Multivariant Crystallization of Tetraplatin Precursors from Solutions Containing 1 , 2-C 6 H 10 ( NH 3 ) 2 2 + and [ PtCl 6 ] 2 – Ions

Seven new phases containing hexachloroplatinate [PtCl6] 2− and trans-1,2-dl-diammoniumcyclohexane 1,2-C6H10(NH3)2 2+ ions were obtained by crystallization from solutions with minor variation of synthesis conditions. The compounds can be applied as precursors for the synthesis of effective anticancer drug tetraplatin ([PtC6H10(NH2)2Cl4]). The phase diversity was achieved by alterations including solvent acidity, crystallization rate, temperature, type of solvent, and the reagents ratio. The compounds were characterized by chemical and thermal analysis, IR, and H NMR spectroscopy. Crystal structures of the five compounds were determined by X-ray powder diffraction technique. The phases have ionic structures involving H2O, HCl molecules, or Cl − ions as supplementary species in the lattices. It helps to arrange some frames additionally interconnected by hydrogen bonds between ions and solventmolecules. It was suggested that crystal lattices adapted associated particles presented in solutions. It results in observed variety of the crystal structures. Besides the basic interest the obtained results are important for tetraplatin synthesis control.

Recently, a new simple synthetic approach capable of high yield and purity was suggested [23,24].The approach consists in the application of soluble precursors as crystalline ionic salts containing anions [PtCl 6 ] 2− and cations 1,2-C 6 H 10 (NH 3 ) 2 2+ in 1 : 1 molar ratio.Developing the synthesis it was revealed that the crystallization of the solution with mentioned ionic salt gave a number of distinctive crystalline phases under small variation of the synthetic conditions.As a rule it gave multiphase product.The phenomenon was repeatedly mentioned in the literature [25][26][27][28][29][30].Every case has specific features.It impedes a comprehensive control which plays critical role when dealing with the synthesis of important substances such as anticancer drugs.It was the reason why the crystallization stage was separated out from whole synthetic process of the drug and investigated.
It is well known that the synthesis of many complex and organometallic compounds passes through the formation of ionic compounds [31].The reacting species in a solution can form a variety of spatial associations due to variety of size, shape, charge, presence of hydrogen bond donor, or acceptor.Subsequent crystallization under certain conditions adapts the association of the particles existing in the solution to form crystalline solids.Understanding crystallization features can be used to increase the yield and purity of the required products.Current methods of the solution structure investigation are not able to provide the necessary information −2 2 −2 − Scheme 1 about the spatial coordination of complex ions.However, crystal structures of precipitated solid phases accept definite imprint of these interactions.
In this work seven new crystalline phases were precipitated from the solutions containing ionic pair [PtCl 6 ] 2− and 1,2-C 6 H 10 (NH 3 ) 2 2+ at mild variation of the crystallization conditions.The chemical compositions, thermal stability, IR, and NMR spectra were used for samples characterization.The crystal structures of five compounds have been determined by X-ray powder diffraction technique.The data can be the basis for the interpretation of the particle association at precrystallization state in the solution.Besides the basic interest to the phenomenon of multiphase crystallization the obtained results are important for tetraplatin synthesis controlling.

Experimental
All reagents were commercially supplied by "Reahim" (Russia) and "Sigma-Aldrich."Acetone, chloroform, and diethyl ether were purified and dried according to standard procedures [33].The reagents H 2 [PtCl 6 ]⋅6H 2 O and Na 2 [PtCl 6 ]⋅ 6H 2 O were obtained in accordance with [34].The integrated scheme of the compound synthesis is presented in Figure 1.The detailed synthesis description and some spectroscopic and chemical composition data are given in supporting information (see Supplementary Materials available online at https://doi.org/10.1155/2017/3695141).
Elemental H, C, N analysis was carried out on Analyzer CHNS-OEA 1108 (Carlo Erba Instruments).The platinum content in compounds was analyzed by heating in air with a gravimetric determination of the residue.Thermal stability was studied using NETZSCH STA 449 thermal analyzer.Decomposition was carried out by heating up to 1073 K in air at the rate 5 ∘ /min.IR spectra were recorded in the 400-4000 cm −1 region as KBr (0.1%) pellets on Bruker IFS-85 IR spectrophotometer. 1 H NMR data were collected on Bruker Avance 600 spectrometer at 295 K.

X-Ray Powder Diffraction Study
The obtained samples were analyzed for crystallinity, singlephase purity, and the possibility of crystal structure determination.The X-ray powder diffraction technique was applied for this purpose.Diffractometer X'Pert PRO (PANalytical) with a PIXcel detector, equipped with a graphite monochromator, was used for scanning X-ray diffraction patterns.
CuK radiation was used.The sample was grinded up in an agate mortar and placed in a cuvette of 25 mm diameter by direct loading with a small pressing.The excess of sample was cut off with a razor to prevent preferred orientation on the surface.Scanning was performed at  = 295 K in the range from 3 to 90 ∘ 2 with step 0,026 ∘ and Δ-50 c.The angular limit for scanning was caused by the lack of significant diffraction peaks in the high angle region.
Compounds (I)-(VII) were suitable for diffraction studies.The unit cell search, the cell parameters refinement, and the space group choice were carried out in the programs described in [35,36].The structure modeling was completed in the direct space using the "simulated annealing" approach [37], with help of the computer program FOX [38].The octahedral anionic complex [PtCl 6 ] 2− with the regular geometry and cyclohexane-1,2-diammonium ion in the chair configuration was the basic molecular blocks for the structure modeling.Actually the structure determination consisted in finding an optimal positions and orientations of the molecular particles in the space of a unit cell.The final LS structure optimization was carried out by full-profile analysis (Rietveld method) using the program FullProf [39].Hard and soft constraints were applied to refined atomic coordinates [40,41] using the weight coefficients with the average values of distances and angles [1].Optimization of the structure was done by the gradual removal of restrictions on parallel to the refinement of the background and some profile parameters.Thermal parameters for the platinum and chlorine atoms were refined in the anisotropic approximation but for light atoms in isotropic.At the final step hydrogen atoms were rigidly attached to the respective carbons and nitrogen in a structure model [42].The resulting structural data have been deposited on CCDC ##1023411-1023415.

Results and Discussion
The discussed crystallization phenomena seem to be rather typical but are not well investigated because of the absence of proper samples for crystal structure analysis.There are some common features which define crystal phase formation.On the one hand, there are no significant chemical bonding alterations within the particles in the system, and on the other, the type of the product as a crystalline precipitate in each case has a highly specific identity.The resulting compounds are ionic salts, so their states and relationships must be described in accordance with the chemical thermodynamics using, for example, the phase diagrams.However, some irreversible processes at a chemical phase formation prevent the precise

Initial solution
Crystalline products Drying over NaOH (7-10 days) Drying over NaOH (7-10 days) Drying over NaOH (7-10 days) compliance with the rules of the classical thermodynamics.In particular, the order of weak hydrogen bonds formation taking place in a solution is important.The control of lowenergy alterations in a solution is extremely difficult, and as a consequence, there are insufficient data for phenomena understanding and successful prediction.In the present paper we consider the example of the salt crystallization with cation and anionic pair 1,2-dachH 2 2+ (where "dachH 2 2+ " is ) and [PtCl 6 ] 2− in which small changes in physicochemical conditions significantly diversify the phase formation during crystallization.By adjusting the molar ratio between main components 1,2-dachH 2 2+ and [PtCl 6 ] 2− , changing solution acidity, temperature, rate of crystallization, and varying the type of solvent the crystallization can be directed to any of different compounds shown in Figure 1.
Phase (I) formation requires a neutral or slightly acidic solution at the room temperature.Phase (II) crystallizes when the aqueous solution is changed into the water-acetone solution in the presence of hydrochloric acid under of slow evaporation conditions.The isoformular compounds (III) and (IV) can be obtained as a result of solid phase transition of (I) in the presence of drying agent such as acetyl chloride or acetic anhydride in glacial acetic acid at elevated temperature.Phase (V) crystallization occurs in weak acidic solutions with a molar ratio 1,2-dachH 2 2+ /[PtCl 6 ] 2− ≥ 2. The formation of phase (V) in a strong acidic solution may be accompanied by coprecipitation of (VI) and (VII) phases with the ratio of basic ions differing from 1 : 1.However, the crystallization at slow solvent evaporation at 303-333 K leads to the precipitation of pure phase (V).Phase (VI) is formed in the temperature range of 293-323 K if hydrochloric acid or glacial acetic acid is added up to the strong acidic solution with molar ratio 1,2-dachH 2 2+ /[PtCl 6 ] 2− ≥ 1.If the temperature of the solution is up into the range 323-383 K phase (VII) precipitates rapidly.
It is relevant to note that similar experiments performed with respect to organic cations lysinium ) in the similar range of crystallization conditions have revealed only one distinctive crystalline phase [1].It indicates the importance of the spatial geometry of the main particles, both in solution and in the solid state.
At heating in air the synthesized phases have the similar stages of decomposition.For example, Figure 2  + and -CH 2 groups, which should be attributed to the protons of the water molecule.The appearance of new spots out of the main diagonal indicates interaction of water molecules with -NH 3 + groups.It is reasonable to assume the formation of hydrogen bonds between NH 3 + groups and oxygen of water molecules.The presence of hydrogen bonds is evidenced by the deformation of the NH 3 + spot too.However hydrogen atoms of water molecules are not involved in hydrogen bonding.2.
Investigated substances have ionic structure.It may be suggested that Coulomb forces determine the most advantageous configuration for ions packing.However, there are at least two other additional factors influencing packing.The first factor relates to the ion shapes and charge distribution in polyatomic particles.Ions C 6 H 10 (NH 3 ) 2 2+ and [PtCl 6 ] 2− are significant in size and different in shape.The [PtCl 6 ] 2− anion has high molecular symmetry (O h ), but it is unlikely that the symmetry of the electric field is of the central character.In the ideal case the symmetry of C 6 H 10 (NH 3 ) 2 2+ cation is limited by twofold axis (C 2 ).Apparently the cations lose this poor symmetry in the lattice.The second factor deals with the localization of donors and acceptors of hydrogen bonds.It plays considerable role in the association of the ions into various groups.The mentioned factors essentially reduce the influence of the Coulomb forces on packing geometry.The "packing factor" presented in Table 1 reflects the variable role of the discussed factors on crystal structures.In the studied crystal structures the layers formed by alternating cation-anion pairs can be distinguished.Noticeable structural variation can be reduced to some shifts of adjacent layers relatively each other.Different layer shifts induce different  3).
The spatial configurations of associated particles in the investigated structures are presented in Figures 6(a      ( = 2.45 >) (Figure 6(a)).Charged centers of the cation do not locate on the line between the anion and the center of the cation.It can be reasonably assumed that the species of C 6 H 10 (NH 3 ) 2 2+ ⋅X 2 O-type participate in the crystallization.The packing seems to obey the principle of dense space filling rather than the orientation according to electric field.The situation is somewhat different for phase (II).HCl molecule differs from H 2 O due to the possibility of easy dissociation just in the crystal structure.As a result, the charge compensation of the cation can be achieved at the less cost than involving big anion as [PtCl 6 ] 2− .Additionally the hydrogen bonds are formed.Apparently, the energy gain  6(e)).It should be also noted there is the correlation between the presence of HCl in the crystal structure and the "packing index" (Table 1).
Phase (V) can be attributed to double salts with 1,2-dachH 2 [PtCl 6 ] and 1,2-dachH 2 Cl 2 cocrystallized in mutual lattice.Cations are the same but anions are strongly different in size.It is surprising, but the anions form the joint sublattice.The structure has the most saturated system of hydrogen bonds which are responsible for connecting the ions within the layers.Every amine group forms three different H-bonds with chlorine atoms from neighboring anions.Cations 1,2-dachH 2 2+ are oriented relatively [PtCl 6 ] 2− complexes as well as Cl − ions (Figure 6(d)).
Phase (III), unlike all previous ones, does not contain solvent molecules in the structure.This is certainly a consequence of its preparation procedure.The absence of solvent molecules in the crystal structure leads to the formation of more dense packing in comparison with other phases.The investigated phase formation in the ionic system 1,2-C 6 H 10 (NH 3 ) 2 2+ -[PtCl 6 ] 2− leads to the number of conclusions.The diversity of crystalline forms in the system is due to the peculiarities of the ions structure.Basically dissimilar symmetry and shape of [PtCl 6 ] 2− and C 6 H 10 (NH 3 ) 2 2+ ions, significant charge, and predisposition to dissolution are prerequisites for crystallization of various types of packaging, with negligible energetic difference of the crystal lattices.This fact is confirmed by similar interionic distances in the crystal structures.Due to the presence of donors and acceptor of hydrogen bonds, there is the possibility of hydrogen bonding in the crystal structures and even in the solution.The hydrogen bonds established in solution affect the direction of crystallization.Small alterations in the solution relating to individual components of the solvent, pH, and temperature may provide a path of the crystallization terminated by one of the possible crystals.

Conclusion
The crystallization of the ionic salts from the solution containing [PtCl 6 ] 2− and 1,2-C 6 H 10 (NH 3 ) 2 2+ ions was investigated at varied conditions including solvent acidity, crystallization rate, reactants mole ratio, temperature, and type of
), 5(b), 5(c), 5(d), and 5(e) show the X-ray diffraction patterns (Rietveld's plots), including experimental and calculated diffraction patterns in comparison, the difference between them, and the reflections position.Structures of the compounds in the projection on the ()-plane are also shown in Figures 5(a), 5(b), 5(c), 5(d), and 5(e).The basic bond lengths and angles are collected in Table
), 6(b), 6(c), 6(d), and 6(e).A number of features can be identified considering the structures of phases (I), (II), and (VI) with neutral molecules HCl or H 2 O. Phase C 6 H 10 (NH 3 ) 2 [PtCl 6 ]⋅H 2 O (I) was obtained at rapid crystallization (a few minutes) in neutral medium.The contact between cation C 6 H 10 (NH 3 ) 2 2+ and neutral molecule of water is provided by one hydrogen bond (O⋅ ⋅ ⋅ H-N)
Counterions orientate towards each other by their electron donating and electron accepting centers.It makes possible the formation of hydrogen bonds.Half of the chlorine atoms of [PtCl 6 ] 2− anions are involved in hydrogen bonding (Figure 6(c)), which form zigzag chains.From a thermodynamic point of view, phase (III) is an unstable compound.As mentioned above, phase (III) transforms into (I) in the air.This indicates benefit from the inclusion of solvent molecules in the structure.

Table 3 :
The lengths of the suggested hydrogen bonds in compounds (I)-(III), (V), and (VI) in >.
1 H NMR spectrum and two-dimensional pattern for phase C 6 H 10 (NH 3 ) 2 [PtCl 6 ]⋅2HCl (II) are depicted in Figure 4(c).The number of spots on the main diagonal becomes equal to four.It means the presence of two unequal protons additionally.Free chlorine atoms strongly influence the protons of NH 3 + groups and induce significant peak overlapping.It is reasonable to attribute two additional protons to nonequivalent HCl molecules in the structure.It well corresponds to structural data and proves that HCl molecules are involved into the structure.Crystal structures of C 6 H 10 (NH 3 ) 2 [PtCl 6 ]⋅H 2 O (I), C 6 H 10 (NH 3 ) 2 [PtCl 6 ]⋅2Hbl (II), C 6 H 10 (NH 3 ) 2 [PtCl 6 ] (III), (C 6 H 10 (NH 3 ) 2 ) 2 [PtCl 6 ]Cl 2 (V), and C 6 H 10 (NH 3 ) 2 [PtCl 6 ]⋅ Hbl (VI) were determined by X-ray powder diffraction technique.Because of impurities in the substances the final results for phases (IV) and (VII) were not obtained.Some experimental data and characteristics of the crystal structures after refinement are collected in Table 1.Figures 5(a

Table 1 :
Crystal data and experimental conditions for compounds (

Table 2 :
Some of the bond lengths and angles in compounds (

I)-(III), (V), and (VI).
H 10 (NH 3 ) 2 2+ , being in double excess, and the HCl molecule in solution.Due to the reasons described above HCl molecule wins in this competition.Its role in the structure is to reduce electric field.It is implemented during the formation of the layer which consisted of Cl 1− anions (Figure 6(e)).The system of hydrogen bonds between pairs of C 6 H 10 (NH 3 ) 2 2+ and [PtCl 6 ] 2− presents a zigzag chain (Figure