Pt IV complexes

This yellow crystalline Pt(IV) complex decomposes slowly at 20° C with evolution of hydrogen and formation of tra r-Hl2SiPtI(PEt3)2. The proposed mechanism is shown in Eq. (63). 

Basolo et al., have found similar platinum(II)-catalysed chloride exchange reactions with other Pt(IV) complexes, including cis- and ran5-Pt(NH3)4Cl, Pt(NH3)5CP and rra J-Pt(NH3)3Cl3. These reactions proceed by the chloride bridge mechanism above and the apparent rate coefficients k P.mole . sec, 25 °C) for platinum exchange, which was concluded to occur via this pathway. 

The work with iodide (preceding sub-section) was extended to thiosulphate , and isosbestic points and second-order kinetics were again obtained with the various Pt(IV) complexes (Table 8). Two 8203 ions are consumed per mole of Pt(IV) reduced, suggesting tetrathionate to be the product of oxidation, viz. 

In different oxidation states metals build different geometries, e.g. Pt(II) is planar and Pt(IV) is octahedral, and it is only to be expected that Pt(IV) will exchange ligands less readily than Pt(II). In general this is so. Thus on this basis Pt(IV) complexes would be expected to be more slowly acting , than Pt(II). It is not possible to make generaliza-... 

In cytochrome-c [PtCU]2- binds to methionine 65 on the outside of the protein (64). Again the chloride is probably displaced as the reagent is applied in phosphate buffer. Dickerson and co-workers consider that the platinum is oxidized to a Pt(IV) complex but this seems unlikely as it does not occur in the reaction of [PtClJ2- with simple amino-acids. 

The kinetically-stabilized complexes of the cage ligands normally yield redox reagents free of the exchange problems often associated with simple complexes. Indeed, the redox chemistry of the complexes shows a number of unusual features for example, saturated cages of the type mentioned in Chapter 3 are able to stabilize rare (monomeric) octahedral Rh(n) species (d7 electronic configuration) (Harrowfield etal., 1983). In a further study, radiolytical or electrochemical reduction of the Pt(iv) complexes of particular cages has been demonstrated to yield transient complexes of platinum in the unusual 3+ oxidation state (Boucher et al., 1983). 

Fig. 3. Photoactivation of Pt(IV) complexes as a prodrug strategy for metallochemotherapeutics (a) general scheme of prodrug activation by photoreduction (b) photosubstitution and photoisomerization are competing photoreaction pathways, which can result in different reactive species upon reduction (c) an example of a photoactive platinum(IV) diazido complex developed in our lab.

The iodido-Pt(IV) complexes thus provided a proof-of-principle being photoactive, but the complexes still suffered from slow photoreactions and, importantly, limited stability in the dark especially against biological reducing agents such as glutathione, which results in undesired toxicity of the anticancer agents in the dark. 

Complex 6 exhibits an intense LMCT absorption band at 285 nm, which is shifted to longer wavelength and is more intense compared to the cis-isomer. Irradiation led to the disappearance of this band, indicating loss of azide. Photoactivation of the ira7zs-isomer initially resulted in the appearance of new Pt(IV) complexes (probably substitution of N3 for OH), as judged by 2D [1H, 15N] HSQC NMR, and after 60 min peaks for Pt(II) species appeared, including trans- [Pt(NH3)2(OH2)2]2+ (6r). 

SH-SY5Y neuroblastoma, cisplatin-sensitive A2780 and cispla-tin-resistant A2780cis human ovarian cancer cells was observed, but upon irradiation 7 strongly reduced the viability of the cancer cells (Fig. 8). In the A2780 cell line, the complex was 80x more toxic than cisplatin under identical conditions, and ca. 15 x more effective against the cisplatin-resistant A2780cis cell line (33). The trans diazido-Pt(IV) complex therefore has remarkable cytotoxic properties. 

There are now a number of quite stable Pt(IV) alkyl hydride complexes known and the synthesis and characterization of many of these complexes were covered in a 2001 review on platinum(IV) hydride chemistry (69). These six-coordinate Pt(IV) complexes have one feature in common a ligand set wherein none of the ligands can easily dissociate from the metal. Thus it would appear that prevention of access to a five-coordinate Pt(IV) species contributes to the stability of Pt(IV) alkyl hydrides. The availability of Pt(IV) alkyl hydrides has recently allowed detailed studies of C-H reductive elimination from Pt(IV) to be carried out. These studies, as described below, also provide important insight into the mechanism of oxidative addition of C-H bonds to Pt(II). 

The two different routes, direct reductive elimination and a preliminary ligand dissociation pathway, were similarly investigated for the Pt(IV) complexes, (PR3)2Cl2PtCH3(H) (R = Me, H) (132,133). A part of this study (dealing with one possible isomer) is summarized in Fig. 3. 

A transition state for the direct methane elimination from the Pt(IV) complex having two PH3 ligands was not observed. Phosphine loss occurred concomitantly with the reductive elimination. However, the authors were able to estimate an activation barrier of ca. 16 kcal/mol for direct elimination from this Pt(IV) complex (PH3)2Cl2PtCH3(H) using artificial restraints for the geometry optimization. This value is very close to the 16.5 kcal barrier obtained for reductive elimination... 

Further insight into the carbon-oxygen reductive elimination from Pt(IV) and the involvement of five-coordinate Pt(IV) intermediates has been provided recently. The first direct observation of high-yield C-0 reductive elimination from Pt(IV) was described and studied in detail (50,51). Carbon-oxygen coupling to form methyl carboxylates and methyl aryl ethers was observed upon thermolysis of the Pt(IV) complexes ( P2 )PtMe3(OR) ( P2 =bis(diphenylphosphino)ethane or o-bis(diphenyl-phosphino)benzene OR=carboxylate, aryl oxide). As shown in Scheme 47, competitive C-C reductive elimination to form ethane was also observed. 

Sensitive materials, such as certain metal salts or organometallic compounds used as catalyst precursors, may decompose during XPS analysis, particularly in equipment with standard X-ray sources. Heat and electrons generated by the source are usually responsible for damage to samples. In these cases the monochromatic XPS offers a solution. For example, reliable spectra of the organoplati-num complexes in Figs. 3.4 and 3.5 could only be obtained with a monochromatic source. Under the standard source the Pt(IV) complex indicated in Figs. 3.4 and 3.5 decomposed into the Pt(II) precursor and Cl2 gas. 

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