Oxidation of the Platinum(II) Anticancer Agent [Pt{(p-BrC₆F₄)NCH₂CH₂NEt₂}Cl(py)] to Platinum(IV) Complexes by Hydrogen Peroxide

Abstract

Pt^IV coordination complexes are of interest as prodrugs of Pt^II anticancer agents, as they can avoid deactivation pathways owing to their inert nature. Here, we report the oxidation of the antitumor agent [Pt^II(p-BrC₆F₄)NCH₂CH₂NEt₂}Cl(py)], 1 (py = pyridine) to dihydroxidoplatinum(IV) solvate complexes [Pt^IV{(p-BrC₆F₄)NCH₂CH₂NEt₂}Cl(OH)₂(py)].H₂O, 2·H₂O with hydrogen peroxide (H₂O₂) at room temperature. To optimize the yield, 1 was oxidized in the presence of added lithium chloride with H₂O₂ in a 1:2 ratio of Pt: H₂O_2, in CH₂Cl₂ producing complex 2·H₂O in higher yields in both gold and red forms. Despite the color difference, red and yellow 2·H₂O have the same structure as determined by single-crystal and X-ray powder diffraction, namely, an octahedral ligand array with a chelating organoamide, pyridine and chloride ligands in the equatorial plane, and axial hydroxido ligands. When tetrabutylammonium chloride was used as a chloride source, in CH₂Cl₂, another solvate, [Pt^IV{(p-BrC₆F₄)NCH₂CH₂NEt₂}Cl(OH)₂(py)].0.5CH₂Cl_2, 3·0.5CH₂Cl₂, was obtained. These Pt^IV compounds show reductive dehydration into Pt^II [Pt{(p-BrC₆F₄)NCH=CHNEt₂}Cl(py)], 1H over time in the solid state, as determined by X-ray powder diffraction, and in solution, as determined by ¹H and ¹⁹F NMR spectroscopy and mass spectrometry. 1H contains an oxidized coordinating ligand and was previously obtained by oxidation of 1 under more vigorous conditions. Experimental data suggest that oxidation of the ligand is favored in the presence of excess H₂O₂ and elevated temperatures. In contrast, a smaller amount (1Pt:2H₂O₂) of H₂O₂ at room temperature favors the oxidation of the metal and yields platinum(IV) complexes.

1. Introduction

The serendipitous discovery of cisplatin as an anticancer drug has served humankind for decades [1,2]. Despite its success in treating testicular, ovarian, head and neck, small-cell lung, and bladder cancers, with a 90% cure rate for testicular cancer [3,4,5,6,7,8], cisplatin still has limited applications owing to natural and acquired resistance against tumors [9,10]. Additionally, it causes severe side effects, such as nephrotoxicity, neurotoxicity, and myelosuppression [9,10,11,12,13,14,15,16], and it can only be administered intravenously. The need to address these limitations and increase their applications to a broader spectrum of cancers produced cisplatin derivatives and new Pt^II compounds. However, only Pt^IV compounds showed the potency to shift the paradigm because their relatively inert nature reduces the extent of side reactions—it makes them less toxic and provides the possibility of their oral administration [8,17,18,19,20] for improved quality of life of cancer patients. Furthermore, they are more water-soluble than Pt^II drugs and are more easily absorbed in the gastrointestinal tract; their high lipophilicity causes enhanced diffusion through the cell membrane, and they are not cross-resistant with cisplatin [21,22,23].

Generally, Pt^IV compounds (e.g., tetraplatin, iproplatin, and satraplatin) are considered to be Pt^II prodrugs [24,25]. They are relatively inert to ligand substitution reactions due to their electronic configuration, but liable to two-electron reduction. They are reduced to their active Pt^II analogue in vivo by biomolecules, such as glutathione (GSH), by the loss of their axial ligands [8,26,27]. The ease with which Pt^IV complexes are reduced to Pt^II depends on the nature of the axial ligands [28], which affect the reduction potential (E^red) for the Pt^IV/II process. For example, the order of the ease of reduction of Pt^IV [28] in tetraplatin (axial ligand Cl⁻) [29], JM216 (axial ligand CH₃COO⁻) [30], and Iproplatin (axial ligand OH⁻) [31] is Cl⁻ > RCO₂⁻ > OH⁻. Photoactive Pt^IV complexes have also been explored for better efficiency [32,33]. Nanoparticle-based drug delivery of Pt^IV complexes has been introduced to address the resistance issues and further lower the toxicity [34,35]. In most cases, the reduction of the Pt^IV prodrug generates the parent Pt^II compound by the loss of two axial ligands [27,36]. Some reports also mentioned the formation of more than one reduction product, depending on the reducing agents used [37,38].

The need to find better drugs led to “rule breaker” [39] or “non-traditional” drugs [40], which violate structure–activity rules [41]. One such example is the polynuclear platinum compound BBR3464 [42,43,44]. Other “rule breakers” include two classes of organoamidoplatinum(II) compounds, namely, Class 1, [Pt{N(R)CH₂}₂(py)₂] (R = polyfluoroaryl), with no H atoms on the N-donor atoms, and Class 2, trans-[Pt{N(R) CH₂CH₂NRʹ₂}X (py)] (R = polyfluoroaryl; R′ = Et, Me; and X = Cl, Br, I), with trans amine ligands and trans anionic ligands, and no H atoms on the N-donor atoms (see Figure 1). Both classes show promising anticancer activity in vitro and in vivo [45,46,47]. The investigation of DNA binding properties by Resonant X-ray emission spectroscopy (RXES) shows that after hydrolysis of [Pt{N(p-HC₆F₄)CH₂}₂(py)₂] (Pt-103) (py = pyridine), the [N(p-HC₆F₄)CH₂]₂²⁻ moiety behaves as a leaving group, and hydroxylation of the Pt center generates a hydrolyzed species, which then reacts with DNA and preferentially coordinates to the adenine site, rather than the guanine site [48]. This could explain why Pt-103 is biologically active against cisplatin-resistant cell lines.

Pt^IV compounds are generally six coordinate octahedral complexes and can be synthesized by oxidative addition of four coordinate square planar Pt^II compounds. However, some five coordinat Pt^IV complexes also have been reported to be formed in the oxidation of Pt^II to Pt^IV [49]. The Platinum Group Metals (PGMs) in higher oxidation states (as Pt^IV) have been reported as possible intermediates in some organic synthetic procedures due to their lower stability [50,51,52,53].

Oxidation of platinum(II) complexes with H₂O₂ has been reported to produce trans dihydroxidoplatinum(IV) complexes [54,55,56,57,58,59,60]. Some Class I (organoamido)platinum(IV) compounds have shown high anticancer activity in vivo against the ADJ/PC6 tumor line [54]. Some Pt^IV complexes with large negative E^red values, such as [Pt{((p-HC₆F₄)NCH₂)₂(py)₂}(Cl)₂], [Pt{((p-HC₆F₄)NCH₂)₂(py)₂}(OH)₂] (Pt103(OH)₂), and [Pt{((p-HC₆F₄)NCH₂)₂(py)₂}(Cl)(OH)], are effective against cisplatin-resistant cell lines [54]. The last two are even more active than the Pt^II precursor Pt-103. This suggests that either the Pt^IV complexes themselves are active, or they are reduced in vivo near the target and prevent premature reduction [54]. The electrochemical oxidation of Class 2 complexes produced mononuclear, formally Pt^III, species [61,62]. The formation of Pt^IV species was not observed in these electrochemical studies. Recently, we reported the oxidation of the Class 2 complex [Pt(p-BrC₆F₄)NCH₂CH₂NEt₂}Cl(py)], (1) by an excess of H₂O₂ under forcing conditions, which involved heating in different solvents [47]. Under these conditions, two types of ligand oxidized organoenamineamidoplatinum(II) complexes, namely, unsubstituted [Pt(p-BrC₆F₄)NCH=CHNEt₂}Cl(py)], 1H and ethene-substituted [Pt(p-BrC₆F₄)NCH=C(X)NEt₂}Cl(py)], 1X (X = Cl, Br), along with [Pt(p-BrC₆F₄)NCH=C(H₀.₂₅Br_0.75)NEt₂}Cl(py)], 1H_0.251Br_0.75, were obtained. (Scheme 1 top) [47]. However, the formation of Pt^IV complexes was not observed.

Here, we report the formation of Pt^IV dihydoxidoplatinum(IV) complexes, which are isolated from the oxidation of 1 with H₂O₂ under milder conditions without heating. Changes in stoichiometry, temperature, solvents, and the addition of chloride were used to achieve higher selectivity of the products. These Pt^IV compounds undergo reductive dehydration, that is, reduction of Pt^IV to Pt^II over time in the solid state, as determined by X-ray powder diffraction characterization, forming organoenamineamideplatinum(II) complexes with an oxidized coordinating ligand.

2. Results and Discussion

In the present work, the chemical oxidation of 1 was undertaken with H₂O₂ at room temperature in a range of solvents to determine if isolable Pt^IV complexes could be obtained under mild conditions. The H₂O₂ oxidation in acetone produced the gold-colored dihydroxidoplatinum(IV) compound 2·H₂O_(gold) as a hydrate, along with 1H, and 1H_0.251Br_0.75 organoenamineamidoplatinum(II) compounds as minor products (Scheme 1(bottom, red)).

The Pt^IV complex 2·H₂O_(gold) showed slow reductive dehydration in the solid state to produce the organoenamineamide Pt^II complex 1H, which is the product of oxidation of the ligand [47] (see below). Earlier studies showed that some Pt^IV complexes also exhibit reductive elimination similar to what is better known for Pd^IV complexes [50].

The selectivity for formation of Pt^IV compounds was enhanced by optimizing the experimental conditions to produce the outcome shown in Scheme 2. We proposed previously that, in the absence of any other source of Cl⁻ in the reaction mixture, the chloride needed to form 1Cl is generated from the oxidation of the Pt-Cl bond of 1 [47]. Thus, H₂O₂ oxidation reactions of 1 were also performed with deliberately added chloride to examine whether this would enhance the yield of 1Cl or would promote the formation of Pt^IV complexes, as the Pt-Cl bond should remain intact due to the presence of excess chloride. Scheme 2 is a schematic representation of the major products obtained from the oxidation of 1 with limited H₂O₂ under a range of experimental conditions. Two differently colored samples of 2·H₂O, red and gold (2·H₂O_(red) and 2·H₂O_(gold)), were isolated. The amounts of the reagents and the yields of the products are shown in

Table 1. Quantities of reagents and product yields (crystalline) for the oxidation of 1 with 30% H₂O₂ reactions performed at room temperature.

Compound	Cl Source	H2O2	Solvent	Time	Products with Yields
1 (1.0 mmol)	none	2.0 mmol	CH3COCH3	12 d	1H = 1.4%, 2·H2O(gold) = 25%; 1H0.251Br0.75 = 7%
1 (0.5 mmol)	LiCl (0.5 mmol)	1.0 mmol	* CH2Cl2	7 d	2·H2O(red) = 50%, 2·H2O(gold) = 14%
1 (0.48 mmol)	NBu4Cl (0.48 mmol)	1.0 mmol	* CH2Cl2	4 d	3·0.5CH2Cl2 = 49%, 2·H2O(gold) = 10%

* workup differs (see experimental).

. The results demonstrate that the addition of chloride enhances the formation of dihydroxidoplatinum(IV) complexes.

The H₂O₂ oxidation reaction of 1 in the presence of LiCl in CH₂Cl₂ at room temperature produced the Pt^IV complex 2·H₂O in two colors, red and golden crystals (see experimental section). Both were characterized by X-ray crystallography (see below) and microanalyses. Both have one molecule of water of crystallization per molecule of the complex (some previous works have also reported the observation of transient red color upon oxidation of cisplatin with chlorine [63,64]). Related results were obtained with added tetrabutylammonium chloride, in CH₂Cl₂ (see Table 1 and Experimental section). In this case, a deep-red-colored Pt^IV complex containing 0.5 of a CH₂Cl₂ molecule in the asymmetric unit, 3·0.5CH₂Cl₂, with some 2·H₂O_(gold) was obtained. A few crystals of NBu₄[PtCl₃(py)] also were obtained and characterized by X-ray crystallography only. All the experimental results suggest that adding chloride simplifies the reaction by preventing the dissociation oxidation of the Pt-Cl bond.

The mechanism for H₂O₂ oxidation of Pt^II to Pt^IV has been reported as single-step two-electron oxidation or as two very rapid one-electron processes that exclusively produce trans-hydroxide complexes [65]. In this oxidation reaction, the square planar configuration of the original Pt^II complex is retained, and the two hydroxido ligands coordinate trans to each other. A ¹⁹⁵Pt NMR study has suggested that one of the trans-coordinated hydroxido ligands originates from H₂O₂ and the other from the solvent water [66,67].

Notably, all Pt^IV solvate complexes show reductive dehydration, i.e., from Pt^IV to Pt^II species. However, the resulting Pt^II species is not the parent compound 1, as is generally the case with Pt^IV species. Instead, an organoenamineamidoplatinum(II) compound 1H with an oxidized coordinating ligand is formed (below).

2.1. X-ray Crystal Structures

The molecular structures of 2·H₂O_(red) and 2·H₂O_(gold) Pt^IV complexes are shown in Figure 2, and that of 3 in Figure 3. 2·H₂O_(gold) crystallizes in the space group (C2/c), whereas 2·H₂O_(red) crystallizes in the Cc space group. Despite these space group differences, their unit cells are virtually identical (

Table 2. Crystallographic data for the molecular structures of 2·H₂O_(gold), 2·H₂O_(red), and 3·0.5CH₂Cl₂.

	2·H2O(gold)	2·H2O(red)	3·0.5CH2Cl2
Empirical formula	C17H19BrClF4N3O3Pt	C17H19BrClF4N3O3Pt	C17.5H22BrCl2F4N3O2Pt
Formula weight	703.83	703.83	728.28
Crystal system	Monoclinic	Monoclinic	Monoclinic
Space group	C2/c	Cc	C2/c
a (Å)	19.719(4)	19.6389(16)	14.948(3)
b (Å)	13.357(3)	13.3360(11)	14.302(3)
c (Å)	16.946(3)	16.9327(13)	21.743(4)
α (°)	90	90	90
β (°)	105.29(3)	104.857(2)	104.53(3)
γ (°)	90	90	90
vol (Å3)	4305.4(16)	4286.5(6)	4499.7(17)
Z	8	8	8
ρ (calcd) (g/cm3)	2.172	2.169	2.150
µ (mm−1)	8.557	8.594	8.303
F (000)	2688.0	2656.0	2776.0
Reflections collected/unique	31,692/5071	35,311/12,158	40,998/6383
Rint	0.1016	0.0537	0.0504
2θmax (°)	56.33	61.2	63.5
Goodness-of-fit on F2	1.287	1.044	1.060
R1 indices [I ≥ 2σ (I)]	0.0712	0.0387	0.0342
wR2 indices [I ≥ 2σ (I)]	0.1431	0.0634	0.0841
Flack parameter	n/a	0.398(5)	n/a

n/a = not applicable.

), as are their X-ray powder diffractograms generated from their single-crystal data (Figure S1). Accordingly, the structures are the same, despite the optimum solutions being in different space groups. The molecular structure of 2·H₂O_(red) has the same ratio of complex to solvent of crystallization (water) as in 2·H₂O_(gold). In 2·H₂O_(red), two dihydroxidoplatinum(IV) molecules bridged with two water molecules by H-bonding are present in the asymmetric unit (Figure 2c), whereas in 2·H₂O_(gold), a single molecule of 2 is associated with a single water molecule of crystallization (Figure 2a). However, the crystal structure of 2·H₂O_(gold) extended to two asymmetric units (Figure 2b) reveals the same structure as in the asymmetric unit of 2·H₂O_(red). Red and yellow compounds with essentially the same structure are observed in the case of yellow and red mercuric oxide, ref [68] where the difference is attributed to particle size. Likewise, [RuBr₂(CO)₂(tpy)] (tpy = 2,2′:6′,2′′-terpyridine) exists in red and yellow forms with essentially the same structure [69]. Although the powder diffractograms of bulk 2·H₂O_(red) and 2·H₂O_(gold) show significant differences (Figure S7), this is attributed to different rates of reductive dehydration in the solid state (see below). 3·0.5CH₂Cl₂ crystallizes in the C2/c space group with one formula unit in the asymmetric unit (Figure 3a), and the crystal packing shows a hydrogen-bonded dimer (Figure 3b).

All Pt^IV solvate complexes have an octahedral stereochemistry around the Pt metal atom with trans hydroxido axial ligands. The bond lengths are listed in

Table 3. Selected bond lengths for compounds 2·H₂O_(gold), 2·H₂O_(red) (given for both molecules in asymmetric units), and 3·0.5CH₂Cl₂.

Bond	2·H2O(gold) C17H23BrClF4N3O3Pt (Å)	2·H2O(red) C17H23BrClF4N3O3Pt (Molecules A and B in Asymmetric Unit) (Å)		3·0.5CH2Cl2 C17.5H22BrCl2F4N3O2Pt (Å)	103(OH)2 C24H18F8N4O2Pt [54] (Å)
Pt-O1	2.029(9)	2.015(6)	2.028(7)	2.061(3)	2.017(3)
Pt-O2	2.003(8)	1.999(6)	2.016(6)	2.018(3)	2.008(3)
Pt-Cl	2.349(3)	2.359(3)	2.345(3)	2.3662 (11)	n/a
Pt-N1(amide)	2.031(9)	2.026(9)	2.037(9)	2.047(3)	2.033(3)
Pt-N2(amine)	2.119(7)	2.119(8)	2.132(9)	2.124(3)	n/a
Pt-N3(py)	2.078(7)	2.087(8)	2.066(9)	2.061(3)	2.083(3)
N1(amide)-C6F4	1.395(13)	1.387(15)	1.380(14)	1.391(5)	1.392(5)
C7(deen)-C8(deen)	1.492(16)	1.507(15)	1.497(15)	1.506(6)	1.473(5)
N1(amide)-C7(deen)	1.459(12)	1.456(13)	1.469(13)	1.467 (5)	1.470(5)
N2(amine)-C8(deen)	1.508(14)	1.497(13)	1.504(13)	1.510(6)	n/a
N2(amine)-C9(Et) N2(amine)-C11(Et)	1.510(14) 1.502(13)	1.510(13) 1.508(14)	1.514(14) 1.508(13)	1.497(5) 1.521(5)	n/a

n/a = not applicable.

, the bond angles are in Tables S1 and S2, and the crystal data are in Table 2. The OPtO angles in 2·H₂O_(gold), 2·H₂O_(red), and 3·0.5CH₂Cl₂ are 177.7(3), 177.9 (3)/ 177.8(4) (molecules A and B), and 176.57(13), respectively. These angles are comparable to 179.73(9) in [Pt{((p-HC₆F₄)NCH₂)₂}(py)₂(OH)₂] ([Pt103(OH₂)]) [54], as expected for a linear and trans arrangement of axial ligands. Equatorial positions have a square planar arrangement of the donor atoms, as in the parent compound 1. The Pt-O bond lengths shown in Table 3 are similar to those for the dihydroxidoplatinum(IV) complex, [Pt103(OH₂)] [54], shown in Table 3. The Pt-N bond lengths are expected to lengthen with an increase in the coordination number from 4 to 6. However, an increase in the oxidation state from +2 to +4 is expected to shorten the Pt-N bond lengths. Apparently, these contrary effects cancel each other out, so the Pt-N bond lengths remain close to those of the parent platinum(II) compound (1) at the three-esd level. The angles between OH and other donor atoms in the square planar arrangement are close to 90°, consistent with octahedral stereochemistry.

The bond angles around the amide N in 2·H₂O_(red)) (108.8 (7) + 117.4 (8) + 118.2 (7) = 344.4°) and in 3 (108.054 (18) + 117.856 (17) + 116.878 (6) = 344.8°) show distortion from tetrahedral (∑328.5°) towards triangular (∑360°). However, the N atoms have less trigonal character than in the platinum(II) complexes 1 (∑356.9°) and 1H (∑357°).

These Pt^IV complexes show a range of inter- and intramolecular H-bonding (Figure 2 and Figure 3), as also observed for related Pt^II compounds [70]. The interaction distances are listed in

Table 4. Inter- and intramolecular H-bonding interaction distances for 2·H₂O_(gold) and 3·0.5CH₂Cl₂.

2·H2O(gold)		3·0.5CH2Cl2
Interactions	Distance	Interactions	Distance
F1⋯HO2	2.412(7)	O2⋯ H(CH2CH3)	2.3561(8)
F4⋯ HO1	2.438(7)	F4⋯HO2	2.7065(7)
O1⋯ H(py)	2.322(7)	Cl⋯H(CH3)	2.7529(7)
O2⋯ H(py)	2.227(7)	(CH2Cl2)Cl⋯H(CH2N(p-BrC6F4)	3.0946(7)
O1⋯ H(CH2CH3)	2.380(7)
Cl⋯H(CH3)	2.738(3)	Inter (CH2Cl2)Cl⋯H(CH2CH3)	2.8282(4)
Inter O3H⋯O1	2.198(7)

. In 2·H₂O_(red) and 2·H₂O_(gold), both H atoms of the trans-OH groups are facing toward the o-F atoms of the polyfluoroaryl ring. However, in 3, one of the H atoms of the trans-OH ligands, faces away, as it makes an H-bond with Br(p-BrC₆F₄) of an adjacent molecule with an H⋯Br distance, 3.0993(5), as shown in Figure 3.

A few crystals of [NBu₄][PtCl₃(py)] were obtained as a minor product from the H₂O₂ oxidation reaction of 1 with added tetrabutylammonium chloride in CH₂Cl₂ (see Experimental). The compound [NBu₄][PtCl₃(py)] could only be characterized by X-ray crystallography due to the poor yield. The molecular structure of [NBu₄][PtCl₃(py)] is shown in Figure S2. In the asymmetric unit, only half of the molecule is present, and the other half is symmetrically generated. Crystallographic data are given in Table S3, and selected bond lengths and angles are listed in Table S4.

Satisfactory microanalyses were obtained for all three 2·H₂O_(red), 2·H₂O_(gold), and 3·0.5CH₂Cl₂ Pt^IV complexes. All were consistent with the presence of H₂O in 2 and 0.5 CH₂Cl₂ in 3 crystal lattices (see Experimental section). The characteristic ν(OH) bands of dihydroxidoplatinum(IV) complexes were observed in IR spectra between (3500 and 3700 cm⁻¹) in the expected range (ν(OH) 3760–3500 cm⁻¹) for metal hydroxides [54,71]. Strong ν(C-F) absorption bands appear at a comparatively higher wavenumber, i.e., at 968 cm⁻¹ in 2_(red) and 3 as compared to the Pt^II precursor 1 (956 cm⁻¹), as also observed for Pt103 (926 cm⁻¹) and Pt103(OH)₂ (938 cm⁻¹) [54]. The spectra show C-H out-of-plane deformation bands of py at 763 cm⁻¹.

2.2. Powder X-ray Diffraction (PXRD) Study

Powder diffraction patterns for bulk 2·H₂O_(red) and 2·H₂O_(gold) exhibit differences (Figure S7) and also differ from the identical patterns generated from single-crystal data (Figure S1). These solids, especially red 2·H₂O, changed in physical appearance with time (over almost 90 days) and turned from deep-red crystals (block) into a mixture of red powder and some yellow solid.

A comparison of the PXRD pattern for a bulk sample of 2·H₂O_(red) with those calculated from the single-crystal data for the platinum(II) complex [Pt(p-BrC₆F₄)NCH=CHNEt₂}Cl(py)], 1H [47] (Scheme 1) and single crystals of 2·H₂O_(red) (see Figure S8) clearly shows that Pt^IV 2·H₂O_(red) and 1H both are present in the bulk sample of stored 2·H₂O_(red). A comparison between the PXRD patterns of the bulk sample of 2·H₂O_(gold) with those calculated from the single-crystal data for 1H and single crystals of 2·H₂O_(gold), (Figure S9), clearly shows 2·H₂O_(gold) and 1H both are present in the bulk sample of 2·H₂O_(gold). However, 1H is present in larger amounts in this bulk sample than in the bulk sample of 2·H₂O_(red).

All observations and the experimental facts confirm that these Pt^IV samples undergo reductive dehydration to produce a Pt^II complex with an oxidized ligand, where the rate is faster for 2·H₂O_(gold) than for 2·H₂O_(red).

A yellow crystal of 1H was collected from the bulk sample of 2·H₂O_(red), and X-ray diffraction data were obtained (see Table S5). The crystal structure showed twinning, but the cell parameters were consistent with 1H [47]. Another yellow crystal of co-crystallized ([Pt(p-BrC₆F₄)NCH=CHNEt₂}Cl(py)], 1H and [Pt(p-BrC₆F₄)NCH=C(Cl)NEt₂}Cl(py)], 1Cl, 1H/Cl) also was collected from a bulk sample of 2·H₂O_(gold), and X-ray diffraction data were obtained (see Table S5). The crystal structure showed twinning, but the cell parameters were consistent with co-crystallized (1H/Cl) [47]. The mechanism for formation of 1Cl by reductive dehydration in the solid state is not fully understood, but it is probably via a similar path to that proposed for its formation in the oxidation of 1 by H₂O₂ under aggressive conditions [47].

2.3. Isolation of PtIV from the Solution of an Aged Bulk Sample

To examine if platinum(IV) species can be recovered from solution, an aged sample of 3·0.5CH₂Cl₂ was returned to the reaction mixture from which 3·0.5CH₂Cl₂ was isolated in the first place and was completely dissolved in CH₂Cl₂ to obtain an homogeneous solution. Crystallization from the CH₂Cl₂/hexane mixture enabled the isolation of red crystals of [Pt^IV{(p-BrC₆F₄)NCH₂CH₂NEt₂}Cl(OH)₂(py)].H₂O, 2·H₂O_(red) having the same cell parameters (see Table S6) as in Table 2. However, 3 (with 0.5 CH₂Cl₂ in the crystal lattice) could not be isolated. A yellow crystal of co-crystallized (1H/Cl) again was isolated from the solution, and the unit cell parameters collected (Table S6) are in agreement with those reported in Table S5. Some pale-yellow crystals were also isolated from the solution, and X-ray diffraction data were obtained, establishing the identification as [NBu₄][PtCl₃(py)] (Figure S2), as also isolated from the preparation of 3·0.5CH₂Cl₂ (above).

2.4. NMR Spectroscopy

The rearrangement of the Pt^IV complexes into the Pt^II species, 1H, was initially detected by NMR spectroscopy. Notably, no Pt^IV species was detected in the NMR spectra of 2·H₂O_(gold), and only 1H was observed (see Experimental section), showing that the rate of reductive dehydration for 2·H₂O_(gold) is fast in solution. In the ¹⁹F NMR spectrum of 2·H₂O_(red) in deuterated acetone, four resonances in a 1:1:1:1 ratio are present at −138.24, −138.34, −140.64, and −148.16 ppm, together with very low-intensity resonances of precursor compound 1. The highest and lowest frequency resonances correspond to those of 1H [47]. The other two resonances show the small separation observed for F2,6 and F3,5 of the p-HC₆F₄ group in other 2,3,5,6-tetrafluorophenylethane-1,2-diaminatoplainum(IV) complexes [54]. The signals are shifted to a higher frequency than for the corresponding resonances of the Pt^II precursor due to the higher oxidation state.

In the ¹H NMR spectrum of 2·H₂O_(red) in (CD₃)₂CO, two separate resonance sets were observed for ortho, meta, and even for the para protons of the pyridine ligands. That is only possible when two species are present in the solution. One set of resonances corresponds to those reported for 1H [47]. The remaining resonances are attributed to those of the platinum(IV) complex 2 in a 1:1 ratio with 1H. Further to this assignment, in the ¹H NMR spectra, one of the two sets of pyridine ¹H resonances appears at a higher frequency than the other set. This set of resonances is assigned to pyridine of a platinum(IV) species. ¹H and ¹⁹F NMR spectra of 2·H₂O_(red) in CD₂Cl₂ also showed both species, confirming that this observation is not solvent-specific.

Similar behavior was shown by 3·0.5CH₂Cl₂. In the solution, 3·0.5CH₂Cl₂ produces a Pt^IV species and 1H, as observed for 2·H₂O_(red). However, this compound also shows the chloro-substituted organoenamineamide species [Pt(p-BrC₆F₄)NCH=C(Cl)NEt₂}Cl(py)], 1Cl [47] in solution. In the ¹⁹F NMR spectrum, the resonances at −137.96 and −148.61 ppm (almost 10 ppm apart) are due to F 3, 5 (2F) and F 2, 6 (2F) of 1H. Those at −137.63 and −142.25 ppm (almost 4 ppm apart) represent 2F (F 3, 5) and 2F (F 2, 6) of the Pt^IV species, 3, and at −137.27 and −148.46 ppm (almost 10 ppm apart), they are 2F (F 3, 5) and 2F (F 2, 6) of 1Cl. Some extracted data from complex NMR spectra of these compounds are shown in

Table 5. ¹H and ¹⁹F NMR chemical shifts and assignments for 1H, 2·H₂O_(red), and 3·0.5CH₂Cl₂ in (CD₃)₂CO.

1H NMR Chemical Shifts Assignment	1H * (ppm)	2·H2O(red) (ppm)	3·0.5CH2Cl2 (ppm)
-NCH2CH3	1.56, td	1.23, t	1.26, t
-CH2NEt2	-	2.30, m	2.30, m
=CHNEt2	3.75, d	-	-
-NCHAHBCH3	2.30, m	3.00, m	3.00, m
-NCHAHBCH3	3.43, m	3.13, m	3.00, m
-CH2N(p-BrC6F4)	-	3.33, m	3.47, m
=CHN(p-BrC6F4)	6.07, m	-	-
Pt-OH	-	4.03, m	4.03, m
H 3, 5 (py)	7.19, m	7.33, t	7.19, t
H 4 (py)	7.74, tt	7.86, t	7.72, t
H 2,6 (py)	8.42, d	8.98, d	8.98, d
19F NMR chemical shifts Assignment	1H * (ppm)	2·H2O(red) (ppm)	3·0.5CH2Cl2 (ppm)
(p-BrC6F4) F 3,5	−138.20, m	−138.34, m	−137.63, m
(p-BrC6F4) F 2,6	−148.20, m	−140.64, m	−142.25, m

The data are extracted from complex NMR spectra of the compounds plus their reductive dehydration products. The full NMR data and integrations showing relative amounts are provided in the Experimental section. * For 2·H₂O_(gold), only 1H was observed. Pt^IV was not observed.

. For 2·H₂O_(gold), only 1H was observed, and the Pt^IV complex was not observed; therefore, only the data for 1H are shown in Table 5. The complete NMR data and integrations showing relative amounts are provided in the Experimental section.

All the above observations indicate that Pt^IV complexes show reductive dehydration to Pt^II species, mainly 1H, in solution (Equation (1)) and in the solid state. In this rearrangement, the metal is reduced, and the ligand is oxidized with water loss. This is a net dehydration reaction, as given in Equation (1). The rate at which Equation (1) occurs is strongly dependent on the environment. After the peroxide reaction, these Pt^IV complexes were isolated with the addition of water (see Experimental section), so Equation (1) is not favored. In the solid state, slow loss of water or dehydration occurs. In an organic solvent with minimal water content, water loss is facilitated and faster than in the solid state.

$$\left[{\mathrm{P}\mathrm{t}}^{\mathrm{I}\mathrm{V}}\left\{\left(p-{\mathrm{B}\mathrm{r}\mathrm{C}}_6{\mathrm{F}}_4\right){\mathrm{N}\mathrm{C}\mathrm{H}}_2{\mathrm{C}\mathrm{H}}_2{\mathrm{N}\mathrm{E}\mathrm{t}}_2\right\}\mathrm{C}\mathrm{l}\left(\mathrm{O}\mathrm{H}{)}_2\left(\mathrm{p}\mathrm{y}\right)\right]⟶{\mathrm{P}\mathrm{t}}^{\mathrm{I}\mathrm{I}}\left\{\left(p-{\mathrm{B}\mathrm{r}\mathrm{C}}_6{\mathrm{F}}_4\right)\mathrm{N}\mathrm{C}\mathrm{H}={\mathrm{C}\mathrm{H}\mathrm{N}\mathrm{E}\mathrm{t}}_2\right\}\mathrm{C}\mathrm{l}\left(\mathrm{p}\mathrm{y}\right)\right]+2{\mathrm{H}}_2\mathrm{O}$$

(1)

Variable-Temperature NMR Spectra

To monitor Equation (1) in solution further, the temperature dependence of ¹H and ¹⁹F NMR resonances was examined. The spectra were taken at 20° intervals, from 25 °C to −60 °C, and are shown in Figures S3–S6. The temperature variation study was performed almost 60 days after the NMR spectra were first recorded for 2·H₂O_(red) (Experimental section), when Pt^II and Pt^IV were present in an almost 1:1 ratio. The integration ratios of Pt^IV to Pt^II are 40% and 60%, respectively, at 25 °C.

¹H and ¹⁹F NMR spectra do not show a any significant change in the temperature range of 25 °C to −60 °C. The F 2, 6 and F 3, 5 resonances for Pt^II do not show any change with variation in the temperature. However, a slightly increased separation between F 3, 5 resonances of Pt^II and Pt^IV was observed in the ¹⁹F NMR spectra, with some broadening and reduced definition of F 3, 5 of the Pt^IV species. The broadening is attributed to crystallization at lower temperatures. The integration ratio of Pt^IV to Pt^II decreases upon cooling, consistent with partial crystallization of the former.

When the solution was heated from 25 °C to 50 °C and the spectra were collected, the 1H resonances showed an increase in intensity in the ¹⁹F NMR spectra consistent with the further extent of the reaction in Equation (1), as shown in Figure S6.

2.5. Electrospray MS Measurements

As described in the supporting information, no Pt^IV complexes were detected via electrospray MS measurements. Similar to what was observed for trans-organoenamineamidoplatinum(II) complexes [47], the starting material 1 was observed.

3. Materials and Methods

3.1. Chemicals

The solvents acetone, dichloromethane, acetonitrile, ethyl acetate, and n-hexane were HPLC grade. Hydrogen peroxide (30% solution in water) (Merck) was stored at −4°C. MnO₂, NBu₄Cl, and LiCl were from Sigma Aldrich and used as received. The Class 2 organoamidoplatinum(II) complex, trans-[Pt{(p-BrC₆F₄)NCH₂CH₂NEt₂}Cl(py)] (1), was synthesized by using the literature method [62].

3.2. Instrumentation/Analytical Procedure

NMR spectra were recorded in deuterated solvents with Bruker DPX 300, 400, or 600 spectrometers (Billerica, MA, USA) supported by Top Spin NMR 4.3.0 software on a Windows NT workstation. CFCl₃ and tetramethylsilane were used for the internal calibration of ¹⁹F NMR and ¹H NMR spectra, respectively. Infrared spectra were recorded on a Perkin-Elmer 1600 FT-IR spectrophotometer as Nujol and hexachlorobutadiene (HCB) mulls between NaCl plates or recorded with an Agilent Cary 630 (Agilent Technologies Ltd., Yarnton, UK) attenuated total reflectance (ATR) spectrometer in the range 4000–600 cm⁻¹. Low-resolution ESI measurements were recorded on a Waters micromass ZQ QMS connected to an Agilent 1200 series HPLC system. High-resolution accurate mass measurements were performed on a TOF (Agilent) instrument with a multimode source by using the dual methods ESI (electrospray ionization) and APCI (atmospheric pressure chemical ionization). Microanalyses were carried out by the Science Centre, London Metropolitan University Elemental Analysis Service. An electrothermal IA6304 apparatus was used to measure the melting points (uncalibrated) of the compounds. PXRD patterns were measured using a Bruker D8-Focus diffractometer (Billerica, MA, USA) with a 1° divergence slit, 0.2° receiving slit, and carbon monochromators (Cu-Kα radiation, λ = 1.5406 Å) in the range 2θ = 2–60° at 0.02° increments, at room temperature. The Mercury 4.3.0 software was used to generate the calculated powder patterns generated from the single-crystal diffraction models.

3.3. X-ray Crystallography

X-ray diffraction data obtained from single crystals of 2·H₂O_(gold), [NBu₄][PtCl₃(py)], and 3 were collected at a wavelength of λ = 0.712 Å using the MX1 beamline at the Australian Synchrotron, Victoria, Australia, with Blue Ice [72], a GUI using the same method as mentioned in the Experimental section of the previous report [62]. Data were processed with the XDS [73] version 20230630 software package. The structures were solved using direct methods with SHELXS-97 [74] and refined using conventional alternating least-squares methods with SHELXL-97 [74]. Single crystals of 2·H₂O_(red) were loaded onto a fine glass fiber or cryoloop using hydrocarbon oil and the data collected at 123K using an open-flow N₂ Oxford Cryptosystem. A Bruker Apex II diffractometer was used to collect the data, which was processed using the SAINT [75] program. The program OLEX2 [76] was used as the graphical interface. All non-hydrogen atoms in the structures were refined anisotropically, and hydrogen atoms attached to carbon were placed in calculated positions and allowed to ride on the atom to which they were attached. The positions of the hydrogen atoms attached to the oxygen atoms were experimentally located and refined by using multiple refinement cycles.

Crystallographic data for all the structures reported in this paper have been deposited with the Cambridge Crystallographic Data Centre as supplementary number CCDC 2272032 for 2·H₂O_(gold), 2272033 for 2·H₂O_(red), 2272037 for 3, and 2280550 for [NBu₄][PtCl₃(py)]. Copies of the data can be obtained free of charge at www.ccdc.cam.ac.uk/data_request/cif (accessed on 31 July 2023).

3.4. Experimental Section

3.4.1. Oxidation of 1 with H₂O₂

In acetone: 1 (0.630 g, 1.0 mmol) was dissolved in 16 mL acetone, and (0.2 mL, 2.0 mmol) of 30% H₂O₂ solution was added. The reaction mixture was stirred at room temperature for 12 days. The color of the solution changed from initially yellow to deep red and then to reddish-orange; MnO₂(see the warning below) [77] (2 g) was added at that time. After filtration and evaporation of the solution to 5–6 mL, distilled water (20 mL) was added, producing a cloudy solution with deep-red oil. The cloudy solution was decanted off, filtered, and a red–brown powder was collected. Crystallization of the red–brown powder from acetone/hexane produced crystals of 1H by slow evaporation, characterized by X-ray single-crystal diffraction, ¹H and ¹⁹F NMR, and mass spectrometry.

(a) [Pt{(p-BrC₆F₄)NCH=CHNEt₂}Cl(py)] (1H): Metallic gold-colored blocks. (0.002 g, 1.4% crystal yield). ¹⁹F NMR (CD₃(CO)₂): −148.2 [m, 2 F, F 2, 6], −138.2 [m, 2 F, F 3,5]. ¹H NMR (CD₃(CO)₂): 1.56 [td, 6 H, ³J_H,H 7 Hz, NCH₂CH_3,], 2.30 [m, 2 H, NCH_AH_BCH_3,], 3.43 [m, 2 H, NCH_BH_ACH_3,], 3.75 [d, ³J_H,H 3.45 Hz, ³J_H,Pt 34 Hz, 1 H, CHNEt₂], 6.07 [m with ¹⁹⁵Pt satellites, ³J_H,Pt 50 Hz, 1 H, CHN(p-BrC₆F₄)], 7.19 [m, 2 H, H 3, 5 (py)], 7.74 [tt, ³J_H,H 7.8 Hz, ⁴J_H,H 1 Hz, 1 H, H 4 (py)], 8.42 [d with ¹⁹⁵Pt satellites, ³J_H,H 5.6 Hz, ³J_H,Pt 30 Hz, 2 H, H 2, 6 (py)]. All these data (IR and ESI m/z (+ve) are given in SI) agree withthose reported for 1H [47].

The remaining red–orange filtrate was concentrated using a rotatory evaporator. The entire solution changed color from reddish-orange to gold, and more red–brown oil was obtained. After separation from the oil, the gold-colored filtrate produced shiny golden flakes upon cooling at −10 °C. These golden flakes were recrystallized from acetone/water, and gold-colored crystals of the platinum(IV) complex 2·H₂O(H₂O) were obtained. After collecting crystals, slow evaporation of the remaining mother liquor produced [Pt{(p-BrC₆F₄)NCH=C(H_0.25Br_0.75)NEt₂}Cl(py)], 1H_0.25Br_0.75, as characterized by X-ray crystallography, yielding the same unit cell as reported earlier [47]. The red–brown oil was dissolved in acetone, and many unsuccessful attempts of crystallization were made with various solvents. ¹H and ¹⁹F NMR revealed the presence of Pt^IV species, 2·H₂O(H₂O), with some Pt(py)₂Cl₂. Some colorless shiny crystals of trans-Pt(py)₂Cl₂ were obtained after a long period and were characterized by X-ray diffraction.

(b) cis, cis, trans- [Pt{(p-BrC₆F₄)NCH₂CH₂NEt₂}Cl(py)(OH)₂].H₂O 2·H₂O_(gold): Metallic gold blocks. (0.160 g, 25% yield). M.P. = 192 °C (dec.). Elemental analysis calcd for C₁₇H₂₃Cl₁F₄N₃Pt₁Br₁O₃ (M = 702.02): C, 29.03%; H, 3.30%; N, 6.04%. Found: C, 29.20%; H, 3.17%; N, 6.08%.

*In solution, 2·H₂O_(gold) yielded 1H:

¹⁹F NMR, ¹H NMR, and MS data agree with those of 1H above.

3.4.2. Oxidation of 1 with 30% H₂O₂ in the Presence of LiCl

1 (0.325 g, 0.5 mmol) was dissolved in 15 mL CH₂Cl₂ and lithium chloride (0.021 g, 0.50 mmol), and a 30% solution of H₂O₂ (0.1 mL, 1 mmol) was added. The reaction mixture was stirred at room temperature for 7 days. The color of the solution changed from initial orange to deep red after 2 days and then to orange–red. MnO₂ (2 g) was added, the solution was stirred for 0.5 h, filtered, and MnO₂ was washed with acetone. After concentrating the filtrate, distilled water (6 mL) was added until it became cloudy. A deep-red-colored oil formed with a cloudy solution. The red oil was separated and dissolved in acetone, and crystallization from acetone/hexane at −10 °C produced deep-red-colored blocks of the platinum(IV) species, 2·H₂O_(red) (0.1637 g, yield = 50%). The cloudy solution was evaporated until dryness and then dissolved again in acetone; crystallization from acetone/hexane produced the mononuclear platinum(IV) species golden 2·H₂O in a 14% yield, identified by X-ray crystallography.

WARNING: Concentrated H₂O₂ in the acetone in presence of an acid catalyst can form the shock and friction-sensitive explosive triacetone triperoxide (TATP). MnO₂ was used to decompose any residual H₂O₂ catalytically before workup [77].

(a) cis, cis, trans- [Pt{(p-BrC₆F₄)NCH₂CH₂NEt₂}Cl(py)(OH)₂].H₂O 2·H₂O_(red): Metallic deep-red-colored blocks. (0.164 g, 50% yield). M.P. = 172 °C. (dec). Elemental analysis calcd for C₁₇H₂₃Br₁Cl₁F₄N₃Pt₁O₃ (M = 702.2): C, 29.01%; H, 3.29%; N, 5.97%. Found: C, 29.28%; H, 3.16%; N, 6.03%.

*Both Pt^II (1H) and Pt^IV 2 were observed in the solution in a 1:1 ratio.

¹⁹F NMR (CD₃(CO)₂): Pt^II, 1H: −148.16 [m, 2 F, F 2,6], −138.24 [m, 2 F, F 3,5]; Pt^IV, 2: −138.34 [m, 2 F, F 3,5], −140.64 [m, 2 F, F 2, 6].¹H NMR (CD₃(CO)₂): 1.23 [t, 6H, ³J_H,H 7 Hz, ⁴J_H,H 3Hz, NCH₂CH₃ (2)], 1.56 [t, 6H, ³J_H,H 7 Hz, ⁴J_H,H 3Hz, NCH₂CH₃ (1H)], 2.30 [m, 2H, CH₂NEt₂ (2)], 2.77 [m, 2H, NCH_AH_BCH₃ (1H)], 3.00 [m, 2H, NCH_AH_BCH_3, (2)], 3.13 [m, 2H, NCH_BH_ACH₃ (2)], 3.33 [m, 2H, CH₂N(p-BrC₆F₄) (2)], 3.43 [m, 2H, NCH_BH_ACH₃ (1H)], 3.75 [d with ¹⁹⁵Pt satellites, ³J_H,H 3.45 Hz, ³J_H,Pt 34 Hz, 1H, CHNEt₂ (1H)], 4.03 [m, 2H, not exchangeable with D₂O], 6.07 [m with ¹⁹⁵Pt satellites, ³J_H,Pt 50 Hz, 1H, CHN(p-BrC₆F₄) (1H)], 7.19 [m, 2H, H3,5 (py)], (1H)] 7.33 [t, ³J_H,H 7 Hz, 2H, H3,5 (py) (2)]], 7.74 [tt,³J_H,H 7.8 Hz, ⁴J_H,H 1Hz, 1H, H4 (py) (1H)], 7.86 [t, ³J_H,H 7.7 Hz, 1H, H4 (py) (2)], 8.42 [d with ¹⁹⁵Pt satellites, ³J_H,H 5.6 Hz, ³J_H,Pt 35 Hz, 2H, H2,6 (py) (1H)], 8.98 [d with Pt satellites, ³J_H,H 5.6 Hz, ³J_H,Pt 35 Hz, 2H, H 2,6 (py) (2)]. IR: 3549m, 3050w, 2964w, 2929w, 2871w, 2372w, 2108w, 1922w, 1704w, 1655s, 1620s, 1475s, 1451w, 1374m, 1287w, 1261w, 1223m, 1141s, 1061m, 1014w, 968s, 917m, 834w, 820s, 763s, 741s, 694s, 638w cm⁻¹. (ESI m/z (+ve) are given in SI).

3.4.3. Oxidation of 1 with Excess H₂O₂ in the Presence of Tetrabutylammonium Chloride (TBACl)

In a solution of 1 (0.314 g, 0.48 mmol) in 20 mL CH₂Cl₂, 0.127 g TBACl (0.48 mmol) in 2 mL of CH₂Cl₂ and (0.1 mL, 1.0 mmol) of 30% solution of H₂O₂ were added. The solution was heated at near refluxing temperature for 6 h and then stirred at room temperature for 4 days. The color of the solution changed from yellow to dark orange, but not deep red; MnO₂ was added at this stage. After filtration, the solution was concentrated to 5 mL, and a deep-red-colored oil formed when hexane (6 mL) was added. This mixture was cooled at −10 °C. Deep-red-colored blocks of the platinum(IV) complex 3 were collected by filtration and then air-dried. Some 2·H₂O_(gold) was collected from the filtrate with a few pale-yellow crystals of [NBu₄][PtCl₃(py)] characterized by single-crystal X-ray crystallography only.

(a) cis, cis, trans- [{Pt{(p-BrC₆F₄)NCH₂CH₂NEt₂}Cl(py)(OH)₂}₂].CH₂Cl₂, 3·0.5CH₂Cl₂: Metallic red-colored blocks. (0.152.9g, 49% crystal yield). Elemental analysis calcd for C₃₅H₄₄Cl₄F₈N₆Pt₂Br₂O₄ (M = 1456.56): C, 28.86%; H, 3.04%; N, 5.77%. Found: C, 29.05%; H, 3.13%; N, 5.65%.

*In the solution Pt^II (1H and 1Cl) and Pt^IV are present. The ratio of platinum(IV), 1H, and 1Cl is 1:2:0.7, respectively. Most of the NMR resonances of 1H and 1Cl are overlapped.

¹⁹F NMR (CD₃(CO)₂): 1H: −148.61 [m, 2 F, F 2, 6], −137.96 [m, 2 F, F 3,5]; 1Cl: −148.46 [m, 2 F, F 2, 6], −137.27 [m, 2 F, F 3,5]; Pt^IV,(3): −137.63 [m, 2 F, F 3,5], −142.25 [m, 2 F, F 2,6]. ¹H NMR (CD₃(CO)₂): 1.26 [t, 6H, ³J_H,H 7 Hz, ⁴J_H,H 3Hz, NCH₂CH_3, (3)], 1.61 [t, 6H, ³J_H,H 7 Hz, ⁴J_H,H 3Hz, NCH₂CH₃, (1H+1Cl)], 2.30 [m, 2H, CH₂NEt_2, (3)], 2.70 [m, 2H, NCH_AH_BCH₃, (1H+1Cl)], 3.00 [m, 2H, NCH_AH_BCH₃ and 2H, NCH_BH_ACH_3,(3)], 3.47 [m, 2H, NCH_BH_ACH₃ and 2H, CH₂N(p-BrC₆F₄), (3)], 3.68 [d with ¹⁹⁵Pt satellites, ³J_H,H 3.45 Hz, ³J_H,Pt 34 Hz, 1H, CHNEt₂, (1H)], 4.03 [m, 2H, not exchangeable with D₂O], 6.01 [m with ¹⁹⁵Pt satellites, ³J_H,Pt 50 Hz, 1H, CHN(p-BrC₆F₄), (1H)], 6.43 [t, 0.5 H, CHNEt₂, (1Cl)], 6.47 [t, 0.5 H, CHNEt₂, (1Cl)], 7.04 [m, 2H, H 3, 5 (py), (1H+1Cl)], 7.19 [t, ³J_H,H 7 Hz, 2H, H 3, 5 (py), (3)], 7.59 [tt,³J_H,H 7.8 Hz, ⁴J_H,H 1Hz, 1H, H4 (py), (1H+1Cl)], 7.72 [t, ³J_H,H 7.7 Hz, 1H, H4 (py), (3)], 8.39 [with ¹⁹⁵Pt satellites, ³J_H,H 5.6 Hz, ³J_H,Pt 35 Hz, 2H, H2,6 (py), (1H+1Cl)], 8.98 [d with ¹⁹⁵Pt satellites, ³J_H,H 5.6 Hz, ³J_H,Pt 35 Hz, 2H, H2,6 (py), (3)]. IR: 3652m, 3388br, 2963w, 2875w, 1923w, 1704w, 1655s, 1620s, 1475s, 1451w, 1374m, 1287w, 1261w, 1223m, 1141s, 1061m, 1014w, 968s, 917m, 834w, 820s, 763s, 741s, 694s, 638w cm⁻¹.

The data for 1H and 1Cl agree with that reported [47].

4. Conclusions

The oxidation of [Pt{(p-BrC₆F₄)NCH₂CH₂NEt₂}Cl(py)], 1 by limited H₂O₂ at room temperature produced dihydroxidoplatinum(IV) complexes [Pt^IV{(p-BrC₆F₄)NCH₂CH₂NEt₂}Cl(OH)₂(py)].H₂O, 2·H₂O, and [Pt^IV{(p-BrC₆F₄)NCH₂CH₂NEt₂}Cl(OH)₂(py)].0.5CH₂Cl₂, 3·0.5CH₂Cl₂, depending on the solvent system used. 2·H₂O was obtained as two different colored crystals, red and gold. Identical unit cells and X-ray powder diffraction patterns generated from their X-ray crystal structures verify that they have the same structure. As the initial preparation of 2·H₂O_(gold) was accompanied by the formation of the Pt^II complex with the oxidized ligand [Pt{(p-BrC₆F₄)NCH=CHNEt₂}Cl(py)] 1H, different conditions, including changes in solvents and the addition of chloride salts, were used to make the reactions more selective and produce higher yields in preparations of 2·H₂O_(red) and 3·0.5CH₂Cl₂. These Pt^IV compounds show reductive dehydration, that is, reduction of Pt^IV to Pt^II, accompanied by oxidation of the ligand over time in the solid state, as determined by X-ray powder diffraction and the separation of crystals, and in solution as evident from NMR and Mass spectra. The main product is 1H, but co-crystallized 1H/1Cl (1Cl = [Pt(p-BrC₆F₄)NCH=C(Cl)NEt₂}Cl(py)]) was obtained in some cases. This reveals that the Pt^IV complexes are precursors in the formation of the oxidized ligand species 1H and 1Cl. The rate of reductive dehydration is faster for 2·H₂O_(gold) than for 2·H₂O_(red). Vigorous oxidation conditions lead to complexes of the oxidized ligand [47], whereas the mild conditions currently used provide access to Pt^IV. As a wide range of Class 2 organoamidoplatinum(II) compounds are known [46], access to many derived Pt^IV compounds is possible, and some of which may have greater stability than 2·H₂O and 3·0.5CH₂Cl₂.