Square-planar Substitutions Research Articles

Hydrolysis of chlorido complexes of d8 metals: Old models, new facts

The discovery of the antitumor activity of cisplatin in 1969 has accelerated research in platinum chemistry. In particular, cisplatin hydrolysis, the rate-determining process activating the drug for reaction with DNA, was extensively studied and discussions of the mechanism of square-planar substitutions were rekindled. One intriguing aspect of cisplatin hydrolysis is the fact that the rates of the two aquation steps are almost identical, in spite of the charge-separation effect which would be expected to slow down the second step. This result is analyzed here in the context of the more general observation made by Martin et al. that aquation of chlorido-ammine complexes of Pt(II) proceeds at similar rates, independently of complex charge. Ancient hypotheses put forward to explain this observation are confronted with recent data. The discussion is extended to aquation of chlorido-am(m)ine complexes of Pd(II) and Au(III), and to chloride substitutions by thiourea and pyridine. It is shown that the charge independence is not limited to chloride substitution by water. This new correlation of published data invalidates our recent hypothesis according to which non-conventional hydrogen bonding from the attacking water molecule to the Pt(II) center as acceptor counterbalances the charge separation effect. Recent data also show that the frequently used kinetic model for square-planar substitutions featuring a metastable five-coordinate intermediate does not apply to complexes involving only simple σ-donating ligands such as amines, water, or chloride. By inference, the Martin-Basolo model, explaining the charge-independence of aquation rate constants with the mutual compensation between charge separation and charge neutralization in the transition state, remains the only model compatible with available data.

Kinetic Studies on Interaction of Platinum(II) Complexes with an ‘S’ Containing Ligand in Aqueous Medium

The kinetics of the substitution reactions of [Pt(dach)(H2O)2]2+ and [Pt(en)(H2O)2]2+ (where ‘dach’ and ‘en’ are cis-1,2-diaminocyclohexane and ethylenediamine, respectively) with excess N,N′-diethylthiourea have been studied in aqueous solution by UV–Vis spectrophotometry. The effect of different N–N spectator ligands on the reactivity of platinum(II) complexes was investigated by studying the water lability of the reactant complexes. The kinetic study has been substantiated by product isolation, IR, NMR and ESI-MS spectral analysis and DFT calculations. The reactions follow normal square-planar substitution mainly in an associative way. Rate parameters have been evaluated under different conditions. The substitution rates of the complexes studied can be tuned through the nature of the N–N chelates, which is important in the development of new active compounds for cancer therapy.

The replacement of five-membered N-donor heterocycles from aminotrichlorogold(III) complexes. A comparison with pyridines

The kinetics of the process AuCl3(nu) + Cl−→ AuCl 4 − + nu (nu = one of a number of five-membered N-donor heterocycles covering a wide range of basicity, namely: oxazole, 2,4,5-trimethyloxazole, thiazole, 5-methylthiazole, 4-methylthiazole, 4,5-dimethylthiazole, 2,4-dimethylthiazole, 2,4,5-trimethylthiazole, imidazole and 2-methylimidazole) have been studied in methanol at 25 °C. The reactions follow the usual two-term rate law, rate = (k 1 + k 2[Cl−])[complex], observed in a square-planar substitution associative-mechanism. The second-order rate constants, k 2, indicate that the discriminating ability of Au(III) in these complexes is good and markedly influenced by the nature of the leaving group. A linear-free-energy relationship, logk 2 = 0.53pK a + constant, is observed between the rate constant and the basicity of the leaving group for its replacement by chloride. The results are compared with data from the literature regarding a series of complexes of the type AuCl3(py) (py = one of a number of pyridines) reacting with the Cl− anion under the same experimental conditions. The reactivity depends not only upon ligand basicity but also upon the nature of the ligand in the order: pyridines> five-membered heterocycles. Steric factor due to the presence of a single methyl group ortho to the sp2 nitrogen atom in the ring has no influence on the rate of substitution while, surprisingly, when there are two ortho methyl groups a remarkable steric retardation effect is observable. The results are discussed in terms of reaction-profile in the associative-substitution reaction and bonding interactions in the ground and transition states.

Reactivity studies of trans-[PtClMe(SMe 2) 2] towards anionic and neutral ligand substitution processes

Reaction of trans-[PtClMe(SMe 2) 2] with the mono anionic ligands azide, bromide, cyanide, iodide and thiocyanate result in substitution of the chloro ligand as the first step. In contrast the neutral ligands pyridine, 4-Me-pyridine and thiourea substitute a SMe 2 ligand in the first step as confirmed by 1H NMR spectroscopy and the kinetic data. Detailed kinetic studies were performed in methanol as solvent by use of conventional stopped-flow spectrophotometry. All processes follow the usual two-term rate law for square-planar substitutions, k obs = k 1 + k 2[Y] (where k 1 = k MeOH[MeOH]), with k 1 = 0.088 ± 0.004 s −1 and k 2 = 1.18 ± 0.13, 3.8 ± 0.3, 17.8 ± 1.3, 34.9 ± 1.4, 75.3 ± 1.1 mol −1 dm 3 s −1 for Y − = N 3, Br, CN, I and SCN respectively at 298 K. The reactions with the neutral ligands proceed without an appreciable intercept with k 2 = 5.1 ± 0.3, 15.3 ± 1.8 and 195 ± 3 mol −1 dm 3 s −1 for Y = pyridine, 4-Me-pyridine and thiourea, respectively, at 298 K. Activation parameters for MeOH, N 3 - , Br −, CN −, I −, SCN −, and Tu are Δ H ≠ = 47.1 ± 1.6, 49.8 ± 0.6, 39 ± 3, 32 ± 8, 39 ± 5, 34 ± 4 and 31 ± 3 kJ mol −1 and Δ S ≠ = −107 ± 5, −77 ± 2, −104 ± 9,−113 ± 28, −85 ± 18, −94 ± 14 and −97 ± 10 J K −1 mol −1, respectively. Recalculation of k 1 to second-order units gives the following sequence of nucleophilicity: MeOH < N 3 - < Br - ∼ py < 4 - Me - py ∼ CN - < I - < SCN - < Tu (1:13:42:57:170:200:390:840:2170) at 298 K. Variation of the leaving group in the reaction between trans-[PtXMe(SMe 2) 2] and SCN − follows the same rate law as stated above with k 2 = 75.3 ± 1.1, 236 ± 4 and 442 ± 5 mol −1 dm 3 s −1 for X − = Cl, I and N 3, respectively, at 298 K. The corresponding activation parameters were determined as Δ H ≠ = 34 ± 4, 32 ± 2 and 39.3 ± 1.7 kJ mol −1 and Δ S ≠ = −94 ± 14, −86 ± 8 and −68 ± 6 J K −1 mol −1. All the kinetic measurements indicate the usual associate mode of activation for square planar substitution reactions as supported by large negative entropies of activation, a significant dependence of the reaction rate on different entering nucleophiles and a linear free energy relationship.

Reactivity of neutral nitrogen donors in square-planar d 8 metal complexes: The system chloro(2,2′:6′,2″-terpyridine)platinum(II) cation with five-membered N-donor heterocycles in methanol

The kinetics of the forward and reverse steps of the reaction [Pt(terpy)Cl] + + nu ⇌ [Pt(terpy)(nu)] 2+ + Cl − (terpy = 2,2′:6′,2″-terpyridine, nu = one of a number of thiazoles, oxazole, isoxazole, imidazole, pyrazole and 3,5-dimethylpyrazole, covering a wide range of basicities) have been studied in methanol at 25 °C. Both forward and reverse reactions obey the usual two-term rate law observed in square-planar substitution. The second-order rate constants for the forward reactions, k 2 f , show a slight dependence upon the basicity of the entering nu, while the steric hindrance due to the presence of one methyl group in the α position to the nitrogen markedly decreases the reactivity. The second-order rate constants for the reverse reactions, k 2 r , are very sensitive to the nature of the leaving group and a plot of log k 2 r against the p K a of the conjugate acids of the unhindered five-membered N-donors is linear with a slope of −0.51. The results are compared with data from the literature regarding a series of pyridines reacting with the [Pt(terpy)Cl] + cation under the same experimental conditions. Both in the forward and in the reverse reaction, the reactivity depends not only upon the ligand basicity but also upon the nature of the nucleophile in the order: (thiazoles, oxazole, isoxazole, imidazole, pyrazoles) > pyridines for the entry of N-donors and on the contrary for the displacement by Cl −. Steric retardation, due to the presence of a methyl group in the α position to the nitrogen, is remarkably lower for five-membered N-donors if compared to pyridines both in the forward and in the reverse reaction.

Kinetics and mechanisms of substitution and ring opening of platinum(II) complexes with N-heterocyclic bases

The kinetics of the substitution reactions of [Pt(dipic tr)(H 2O)] and [Pt(dipic tr)(L)] where H 2dipic=2,6-pyridinedicarboxylic acid with the subscript ( tr) denoting its tridendate mode of bonding and L=imidazole, benzimidazole and pyrazole with excess L have been studied in dimethylformamide solution by UV–Vis spectrophotometry. The reactions show mono- and bi-phasic features depending on the Pt II substrate. The tridentate dipic ligand transforms to a bidentate one allowing the entry of the second molecule of the N-bases in the course of the reaction. The kinetic study has been substantiated by product isolation, IR and NMR spectral analysis. The reactions follow normal square-planar substitution mainly in an associative way. Rate parameters have been evaluated under different conditions.

The reactivity of neutral nitrogen donors in planar d8 metal complexes. Part 3. The system chloro(2,2′ : 6′,2″-terpyridine)platinum(II) cation with pyridines and ammonia in methanol. Effect of basicity, π-acceptor capacity and steric hindrance

The kinetics of the forward and reverse steps of the process [Pt(NNN)Cl] + + am ⇌ [Pt(NNN)(am)] 2+ + Cl − (NNN = 2,2′ : 6′,2″-terpyridine; am = one of a number of pyridines and NH 3 covering a wide range of basicity) have been studied in methanol at 25°C. Both forward and reverse reactions obey the usual two-term rate law observed in square-planar substitution. The reactivity and the ability of the chloro-complex to discriminate among the nucleophiles, as well as the sensitivity of the rate of the chloro entry upon the nature of the displaced base and the steric factors in both the forward and reverse processes are discussed in terms of intimate mechanism and compared with data for a number of different Pt II systems. The equilibrium constants for the reactions have been determined from the ratio of the rate constants.

Reactivity of neutral nitrogen donors in planar d8metal complexes. Part 2. The system [2,6-bis(methylsulfanyl-methyl)pyridine]chloroplatinum(II) with pyridines and amines in methanol. Effect of basicity, π-acceptor capacity and steric hindrance

The kinetics of the forward and reverse steps of the process [Pt(C5H3N(CH2SMe)2}Cl]++ am ⇌[Pt{C5H3N(CH2SMe)2}(am)]2++ Cl–[C5H3N(CH2SMe)2= 2,6-bis(methylsulfanylmethyl)pyridine; am = one of a number of pyridines and some heterocyclic and aromatic amines covering a wide range of basicity] has been studied in methanol at 25°C. Both forward and reverse reactions obey the usual two-term rate law observed in square-planar substitution. The second-order rate constants for the forward reactions, k2f, show only a slight dependence upon the basicity of the entering am, and steric hindrance markedly decreases the reactivity. The second-order rate constants for the reverse reactions, k2r, are very sensitive to the nature of the leaving group and plots of log k2r against the pKa, of the conjugate acids of unhindered pyridines with different π systems are linear with a slope of –0.45. A comparison among the different pyridines and sp3 nitrogen donor bases indicates an appreciable π contribution to the stability of the Pt–N(sp2) bond. The equilibrium constants for the reactions have been determined in a number of cases from the ratio of the rate constants and a plot of log K against the pKa is linear with a slope of 0.66. The results are compared with data from the literature.

Reactivity of neutral nitrogen donors in planar d8 metal complexes. Part 1. The system [1,2-bis(phenylsulfanyl)-ethane]dichloroplatinum(II) with pyridines in methanol. Effect of basicity and steric hindrance

The kinetics of the forward and reverse steps of the process [Pt(PhSCH2CH2SPh)Cl2]+ am ⇌[Pt(PhSCH2CH2SPh)(am)Cl]++ Cl–(am = one of a number of pyridines and other heterocyclic nitrogen bases covering a wide range of basicity) has been studied in methanol at 25 °C. Both forward and reverse reactions obey the usual two-term rate law observed in square-planar substitution. The second-order rate constants for the forward reactions, k2f, show only a slight dependence upon the nature of the entering pyridine, and steric hindrance due to the presence of one or two methyl groups in α position to the nitrogen markedly decreases the reactivity. The first- and second-order rate constants for the reverse reaction are very sensitive to the basicity of the leaving group and a plot of log k2r against the pKa, of the conjugate acids of unhindered pyridines is linear with a slope of –0.56. Steric retardation for monosubstituted α-methylpyridines is relatively small. The equilibrium constants for these reactions have been determined from the ratio of the rate constants and a plot of log K against the pKa. of the unhindered pyridines is linear with a slope of 0.58. The results are compared with data from the literature and discussed in terms of the reaction profile.

Solvent paths for square-planar substitutions. Part 2. Reactions between aqua chloroplatinates(II) and ethene

The kinetics for the reactions between the complexes PtCl n(H 2O) 2−n 4−n, n = 0,1,2,3,4, (including cis- and trans-isomers for n = 2) and ethene have been studied. In the case of trans-PtCl 2(H 2O) 2, product analysis shows that both the chloride ligand and the aqua ligand are substituted by ethene in two parallel paths, differing in rate by a factor of only 1.5. The experiments show that ethene, and probably olefins in general, are inefficient entering ligands, similar to dimethyl sulphoxide. Steric reasons might be responsible. Changes in relative cis- and trans-effects are compatible with an associative mechanism. The aqua complexes are sufficiently reactive with ethene to be steady-state intermediates in associative solvent paths. Reactions models and rate laws for associative square-planar substitutions are discussed, with special reference to reported non-reactivity of solvento intermediates in some previously studied systems.

The solvent path in square-planar substitutions. kinetics and mechanism for reactions of tetrachloroplatinate(II) andaquachloroplatinates(II) with halides, thiocyanate and dimethyl sulfoxide

The kinetics for the reactions between the six complexes PtCln(H2O)−2n4−n n = 0,1,2,3,4 (including cis- and trans-isomers for n = 2) and the entering ligands Y = Cl−, Br−, I−, SCN−, and DMSO have been studied. The experiments with PtCl2−4 and trans- PtCl2(H2O)2 give the usual two-term rate constant kexp = k1 + k2[Y], when no extra chloride has been added to the solutions. The parameter k1 can be iden- tified as the acid hydrolysis rate constant for PtCl2−4 and trans-PtCl2(H2O)2, respectively. It is shown that both PtCl3H2O− and PtCl(H2O+3 are sufficiently reactive for all Y to be the intermediates in the k1- paths of these two reactions. An associative process with the solvent is therefore probable.

The unusual substitution behaviour of terpyridylplatnium(II) complexes

The kinetics of reaction of Pt(terpy)Cl+ with various ligands were measured. The complex is approximately 103–104 times more reactive than its dien analogue. The relative reactivity order observed for the ligands studied from that expected on the basis of their n°Pt values. These data are discussed in the light of the ability of aromatic ligands to enter into π-bonding with the metal, and of the biphilic properties of the incoming groups involved. Although each ligand obeys the usual two-term rate law common for square-planar substitution, kobs = k1 + k2[Y], the value of k1 is not common to all the incoming groups. A mechanism is proposed to account for this departure from “classical” behaviour.

Kinetics of the monosubstitution of chloride by thiocyanate, bromide, and iodide in tetrachloroaurate(III) ions in aqueous solution: the spectroscopic detection of reaction intermediates, and catalysis by chloride ions

Kinetic and spectroscopic evidence is presented for the occurrence of intermediates in monosubstitution of [AuCl4]– ions by thiocyanate and bromide ions in aqueous solution. The intermediate(s) isformed in a pre-equilibrium and then undergoes unimolecular decomposition to the products. The rates of both stages of the reaction have been studied using stopped-flow spectrophotometry; both stages exhibit a mild catalysis by added chloride ions. The monosubstitution of [AuCl4]– by iodide ions displays no evidence for an intermediate but the overall reaction is again catalysed by chloride ions, here powerfully. Possible reaction mechanisms are discussed in the light of previous conclusions about the mechanisms of similar square-planar substitutions.

ChemInform Abstract: KINETICS AND MECHANISM OF SUBSTITUTION ON SQUARE‐PLANAR PALLADIUM(II) COMPLEXES IN MIXED AQUEOUS SOLVENTS

The kinetics of halide replacement in the complexes[Pd(iea)X]X and [Pd(ieda)X]X [iea = iminobis(ethyleneamine) and ieda = iminobis(ethylenediethylamine); X = Cl- or l-] have been measured in a variety of mixed aqueous organic solvents. The rate expression is Rate =k1+K2[X–]. Plots of log k1 and log k2 against the Grunwald–Winstein Y values are linear with gradients of between 0.33 and 0.63. The results are interpreted in terms of a similar associative mechanism for each reaction, involving appreciable Pd–X bond cleavage in the rate-determining transition state. The utility of log k against Y plots and other linear free-energy relations (such as rate–equilibrium correlations) in elucidating the intimate mechanisms of square-planar substitutions are discussed.

Kinetics and mechanism of substitution on square-planar palladium(II) complexes in mixed aqueous solvents

The kinetics of halide replacement in the complexes[Pd(iea)X]X and [Pd(ieda)X]X [iea = iminobis(ethyleneamine) and ieda = iminobis(ethylenediethylamine); X = Cl- or l-] have been measured in a variety of mixed aqueous organic solvents. The rate expression is Rate =k1+K2[X–]. Plots of log k1 and log k2 against the Grunwald–Winstein Y values are linear with gradients of between 0.33 and 0.63. The results are interpreted in terms of a similar associative mechanism for each reaction, involving appreciable Pd–X bond cleavage in the rate-determining transition state. The utility of log k against Y plots and other linear free-energy relations (such as rate–equilibrium correlations) in elucidating the intimate mechanisms of square-planar substitutions are discussed.

Nucleophilic square-planar substitutions — VI. Substitutions of bromodiethylene triamineplatinum(II) complex by primary aliphatic amines

Nucleophilic square-planar substitutions — VI. Substitutions of bromodiethylene triamineplatinum(II) complex by primary aliphatic amines

Nucleophilic square-planar substitutions. IV. The reaction of thioethers with halogenodiethylenetriamineplatinum(II) cations in aqueous ethanol

The second-order rate constants for the direct replacement of halogens in halogenodiethylenetriamineplatinum(II) cations by dimethyl sulphide have been determined and the activation parameters calculated. The relative ease of replacement of the outgoing groups are found to follow the order Cl⪡Br⪡I, a pattern which depends entirely on activation entropy. The results are discussed in terms of an associative mechanism involving the formation of a five-coordinated intermediate, with second transition state rate-limiting. For the bromo complex, the kinetic studies are extended to di-butyl sulphides and the results provide further support for the associative mechanism.

Nucleophilic square-planar substitutions. Part III. The application of the generalisation of group mobility factors to substitutions of halogenodiethylenetriamineplatinum(II) complexes in aqueous solutions

The kinetics for the direct replacement of halogens in halogenodiethylenetriamineplatinum(II) cations by pyridine have been determined over a range of temperatures. The relative mobilities of the outgoing groups are compared with the corresponding data for organic compounds. These reactions are mechanistically more similar to aromatic than to aliphatic substitutions. The kinetic results are discussed and an attempt is made to interpret them in terms of the electronegativity of the halogens, which facilitates bond formation with the incoming nucleophile in an associative mechanism. By analogy with aromatic substitutions, the rate order is expected to depend entirely on activation energy, and in this way, square-planar substitutions differ from octahedral substitutions where the entropy of activation exerts a significant influence on rate.

Nucleophilic square-planar substitutions. II. Substitutions of the bromodiethylenetriamineplatinum(II) complex by pyridine derivatives

The second-order rate constants for the replacement of coordinated bromide from bromodiethylenetriamineplatinum(11) bromide by a series of pyridine derivatives have been determined over a range of temperatures and the Arrhenius parameters calculated. With the exception of the cyano derivative, replacements of 2-substituted pyridines are considerably slower than those by the corresponding 3- or 4-substituted nucleophiles. This is explicable on the basis of the associative mechanism by invoking steric effects of the substituents. The activation energies for the reaction depend mainly on a combination of two factors, steric and inductive, with the former predominating. These decrease as the position of a given substituent in the nucleophile changes in the order 2, 3, and 4. The inductive effects of the various substituents may be demonstrated with the 4-substituted pyridines, which are sterically similar to the unsubstituted pyridine itself. The methyl substitutent has a small effect, while the cyano and chloro substituents lead to significant increases in activation energy.

Nucleophilic square-planar substitutions. Part I. Ionic-strength effects on the substitution of chloro- and bromo-diethylenetriamineplatinum(II) complexes by iodide ions

The kinetics for the replacement by iodide ions of co-ordinated halogen from chloro- and bromo-diethylenetriamineplatinum(II) cations have been investigated at 25° over a range of concentrations of the nucleophile. At constant ionic strength, the plots of the pseudo first-order rate constants against iodide ion concentration are straight lines which pass virtually through the origin. The apparently large intercepts obtained from data previously reported by Gray are due to the fact that the ionic strength of the medium was not held constant, rather than to a relatively rapid background solvolysis. The second-order rate constants, k2, calculated from the linear plots, obey the equation log k2=A+Bµ½, where A and B are constants at constant temperature, and µ is the ionic strength of the solution.