Platinum ammine coordination

Platinum (IV) Structures. The oxidation state of the platinum atom in platinum coordination compounds determines the steric configuration of the molecule platinum(II) structures are planar molecules, while platinum(IV) derivatives assume an octahedral shape. Though it was hoped that these differences could be used to circumvent platinum resistance, the two compounds developed in the clinic, iproplatin and ormaplatin, have not proven useful. In the case of the former, testing in Phase-II trials failed to reveal activity. In the case of ormaplatin, the platinum(IV) configuration is not maintained under biological conditions conversion to a platinum(II) metabolite occurs within minutes [14], A series of novel platinum(IV) and mixed ammine/amine derivatives being developed at the Institute for Cancer Research are described in this volume by Kelland. 

Ammonia forms a great variety of addition or coordination compounds (qv), also called ammoniates, ia analogy with hydrates. Thus CaCl2 bNH and CuSO TNH are comparable to CaCl2 6H20 and CuSO 4H20, respectively, and, when regarded as coordination compounds, are called ammines and written as complexes, eg, [Cu(NH2)4]S04. The solubiHty ia water of such compounds is often quite different from the solubiHty of the parent salts. For example, silver chloride, AgQ., is almost iasoluble ia water, whereas [Ag(NH2)2]Cl is readily soluble. Thus silver chloride dissolves ia aqueous ammonia. Similar reactions take place with other water iasoluble silver and copper salts. Many ammines can be obtained ia a crystalline form, particularly those of cobalt, chromium, and platinum. 

Louis-Nicolas Vauquelin (1763-1829) discovered the pink compound tetraamminepalladium(II) tetrachloropalladate(II), [Pd(NH3)4][PdCl4].14 This compound, which contains coordinated palladium in both the cation and the anion, is still known as Vauquelin s Salt after its discoverer. The corresponding platinum compound, [Pt(NH3)4][PtCl4], was discovered by Heinrich Gustav Magnus (1802—1870).15 It constitutes the first discovered platinum ammine and is known as Magnus ... 

The next major theory of metal ammines was proposed by Carl Ernst Claus (1796—1864). In 1854, Claus rejected the ammonium theory and suggested a return to Berzelius view of complexes as conjugated compounds. He compared the platinum ammines not with ammonium salts nor with ammonium hydroxide but with metal oxides. He designated the coordinated ammonia molecule as passive, in contrast to the active, alkaline state in the ammonium salts, where it can easily be detected and replaced by other bases . 

In general terms, both steric effects and electronic factors are expected to play a role in determinating the reactivity of square-planar platinum complexes. The presence of planar amine ligands in cis- or /ran.y-Pt(anion )2 complexes and their orientation with respect to the coordination plane, as well as their substituents, can reduce the rates of DNA binding or thio binding compared to aliphatic ammine and amine complexes. Especially, substituents close to the coordination site should be expected to slow down axial substitution reactions at Pt. As there is now little doubt that DNA platina-tion is a key event (or THE key event) in the mechanism of action of platinum anticancer drugs, attention to the process of formation of the major adduct (GG) as an intrastrand cross-link between N(7) atoms of two adjacent guanine (G) residues, will remain important. 

Here, there is no evidence that masking interferes in any way with these reactions. When the complexes of palladium (II) were examined for a similar reactivity, no complexes containing coordinated chloramines could be isolated (43, 44)- The reaction of ammines of platinum (IV) with bromine can be used to introduce bromoamine in the coordination sphere, but the products are somewhat less stable than those obtained with chlorine. The general nature of the processes is similar. One example of a bromination reaction established by Kukushkin is ... 

Another example is found in the various platinum (II) ammines which contain acetonitrile. One such is formed by reaction of [Pt(CH3CN)2Cl2] with ammonia. This gives a product with a formal composition corresponding to [Pt(CH3CN)2(Cl)2(NH3)2]. For many years this was considered to be an unusual complex in which platinum (II) was 6-coordinated. There are very few instances (if any) in which platinum (II) exhibits a coordination number other than 4. It has been shown by x-ray studies (67) that the product of this reaction is [Pt(acetamidine)2Cl2] and that the reaction may be written as shown at the top of the next page. Here, the coordination act accentuates the electron drift from the nitrile carbon atom and makes it more susceptible to attack by nucleophiles—in this case, ammonia. This kind of process had been essentially substantiated by chemical studies carried out previously, and the formation of... 

The dissociation constants for ionizing a proton from one or more coordinated ammine groups have been determined fairly accurately in a number of cases. A representative sampling is shown in Table I. The field strength of the platinum (II) ion is too small to render its ammine complexes sufficiently acidic for the dissociation constant to be determined in aqueous solution. Likewise, the complex ions [Co(NH3)6] , [Co(en)3] ", [Ir(en)3] ", and [Rh(en)3] " all have pKa values less than 10-12 T j0 fQj. [Rh(NH3) has been estimated to be approximately... 

Any detailed description of the mechanism of an octahedral substitution must also account for the stereochemical changes that accompany reaction. Werner recognized this and made use of it in his discussions of the stereochemistry of reactions of cobalt(III) complexes. The available experimental results can be explained on the basis of possible molecular rearrangements and some cautious predictions can even be made. The base hydrolysis of cobalt III)ammines appears to be unique in that it often occurs with rearrangement it also affords the few known examples of optical inversion. These results can be explained by formation of a 5-coordinated species with a trigonal bipyramidal structure. Optically active metal complexes racemize by either an intramolecular or an in-termolecular process. Substitution reactions of platinum metal complexes often occur with retention of configuration. 

Recent studies have shown that coordinated ammonia and amine ligands under basic conditions may effect nucleophilic attack at carbonyl centres in organic compounds, " These reactions occur due to formation of deprotonated amido species which can act as nucleophiles. For example, reaction of cobalt(III) and platinum(IV)ammines with ketones gives the corresponding Co and Pt imine complexes. A similar reaction between [Ru(NH3)6] and diones produces the corresponding Ru diimine (108). It has also been found that nitrilepentaammineruthenium(II)... 

Experiment 2 Molar Conductivity Measurements Considering Arrhenius s electrolytic theory of dissociation, Werner noted that evidence for his coordination theory may be obtained by determining the electrolytic conductivity of the metal complexes in solution. Werner and Jprgensen assumed that acid (ionic) residues bound directly to the metal would not dissociate and would thus behave as nonconductors, while those loosely held would be conductors. Molar conductivities of 0.1 molar percent aqueous solutions of some tetravalent platinum and trivalent cobalt ammines are given in Table 2.3. 

In cisplatin, the +2 oxidation state of the platinum atom forms four coordination bonds in a square plane. Each ammine supplies two electrons... 

---