Synthesis and structure of a complex of copper(I) with l-cysteine and chloride ions containing Cu12S6 nanoclusters

A cluster containing copper(I), l-cysteine and chloride ions was synthesized and characterized by X-ray diffraction and FTIR spectroscopy.

The title hydrated copper(I)-l-cysteine-chloride complex has a polymeric structure of composition {[Cu 16 (CysH 2 ) 6 Cl 16 ]ÁxH 2 O} n [CysH 2 = HO 2 CCH(NH 3 + )CH 2 S À or C 3 H 7 NO 2 S], namely, poly[[tetra-3 -chlorido-deca-2 -chlorido-dichloridohexakis( 4 -l-cysteinato)hexadecacopper] polyhydrate]. The copper atoms are linked by thiolate groups to form Cu 12 S 6 nanoclusters that take the form of a tetrakis cuboctahedron, made up of a Cu 12 cubooctahedral subunit that is augmented by six sulfur atoms that are located symmetrically atop of each of the Cu 4 square units of the Cu 12 cubo-octahedron. The six S atoms thus form an octahedral subunit themselves. The exterior of the Cu 12 S 6 sphere is decorated by chloride ions and trichlorocuprate units. Three chloride ions are coordinated in an irregular fashion to trigonal Cu 3 subunits of the nanocluster, and four trigonal CuCl 3 units are bonded via each of their chloride ions to a copper ion on the Cu 12 S 6 sphere. The trigonal CuCl 3 units are linked via Cu 2 Cl 2 bridges covalently connected to equivalent units in neighboring nanoclusters. Four such connections are arranged in a tetrahedral fashion, thus creating an infinite diamond-like net of Cu 12 S 6 Cl 4 (CuCl 3 ) 4 nanoclusters. The network thus formed results in large channels occupied by solvent molecules that are mostly too ill-defined to model. The content of the voids, believed to be water molecules, was accounted for via reverse Fouriertransform methods using the SQUEEZE algorithm [Spek (2015). Acta Cryst. C71,[9][10][11][12][13][14][15][16][17][18]. The protonated amino groups of the cysteine ligands are directed away from the sphere, forming N-HÁ Á ÁCl hydrogen bonds with chloride-ion acceptors of their cluster. The protonated carboxy groups point outwards and presumably form O-HÁ Á ÁO hydrogen bonds with the unresolved water molecules of the solvent channels. Disorder is observed in one of the two crystallographically unique [Cu 16 (CysH 2 ) 6 Cl 16 ] segments for three of the six cysteine anions.

Chemical context
l-cysteine is an important proteinogenic amino acid widely distributed in living organisms (Lennarz & Lane, 2013). Copper-cysteine clusters are of interest as possible models of active sites of some copper-containing proteins (Kretsinger et al., 2013). It is interesting to observe that there are no structures of copper complexes with both chloride ions and cysteine and even cystine determined by single crystal X-ray diffraction. As part of our studies in this area, we now describe the synthesis and structure of the title cluster compound. ISSN 2056-9890

Structural commentary
The crystallographic analysis of the title compound revealed a complex polymeric structure of composition {[Cu 16 (CysH 2 ) 6 Cl 16 ]ÁxH 2 O} n , [CysH 2 = HO 2 CCH(NH 3 + )-CH 2 S À ]. The copper atoms are linked by thiolate groups to form Cu 12 S 6 copper thiolate nanoclusters ('atlas spheres'), which have the form of a tetrakis cuboctahedron, made up of a Cu 12 cubo-octahedral subunit that is augmented by six sulfur atoms that are located symmetrically atop of each of the Cu 4 square units of the Cu 12 cubo-octahedron. The six S atoms form an octahedral subunit themselves. The exterior of the Cu 12 S 6 sphere is decorated by chloride ions and trichlorocuprate units. Three chloride ions are irregularly coordinated to trigonal Cu 3 subunits of the nanocluster, and four trigonal CuCl 3 -units are linked through each of their chloride ions to each one copper ion on the 'atlas spheres'. The trigonal CuCl 3 units are covalently connected through Cu 2 Cl 2 bridges to equivalent units in neighboring nanoclusters. Four such connections are arranged in a tetrahedral fashion, forming a diamond like network of Cu 12 S 6 Cl 4 (CuCl 3 ) 4 nanoclusters. The rigid diamond-like network results in large channels occupied by solvate molecules, which in most cases were too poorly defined for modeling. The content of the voids, believed to be water molecules, was accounted using reverse Fourier-transform methods using the SQUEEZE algorithm (Spek, 2015). The protonated amino groups of the cysteine ligands are directed away from the sphere, forming N-HÁ Á ÁCl hydrogen bonds with chloride ions of their cluster. The protonated -CO 2 H carboxy groups point outwards into the void and presumably form O-HÁ Á ÁO hydrogen bonds with the unresolved water molecules in the solvate channels (the carboxylate protons are omitted in the structure).
Conclusion about the state of the carboxy groups is based on the following facts: (i) the FTIR spectrum confirms the presence of -CO 2 H groups and the absence of H 3 O + ions in the crystal (see below); (ii) the coordination geometries observed are strongly favored by Cu I ; (iii) the crystals of the complex are colorless, which excludes the presence of copper(II).
Disorder is observed in one of the two crystallographically unique [Cu 16 (CysH 2 ) 6 Cl 16 ] clusters for three of the six cysteine ligands. The asymmetric unit consists of two Cu 12 distorted cubo-octahedra (Figs. 1,2). Almost all of the Cu-S bonds are similar in length (mean 2.25 AE 0.03 Å ) except for the bonds formed by the disordered S1_1, S1_5 and S1_12 atoms, where the Cu-S bond lengths were determined with higher errors. The S-Cu-S angles are clustered in a narrow range (mean 130 AE 4 ). Thus the Cu-S bonds and angles are typical for such Cu 12 S 6 copper thiolate nanoclusters (see Database survey).
In the 'atlas sphere' there are four tetrahedral copper atoms (atoms Cu17, Cu26, Cu28, Cu32 for the first core and Cu1, Cu9, Cu11, Cu16 for the second) surrounded by two 2chloride ions and one 3 -chloride ion (for example, Cu1 ion is surrounded by Cl1, Cl2 and Cl3 atoms), which are close to planar with copper and the 3 -Cl that is almost perpendicular to this imaginary plane wherein the length of Cu-3 -Cl bond is longer than the others (mean 2.58 AE 0.04 Å ). We note that the lengths of the other Cu-3 -Cl bonds are about the same as the Cu-2 -Cl lengths (mean 2.31 AE 0.04 Å ) and the Cl-Cu-Cl angle in the [Cu 2 Cl 2 ] units is 94.9 AE 2.4 . In addition, there are two non-bridging chloride ions: Cl28 and Cl26. The other chloride ions form 2 -bridges between the copper ions in the core except for 3 -Cl15.
The charge distribution per cage is as following: 16 positive charges of Cu + ions are balanced by the negative charges of 16 chloride ions. The 12 amino acid residues occur as neutral CysH 2 = HO 2 CCH(NH 3 + )CH 2 S À zwitterions. The 'atlas spheres' in the asymmetric unit have differences regarding the presence of disorder, viz. three of the six cysteine molecules are disordered in one 'atlas sphere' while the other is not disordered.

Supramolecular features
In the structure, the 'atlas spheres' are linked to form a threedimensional framework with the Cu 2 Cl 2 linkages forming a tetrahedral environment in each of the clusters (Fig. 3). As a result, the 'atlas spheres' form a distorted diamond-like structure (Fig. 4). However, it is not possible to give an exact description of the topology (O'Keeffe et al., 2008). These bridges are based on the 3 -Cl atoms described above, with the exception of Cl15 and eight copper atoms in a distorted tetrahedral environment (four such atoms per cage); thus, Tetrahedral environment of 'atlas-sphere' of the title compound.

Figure 4
Diamond-like extended structure of the title compound.

Figure 2
Displacement ellipsoid plot (50% probability level) of the asymmetric unit. from the point of view of the coordination environment, it is more accurate to talk about Cu 2 Cl 8 bridges. In addition, the cages are connected by a system of hydrogen bonds. Namely, two water molecules (O4_6 and O3_6) act as donors for two amino groups (N1_9 and N1_6, respectively), forming N-HÁ Á ÁO hydrogen bonds. In turn, the water molecules are linked by hydrogen bonds. Thus, a chain of three hydrogen bonds exists between neighboring 'atlas spheres'. The structure has voids in which there are presumably disordered water molecules (Figs. 5,6). Using PLATON SQUEEZE (Spek, 2015), a void was identified occupying 38.6% of the unit-cell volume for the compound. The void volume of 7685 Å 3 contains the equivalent of 3455 electrons, corresponding to about 346 water molecules. The hydrogen-bond geometry is given in Table 1.

Figure 5
Crystal packing of the title compound viewed along c-axis direction.

Synthesis and crystallization
Masses of 0.085 g (0.500 mmol) of CuCl 2 Á2H 2 O and 0.060 g (0.50 mmol) of l-cysteine were mixed in 5 ml of water under inert conditions. A precipitate was formed, which was dissolved by adding approximately 1 ml of a 2 M HCl oxygenfree solution. The resulting solution was left to stand in an inert atmosphere. Colorless crystals of the title compound formed within 24 h.
As a result of the rapid degradation of the crystals in air, it was not possible to perform an elemental analysis. The IR spectra of the crystals were recorded using an FTIR Bruker Vertex 70 spectrometer (400-4000 cm À1 ). The IR spectrum of {[Cu 16 (CysH 2 ) 6 Cl 16 ]ÁxH 2 O} n (1) is shown in Fig. 7, and the spectroscopic parameters are presented in Table 2 in comparison with the corresponding values for the crystal of l-cysteine hydrochloride, l-CysH 2 ÁHCl (Dokken et al., 2009) along with our assignment of the spectroscopic lines.
As follows from Table 2, there is a satisfactory correspondence of most bands of both crystals, 1 and l-CysH 2 ÁHCl. Of particular note is the almost complete coincidence of the position of the most intense line at 1201-1203 cm À1 for both compounds. According to Dokken et al. (2009), this intense band is associated with vibrations of the protonated -COOH group. In this case, the possibility of protonation of water molecules instead of a carboxy group with the hydroxonium ion formation is practically excluded. Indeed, according to numerous experimental and calculated data for crystals and liquid phases, H 3 O + ions show four broad lines in the IR spectra near 1150, 1740, 3160, and 3320 cm À1 (Chukanov, 2014;Yukhnevich, 1973). As follows from Fig. 7 and Table 2, no sign of these bands was detected in the spectrum of the crystal 1. On the other hand, there is a satisfactory agreement between the vibration lines of the -NH 3 + group at $1130,  Table 2 Comparison of infrared band assignments (cm À1 ) for 1 and l-cysteine hydrochloride, l-CysH 2 ÁHCl (Dokken et al., 2009). IR spectrum of the title compound.
$1572, $1610, and $2930 cm À1 for compounds 1 and l-CysH 2 ÁHCl. Thus, according to the IR spectroscopic data, the protons in 1 are localized on the carboxyl and ammonium groups, while the thiol groups are deprotonated and bonded to copper(I).

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 3. All non-hydrogen atoms were refined anisotropically and C-H hydrogen atoms were positioned at geometrically calculated positions (C-H = 0.99-1.00 Å , N-H = 0.91 Å ) and refined using a riding model. The constraint U iso (H) = 1.2U eq (C) or 1.5U eq (N) was applied in all cases. Three of the cysteine ligands were found to be disordered over two sets of sites with refined major occupancies of 0.826 (8), 0.550 (19) and 0.657 (9). Close to one of the disordered cysteine ligands, two partially occupied water molecules were found, which could not be modeled using SQUEEZE (Spek, 2015) because of their proximity to the cysteine disorder. Their occupancy was refined freely and converged to 0.55 (2) and 0.33 (2). The structure was refined with the help of similarity restraints, strong similarity restraints on anisotropic displacement parameters (Mü ller, 2009) and rigid bond restraints (Thorn et al., 2012) on the disordered ligands. One of the partially occupied water molecules was strongly restrained to have a more isotropic behavior using the ISOR instruction as implemented in SHELXL. The unit cell contains a significant amount of solvent, most likely a heavily disordered hydrogen-bonded network of water molecules. To refine the model against the measured data, the SWAT instruction as implemented in SHELXL (Langridge et al., 1960;Driessen et al., 1989) was used. In addition, SQUEEZE (Spek, 2015) as implemented in PLATON (Spek, 2020) was used to model the disordered solvent in the voids of the structure. SQUEEZE identified a void centered at $(0 0.1 0) with a volume of 7685 Å 3 containing the equivalent of 3455 electrons. This would correspond to about 346 water molecules.

Poly[[tetra-µ 3 -chlorido-deca-µ 2 -chlorido-dichloridohexakis(µ 4 -L-cysteinato)hexadecacopper] polyhydrate]
Crystal data   (4) Special details Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes. Refinement. Bruker D8 Venture Dual IµS fixed chi instrument.