Supramolecular architectures and crystal structures of gold(III) compounds with semicarbazones

Abstract The synthesis and crystal structures of two novel semicarbazones and four gold(III) compound derivatives of these semicarbazones are presented. A pattern in the formation of the semicarbazones shows the association of Cl– ions held together by intra- and intermolecular forces. [AuCl4]− and [AuBr4]− anions are co-crystallised with these semicarbazone ligands, and the packing architectures revealed by a single-crystal X-ray diffraction analysis showed the different influences of the anions and the association of these chemical species by intermolecular forces on the crystal packing. Crystal engineering led to gold(III) compounds that are stabilised by relevant hydrogen bonding networks, which demonstrated their importance to the supramolecular organisation of the studied compounds. Interestingly, Cl∙∙∙Br interactions are observed and contribute to the formation of the supramolecular structures. Elemental analysis data and spectroscopic properties in the solid state and solution are also described. Six new compounds were synthesised, including two semicarbazones and four gold(III) compound derivatives of these semicarbazones. The structural characterisation using single-crystal X-ray diffraction studies revealed cation–anion and Cl∙∙∙Br interactions and some H-bond contributions for the formation of supramolecular structures and crystal packing.

are found in the scientific literature, except for gold(I) and gold(III) complexes with thiosemicarbazones, which have gold-sulfur bonds, and interestingly, some of them exhibited antitumour properties (18)(19)(20)(21).

Materials, methods, and instruments
[Hpy][AuCl 4 ] was prepared as described in the related literature (24). All of the other reagents and solvents were commercially available. Elemental analyses were performed with a perkin Elmer/Series II 2400 analyser. Fourier transform infrared spectra were recorded from KBr pellets (4000-400 cm −1 ) using Varian 640 FT-Ir. 1 H and 13 C NMr spectra were obtained from DMSo-d 6 solutions at room temperature on VArIAN Mercury plus 300 MHz and Bruker Avance III HD 600 MHz spectrometers.

Crystal structure determinations
X-ray data collection was accomplished on a Bruker CCD SMArT ApEX II single crystal diffractometer with Mo Kα radiation (0.71073 Å) at 296 K. The data were processed with SAINT (25) and were corrected for absorption using SADABS (26). The structures were solved by direct methods using SHELXS-97 (27), and subsequent Fourier-difference map analyses yielded the positions of the nonhydrogen

Introduction
Several gold(I) and gold(III) compounds have been widely investigated because of their attractive properties for materials science and medicine (1,2). Gold complexes are already known as effective agents for the treatment of rheumatism and arthritis, such as the known drug auranofin (2).
Gold(III) compounds are isoelectronic (d 8 ) and isostructural (square planar geometry) compared to platinum(II) derivatives. The structural similarity of gold(III) complexes with platinum(II) drugs was thought to lead to their interaction with DNA and other biomolecules (3). The success and limitations of these platinum(II) drugs opened up a wealth of research into other classes of metal ion chemotherapeutic agents therefore stimulating the search for new gold compounds with similar properties, such as the antitumour agent cisplatin, which is widely used for cancer treatment (4). recently, the anticancer properties and anti-HIV activities of various gold(I) and gold(III) compounds have been reviewed (5)(6)(7).
Semicarbazones are very promising ligands for pharmacological applications. Studies have already demonstrated the antimalarial, antiviral and antitumour activities of semicarbazone derivatives (8). The versatility of their coordination mode also boosts studies regarding their supramolecular arrangement aiming at a more rational design for new derivatives with considerable interest in view of the biological and industrial importance. Semicarbazone derivatives belong to a class of ligands capable of forming polydentate complexes with several metals such as Zn (9,10), Cu (11,12), Ni (13,14), pd (15,16) and other transition metals (17).
presently, no reports of crystalline structures of gold(I) or gold(III) compounds bearing semicarbazone ligands atoms. The refinement was performed using SHELXL-97 (28). Molecular graphics were generated with poV-ray, orTEp-3 (29) and DIAMoND (30) programs; WinGX-routine software was used to prepare the material for publication (31). The crystal data, experimental details and refinement results are summarised in Table 1.

Di-2-pyridilketone-N 4 -semicarbazone monochloride (1)
Di-2-piridyl ketone (553 mg, 3 mmol) was dissolved in 20 mL of ethanol and mixed with a solution of N 4semicarbazide hydrochloride (335 mg, 3 mmol) in 20 mL of ethanol. Then, 10 mL of water was added. The resulting solution was placed under agitation and reflux for 3 h. After evaporation of the solvent, single yellow crystals were separated out. yield: 824 mg (99%

Preparation of the gold(III) compounds
Synthesis of gold compounds was achieved as shown in Scheme 2.  13

Crystal structure analysis of (1) and (2)
The crystal structures of compounds 1 and 2 were accurately established by X-ray diffraction analysis of single crystals. The molecular structures of 1 and 2 with the atom numbering are shown in Figure 1. The detailed structural analysis shows that the compounds exist in their ketene forms, which was confirmed by the presence of a hydrazinic hydrogen. In the two compounds, the oxygen atom o1 and the hydrazone nitrogen N3 are in the E configuration with respect to the C12-N5 bond (32). The dihedral angles between the least-square planes through the semicarbazone group and the pyridyl ring are 34.9° and 20.1° for compounds 1 and 2, respectively. The torsion angles of the side arm C6-N3-N4-C12 of 178.70(11)° and −178.2(2)° for 1 and 2, respectively, reflect that the compounds are nearly planar.

[HCldpcpsz][AuBr 4 ] (6)
The procedure for the synthesis of (6) was similar to that (5), except that the gold reagent was changed to AuBr 3 (22 mg, 0.05 mmol), and red crystals were obtained. The crystals were separated and collected for the X-ray diffraction analysis. yield: 22 mg (71%).  13   In both 1 and 2, the protonated nitrogen atom N1 acts as a proton donor to bond the chloride ion. The N5 atom also formed a hydrogen bond with the chloride ion to give a bifurcated arrangement. This lower energy configuration helps the formation of N4-H4•••N2 hydrogen bond interactions, subsequently forming a zigzag chain for 1 ( Figure 2). Hydrogen bonding parameters for 1 and 2 are presented in Table 2. Both compounds form intramolecular and intermolecular interactions by hydrogen bonds in the crystal lattices, and the number of such bonds per molecule depends on the molecular topology. The structures of both compounds are comprised of a protonated semicarbazone cation, and Cl anion and, in the case of 2, two water molecules of crystallisation, which all stabilise the crystal lattice through a network of hydrogen bonds.

Crystal structure analysis of (3) and (4)
The asymmetric unit of 3 contains a Hdpksz + cation and 4 contains a H 2 dpksz 2+ cation, which form compounds with gold(III) chloride or bromide crystallising reagent, with the Cl anion from semicarbazide also in the structures of   Symmetry transformations: (i) x, −y + 1/2, z + 1/2; (ii) −x + 1,−y + 2,−z + 1; (iii) x,−y + 2,z + 1/2; (iv) −x + 1,y + 1,−z + 1/2. In both compounds 3 and 4, the uncoordinated organic ligand forms a number of intra-and intermolecular hydrogen bonds in the crystal lattices (see Table 3 and Figures 4 and 5) that are responsible for the supramolecular arrangement. (37) Compound 3, with the [AuCl 4 ]anion, has a much richer hydrogen bond network, and this involves all four Clions of the anion. Through these pronounced interactions with the carbon atoms of the pyridine ring of the semicarbazone, C3 and C8 act as donors through their hydrogen atoms, while Cl1 and Cl2 acts as acceptors in the bonds formed between C3-H3···Cl2 and C8-H8···Cl1. For 3, the hydrogen bond interactions subsequently form a 2D hydrogen-bonding chain along the bc crystallographic plane with the Hdpksz + cation and chloride anion, similarly to that found for 4. The Au-Au lengths are 3.991 and 4.819 Å for compounds 3 and 4, respectively, and this distance indicates that Au•••Au interactions do not exist because for Au•••Au interactions, the usual distances range between 2.8 and 3.5 Å (1, 20).
In 4, both nitrogen atoms in the pyridine ring are protonated and act as proton donors to made intramolecular hydrogen bonds. Interestingly, it is noted that the crystal structure of 4 shows a considerable Cl(1)•••Br(1) i (i: 2−x, 1−y, 2−z) distance of 3.559(2) Å, indicating a significant interaction, which agrees with the work by Desiraju et al. that state that, generally the softer halogens have a greater tendency to form such contacts ( Figure 5) (39). possibly, the polarisability of the chloride and bromide ions corresponds to van der Waals type contacts and formed unsymmetrical Cl•••Br interactions. This type of interaction can contribute a little to the energy for the formation of a supramolecular structure and formation of the crystal the compounds. The structures are interesting because Hdpksz + does not form any coordination to the gold atoms. This result is in contrast with our observed studies and related literature, in which semicarbazone ligands are deprotonated and formed complexes with different metal ions (33)(34)(35).
For 3, the [AuCl 4 ]anion is square planar with a r.m.s. deviation of 0.0 Å from the best least squares planes for the gold atom ( Figure 3). The Au-Cl distances in 3 are 2.279(9) Å, which is typical for this ion (36,37).

Table 3. hydrogen bonding interactions (Å and °) for compounds 3 and 4.
Symmetry transformations: (i) -x + 1, -y + 2, -z + 1; (ii) -x + 2, -y + 1, -z + 1; (iii) -x + 2, -y + 1, -z + 2; (iv) x + 1,y,z. (6)  are essentially square planar with r.m.s. deviations of 0.0 Å from the best least squares planes for the gold atoms. A large number of hydrogen bonds are formed in 5 and 6 (see Table 4). Additionally, we also observed interactions by the hydrogen bonding of carbon atoms of the pyridine ring of the ligands with the negatively charged ions [AuCl 4 ]and [AuBr 4 ]for compounds 5 and 6 and show the influence of the anions in the association of these chemical species by intermolecular forces in the crystal packing. In compound 6, as show Figure 7, a two-dimensional network along the a axis is formed, and these hydrogen bonds extend over the entire crystal structure helping form the molecular conformations. Thus, they are important for the crystallisation of the molecules. No Au•••Au interactions are observed in 5 and 6, with the Au-Au lengths being 8.017 and 8.136 Å, respectively (1,20). Van der Waals type contacts are not observed in 5 and 6 between halogen atoms, and the crystal packing presents only intramolecular and intermolecular hydrogen bonds (Figure 7). packing. Additionally, weak hydrogen bonds with the carbon atoms of the pyridine ring of the semicarbazone are observed, and these carbon atoms also formed forked bonds with Br ions of the [AuBr 4 ]anion, with C⋅⋅⋅Br distances between 3.495 and 3.783 Å.

Crystal structure analysis of (5) and (6)
The X-ray crystal structures of 5 and 6 indicated that the asymmetric units have a Hdpksz + and Hdpkpsz + cation, respectively, and formed compounds with gold(III) chloride or bromide ( Figure 6  salts 5 and 6, a medium band is observed in the range of 3280-3434 cm −1 , which to the ν(NH) of the imino group. Additionally, for 2, the ν(oH) vibration is observed at 3194 cm −1 for the water molecules. The bands observed

FTIR spectra of the compounds
The Ir spectra of compound 1 and gold(III) compounds 3 and 4 exhibit bands due to ν(NH) vibrations in the range of 2923-2928 cm −1 . For 2 compound and gold(III)  between N(2) and N(4), the intensity decay of these chemical shifts is noted. It is observed that the signal at 12.65 ppm for the N2 group indicates the presence of this proton in the free ligand, but its low intensity is observed due to its instability in solution (40). The protons of the NH 2 group exhibit a multiplet at δ = 7.71-7.67 ppm; however due to the abundance of protons and consequently overlapping signals, the intensity decay of the signals due to interactions with the solvent is not observed. The chemical shifts of the pyridyl group protons have specific characteristics pertaining to this chemical group. Two doublets at δ = 8.89 ppm and δ = 8.87 ppm are assigned to the C(8)H and C(4)H protons, respectively. A doublet at δ = 8.75 ppm and a triplet at δ = 8.27 ppm are assigned to the C(9)H and C(3)H protons, respectively. A triplet, which integrates as two hydrogen atoms at δ = 7.78-7.74 ppm, is assigned to the protons attached to the C(2)H e C(10)H. These signals are characteristic of protons present in pyridyl groups.

The 1 H NMr spectra of the chlorine and bromine salts [HCldpksz][AuCl 4 ] 3 and [HCldpksz][AuBr 4 ] 4
show high singlet proton chemical shifts at δ = 11.36 and 11.39 ppm, respectively, referenced to protons attached to N(4) and, resonances consistent with the binding of dpksz. However, it is not possible to observe the signal related to the N(4) proton present in the binder. This is due to the presence of the gold ion in solution, which inhibits the proton presence, and hence, it is not observed in the spectrum. The NH 2 protons have similar characteristics compared to free ligand. The salts exhibit a multiplet at δ = 7.81-7.71 ppm for the bromide salt and δ = 8.05-8.03 ppm for the chlorine salt. It is also possible to observe chemical shifts related to pyridyl groups similar to those of the free ligand, but at approximately 2982 and 2918 cm −1 are assigned to the ν(NH) of the protonated pyridine. The presence of a band due to ν(C=o) appears in the range of 1708-1683 cm −1 showing the uncoordinated semicarbazones and that only keto form is present in the solid state. The azomethine stretching vibrations are observed at 1617 and 1599 cm −1 . The spectra of the compounds have bands due to ν(N-N) in the range of 1236-1201 cm −1 . The bands attributed to ν(AuCl) and ν(AuBr) appear approximately 347-212 cm −1 and δ(AuCl) and δ(AuBr) appear at 171-102 cm −1 , but these bands could not be observed in this Ir spectra of the gold(III) salts.

NMR spectral studies
The 1 H NMr spectrum of the compound di-2-pyridilketone-N 4 -semicarbazone monochloride 1 shows two singlets with high proton chemical shifts for the groups attached to N(2) (δ = 12.65 ppm) and N(4) (δ = 11.44 ppm). Due to the intermolecular interactions between the compound and solvent and the intramolecular interactions Table 4. hydrogen bonding interactions (Å and °) for compounds 5 and 6.
Symmetry transformations: (i) x + 1, y + 1, z + 1; (ii) x, y, z + 1. show up as a multiplet signals from δ = 7.70-7.74 ppm relating to the following protons: C(14)H, C(15)H, C (17) H and C (18)H. There is also one triplet at δ = 7.07 ppm referring to the proton C (16). According to the assignment of the peaks in the compound, it can be indicated that in the solution, the proton at the N1 group is lost. The other peaks at lower chemical shifts are assigned to the signals of the solvent and impurities in the sample.  12)) occurs at δ = 152.24 ppm, because the carbonyl group and the adjacent nitrogen atoms are very electronegative and contribute to a decrease in the field. The non-protonated carbon atom at C(6) is found more downfield in the spectrum at δ = 150.22 ppm, as it is effected by the magnetic interaction of two bulky pyridyl rings and π electron delocalisation on the C=N bond. The 13 C NMr data for the salts 5 and 6 are similar to the characteristics of the free ligand with the same number of peaks but with less intensity due to the presence of ions and interactions with the solvent.

Conclusions
In this paper, we have described an approach adopted for the synthesis of supramolecular architectures based on the self-assembly of semicarbazones and gold(III) compounds through cation-anion interactions and hydrogen bond and halogen interaction contributions. The X-ray crystal structures of 3, 4, 5 and 6 reveal that Hdpksz + and Hdpkpsz + are there is variation in some of the signals due to the presence of ions and interactions with the solvent. A low signal strength is due to the concentration of the sample.
The 13 C NMr spectrum provides direct information about the carbon skeleton of compound 1. The chemical shift at δ = 155.88 ppm can be assigned to C (12), with characteristics of a carbonyl group, but due to the two nitrogenous neighbours, there is a downfield shift. The chemical shift of C(6) is assigned at δ = 150.65 ppm, which is characteristic of the C = N group. The peaks that constitute the carbons of the C1, C9, C7, C11, C3, C10, C8 and C4 ring are assigned as follows: δ = 148.47, 145. 40 In the 13 C NMr data for salts 3 and 4, the same signals are observed as for the free ligand in relation to carbons C(12) δ = 156.15 ppm and C(6) δ = 148.75 ppm, with the chemical shifts being located slightly downfield (41). It is observed that subsequent chemical shifts in the presence of the two salts are similar to those of the free ligand, but the signals of compound (3) from symmetrical carbons C(5)/C(1) and C(2)/C(10) appear overlaid at δ = 148.55 ppm and δ = 126.01 ppm, respectively. It was also observed that for compound (4), the peaks of carbons of the pyridyl group appear to be overlaid: C(5)/C(1) δ = 146.76, C(9)/C(3) δ = 142.56, C(2)/C(10) δ = 127.72 and C(4)/C(8) δ = 126.81 ppm. It can be observed that these compounds in solution lead to the loss of the proton on the N(2) pyridyl group, which consequently becomes symmetrical, therefore the leading to the overlapping of the peaks.
The 1 H NMr spectrum of the compound di-2-pyridilketone-N 4 -phenyl-3-semicarbazone monochloride 2 showed two singlets with high proton chemical shifts for groups attached to N(4) (δ = 11.99 ppm) and N(5) (δ = 11.44 ppm). The N(4) proton is located downfield from that of N(5) due to a hydrogen bond with the N2 atom of the pyridine ring. This intramolecular interaction makes the rings become non-equivalent, and peaks that could appear overlapped are consequently separated. Thus, the peaks of protons related to the pyridine ring N2 show are unshielded in all cases compared to the equivalent protons of the other ring. As expected, the C(1)H δ = 8.81 ppm and C(11)H δ = 8.93 ppm protons show two doublets integrated with a hydrogen for each. This difference occurs because the later proton is adjacent to the N2 atom that also provides hydrogen bonding, which causes the chemical shift of C(11)H appear slightly lower than that of C(1)H. The following signals show two triplets: C(9)H δ = 8.33 ppm and C(3)H δ = 8.17 ppm. one triplet is found for the C(2)H proton at δ = 7.83 ppm, while the C(10)H proton has a higher chemical shift (δ = 8.05 ppm). The peaks related to C(4)H and C(8)H protons show nearly identical chemical environments, and consequently, they overlap as a multiplet. The peaks relating to the phenyl group not able to coordinate to the metal centre in a mono-or multidentate mode to form gold(I) or gold(III) complexes, at least under the reaction conditions employed in this study. rather than coordinating to the gold cation, the reaction formed a salt comprised of [AuX 4 ]and protonated HCldpksz or HCldpkpsz units, but the stabilisation of supramolecular networks is assisted by distinct hydrogen bonding. It is noted that the di-2-pyridilketone-N 4 -semicarbazone and di-2-pyridilketone-N 4 -phenyl-3-semicarbazone ligands have been found coordinated to other metal ions. Therefore, further studies are certainly required to determine if changes in the reaction conditions can form gold complexes.