Ti4, Calcd (%): C, 52.37; H, 7.40; N, 10.10. Found: C, 52.51; H, 7.46; N, 9.96. Synthesis of PTC-108(Λ). This compound was synthesized by substituting (1R,2R)-(-)-1,2-Diaminocyclohexane with (1S,2S)-(+)-1,2-Diaminocyclohexane ((1S,2S-DCH)) in the above synthetic procedure for PTC-108(Δ). X-ray Crystallography. Crystallographic data of PTC-107(Δ,Λ), PTC-108(Δ) and PTC-108(Λ) were collected on a Supernova single crystal diffractometer equipped with graphitemonochromatic Cu Kα radiation (λ = 1.54056 Å) at 100 K. Absorption correction was applied using SADABS.36 Structure was solved by direct method and refined by full-matrix leastsquares on F2 using SHELXTL.37 In these structures, some free solvent molecules were highly disordered and could not be located. The diffused electron densities resulting from these residual cations and solvent molecules were removed from the data set using the SQUEEZE routine of PLATON38 and refined further using the data generated. Crystal data and

Figure 1. (a) Molecular structures of the ΔΔΔΔ-[Ti4L6] and ΛΛΛΛ-[Ti4L6] enantiomers; (b) the Λ-[Mn(1R,2R-DCH)3] unit in PTC108(Δ); (c) two adjacent ΔΔΔΔ-[Ti4L6] cages linked by one Λ-[Mn(1R,2R-DCH)3] unit through hydrogen bonds; (d) highlighting of the N–H···O hydrogen bonds in PTC-108(Δ); (e) the diamondoid cage built from ΔΔΔΔ-[Ti4L6] cages and Λ-[Mn(1R,2R-DCH)3] units in PTC-108(Δ); (f) the 3D framework of PTC-108(Δ). Atom color code: green, Ti; olive, Mn; red, O; blue, N; gray, C.


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Chemistry of Materials details of data collection and refinement of PTC-107(Δ,Λ), PTC-108(Δ) and PTC-108(Λ) were summarized in Table S1. CCDC 1855887-1855889 contain the supplementary crystallographic data for this paper. These data are provided free of charge by The Cambridge Crystallographic Data Centre. Chiral molecules recognition measurements. Recognition of chiral organic or drug molecules, such as mandelic acid (D/LMan), malic acid (D/L-Mal), lactic acid (D/L-Lac) and naproxen (D/L-Nap), by the pure homochiral Ti4L6 cages was investigated in liquid state and monitored by CD spectra. Typically, 12 mg crystals of PTC-108(Δ) or PTC-108(Λ) were dissolved in 200 mL DMF/H2O (99:1, v:v) solvent to get a solution with a concentration of 10−2 mM, respectively. Then different concentrations (0.3 mM; 0.6 mM; 0.9 mM; 1.5 mM; 2.4 mM; 3 mM; 6 mM; 9 mM; 15 mM; 24 mM; 30 mM; 36 mM; 45 mM; 60 mM; 90 mM) of chiral molecules in DMF (1 mL) was added to 2 mL above solution of ΔΔΔΔ-[Ti4L6] or ΛΛΛΛ-[Ti4L6] cages for CD spectrum detection, respectively. RESULTS AND DISCUSSION Compound PTC-101 ((Me2NH2)8[Ti4L6](guest), L = embonate) has been applied as the starting material to realize the homochiral tale of the tetrahedral Ti4L6 cages. Both anionic ΔΔΔΔ-[Ti4L6] and ΛΛΛΛ-[Ti4L6] cages exist in the achiral structure of PTC-101 (Figure 1a), and such Ti4L6 cages are ultra-stable in water and common solvents. Spontaneous resolution can separate ΔΔΔΔ-[Ti4L6] and ΛΛΛΛ-[Ti4L6] cages into single crystals (PTC-102),35 whose bulk sample is a conglomerate with equal mixture of crystals with opposite handedness. To obtain homochiral samples for enantioselective study, the optical resolution approach should be developed. Since PTC-101 has good solubility and stability in DMF/H2O solution, (1R,2R)-DCH (or (1S,2S)) and Mn2+ ions were dissolved into the DMF/H2O solution of PTC-101 for resolution. Orange crystals of PTC-108(Δ) and PTC-108(Λ) were obtained, respectively. Single-crystal X-ray diffraction analysis revealed both PTC-108(Δ) and PTC-108(Λ) crystallized in cubic chiral space group F4132 (Table 1). Only the detailed structure of PTC-108(Δ) will be described here. As shown in Figure 1b, each Mn center is chelated by three (1R,2R)-DCH ligands, giving rise to a Λ-[Mn(1R,2RDCH)3]2+ cation with three-bladed propeller-like structure. Interestingly, such in situ generated Λ-[Mn(1R,2R-DCH)3] unit further connects two adjacent ΔΔΔΔ-[Ti4L6] cages through rich N−H···O hydrogen bonds, and the calixarene-like oxygen vertices of each ΔΔΔΔ-[Ti4L6] cage match very well with four Λ-[Mn(1R,2R-DCH)3] units (Figure 1c and 1d). Such H-bonding connectivity between [Mn(1R,2R-DCH)3] units and ΔΔΔΔ-[Ti4L6] cages creates a 3D supramolecular architecture (Figure 1f). It is notable that there are 3D channels with an effective window size of 10 Å in such Hbonding framework, and the void volume is 77 % per unit cell calculated by PLATON. From the viewpoint of topology, it can be described as a 4-connected network with dia topology by reducing each tetrahedron as a 4-connected node (Figure S2). A new diamondoid cage is built from 10 ΔΔΔΔ-[Ti4L6] cages and 12 Λ-[Mn(1R,2R-DCH)3] units (Figure 1e), and it has a minimum edge distance of 22 Å and a maximum distance

Figure 2. Solid-state CD spectra of PTC-107(Δ, Λ), PTC-108(Δ), PTC-108(Λ).

of 47 Å. Expectedly, the opposite Δ-[Mn(1S,2S-DCH)3]2+ units and ΛΛΛΛ-[Ti4L6] cages as well as the opposite Hbonding framework can be observed in PTC-108(Λ) (Figure S1, ESI). When racemic DCH ligands were used, no resolution occurred and the achiral compound PTC-107(Δ,Λ) was produced. Similar hydrogen bonds also exist in PTC-107(Δ,Λ). But the [Mn(DCH)3] units present different matching modes with neighboring Ti4L6 cages as following: [(ΔΔΔΔ-Ti4L6)(ΛMn(1R,2R-DCH)3)3], [(ΛΛΛΛ-Ti4L6)(Δ-Mn(1S,2SDCH)3)4], [(ΛΛΛΛ-Ti4L6)(Δ-Mn(1S,2S-DCH)3)3], and [(ΔΔΔΔ-Ti4L6)(Λ-Mn(1R,2R-DCH)3)4], which further pack into a 3D achiral superstructure (Figure S3-4, ESI). Solid-state CD measurements at room temperature were performed on the bulk samples of PTC-107(Δ,Λ), PTC-108(Δ) and PTC-108(Λ). The CD spectrum of PTC-108(Δ) exhibits four peaks around 465, 360, 294, and 270 nm (Figure 2). A mirror image of the spectra is also observed for the opposite chiral isomer PTC-108(Λ), indicating their absolute configuration and enantiomeric nature as well as complete separation. It is worth mentioning that their CD peaks are similar to those of spontaneously resolved PTC-102 with only ΔΔΔΔ-[Ti4L6] or ΛΛΛΛ-[Ti4L6] isomers in its chiral structure (Figure S9, ESI). Thus, the CD peaks of PTC-108(Δ) and PTC108(Λ) can be assigned to the intrinsic CD characteristics of the ΔΔΔΔ-[Ti4L6] or ΛΛΛΛ-[Ti4L6] cage. As predicted, there is no obvious CD signal for the racemic structure of PTC107(Δ,Λ). The CD spectra of PTC-108(Δ) and PTC-108(Λ) show the π → π* transitions of the naphthyl moieties of L ligand around 268 nm39-40, which can also be demonstrated by the UV adsorption spectrum (Figure S10, ESI). The intense negative and positive exciton splitting patterns centered at 318 nm could be ascribed to the π → π* transition of the phenol and carboxylic oxygen moieties, indicating that each Ti center in PTC-108(Δ) and PTC-108(Λ) are in the Δ and Λ configuration, respectively.21 These results are in accordance with the foregoing crystal structure analysis. The band around 465 nm may be assigned to the π → Ti (ligand-to-metal) charge transfer.21-22 Further study found that the crystals of PTC-108(Δ) and PTC-108(Λ) could be slightly dissolved in some solvents with



greater polarity (such as DMF and H2O), and the solubility significantly increased in mixed DMF/H2O solvents. Interestingly, their CD spectra also show the characteristic CD peaks of the ΔΔΔΔ-[Ti4L6] and ΛΛΛΛ-[Ti4L6] cages in DMF and H2O, respectively. These results directly confirm the stability of the chiral Ti4L6 cage in these solvents (Figures S11-

12, ESI), although the H-bonding frameworks of PTC-108(Δ) and PTC-108(Λ) were destroyed. Besides, in a certain concentration range, the intensity of liquid-state CD peaks increases as the concentration of pure chiral cages increases in DMF/H2O (Figure S14, ESI), presenting a near linear relationship between the intensity and the concentration.

Figure 3. Photo of solution of PTC-108, and families of the liquid-state CD spectra of ΔΔΔΔ-[Ti4L6] and ΛΛΛΛ-[Ti4L6] cages (6.7 µM) upon different concentrations of Man (a) and Nap (b).


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Chemistry of Materials Except for the complete resolution of anionic ΔΔΔΔ-[Ti4L6] and ΛΛΛΛ-[Ti4L6] cages, the stepwise transfer of homochirality presented in the resolution process is also of high significance. The origin of achieved homochirality is from the enantiopure (1R,2R)-DCH or (1S,2S)-DCH ligand. The absolute configuration of the ligand further determined the absolute configuration of the related coordination cation (e.g. (1R,2R)-DCH for single Λ-[Mn(1R,2R-DCH)3] and (1S,2S)DCH for single Δ-[Mn(1S,2S-DCH)3]). Next, the [Mn(1R,2R-DCH)3] (or [Mn(1S,2S-DCH)3]) cations carried out their enantioselectivity towards anionic Ti4L6 cages through suitable H-bonding interactions, making successful resolution and creating a new diamondoid cage to amplify the homochirality. Finally, a dia-type H-bonding framework with large porosity and homochirality is generated, revealing a resolution-dependent framework construction strategy. Thus, both coordination and supramolecular interactions played crucial roles for the observed optical Ti4L6 cage resolution. On the basis of the solubility/stability and homochirality of the resolved Ti4L6 cage, its recognition for some chiral organic and drug molecules in solution was investigated. It is very interesting to find that the homochiral Ti4L6 cages show enantioselective recognition towards mandelic acid (Man) in DMF/H2O solution (Figure 3a). When the concentration of the ΔΔΔΔ-[Ti4L6] cage was fixed at 6.67 μM, the intensity of its CD peak around 266 nm was gradually decreased along with the increased concentration of added D-Man in the range of 0–30 mM. Meanwhile, other CD peaks of the ΔΔΔΔ-[Ti4L6] cage remained almost unchanged, confirming that the intensity change at 266 nm was due to micro-environment changes not structure destruction. Moreover, when L-Man was added to the solution of the ΔΔΔΔ-[Ti4L6] cage instead of D-Man, the whole CD spectrum could be retained (Figure S15, ESI). These observations demonstrate the remarkable enantioselectivity of the ΔΔΔΔ-[Ti4L6] cages towards D-Man over L-Man. Correspondingly, the ΛΛΛΛ-[Ti4L6] cages can selectively recognize L- Man, and show poor sensibility to DMan. Homochirality of drug molecule is extremely important for their efficacy. To demonstrate the potential application of our homochiral Ti4L6 cage in pharmacy, its recognition behavior towards naproxen (Nap) was studied (Figure 3b). Interestingly, the L-Nap can be efficiently recognized by the ΔΔΔΔ-[Ti4L6] cages in a lower concentration range (0–0.5 mM). With the concentration of L-Nap up to 0.5 mM, the intensity of the CD peak around 266 nm decreased up to 4 fold. Therefore, the recognition of the Ti4L6 cage towards Nap is much more sensitive than Man. Correspondingly, the ΛΛΛΛ[Ti4L6] cages displayed excellent recognition effect on the DNap (Figure S17, ESI). Surprisingly, the chiral recognition ability of the Ti4L6 cage also presents special selectivity on the substrate molecules. Some other chiral molecules with similar chiral groups but different skeletons, e.g. lactic acid (Lac) and malic acid (Mal), could not be recognized by either ΔΔΔΔ-[Ti4L6] or ΛΛΛΛ[Ti4L6] cages (Figure S19 and S21, ESI). These results provide us with some information for understanding the mechanism of the observed enantioselective recognition. As we all know, weak intermolecular forces lie at the heart of biochemical recognition phenomenon, and the main driving

Scheme 2. Illustration of the proposed recognition models of the ΔΔΔΔ-Ti4L6 cage towards D/L-Man and D/L-Nap through hydrogen bonds and ··· interactions (These theoretical models are calculated using DFT, and some hydrogen atoms are removed for clarity).

forces come from the hydrogen bonding and π···π stacking force in molecular recognition.41 As mentioned above, in each calixarene-like vertex of the Ti4L6 cage there are six exposed oxygen atoms, and the dihedral angle between two naphthalene rings in embonate ligand is close to 90°, forming a special geometric environment. For the above recognition behavior, we made a theoretical simulation calculation using density functional theory (DFT) (scheme 2)42. The results show that there are hydrogen bonding interactions between the Man (or Nap) molecules and the Ti4L6 cage. Except that, π···π interactions occur between the naphthalene rings of L ligand and the benzene rings of Man or the naphthalene rings of Nap. And then aromatic π···π stacking may affect the π → π* transitions of the naphthyl moieties of the Ti4L6 cage, resulting in a change in the intensity of the CD peak around 266 nm. On one hand, this accounts for the absence of recognition phenomenon for lactic acid (Lac) and malic acid (Mal) without aromatic rings, despite Lac or Mal also having the Hbonding interactions with the O-vertex of the Ti4L6 cage. On the other hand, it also explains that the Ti4L6 cage is more sensitive to Nap than Man, which can be attributed to the stronger π···π interactions between two naphthalene rings compared to the π···π interactions between the naphthalene ring and the benzene ring. Thus Nap brings a greater effect on the π → π* transitions of the naphthyl moieties of the Ti4L6 cage and accordingly the 266 nm CD peak intensity. Furthermore, we think the presented enantioselectivity recognition of the Ti4L6 cage might be attributed to the different strength of aromatic stacking forces towards D- and L-configuration chiral molecules. Herein, only the ΔΔΔΔ[Ti4L6] cage is selected to discuss in detail. As illustrated in Scheme 2, except for the H-bonding interactions (also serving as pivot point for geometry immobilization), strong π···π



stacking interactions between the naphthyl moiety of the Ti4L6 cage and the benzene ring of the D-Man can form due to the perfect geometry matching. But for L-Man, its configuration makes the benzene ring away from and unparallel with the naphthyl of the Ti4L6 cage, hindering the formation of strong π···π stacking interactions. In the case of L-Nap and D-Nap, the configuration induced spatial arrangement of the naphthalene rings also influences the π···π stacking. Strong π···π stacking forces can be generated on L-Nap, but be blocked on D-Nap because of steric effect. Considering that only strong π···π interactions can effectively affect the π → π* transitions, thus D-Man and L-Nap can be recognized by the ΔΔΔΔ-[Ti4L6] cages as indicated by the intensity decrease of the 266 nm CD peak. Contrarily, ΛΛΛΛ-[Ti4L6] cages can be used to recognize L-Man and D-Nap. CONCLUSIONS In summary, we realized the homochiral tale of a tetrahedral Ti4(embonate)6 cage. Through appropriate hydrogen bonding interactions, the anionic ΔΔΔΔ-[Ti4L6] and ΛΛΛΛ-[Ti4L6] cages have been successfully resolved by enantiopure Λ[Mn(1R,2R-DCH)3] and Δ-[Mn(1S,2S-DCH)3] cations, respectively. Such unusual resolution process is accompanied by stepwise transfer of homochirality, leading to chiral amplification from an enantiopure molecule to a resolved hydrogen-bonding aggregation and a final homochiral framework with dimondoid cages. In addition, the separated homochiral Ti4L6 cages have interesting enantioselective applications on recognition of chiral organic and pharmaceutical molecules. We noted that H-bonds assisted π···π stacking interactions between the homochiral Ti4L6 host and racemic guests might be the chief factor for effective recognition, which is supported by DTF studies. The success of our work not only opens a new resolution-dependent way for the construction of homochiral frameworks, but also provides a promising homochiral tetrahedral Ti4L6 cage with high solubility and stability for applications in enantioselective recognition.

ASSOCIATED CONTENT Supporting Information The additional experimental details and figures. This material is available free of charge via the Internet at http://pubs.acs.org. The X-ray crystallographic coordinates for structures reported in this article have been deposited at the Cambridge Crystallographic Data Centre (CCDC) under deposition numbers 18558871855889 (PTC-107(Δ, Λ), PTC-108(Δ) and PTC-108(Λ)). These data can be obtained free of charge from the Cambridge Crystallographic Data Centre via http://www.ccdc.cam.ac.uk/data_request/cif.

AUTHOR INFORMATION Corresponding Author [email protected]; [email protected].

Author Contributions

#These

authors contributed equally to this work.

ACKNOWLEDGMENT This work is supported by National Key Research and Development Program of China (2018YFA0208600), NSFC (21425102, 21521061 and 21673238), the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB20000000) and Natural Science Foundation of Fujian Province (2017J06009). Dedicated to Professor Jin-Shun Huang on the occasion of his 80th birthday.

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