Persistence of oxidation state III of gold in thione coordination

Ligands N,N´-tetramethylthiourea and 2-mercapto-1-methyl-imidazole form stable Au(III) complexes [AuCl 3 (N,N´-tetramethylthiourea)] (1) and [AuCl 3 (2-mercapto-1-methyl-imidazole)] (2) instead of reducing the Au(III) metal center into Au(I), which would be typical for the attachment of sulfur donors. Compounds 1 and 2 were characterized by spectroscopic methods and by X-ray crystallography. The spectroscopic details were explained by simulation of the UV-Vis spectra via the TD-DFT method. Additionally, computational DFT studies were performed in order to find the reason for the unusual oxidation state in the crystalline materials. The preference for Au(III) can be explained via various weak intra-and intermolecular interactions present in the solid state structures. The nature of the interactions was further investigated by topological charge density analysis via the QTAIM method.


Introduction
The chemistry of gold at oxidation state I is an area of intense practical and theoretical studies, especially in medicinal and photochemical applications.However, the chemistry of gold(III) complexes is less studied than that of gold(I), mainly due to their notorious toxicity and lower solubility and stability in aqueous media.Although gold at oxidation state I has been used in most studies of biochemical and pharmaceutical applications, Au(III), isostructural with Pt(II), has lately begun to receive more attention.For example, the combination of Au 3+ with antibiotics has offered promising results against resistant bacteria and seems to serve a broad range of medical applications.[1] High cytotoxicity of some Au(III) derivatives towards cancer cells at low concentrations has also been discovered.[2,3,4,5] Reduction of gold(III) to gold(I) species is often involved in reactions with soft nucleophiles, such as sulfur compounds.The reduction mechanism and kinetics have been studied in greater detail, e.g. for thioethers and thiocyanate.Coordination has been found to proceed via a direct two-electron transfer without observable intermediates.Another possibility includes at the first stage a substitution of, for example, the halogen by the ligand.Further attack of the ligand leads finally to the reduction of the metal center.[6,7,8] Consequently, reactions of both Au(I) and Au(III) species with monodentate heterocyclic thiones[9] and thiourea derivatives[10] typically give linear gold(I) complexes [AuXL] (X=Cl, Br) or [AuL 2 ] + .For example, the reductive halide substitution by basic thiourea of the metal in [AuBr 4 ] -or [AuCl 4 ] -has led to formation of [Au(thiourea) 2 ] + with counterions Br - [11], Cl -, SO 4 2- [12] or ClO 4 - [13].The solid state structures were found to constitute linear S-Au-S moieties, which is typical for Au(I) compounds.Moreover, in the solid state structure of [Au(thiourea) 2 ] + Br -the Au atoms formed a linear chain-like arrangement with Au … Au interactions of adjacent units.
However, variation in the reaction type has been observed.Fabretti  The anionic part is linearly coordinated dibromoaurate(I).[14] Tetramethylthiourea seems to be a ligand offering competitive reaction routes and variation of products.

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ACCEPTED MANUSCRIPT 3 Among the gold(III) compounds with sulfur ligands, some solid state structures of thioether derivatives of Au(III)X 3 -SR 2 [15,16,17,18,19] have been reported, but the studies have mostly concentrated on solution chemistry and characterization with spectroscopic methods.[20] A large number of mixed ligand species of the type R 3 P-Au(I)-S=R' have also attracted interest, due to their potential for biological and photophysical applications.[21,22,23,24,25] Thiosemicarbazones and their metal complexes have been the subject of numerous studies because of their chemical and biological properties.The square planar gold(III) complexes with thiosemicarbazones and complexes containing both gold(III) and gold(I) centers are known.In the reports on thiosemicarbazone derivatives of Au(III), the role of stabilizing organometallic ligands and formation of additional Au-C-bond have been discussed.[26,27] Hard donor ligands, such as nitrogen compounds, favor simple addition reactions to Au(III) centers.
With soft donors, reduction of the metal center usually takes place as a consequence of addition/reductive elimination.In this study, we wanted to further clarify the subtle modifications of donor properties and their impact on reaction pathways.In our previous studies we have concentrated on thione ligands with mixed S/N-donor moieties, reduction of the metal center was observed.
[28] Now we have brought a N/N heteroatom system into contact with the thione group by investigating the reactions of AuCl

Selected bond lengths [Å] and angles
1.748( 7) Cl( 1  Additional Cl(1) … Cl(1) contacts with a distance of Cl(1)-Cl(1) 3.4333(1)Å between the neighboring molecules are found in these units.The distance is diminished by 2% compared to the sum of the van der Waals radii (3.5Å) and the existence of a weak amphoteric halogen bond can be assumed.
In this type of interaction the chlorine atoms simultaneously act as electron donors and acceptors.[32] These tetrameric units form an extended chain structure with weak interactions Cl(2)-H(4B) 2.8266(1)Å.It can be suggested that the chloro ligands have the key role in the formation of the supramolecular structure.In the solid state of 2, there is a weak intramolecular hydrogen bond Cl(3)-H(2A) 2.8319(2)Å (Fig. 4a).Intermolecular Cl-H hydrogen bonds prevail to give a 3D supramolecular structure.The shortest and thus the strongest interaction is between the chloro ligand and the hydrogen at 2D structure for 2 at the ac plane (a) and the bc plane (b) The coordination process of neutral sulfur ligands to the Au(III) center generally depends on the metal to ligand ratio.The relative rates of reduction and substitution define the stoichiometry of the product.To study this behavior, we also carried out reactions with a metal:ligand ratio of 1:2.
However, 1 and 2 were obtained from a one hour reaction at room temperature and successive crystallization at low temperature.In a separate test, 1 was stirred with tetramethylthiourea (1:1) in CH 2 Cl 2 for 48 h at room temperature, whereby the orange color slowly vanished suggesting reduction of gold.
The idea of the formation of a new Au(I) complex e.g.
[AuCl(tetramethylthiourea)] (1b) was also supported by the growth of an additive signal at a higher field (3.23 ppm) in the 1 H NMR spectrum.The shift is linked to reduction of gold and thus higher electron density at Au(I) compared to Au(III).The growth of the signal was also detected when 1 was stored several months in air, showing partial reduction.However, several attempts to purify and characterize the product in detail failed.In these conditions, the formation of stable solid Au(III) species is favored even though in solution and in precipitated product both Au(I) and Au(III) species are present.In the case of the second reaction, similar behavior was observed; the minor 1 H signals of the reduction product, e.g.[AuCl(2-mercapto-1-methyl-imidazole)] (2b), appeared at higher field.In our previous study with a N-methylbenzotiazolidinethione ligand, a similar balance between two oxidation states was observed, but the product with an Au(I) center was crystallized. [28]

Computational TD-DFT studies
In order to verify the oxidation state of gold, and its effect on the solid state structures, we performed computational DFT calculations on the single molecules of Dashed lines represent non-covalent intramolecular interactions obtained via the QTAIM method, and small green dots the corresponding bond critical points.
The experimental UV-VIS spectra showed charge transfer absorbance at 328 and 241nm for 1, and the wavelengths of the largest bands for 2 were 353 and 224 nm, as can be seen in Table 4 and in the experimental details.A detailed analysis of the UV-Vis bands was performed by simulating the corresponding spectra in the CH 2 Cl 2 solvent with the TD-DFT method.Table 4 lists the most important excitations and their properties.The simulated spectra can be found as supporting information (Figures S1 and S2).

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12 The calculated excitation energies were similar to the experimental values, thus they support the interpretation of the bands.In particular, the oxidation state of gold in the complexes could be seen in the larger wavelengths of the spectra of 1 and 2 rather than in the corresponding Au(I) complexes 1b and 2b (Table 4), even though the lowest energy bands (at 472 nm and 487 nm for 1 and 2, respectively) were very weak and could only be seen in the experimental spectra as strong tailing of the bands.Fig. 6. shows the appearance of the MOs in complex 1 that correspond to the excitations in Table 4.
The representation of the MOs for compounds 1b, 2 and 2b can be seen in Figures S3 and S4.

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Fig. 6.The appearance of the molecular orbitals, which give rise to the most important excitations in the UV-Vis spectra in 1.For detailed interpretation of the bands, see Table 4.
The HOMOs are mostly concentrated in the axial direction, with a large contribution to it from both thione sulfur and the chlorine trans.The gold d-orbitals take part in forming these higher occupied molecular orbitals.LUMO is represented by the orbitals at the square planar plane of sulfur, gold and the three chlorines, therefore verifying the importance of the donor properties of thione sulfur in the charge transfer process.Furthermore, since the contribution of the Cl(1) trans to thione S is slightly larger than that of the other two chlorines, more charge is transferred via the axial line.However, the most striking difference in the frontier molecular orbitals between Au(III) and Au(I) complexes can be seen in the constitution of LUMO, which in Au(III) compounds is almost completely concentrated on the S-Au-Cl 3 plane (Fig. 6 and S3-S4), but in the Au(I) complex it is mainly spread over the ligand.The contribution from the metal orbitals stabilizes the LUMO, which is the main reason for smaller energies in the excitations with Au(III) complexes 1 and 2. On The experimental IR spectrum of 1 and 2 showed C-N vibrations at 1587 and 1475 cm -1 and S-C vibrations at 1497 and 1168 cm -1 , respectively.However, the oxidation state of gold could not be deduced from the IR spectra only, since the computational simulation showed only very minor differences in the bands of the Au(III) and Au(I) compounds.The calculated spectra are shown as supporting information in Figures S5 and S6.

Topological charge density analysis
Properties of the electron density around each nuclei can give a lot of information regarding the existence and nature of the intra-and intermolecular interactions in the solid state structures.We analyzed the charge density by using Bader's Quantum Theory of Atoms in Molecules (QTAIM) [40], which has been successfully used to study the nature of these normally weak interactions.For the first stage, we studied the electronic properties of free ligands and how these properties change in the formation of either Au(I) or Au(III) complexes with structurally rather similar N,N ligand 2-mercapto-1-methyl-imidazole (complexes 2b and 2) or N,S ligand Nmethylbenzotiazolidinethione (3b and 3).The results are listed for selected bond critical points in Table 5.The structures of the optimized complexes with the bond paths and bond critical points are shown in Fig. 5 The numbering of the atoms in Table 5 follows the numbering scheme in Figures 1   and 3.

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Table 5.The larger electron density at the S(1)-Au bond, the larger interaction energy, and the larger bond delocalization index all indicate stronger interaction and more stability for the Au(I) complexes.In addition, experimental findings indicated that both oxidation states are present in solution, which means that the stability of the complexes would be rather similar.

Selected computational parameters
Another aim was to obtain information on the interactions which determine the crystallization of the Au(III) compounds 1 and 2. The extended model of the crystal structure of 2 including four molecules at the same layer is shown in Fig. 7a.The results were compared to a previously studied crystal structure of Au(I) compound 3b with an N-methylbenzotiazolidinethione ligand (Fig. 7b).
[28] It should be noted that also larger models, including 7 or 8 molecules for 1 and 2, respectively, in two adjacent layers, were calculated in order to study the intermolecular interactions between the layers.The larger models are presented as supplementary material (Figures S7 and S8) In both structures (and also in the structure of 1), most of the intermolecular interactions originate from the chlorine trans to the thione sulfur (BCPs 1-4 in Fig. 7).This is again an indication of larger charge transfer from the ligand all the way to the Cl(1) atom, which is able to form stronger hydrogen bonding interactions.The H(N) proton of the imidazole ring in 2 forms an especially strong H … Cl interaction (BCP#1, E INT = -18 kJmol -1 ) compared to H(Me) in 3b (E INT =-5 kJmol -1 ), indicating the importance of the (N)H … Cl interaction in stabilizing the crystal structure of 2.
Notably, the optimized molecular structure of a corresponding Au(I) complex [Au(2-mercapto-1methyl-imidazole)Cl] showed that the H(N) proton is involved in an intramolecular Au … H(N) interaction (Fig. 5), and is not free for further intermolecular interactions.Furthermore, in Au(III) complex 2, the other two chlorines are able to form amphoteric Cl … Cl contacts (BCP#6), which further stabilize the crystal structure and explain the preferred crystallization of the Au(III) complex over Au(I).
instrument. 1 H and 13 C NMR spectra were measured with a Bruker Avance 400 MHz spectrometer and the UV-VIS spectra in CH 2 Cl 2 with a Perkin Elmer Lambda 900 UV/VIS/NIR spectrometer.

X-ray Structure Determinations
The crystals of 1 and 2 were immersed in cryo-oil, mounted in a Nylon loop, and measured at a temperature of 100 and 120K, respectively.The X-ray diffraction data were collected on a Nonius KappaCCD (1) or NoniusKappa Apex II (2) diffractometer, using Mo Kα radiation (λ = 0.710 73 Å).The Denzo-Scalepack [33], program package was used for cell refinements and data reductions.
The structures were solved by direct methods using the SHELXS-97 [34] program with the WinGX [35]graphical user interface.A semi-empirical absorption correction (SADABS) [36] was applied to all data.Structural refinements were carried out with the use of SHELXL-97.[34] For both 1 and 2, hydrogen atoms were positioned geometrically and constrained to ride on their parent atoms, with C-H = 0.95-0.98Å and U iso = 1.2-1.5 U eq (parent atom).The crystallographic details for 1 and 2 are summarized in Table 1.

Computational Details
et al. have studied the reaction between tetramethylthiourea and gold(III), where the expected process of ligand attachment and consecutive reduction gave [Au(I)Br(tetramethylthiourea)].Distinct behavior and additional formation of [Au(tetramethylthiourea) 2 Br 2 ][AuBr 2 ] was found.The structure consists of ionic units, where the gold atoms are four and two coordinated.The tetramethylthiourea ligands are trans coordinated to the gold(III) in the cationic part together with two bromide ligands forming square planar geometry.
, in the Au(I) complexes the possibility for intramolecular hydrogen bonding interactions between Au and H(Me) or H(N) from the N,N ligands stabilizes the HOMO energies, therefore leading to larger energies (and smaller wavelengths) for excitations for 1b and 2b.

a
Cl trans to thione S Initially, the ligands exhibit rather different charge distributions at the C(1)-S(1) bond, originating from the different resonance effect of the aromatic ring systems.When the complexes are formed, both S(1) and C(1) become more positive when electron density is donated to gold ions.The change in the charge was larger for the N,N ligands, again an indication of larger electron donation, which can be understood to facilitate formation of the Au(III) complex.However, the different resonance effect does not solely explain why the N,N ligands are crystallizing in the Au(III) oxidation state M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT 16 and N,S ligands preferably as Au(I) complexes, since the calculations indicated that the molecular compounds with different oxidation states should be rather similar for both N,N and N,S ligands.

Fig 7 .
Fig 7. Bond paths and bond critical points (BCPs) in the extended models with four molecules of the crystal structures of compounds a) 2 and b) 3b.Lines represent the bond paths, and small green dots the BCPs obtained in the QTAIM analysis.

Table 4 .
The most important excitations in the UV-Vis spectra of Au(III) complexes 1 and 2.