Incidental Polymorphism , Non-Isomorphic and Isomorphic Substitution in Calcium-Valine Coordination Polymers

Five coordination polymers with the stoichiometry CaX2(valine)2(H2O)2 (X = Cl, Br) were obtained from the corresponding calcium halides and either racemic and enantiopure valine. In all cases the zwitterionic amino acid is exclusively O coordinated and the halides act as counteranions for the resulting one-dimensional cationic chains. The enantiopure chloride shows dimorphism; both forms differ in connectivity from the bromide. In contrast to this structural variability for L-valine, the derivatives of the racemic amino acid are isomorphous.


Introduction
While amino acids are often used in chemistry and certainly represent an essential class of compounds in biochemistry, their fundamental coordination chemistry has been investigated to a lesser extent than expected.Although numerous structures containing amino acids in some form are reported, only a few systematic investigations with focus on amino acid coordination chemistry have been pursued.
Tackling this gap, we recently reported on the coordination chemistry of the amino acids proline and alanine with the halide salts of the oxophilic cations manganese and calcium.Both amino acids have shown to be useful ligands, since their chirality and hydrogen bond interactions led to a versatile asset of coordination compounds.On the one hand, L-proline formed coordination polymers with manganese chloride, bromide, and iodide in equimolar stoichiometry.On the other hand, a series of molecular, isomorphous products in 1:2 stoichiometry was obtained with racemic proline [1].Enantiopure alanine even allowed for isomorphous substitution of the heavy manganese and calcium halides to form a series of chiral coordination polymers in 1:3 stoichiometry, while racemic alanine yields different structures for the two metals [2].Calcium, a cation without crystal field effects exerted from partially filled d-orbitals, exhibited its versatility in the coordination chemistry with proline: two polymorphs were found for reactions of CaCl 2 with both enantiopure and racemic proline.One molecular complex resembles a structure from MnCl 2 , two unique coordination networks with Ca in octahedral environment are more characteristic for transition metals, and one coordination polymer features 7-fold Ca 2+ coordination; all these solids show unusual Ca-Cl contacts [3].No polymorphism is encountered for the CaBr 2 derivatives.Here the network motif is established for enantiopure proline, whereas racemic proline once again yields a unique polymer with eight-fold coordination [4].A comprehensive overview of crystal structures from amino acids has been published by Fleck and Petrosyan [5].With respect to coordinative bonds, zwitterionic amino acids can be considered a special case of carboxylates, and carboxylates count among the most widely used ligands for the design of extended structures (e.g., [6][7][8][9]).
In this contribution we compile five structures, formed by reaction of CaCl 2 or CaBr 2 with the amino acid valine and discuss polymorphism, isomorphism and other structural relationships.Reaction of L-valine with CaCl 2 in aqueous solution reproducibly yields coordination polymer 1a.In one instance an individual crystal of a second polymorph 1b was detected, and this alternative structure is included here for comparison.Despite variations in solvent, stoichiometry, concentration and crystallisation temperature, we have not been able to reproduce this second crystal form.Even the bulk material from which the single 1b specimen was selected consisted of the ubiquitous phase 1a, and the alternative polymorph 1b did not contribute detectable reflections to the powder pattern.A different polymer was obtained by reaction with the heavier CaBr 2 (2).Two isomorphous structures are obtained by using racemic valine with CaCl 2 (3) and CaBr 2 (4).The chloride analogue has been reported before [10] but we provide a low temperature crystal structure for comparison.A scheme of the discussed structures is given as Figure 1.

Results and Discussion
All structures obtained from calcium chloride and bromide with valine in enantiopure and racemic form are coordination polymers with bridging carboxylato groups and uncoordinated halides.They all share the formal composition CaX 2 (valine) 2 (H 2 O) 2 but differ significantly with respect to their detailed connectivity.Data collection and refinement details for all structures are given in Table 1.

Structural Details of 1a and 1b
1a and 1b, the alternative polymorphs of CaCl 2 (L-valine) 2 (H 2 O) 2 , are associated with a different ratio of volume per formula unit (V /Z, see Table 1); the formula unit requires a larger volume in 1a (465.8Å 3 ) than in 1b (447.8Å 3 ).This relationship is of course also reflected in a higher linear absorption coefficient and density of the latter compound.Although 1b shows positional disorder for a chloride counteranion (see refinement section), it is associated with better space filling.We wish to communicate this fact but cannot provide a simple explanation; we are aware of examples for the opposite case, i.e., more efficient packing for the well-ordered phase [11,12].
The main polymorph 1a crystallises in the triclinic spacegroup P 1 with one Ca(II) cation, two bridging L-valine molecules, two coordinating water ligands, and two uncoordinated chlorides in the asymmetric unit (see Figure 2).The same applies for 1b but in the orthorhombic spacegroup P 2 1 2 1 2. In both polymorphs, the calcium atom is enclosed in distorted octahedral geometry by two axial water ligands and four equatorially bridging µ 2 -η:η carboxylate groups in syn-anti conformation.Ca-O distances range from 2.300 (5) to 2.390 (5) Å in 1a and from 2.272 (3) to 2.400 (3) Å in 1b (see Table 2).interactions lead to different packing of the chains in the two polymorphs.While each amino group forms an N-H• • • O hydrogen bond towards the anti coordinating carboxylato-O of the next chain fragment, all other hydrogen bond donor groups find chlorides as suitable acceptors (see Table 3).The chains in 1a are crosslinked by those intermolecular hydrogen bonds in c-direction to form a two dimensional network.In 1b multiple hydrogen bonds link two neighbouring chains, forming a double strand that encloses the chlorides.The water molecule (O6) crosslinks these strands via O-H• • • Cl hydrogen bonds to form an overall three dimensional network (Figure 3).

Structural Details of 2
Solid 2 is formed from L-valine and calcium bromide and crystallises in the monoclinic spacegroup C2.The asymmetric unit is formed by two independent Ca atoms on twofold axes (Wyckoff positions 2a and 2b), one simultaneously chelating and bridging L-valine lingand (µ -η 2 :η 1 ), one syn-syn bridging L-valine ligand, two coordinating water molecules and two bromide counterions (Figure 4).The resulting cationic polymer chain (extending along the shortest unit cell axis c) is build by alternating eightfold coordinated Ca1 and six-coordinated Ca2.Ca-O distances range from 2.279 to 2.660 Å (see Table 2).The higher coordination number of Ca1 is due to the two chelating carboxylato groups, whereas Ca2 is only coordinated by one oxygen of each of the four connected amino acids.By action of the crystallographic axes perpendicular to the polymer, each chain segment consists of the same residues: one bridging and one simultaneously bridging and chelating carboxylate (Figure 4).  4. Overall, interstrand hydrogen bonds connect adjacent polymeric chains in a direction to form a two dimensional network in the ac plane.Herein, four amino groups and four bromide ions form a cube shaped motif (see Figure 5).Table 4. Hydrogen bond geometry in 2. Symmetry operations: a x, y, -1 + z; b 1 -x, y, 1 -z; c x, y, 1 + z.

The Isomorphous Structures 3 and 4
The two compounds obtained from racemic valine with CaCl 2 (3) or CaBr 2 (4) are isomorphous and crystallise in the orthorhombic spacegroup P cca.Their asymmetric unit comprises only half the size of that in the aforementioned structures: Ca 2+ is situated on Wyckoff position 4c (twofold axis), and one simultaneously bridging and chelating valine molecule, one aqua ligand, and one uncoordinated chloride are in general position (Figure 6).Thus, the metal cation is in eightfold coordination geometry, enclosed by two chelating valine molecule of one enantiomer (four oxygen atoms), two water molecules, and two bridging valine molecules from the adjacent chain fragments (two oxygen atoms of the opposite enantiomer).
Ca-O distances are compiled in Table 2 and differ slightly between the two structures: While only one distance of the chelating carboxylate group is elongated in 4, the water coordination actually gets shorter whereas the chain-separating Ca-O bridge gets longer.This is reflected in the Ca• • • Ca distances within the chain direction c (3.9927(12) Å in 3 vs 4.0043(13) Å in 4).
Although 3 and 4 are racemic and only show µη 2 :η 1 configured carboxylate bridging, the chain structure has high similarity to 2, which is reflected in similar c axes.An overlay of the chains (Figure 7) shows that the µη 2 :η 1 coordinating valine in 2 coincides with the L-valine positions in 3 and 4, whereas the non-chelating µη:η carboxylate of 2 comprises almost the same space as the D-valine molecules in 3 and 4. Through the adoption of a different coordination mode both structure types allow for almost the same intermolecular interactions: The amino group engages in three hydrogen bonds towards neighbouring halide ions, whereas the water ligand forms one hydrogen bond towards a carboxylate group of the next chain fragment and a second towards a halide.Details about hydrogen bond geometry are provided in Table 5.
The intermolecular hydrogen bonds link neighbouring chains in a-direction to form a two dimensional layer in the ac-plane.In contrast to the staggered arrangement in the C centered cell of 2, successive layers in 3 and 4 are eclipsed.The cube-shaped motif of four amino groups and four chlorides between two chains remains.Though, altering the orientation of two amino groups because of the different chirality (and hence, different coordination) of every second valine ligand, switches two hydrogen bond vertices to open the cube-motif and connect it with the square base of the next cube (Figure 8).

Conclusions
CaCl 2 (L-valine) 2 (H 2 O) 2 is an instructive example for a dimorphic compound with an easily available main polymorph and a second crystal form discovered by serendipity.We have not been able to reproduce this second phase, despite considerable efforts including alteration of the crystallisation temperature, deliberate contamination with trace amounts of related compounds, and variation of the pH-value.The relationship between the alternative forms is surprising, with higher space filling for the disordered phase.
Both polymorphs and also the other three solids obtained from calcium chloride or bromide and from L-or DL-valine share common features: In all structures, the carboxylato groups act as bridges between neighbouring Ca 2+ .The cations are exclusively oxygen coordinated, and the halides act as counteranions for the resulting cationic scaffolds.In addition to electrostatic interactions, classical hydrogen bonds link the ionic residues.Each individual structure is unexceptional, but their relationship can teach a lesson with respect to isomorphous substitution: Retention of a structure type among these halides may be as unpredictable as their polymorphism.

Syntheses
All products were obtained quantitatively as crystalline solids by dissolving the reactands in water in the stoichiometry of the target products.Subsequently, the solvent was evaporated under controlled conditions [2] at 50 • C. Variations in stoichiometry only altered the yield but not the composition of the product.1a was obtained as main phase from 44 mg CaCl 2 (0.4 mmol) and 92 mg L-valine (0.8 mmol) in 1 mL H 2 O in form of colorless elongated plates after two days.A needle shaped single crystal of 1b could be isolated from the same reaction.However, this polymorph could not be reproduced and has only been present as minority in the original sample.Seeding with 1b could therefore not be carried out as only one individual crystal of 1b could be isolated.However, several crystallisation experiments were done, including crystallisation at higher and lower temperature, intentional contamination with small amounts of other calcium salts/metal chlorides/amino acids, and variation of the pH-value.2 was obtained from 87 mg CaBr 2 • xH 2 O (0.4 mmol) and 92 mg L-valine (0.8 mmol) under the same conditions as needle shaped colorless crystals.Using a racemic mixture of both valine enantiomers yielded the products 3 (with CaCl 2 ) and 4 (with CaBr 2 ).X-ray powder diffractograms are shown as Figure 9. Experimental data collected at room temperature.The asterisk indicates a reflection from unreacted valine.

Data Collection and Refinement
Data were integrated with SAINT-Plus [15] and corrected for absorption with SADABS [15].The structures were solved by the Patterson method and refined by full matrix least squares procedures on F 2 as implemented in SHELXL-13 [16].Non hydrogen atoms were refined with anisotropic displacement parameters.Hydrogen atoms connected to carbon were set to idealized positions and treated as riding with U iso (H) = 1.2U eq (C) for CHR 3 and U iso (H) = 1.5U eq (C) for methyl groups.Hydrogen atoms attached to hetero atoms were found in difference Fourier maps.In each structure O-H and N-H distances were each restrained to similarity (SADI, σ = 0.02 Å).U iso of the hydrogen atoms were constrained to multiple values of the U eq of their parent atoms.Additionally, the H separation of the water molecules in 2 were also restrained to similarity (SADI, σ = 0.02 Å).In structure 1b two alternative positions were found for Cl1.Both could be assigned independent anisotropic displacement parameters; the sum of their refined occupancies (0.517 (8) for Cl1A and 0.483(8) for Cl1B) was constrained to unity .

Figure 1 .
Figure1.Overview of the performed reactions and reaction products.

Figure 2 .
Figure 2. Left: Asymmetric unit of 1a and 1b with labeling scheme as displacement ellipsoid plot (80% probability) and adjacent atoms as stick model.Right: Polymeric chains of 1a and 1b with kite (red) and parallelogram (blue) shaped bridges, approximate twofold symmetry with circles highlighting the stereo chemistry of the amino groups, and labeled syn and anti bridges.

Figure 3 .
Figure 3. Left: Hydrogen bonds (dashed light blue lines) extending from the asymmetric units of 1a and 1b.Right: Networks built by intermolecular hydrogen bonds in 1a and 1b.

Figure 4 .
Figure 4. Left: Asymmetric unit of 2 drawn as ellipsoid pot at 80% probability and connected atoms as stick model.Right: Cationic chain of 2.

Figure 5 .
Figure 5. Left: Hydrogen bonds extending from the asymmetric unit of 2. Middle: Resulting two dimensional network built by intermolecular hydrogen bonds in 2. Right: Cube motif built by intermolecular hydrogen bonds in 2.

Figure 6 .
Figure 6.Left: Asymmetric units of 3 and 4 as displacement ellipsoid plots (80% probability) and adjacent atoms as stick model.Right: Packing of a cationic chain exemplary shown for 3 (hydrogen atoms omitted for clarity).

Figure 7 .
Figure 7. Overlay of 2 (yellow) and 4 (green).View in chain direction (left) and perpendicular (middle) with highlighted overlap of same (red) and opposite (blue) chirality.Right: Closeup of one chain fragment.

Figure 8 .
Figure 8. Left to right: Hydrogen bonds emerging from the asymmetric unit in 3; the situation for 4 is analogous.View in c direction illustrating the resulting two dimensional network.Opened cube motif connecting two chains.Schematic drawing of cube and opened cube motifs.

Figure 9 .
Figure 9. Simulated and experimental X-ray powder diffractograms of all products.Experimental data collected at room temperature.The asterisk indicates a reflection from unreacted valine.

Table 2 .
Selected interatomic distances of all structures.