Chinese Chemical Letters  2019, Vol. 30 Issue (5): 1005-1008   PDF    
In situ generated pyroglutamate bridged polyoxotitaniums with strong circular dichroism signal
Guo-Liang Dong, Wei-Hui Fang*, Lei Zhang*, Jian Zhang     
State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou 350002, China
Abstract: In this text, we use inexpensive and natural amino acid, successfully obtained the asymmetric crystallization of three PTCs, [Ti6(OiPr)14(μ2-O)(μ3-O)2(D/L-pGlu)2] (D-PTC-53; L-PTC-53; H2pGlu=pyroglutamic acid) and [Ti6(OiPr)14(μ2-O)(μ3-O)2(D-pGlu)2][Ti6(OiPr)14(μ2-O)(μ3-O)2(L-pGlu)2] (D, L-PTC-53). Interestingly, in situ lactamide reaction starting from glutamic acid to pyroglutamic acid was observed. In addition, the chirality features of these PTCs have been thoroughly discussed. The two enantiomers crystallize in chiral P21 space group. The optically pure pGlu ligands transform its chirality to the inorganic titanium oxo clusters. As a result, the stack of these inorganic clusters generates homochiral helical chains along the characteristic axial direction. Apart from the microscopic structural analysis, the macroscopic solid-state samples exhibit unusual strong circular dichroism (CD) signals, further verified the homochiral feature of the enantiomers.
Keywords: In situ     Gyroglutamate     Polyoxotitaniums     Circular dichroism     Chirality    

Recent years, the research on crystalline polyoxotitaniums (PTCs) has experienced rapid development spanning from synthetic methods, structural diversity to potential applications [1-4]. The enthusiasm and motivation is original from mimicking, improving and then gradually substituting commercialized titanium dioxide (TiO2) photocatalyst [5-8]. Chirality is particularly attractive in modern pharmaceutical industry for enantiomers of a racemic drug may have different pharmacological activities, different pharmacokinetic or pharmaceutical effects [9, 10]. Because the assembly and modification of crystalline PTCs are tunable through coordination chemistry strategy, the incorporation of chiral molecular will endowed additional applications like asymmetric catalysis. Such modification from the molecular level is comparably difficult accomplished by TiO2. Currently, the majority chiral related work of PTCs is focused on 1, 10-bi-2-naphthol (BINOL) and their derivatives [11-14].

In order to synthesize PTCs with chiral features, an effective strategy is the employment of chiral ligands because the chirality of these organic ligands can be transferred to the inorganic cores and later to the final crystalline products. Such approach normally leads to enantiomerically pure or enantiomerically enriched products [15]. The absorption bands of optically active chiral molecules can be detected by circular dichroism (CD). There is no doubt that amino acids represent the most potential candidates [16, 17]. Firstly, they can be viewed as a library for chiral ligands selection. About 500 naturally occurring amino acids are known, though only 20 appear in the genetic code. Secondly, natural amino acids may be the inexpensive and ideal enantiopure bridges for the formation of chiral PTCs. The abundant coordination sites and coordination mode provides high affinity toward Ti ions. Thirdly, natural amino acids play an essential role at the catalytic site. Till now, the use of amino acid in the synthesis of chiral titanium is extremely rare. Thereinto, D-mandelic acid had been successfully applied in the assembly of dimeric, hexa- and nonanuclear enantiopure PTCs by Mahrwald et al. [18]. Moreover, a high degree of regioselectivity in direct aldol additions of aromatic and aliphatic aldehydes to functionalized unsymmetrical ketones was realized [18, 19]. Very recently, Wang et al. [20] reported a novel family of water-soluble polyoxocationic titanium-oxide host-guest clusters capped by a variety of amino acid ligands.

In previous work, we have managed to assemble enantiopure Ti4(OH)4(R/S-BINOL)6 into the pores of an achiral HKUST-1 framework by using a modified liquid phase epitaxy layer-bylayer approach [21]. Based on the combination research background of chiral porous metacrystals, crystalline PTCs and amino acid related work in metal organic frameworks, we carried out the study on synthesis and properties of chiral PTCs. Herein, we choose a pair of enantiopure amino acids (D-glutamic acid and L-glutamic acid) as linkers to probe the feasibility of fabricating homochiral PTCs. As a result, two enantiomorphic homochiral PTCs with the same formula are successfully obtained, [Ti6(OiPr)14(μ2-O)(μ3-O)2(D/L-pGlu)2] (D-PTC-53; L-PTC-53; H2pGlu = pyroglutamic acid). Interestingly, the in situ formation of pyroglutamic acid from glutamic acid was identified. When racemic D, L-pyroglutamic acid was used in place of enantiopure D- or L-glutamic acid, the resulting bulk sample is a racemic [Ti6(OiPr)14(μ2-O)(μ3-O)2(D-pGlu)2] [Ti6(OiPr)14(μ2-O)(μ3-O)2(L-pGlu)2] (D, L-PTC-53) (Table S1 in Supporting information). These compounds are fully characterized and structurally determined. In addition, their band gaps, photocurrent response and chirality features are discussed.

One unexpected result occurring during the course of the synthesis is the in situ lactamide reaction. H2pGlu is a ubiquitous but little studied natural amino acid derivative found in many proteins including bacteriorhodopsin. However, the generation of it can be achieved by spontaneously cyclization of glutamic acid [22-24]. Wilson and Cannan reported that the conversion of Glu to pGlu could occur at relatively harsh incubation. The reaction is rapid and practically complete in solutions of strong acids or strong bases [25]. Even though the in situ esterification of the acid ligands with alcohols has been reported in the synthesis of crystalline PTCs [26, 27], the lactamide reaction herein was unprecedented observed. This reaction illustrated in Scheme 1a involves the cyclization and the subsequent loss of H2O molecular. As also revealed in the above synthesis section, the final products are exclusively pyroglutamate compounds weather the starting ligand is H2pGlu or H2Glu (Fig. S1 in Supporting information).

Scheme 1. (a) Formation of H2pGlu from H2Glu. (b) Illustration of four crystallization processes showing the absolute chirality of crystals under the controls of H2pGlu ligand.

One more significant point is the chiral transfer from the amino acid to the final crystallization products. As shown in Scheme 1b, when we use a pair of enantiopure D-pGlu and L-pGlu as chiral transfer agents, corresponding homochiral PTCs of D-PTC-53 and L-PTC-53 were obtained. While racemic D, L-pyroglutamic acid was applied, the resulting crystal is a racemic compound. Obviously, the inexpensive chiral chemicals can effect homochiral crystallization. Moreover, without the addition of chiral transfer, a achiral compound of [Ti3(μ3-O)(μ3-OH)(OiPr)9] [28] was formed under identical reaction conditions. A comparative study of these four different crystallization processes demonstrates the role of optical pure amino acid in homochiral crystallization and the control of the absolute chirality.

The phase purity of crystalline samples was confirmed by powder X-ray diffraction (PXRD) analyses (Figs. S1 and S2 in Supporting information). These crystalline products are well soluble in dichloromethane solvent. Since these three compounds possess the same composition, the FT-IR spectra of these compounds are very similar (Fig. S3 in Supporting information). The characteristic features of pyroglutamate ligands and OiPr groups dominate the IR spectra. Single crystal X-ray diffraction analysis is an effective way to identify the isomers, which is hardly for general composition and spectra analysis.

One prominent feature of D-PTC-53 is the presence of an inorganic core made up of two trinuclear titanium clusters linked by one μ2-O linker. According to the literatures, hexanuclear PTCs can be classified into two types: one is the hexagonal columns configuration associated by six Ti ions and six μ3-O bridges (Fig. 1a) [29-31]; the other one is the combination form of two trinuclear Ti3(μ3-O) clusters (Figs. 1b-d) [32-34]. However, the latter one can be additionally divided into three different situations. In the first case, two Ti3(μ3-O) clusters are fused by a pair of μ3-O (Fig. 1b) bridges to give edge-to-edge belt-like hexanuclear cores. In the second cases, two trinuclear subunits are linked by a pair of μ2-O bridges into belt-like (Fig. 1c) [21] or parallel (Fig. 1d) hexanuclear cores [35, 36]. Even though the two trinuclear titanium clusters connected by only one μ2-O linker has been reported, while the calculated dihedral angle between the is 48.062° (Fig. 1e), and the corresponding value in D-PTC-53 is 14.533° (Fig. 1f). Such type of hexanuclear core does not appear to have been previously reported. Moreover, a pair of pGlu ligands and 14 isopropyl groups form a sheath around the periphery of the core (Fig. 1g). The presence of one μ2-O linker is crucial for the formation of the helical packing of inorganic core as revealed hereinafter. The pGlu ligands adopt μ4-η1:η1:η1:η1 coordination mode connecting neighbouring Ti3(μ3-O) clusters (Fig. S5 in Supporting information). Six terminal isopropyl groups arranged in the axial position of two Ti3(μ3-O) clusters. The other four terminal and bridged ones are alternatively distributed around the equator position of two Ti3(μ3-O) clusters (Fig. S6 in Supporting information). Additional strong intramolecular hydrogen bonds between pGlu ligands and oxygen acceptors, as well as between neighbouring isopropyl groups further stabilize the whole molecular (Table S3 in Supporting information).

Fig. 1. (a–e) Ball-stick view of the inorganic core of documented hexanuclear PTCs. (f–g) Inorganic core and molecule of D-PTC-53.

Structural analysis reveals that L-PTC-53 and D-PTC-53 are enantiomers of each other and present similar structures. In contrast with the reported centrosymmetric hexanuclear PTCs, D-PTC-53 and L-PTC-53 are non-centrosymmetrical ones. One question that one would ask is their original of the noncentrosymmetry? Three sources of chirality could be identified in these complexes. They are chiral amino acid ligand, chiral space group and chiral molecule packing. Firstly, colourless crystals of D-PTC-53 and L-PTC-53 crystallizes in the monoclinic system with chiral space groups P21, and the Flack parameter of -0.016(8) and -0.015(8) demonstrates their homochiral nature. Secondly, when have a close-up view of the two pGlu ligands in each structure, we can find that they all exclusively belong to homochiral configuration. So the use of chiral amino acid plays an important role on the asymmetry crystallization. Thirdly is the chirality transfer from optically pure ligands to inorganic core. The axial chirality can be found by the stack of inorganic core of hexanuclear molecules. There are a pair of homochiral helical chains with a pitch of 23.4468(9) Å and 23.4636(10) Å (equivalent to the length of the b axis) running along the 21 axis in D-PTC-53 and L-PTC-53 respectively (Figs. 2a and b). Instead, the structure of D, L-PTC-53 is centro-symmetric and has two molecules in the asymmetric unit, which can be intuitively viewed as the sum of a D-PTC-53 and a L-PTC-53 molecules (Fig. 2c).

Fig. 2. Perspective view of the helical arrays of the packing of the hexanuclear in D-PTC-53 (a), L-PTC-53 (b) and D, L-PTC-53 (c).

The solid-state UV absorption spectra of D-PTC-53, L-PTC-53 and D, L-PTC-53 indicates that they are transparent in the range of 400 - 800 nm (Fig. S7 in Supporting information) from the UV–visNIR absorption, which is consist with their colourless colour of the crystals. In addition, we measured the photocurrent responses of the prepared materials (Fig. S11 in Supporting information). The measurement was carried out by use of a three-electrode cell with the cluster film-coated ITO electrodes. The result indicated these materials with similar formula possessed similar photocurrent signals as well. However, their photocurrent response at approximately 40nA is weak than those reported hexanuclear PTCs [37]. The IR spectra of the samples after photocurrent studies were similar to those of the original crystals, indicating that the compounds were stable during measurement (Fig. S12 in Supporting information).

Besides the above mentioned chirality information acquired from the detailed structure analysis, a direct and additional evidence for the homochiral crystallization comes from CD spectroscopy. The solid-state CD measurements on bulk samples of D -PTC-53 and L-PTC-53 further verify the fact of the homochiral crystallization between titanium cations and enantiopure amino acids (Fig. 3). The CD spectra for the bulk sample of a positive CD signal appears at 310 nm for the bulk sample D-PTC-53, while L-PTC-53 exhibits a negative CD signal at 308 nm. The CD spectra for the bulk samples of them show an almost mirror image of each other, demonstrating they are a pair of enantiomers. The location of the CD signals of D-PTC-53 and L-PTC-53 has been redshift when compared with the amino acid ligand, and the intensity has approximately doubled. Thus such strong CD signals may stem from the interaction of the inorganic titanium oxo cluster and amino acid. These CD signal values are higher than those metal organic frameworks and lanthanide clusters [15, 38]. In comparison, D, L-PTC-53 exhibits no optical activity. The outcomes from the CD spectra are consistent with the results obtained by singlecrystal structure refinements

Fig. 3. The solid (a) and solution (b) state CD spectra of D-PTC-53, L-PTC-53 and D, LPTC-53.

In summary, we established herein a successful example of homochiral crystallization of homochiral PTCs by using enantiopure amino acids. In addition to providing diverse coordination sites facilitate the aggregation of PTCS, the amino acids are also essential to the control of absolute chirality. It is believed that one possible mechanism enabling the formation of high nuclearity PTCs is the hydrolysis of alkoxide ligands and slow in situ formation of water molecules during the esterification process. The in situ lactamide reaction along with the generation of water molecules paves a new way for the formation of high nuclearity PTCs. This work not only provides a new strategy for constructing high nuclearity PTCs with strong CD signals, but also promises an intriguing example of preparing homochiral PTCs with potential application in asymmetry catalysis.


This work is supported by the National Natural Science Foundation of China (NSFC, Nos. 21673238 and 21771181), Youth Innovation Promotion Association CAS (No. 2017345) and Natural Science Foundation of Fujian Province (Nos. 2017J06009 and 2017J05036).

Appendix A. Supplementary data

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