Preferential Enrichment of Enantiomer from Amino Acid Schiff Bases by Coordination Interaction and Crystallization

In this paper, preferential enrichment (PE) is described for three pairs of novel amino acid Schiff base Cu(II)/Cu(I) complexes. Single crystal X-ray diffraction indicated that 1-S/R are one-dimensional coordination polymers (CPs) with helical structures, and 2-S/R and 3-S/R are one-dimensional CPs with auxiliary ligands. By tuning the pH, the solvent and second ligands, the 1-S/R, 3-S/R underwent polymorphic transitions, resulting in enantioselective liberation of excess enantiomers into solution, until the deposited crystals were slightly enriched with the opposite enantiomer, thereby successfully exhibiting PE. However, under the effects of Cu(II), the solvent and low pH, 2-S/R did not exhibit PE and resulted in enrichment of racemic compounds, which was attributed to amino acid Schiff base chiral complex mechanisms of PE. The three pairs of Cu complex structures were characterized by UV-vis, MS and X-ray photoelectron spectroscopy (XPS). All chiral properties were studied by circular dichroism (CD) in the solid and liquid.


Introduction
Chirality, a universal feature that occurs through the whole process of generation and evolution of living organisms, is an important feature of biological organisms [1]. Amino acids are basic building blocks of all living organisms and they participate in all life activities. They typically occur in one of two possible enantiomeric forms, D forms and L forms [2][3][4], and they are also central sources of steric chiral carbon atoms. Salicylaldehyde-modified amino acids are among the most commonly used strategies for obtaining chiral ligands [5][6][7][8][9][10][11]. Their tridentate chelation coordination modes make it easier to interact with metal ions, which have antibacterial and antitumor activities after forming complexes.
There are three main methods for obtaining chiral compounds: chiral source synthesis, chiral catalysis and chiral resolution. Chiral resolution has been the subject of considerable recent developments because it is economically viable, easy to operate and easy to realize industrial production. Preferential enrichment (PE) is an unusual symmetry-breaking spontaneous enantiomeric resolution phenomenon that applies to racemic crystals, the solvent-assisted solid-to-solid polymorphic transition of an initially formed metastable crystalline phase into another more stable one. Then, after partial crystal disintegration inside the crystal lattice, the enantioselective redissolution of excess enantiomers into the mother liquor leads to considerable enrichment of the same enantiomer until deposited crystals are slightly enriched with the opposite enantiomer [12][13][14]. The four conditions that are necessary for PE occurrence include: (i) Solubility difference; (ii) solid-to-solid polymorphic transition; (iii) partial crystal disintegration and (iv) deposition of nonracemic mixed crystals [15][16][17]. The PE phenomenon of amino acids has been reported. Uchida  In this work, the ligand (S, E)-2-((4-chloro-2-hydroxybenzylidene) amino) propano ate, NaHL) previously reported by our group [22][23][24] was studied in coordination wit Cu(I) and Cu(II) ions by tuning the pH, the solvent and the second ligands. Three pairs o enantiomers of coordination complexes were obtained based on the PE principle, the dif ferent PE phenomena of complexes were observed during crystallization. The 1-S/R, 3 S/R initially formed mixed crystals via the solvent-assisted solid-to-solid type polymor phic transition from kinetically formed metastable crystals to the thermodynamically sta ble ones. Subsequently, the partial crystal began to disintegrate, until the opposite enan tiomers were preferentially enriched [17,18]. Under the induction of Cu(II), low pH, th solvent and the second ligands, the 2-S/R failed to exhibit the PE phenomenon. The chira properties of enantiomers were studied via solid and liquid circular dichroisms (CD).

Synthesis of Ligand
The NaHL-S was prepared using 4-chloro-2-hydroxybenzaldehyde and L -alanine a raw materials (Scheme 1a). L -alanine (0.187 g, 5 mmol) and NaOH (0.2 g, 5 mmol) wer added in ethanol (20 mL), the mixtures were stirred and refluxed for 1 h at 80 °C. Th solution of 4-chloro-2-hydroxybenzaldehyde (0.7 g, 5 mmol, 10 mL) was added to th above solution, stirring and refluxing for another 3 h. The yellow solid was obtained (1. The synthesis method of NaHL-R is similar to that of NaHL-S except that L -alanin is replaced with D -alanine. The yellow solid was obtained (1. In this work, the ligand (S, E)-2-((4-chloro-2-hydroxybenzylidene) amino) propanoate, NaHL) previously reported by our group [22][23][24] was studied in coordination with Cu(I) and Cu(II) ions by tuning the pH, the solvent and the second ligands. Three pairs of enantiomers of coordination complexes were obtained based on the PE principle, the different PE phenomena of complexes were observed during crystallization. The 1-S/R, 3-S/R initially formed mixed crystals via the solvent-assisted solid-to-solid type polymorphic transition from kinetically formed metastable crystals to the thermodynamically stable ones. Subsequently, the partial crystal began to disintegrate, until the opposite enantiomers were preferentially enriched [17,18]. Under the induction of Cu(II), low pH, the solvent and the second ligands, the 2-S/R failed to exhibit the PE phenomenon. The chiral properties of enantiomers were studied via solid and liquid circular dichroisms (CD).

Synthesis of Ligand
The NaHL-S was prepared using 4-chloro-2-hydroxybenzaldehyde and L -alanine as raw materials (Scheme 1a). L -alanine (0.187 g, 5 mmol) and NaOH (0.2 g, 5 mmol) were added in ethanol (20 mL), the mixtures were stirred and refluxed for 1 h at 80 • C. The solution of 4-chloro-2-hydroxybenzaldehyde (0.7 g, 5 mmol, 10 mL) was added to the above solution, stirring and refluxing for another 3 h. The yellow solid was obtained (1.33 g, yield 89.8%). Anal. Calcd. (%) for C 10  The synthesis method of NaHL-R is similar to that of NaHL-S except that L -alanine is replaced with D -alanine. The yellow solid was obtained (1.43 g, yield 92.8%). Anal. Calcd. (%) for C 10   The synthesis method of 1-R is similar to that of 1-S except that NaHL-S is replaced with NaHL-R. Additionally, the green stick single crystals were obtained after 8 days (yield: 49.17%). Anal. Calcd. (%) for C 10

Methods
The elemental analyses (C, H and N) were measured on an EA-3000 elemental analyser (Euro Vector, Italy). FT-IR spectra were recorded on Thermo IS 5 FT-IR spectrometers (Walthamm, MA, USA) in the range of 4000-400 cm −1 . The PXRD data of the samples were measured on a Bruker D8 ADVANCE (Karlsruhe, Germany). Thermogravimetric analyses (TGA) were measured using a Japan Shimadzu DTG-60 H thermal analyser (Shimadzu, Tokyo, Japan). The UV-vis absorption spectra were collected on a UT-1950 spectrophotometer (Persee, Beijing, China) in the range of 200-800 nm. The liquid CD spectra were measured on a JASCO J-1500 spectropolarimeter (JASCO, Tokyo, Japan) in the range of 200-800 nm and the solid CD spectra were measured by KBr pellet (sample: KBr = 1: 200). ESI-MS spectra were measured using a Thermo Scientific (Walthamm, MA, USA) Q Exactive HF-X mass spectrometer equipped with an ESI source and in the positive ion mode from m/z 100 to 1600. HPLC were measured with Waters upc2 (Waters, Milford, MA, USA) Chiralpak IG using MeOH/CO 2 = 20:80 with flow rate of 2.0 mL/min and detection at 214 nm. X-ray photoelectron spectra (XPS) were measured with a PHI 5000 Versaprobe III (ULVAC-PHI, Kanagawa, Japan) with monochromatized Al Kα-X-rays (Hv,1486.6 eV) operating at 150 W, and were calibrated by the BE of the C component (BE = 284.6 eV) coming from contamination carbon.

Crystal Structures
Single crystal diffraction data were measured on a Bruker DUO APEX II diffractometer using graphite monochromatic molybdenum Kα (λ = 0.71073 Å) radiation at room temperature, under the conditions of 45 KV and 30 mA. Diffraction data collection adopts ω-2θ scanning mode, and all scanned data are subjected to empirical absorption correction. The crystal structure was obtained by the SHELXL program [25,26]. All non-hydrogen atoms are determined and corrected by Fourier synthesis and refined anisotropically. Hydrogen atoms are in their theoretical positions and refined isotropically. The crystallographic data for 1-S, 2-S and 3-S are presented in Table 1, 1-R, 2-R and 3-R are presented in Table S1. The CCDC number from 1-S to 3-R are 2169253, 2169283, 2206482, 2206484, 2169254 and 2169256, respectively.

Crystal Structures of 1-S and 1-R
Single crystal structure analysis revealed that 1-S and 1-R are a pair of enantiomers, and they both crystallize in the orthorhombic space group of P2 1 2 1 2 1 . Taking 1-S as an example, the asymmetric unit is composed of one Cu (II) ion and one deprotonated ligand. The Cu(II) ion is five-coordinated and located in the centre of distorted square pyramidal coordination geometry of CuNO 4 . The N1, O1 and O2 from the ligand and O2#3 of the carboxyl group from the adjacent ligand occupy the equatorial positions, while the carboxylic acid oxygen atom (O3#4) from another ligand occupies the axis positions ( Figure 1a). The 1-R exhibited a comparable coordination environment as 1-S, except that the C7 carbon atom has an R-configuration ( Figure S4). The ideal parameter for square-pyramidal geometry is α = β (the largest angles around the Cu(II) ion) = 180 • with calculated τ = 0 [27][28][29]. The calculated geometry parameters τ of 1-S and 1-R are 0.03 and 0.04, respectively. Therefore, they both exhibit a distorted square pyramidal coordination geometry (Figure 1b, Tables S3 and S4).
The asymmetric units were further extended into 1D chains along the a axis by the connection of O2#3 and O3#4 between adjacent ligands with Cu-Cu distance of 3.596(7) Å ( Figure S5). A chiral Cu1-O2-Cu1-O2 helical chain was formed via coordination between Cu1 and O2. Structural analysis showed that helical chains in 1-S and 1-R exhibit a P-helical structure (right-hand) and an M-helical structure (left-hand) in space with pitches of 4.951 Å and 4.948 Å, respectively (Figure 1c and Figure S6). Additionally, fluorine atoms of the ligand moved towards the outside of the chain to form a hydrophobic surface. Non-classical hydrogen bonds (C7-H7A . . . Cl, 2.94 Å, 3.669 (4) Å, 132 • ) were formed between adjacent helical chains, which extended the 1D chain into higher 2D and 3D structures (Figure 1d, Figures S7 and S8).

Crystal Structures of 2-S and 2-R
Both 2-S and 2-R crystallized in the triclinic space group of P1. Taking 2-S as an example, the asymmetric unit consisted of two Cu (II) ions, two deprotonated ligands and one 4,4 -bipyridine. The Cu(II) was five-coordinated and the geometry parameter τ was 0.18 for both 2-S and 2-R, exhibiting a distorted square pyramidal geometry. The O1, O2 and N1 from ligand and N2 from 4,4 -bipyridine formed the equatorial plane, while O1#1 from the adjacent ligand occupied the axial position ( Figure 2a and Figure  S9, Table S5). The 2-R exhibited a similar coordination environment as 2-S ( Figure S10). High flack parameters of 0.40 were observed in 2-S (Table 1), proving the existence of enantiomers that come from ligands. Since NaHL was a racemic compound (Scheme 1b, Figure S12a,b), the other molecule in the unit cell, related by an inversion centre, has opposite chirality for both C9 and N1 ( Figure S11) [30]. The ee (%) values were 38.1% and 1.56%, respectively, as determined by HPLC analysis (Figure S12c,d). Meanwhile, 2-S/R pH was slightly higher than that of 1-S/R (Table 2), thus, we postulated that under induction of Cu(II), 4,4 -bipyridine, the solvent and low pH environment, 2-S/R did not exhibit the PE phenomenon [31,32], which produced the final racemic mixture [18].

Crystal Structures of 2-S and 2-R
Both 2-S and 2-R crystallized in the triclinic space group of P1. Taking 2-S as an example, the asymmetric unit consisted of two Cu (II) ions, two deprotonated ligands and one 4,4′-bipyridine. The Cu(II) was five-coordinated and the geometry parameter τ was 0.18 for both 2-S and 2-R, exhibiting a distorted square pyramidal geometry. The O1, O2 and N1 from ligand and N2 from 4,4′-bipyridine formed the equatorial plane, while O1#1 from the adjacent ligand occupied the axial position (Figures 2a and S9, Table S5). The 2-R exhibited a similar coordination environment as 2-S ( Figure S10). High flack parameters of 0.40 were observed in 2-S (Table 1), proving the existence of enantiomers that come from ligands. Since NaHL was a racemic compound (Scheme 1b, Figure S12a,b), the other molecule in the unit cell, related by an inversion centre, has opposite chirality for both C9 and N1 ( Figure S11) [30]. The ee (%) values were 38.1% and 1.56%, respectively, as determined by HPLC analysis (Figure S12c,d). Meanwhile, 2-S/R pH was slightly higher than that of 1-S/R (Table 2), thus, we postulated that under induction of Cu(II), 4,4′-bipyridine, the solvent and low pH environment, 2-S/R did not exhibit the PE phenomenon [31,32], which produced the final racemic mixture [18].   (Figure 2b). The binuclear structure was observed in the 1D chain with a Cu-Cu distance of 3.392(7) Å. Non-conventional hydrogen bonds were formed between O3 from the carboxyl group and H14 from the benzene ring between adjacent chains (C14-H14A . . . O3, 2.37 Å, 3.322(5) Å, 162 • ), which assembled 1D chains into higher-dimensionality 2D structures (Figures 2c and S13a). These layers were stacked together via van der Waals forces to form 3D supramolecular structures exhibiting ABAB packaging with slipping in spaces (Figures 2d and S13c). Moreover, 2-R exhibited similar stacking patterns as 2-S (Figures S10c,d and S13b,d). benzene ring between adjacent chains (C14-H14A…O3, 2.37 Å, 3.322(5) Å, 162°), which assembled 1D chains into higher-dimensionality 2D structures (Figure 2c and S13a). These layers were stacked together via van der Waals forces to form 3D supramolecular structures exhibiting ABAB packaging with slipping in spaces (Figures 2d and S13c). Moreover, 2-R exhibited similar stacking patterns as 2-S (Figures S10c,d and S13b,d).
Under Cu(I) and higher pH conditions, the 3-S/R exhibited the PE phenomenon during crystallization, with flack parameters of 0.00(4) and 0.13(5), respectively (Tables 1 and S1). This implies that they are a pair of enantiomers, and it was observed that the 3-S exhibited an S-configuration with the methyl up.
Under Cu(I) and higher pH conditions, the 3-S/R exhibited the PE phenomenon during crystallization, with flack parameters of 0.00(4) and 0.13(5), respectively (Tables 1 and S1). This implies that they are a pair of enantiomers, and it was observed that the 3-S exhibited an S-configuration with the methyl up. The 3-R exhibited an R-configuration with the methyl down (Figure 3b). Adjacent asymmetric units formed 1D chain structures via Cu-O (phenolic hydroxyl) bonds (Cu1-O4#2, Cu2-O1#1: 2.521(121) Å, 2.527(128) Å). Nonconventional hydrogen bonds were formed between adjacent asymmetric units with O from the carboxyl group on the ligand and H29 from the benzene ring (C29-H29A . . . O6, 2.32 Å,3.207 (2) Å, 161 • ), which assembled the 1D chain into a higher dimensionality 2D structure (Figures 3c and S15). These layers were stacked together and expanded via van der Waals forces to form 3D supramolecular structures exhibiting an ABAB packaging with slipping (Figures 3d and S16).
Non-conventional hydrogen bonds were formed between adjacent asymmetric units with O from the carboxyl group on the ligand and H29 from the benzene ring (C29-H29A…O6, 2.32 Å,3.207 (2) Å, 161°), which assembled the 1D chain into a higher dimensionality 2D structure (Figures 3c and S15). These layers were stacked together and expanded via van der Waals forces to form 3D supramolecular structures exhibiting an ABAB packaging with slipping (Figures 3d and S16).

Thermal Stability and Powder X-ray Diffraction
All complexes from 1-S to 3-R were obtained via the solvent evaporation technique at room temperature. High-quality single crystal structures of 1-S/R, 2-S/R and 3-S/R were obtained in ethanol-water, methanol-acetonitrile and methanol-DMF solutions, respectively. Findings from powder X-ray diffraction (PXRD) were highly consistent with simulated data of single crystals, indicating phase purity of samples (Figure 4). The TGA analysis showed that weight losses for 2-S/R and 3-S/R in the first stage were 4.1%/5.3% and 8%/10%, respectively, which were attributed to preferential loss of solvents, consistent with theoretical values. Decomposition temperatures of 1-S/R, 2-S/R and 3-S/R were 251 °C/248 °C, 221 °C/229 °C and 232 °C/234 °C, respectively, after which the frameworks of complexes began to collapse ( Figure S17).

Thermal Stability and Powder X-ray Diffraction
All complexes from 1-S to 3-R were obtained via the solvent evaporation technique at room temperature. High-quality single crystal structures of 1-S/R, 2-S/R and 3-S/R were obtained in ethanol-water, methanol-acetonitrile and methanol-DMF solutions, respectively. Findings from powder X-ray diffraction (PXRD) were highly consistent with simulated data of single crystals, indicating phase purity of samples (Figure 4). The TGA analysis showed that weight losses for 2-S/R and 3-S/R in the first stage were 4.1%/5.3% and 8%/10%, respectively, which were attributed to preferential loss of solvents, consistent with theoretical values. Decomposition temperatures of 1-S/R, 2-S/R and 3-S/R were 251 • C/248 • C, 221 • C/229 • C and 232 • C/234 • C, respectively, after which the frameworks of complexes began to collapse ( Figure S17).

UV-Vis Spectra of NaHL, and 1-S/R, 2-S/R and 3-S/R
The UV-vis spectra of NaHL and 1-S/R, 2-S/R and 3-S/R in methanol were recorded in the range of 200−800 nm. In Figure 5a,c, absorption peaks of NaHL at 222 nm, 242 nm and 265 nm were attributed to π→π* transitions of benzene rings. Absorption peaks at 350 nm were attributed to charge transfer transitions within the delocalized π-system in the molecular structure [33,34]. Enhanced absorption peaks for 1-S/R, 2-S/R and 3-S/R were observed in the range of 200-400 nm, and the intense high-energy band at 246 nm was attributed to π→π* intra-ligand charge transfer transitions (ILCT) [35,36]. The corresponding absorption peaks of complexes at 365 nm were strongly enhanced compared to that of NaHL, which was attributed to ligand to metal charge transfer (LMCT) transitions by strong interactions between metal ions and ligands [37][38][39][40]. This is consistent with X-ray diffraction crystallographic structures of those complexes. Due to d−d transitions of 1-S/R and 2-S/R, very weak absorption peaks appeared between 600 and 700 nm in the UV-vis spectra (Figure 5b,d) [41][42][43].

UV-Vis Spectra of NaHL, and 1-S/R, 2-S/R and 3-S/R
The UV-vis spectra of NaHL and 1-S/R, 2-S/R and 3-S/R in methanol were recorded in the range of 200−800 nm. In Figure 5a,c, absorption peaks of NaHL at 222 nm, 242 nm and 265 nm were attributed to π→π* transitions of benzene rings. Absorption peaks at 350 nm were attributed to charge transfer transitions within the delocalized π-system in the molecular structure [33,34]. Enhanced absorption peaks for 1-S/R, 2-S/R and 3-S/R were observed in the range of 200-400 nm, and the intense high-energy band at 246 nm was attributed to π→π* intra-ligand charge transfer transitions (ILCT) [35,36]. The corresponding absorption peaks of complexes at 365 nm were strongly enhanced compared to that of NaHL, which was attributed to ligand to metal charge transfer (LMCT) transitions by strong interactions between metal ions and ligands [37][38][39][40]. This is consistent with Xray diffraction crystallographic structures of those complexes. Due to d−d transitions of 1-S/R and 2-S/R, very weak absorption peaks appeared between 600 and 700 nm in the UVvis spectra (Figure 5b,d) [41][42][43].

Chirality and Chiral Recognition
Considerable enantiomeric enrichment and polymorphic transitions have been correlated with chirality. Chiral properties of NaHL and 1-S/R, 2-S/R and 3-S/R were investigated via circular dichroism (CD) spectra in solution. The NaHL-S exhibited positive cotton effects at 271 nm and 335 nm, negative cotton effects at 315 nm and 369 nm, corresponding to absorption of Schiff-base ligands [44,45]. The NaHL-R exhibited the opposite cotton effect at similar wavelengths (Figure 6a). Complexes 2-S/R and 3-S/R exhibited similar CD spectra with 1-S/R (Figure 6b-d). The CD spectrum of 1-R exhibited opposite signals to those of 1-S, indicating that the two complexes are a pair of enantiomers (Figure 6b). Taking 1-S as an example, a strong positive cotton peak was observed at 246 nm in 1-S, which was an obvious blue shift when compared with that of 283 nm in NaHL that was attributed to enhanced conjugation between ligands and metal ions. Negative cotton peaks were observed in the range of 300-400 nm, which was attributed to the LMCT process [5]. In the visible region of 500-800 nm, 1-S/R and 2-S/R exhibited weak CD signal peaks, which was attributed to d-d transitions in Cu(II) ions, corresponding to the UV-vis spectrum. Thus, the chiral information was transferred from the organic ligand to the metal ion ( Figure S18) [46][47][48].
In the solid CD spectrum ( Figure S19), NaHL-S exhibited a strong positive cotton effect at λ = 330 nm and a strong negative cotton effect at 284 nm. Compared with the liquid CD spectrum, signal peak of the π→π* transition absorption was weaker. This was attributed to abundant hydrogen-bond interactions between NaHL molecules in the solid, which inhibited π→π* transitions [49,50]. Furthermore, 1-S showed positive cotton effects at 300 nm and negative cotton effects at 447 nm. Unlike the solution CD spectrum in the 500-800 nm region, CD signal peaks that were attributed to d-d transitions can be clearly observed. Compared to the CD spectra in solution, solid CD spectra of 1-S/R, 2-S/R and 3-S/R exhibited various differences. It is possible that interaction modes between components in the solution had changed due to solvent interference. Complexes from 1-S to 3-R between opposite cotton effects in solution and in solid CD spectra indicate the existence of a mirror-image relationship between complexes from 1-S to 3-R, validating the presence of chiral enantiomers. Chirality of 1-S to 3-R was confirmed by single crystal structures.

Chirality and Chiral Recognition
Considerable enantiomeric enrichment and polymorphic transitions hav related with chirality. Chiral properties of NaHL and 1-S/R, 2-S/R and 3-S/R tigated via circular dichroism (CD) spectra in solution. The NaHL-S exhibit cotton effects at 271 nm and 335 nm, negative cotton effects at 315 nm and 369 sponding to absorption of Schiff-base ligands [44,45]. The NaHL-R exhibited t cotton effect at similar wavelengths (Figure 6a). Complexes 2-S/R and 3-S/R similar CD spectra with 1-S/R (Figure 6b-d). The CD spectrum of 1-R exhibite signals to those of 1-S, indicating that the two complexes are a pair of enantiom 6b). Taking 1-S as an example, a strong positive cotton peak was observed at 2 S, which was an obvious blue shift when compared with that of 283 nm in NaH attributed to enhanced conjugation between ligands and metal ions. Nega peaks were observed in the range of 300-400 nm, which was attributed to the cess [5]. In the visible region of 500-800 nm, 1-S/R and 2-S/R exhibited weak peaks, which was attributed to d-d transitions in Cu(II) ions, corresponding to spectrum. Thus, the chiral information was transferred from the organic lig metal ion ( Figure S18) [46][47][48].  Figure S22). Findings from ESI-MS spectra are consistent with X-ray crystallographic structures of complexes.

X-ray Photoelectron Spectroscopy (XPS) of 1-S/R, 2-S/R and 3-S/R
To characterize the valence states of complexes, X-ray photoelectron spectroscopy (XPS) measurements were performed on 1-S/R, 2-S/R and 3-S/R. Full-scan XPS spectra of complexes from 1-S to 3-R are shown in Figure 7a and Figure S23, which show the presence of Cu, Cl, N, O and C peaks. Table S2 summarizes the Cu 2p 3/2 , Cu 2p 1/2 , binding energy data of the complexes. The 1-S, 2-S and 3-S XPS spectra of Cu2p core level and Cu LMM (Auger spectra) are shown in Figure 7b,c. XPS indicates that the copper cation in 1-S and 2-S is bivalent. The 1-S and 2-S showed Cu 2p 3/2 and Cu 2p 1/2 peaks at 934.6 eV and 934.0 eV and 954.6 eV and 954.3 eV, respectively, while the satellite peaks from 940 to 945 eV were assigned to Cu 2+ [51,52], For 3-S the Cu 2p 3/2 and Cu 2p 1/2 binding energy peaks were observed at 932.4 eV and 954.2 eV, and the Cu LMM (Auger peak) at 570.1 eV can be clearly observed for that of Cu(I) [53,54], indicating the presence of Cu(I) centres [55,56]. Valence results of 1-R, 2-R and 3-R are consistent with those of 1-S, 2-S and 3-S ( Figure S23). In the solid CD spectrum ( Figure S19), NaHL-S exhibited a strong positive effect at λ = 330 nm and a strong negative cotton effect at 284 nm. Compared w liquid CD spectrum, signal peak of the π→π* transition absorption was weaker. T attributed to abundant hydrogen-bond interactions between NaHL molecules in th which inhibited π→π* transitions [49,50]. Furthermore, 1-S showed positive cotton at 300 nm and negative cotton effects at 447 nm. Unlike the solution CD spectrum 500-800 nm region, CD signal peaks that were attributed to d-d transitions can be observed. Compared to the CD spectra in solution, solid CD spectra of 1-S/R, 2-S 3-S/R exhibited various differences. It is possible that interaction modes between c nents in the solution had changed due to solvent interference. Complexes from 1-S between opposite cotton effects in solution and in solid CD spectra indicate the ex of a mirror-image relationship between complexes from 1-S to 3-R, validating th ence of chiral enantiomers. Chirality of 1-S to 3-R was confirmed by single crysta tures.

ESI mass Spectrometry of 1-S/R, 2-S/R and 3-S/R
The ESI-MS spectra was used to identify chemical species of 1-S/R, 2-S/R and in solutions. Molecular fragments in solutions of 1-S and 1-R were detected at 2

X-ray Photoelectron Spectroscopy (XPS) of 1-S/R, 2-S/R and 3-S/R
To characterize the valence states of complexes, X-ray photoelectron spectroscopy (XPS) measurements were performed on 1-S/R, 2-S/R and 3-S/R. Full-scan XPS spectra of complexes from 1-S to 3-R are shown in Figures 7a and S23, which show the presence of Cu, Cl, N, O and C peaks. Table S2 summarizes the Cu 2p3/2, Cu 2p1/2, binding energy data of the complexes. The 1-S, 2-S and 3-S XPS spectra of Cu2p core level and Cu LMM (Auger spectra) are shown in Figure 7b,c. XPS indicates that the copper cation in 1-S and 2-S is bivalent. The 1-S and 2-S showed Cu 2p3/2 and Cu 2p1/2 peaks at 934.6 eV and 934.0 eV and 954.6 eV and 954.3 eV, respectively, while the satellite peaks from 940 to 945 eV were assigned to Cu 2+ [51,52], For 3-S the Cu 2p3/2 and Cu 2p1/2 binding energy peaks were observed at 932.4 eV and 954.2 eV, and the Cu LMM (Auger peak) at 570.1 eV can be clearly observed for that of Cu(I) [53,54], indicating the presence of Cu(I) centres [55,56]. Valence results of 1-R, 2-R and 3-R are consistent with those of 1-S, 2-S and 3-S ( Figure S23).

Conclusions
The PE phenomenon of the three pairs of amino acid Schiff base Cu complexes during crystallization have been assessed. The 1-S/R and 3-S/R exhibited polymorphic transitions during crystallization, resulting in enantioselective liberation of excess enantiomers into solution and preferential enrichment. However, under the effects of Cu(II), solvent and

Conclusions
The PE phenomenon of the three pairs of amino acid Schiff base Cu complexes during crystallization have been assessed. The 1-S/R and 3-S/R exhibited polymorphic transitions during crystallization, resulting in enantioselective liberation of excess enantiomers into solution and preferential enrichment. However, under the effects of Cu(II), solvent and low pH, the 2-S/R failed to exhibit a PE phenomenon, resulting in product racemic complexes. X-ray photoelectron spectroscopy (XPS) was used to characterize the Cu valence state. The solution and solid CD spectra revealed that intrinsic chiral activities of the amino acid Schiff base were transferred to the Cu centre. Based on the above findings, we postulated that PE can become a method for resolution of amino acid Schiff base chiral complexes, and the series of complexes can be applied in studies on resolution of chiral drugs and their synthetic intermediates in medicine and life sciences among others.
Supplementary Materials: The following supporting information can be downloaded at: https: //www.mdpi.com/article/10.3390/ma16020530/s1. See Supporting Information for related data.
Author Contributions: L.Y. is the main contributor for this manuscript and prepared the coordination polymers, performed the structural characterization and CD spectra, wrote the manuscript and so on; Z.L. and X.Z. are responsible for verifying the data to ensure its authenticity; J.D. is responsible for testing and analyzing XPS data; Y.X. and S.P. are responsible for data curation; H.L. is the project leader and a corresponding author of this manuscript. All authors have read and agreed to the published version of the manuscript.
Funding: This work was financially supported by the National Natural Science Foundation of China (Nos. 21271026, 21471017).

Institutional Review Board Statement: Not applicable.
Informed Consent Statement: Not applicable.

Data Availability Statement:
The data that support the findings of this study are available from the corresponding author upon reasonable request.