Kinetics and Mechanism of Oxidation of L-Ascorbic Acid by Pt(IV)(aq) in Aqueous Hydrochloric Acid Medium

Abstract

Reduction of [PtCl₆]²⁻ by L-ascorbic acid (H₂ASc) in 0.1 M aqueous acid medium has been investigated spectrophotometrically under pseudo-first order condition at [PtCl₆]²⁻ = 0.005–0.007 mol dm⁻³, 0.05 ≤ [H₂ASc]/mol dm⁻³ ≤ 0.3, 298 K ≤ 𝑇 ≤ 308 K, [H⁺] = 0.14 mol dm⁻³, 𝐼=0.5 mol dm⁻³. The redox reaction follows the rate law: d[Pt(IV)]/dt = 𝑘[H₂ASc][Pt(IV)], where 𝑘 is the second-order rate constant and [H₂ASc] is the total concentration of ascorbic acid. Electron transfer from [H₂ASc] to Pt(IV) center leading to the release of two halide ions and formation of the reaction products, square planner Pt(II) halide complex, and dehydrated ascorbic acid is suggested. This redox reaction follows an outersphere mechanism as Pt(IV) complex is substituted inert. Activation parameters were calculated corresponding to rate of electron transfer reaction 𝑘. Activation parameters favor the electron transfer reaction.

1. Introduction

The redox reaction of L-ascorbic acid is of fundamental interest in chemistry, biochemistry, pharmacology, and several areas of medicine. It is used as a reducing agent with one or two electron reductants in chemical and biological systems [1–7]. Rate of reduction by ascorbic acid depends on nature of oxidant and pH of the medium. Different mechanisms have been proposed for the reaction between ascorbic acid and metal complexes [5–13].

In recent years there has been significant interest in the chemistry of square planar platinum (II) complex for remarkable anticancer properties [14–16]. Several thousand potentially biological active Pt(IV) complexes have been reported for anticancer properties [16].

We report here the interaction of ascorbic acid with Pt(IV)(aq). Ascorbic acid is a good biological reducing agent. Pt(IV)(aq) appeared attractive because these octahedral complexes are usually substitution inert and require reduction to Pt(II) species to act as potential anticancer drugs. The anticancer activity of Pt(IV) complexes is likely to be due to effective platinum (IV) transport into the cell followed by reduction to the more reactive platinum (II) compounds. The knowledge of the reactivity of Pt(IV) compounds towards the reduction by potential bioreductant like ascorbic acid may be important for understanding the mechanism of where antitumor activity as well as for designing new compounds with the least side effect. Chois et al. [17] reported that there is a correlation between the rate of the reduction and anticancer activity in a series of homologous Pt(IV) complex without going into the details of reaction mechanism. The present study was undertaken with the aim of extending the knowledge of the kinetics and thermodynamic parameters that characterized the reduction of Pt(IV) complex by ascorbic acid and clarifying the mechanism details using the model complex PtCl₆ ²⁻.

2. Experimental

2.1. Materials

All chemicals used were analaR grade. L-ascorbic acid (Merck) and sodium hexachloro-platinate (Merck) were used as received. Sodium hexachloroplatinate stock solution was prepared with 0.1 M HCL. Solutions of different concentrations were prepared by proper dilution of stock solution. Fresh solutions were used for kinetics measurements. Ionic strength was maintained with NaClO₄. All solutions were prepared in freshly prepared double distilled water using an all-glass distillation apparatus containing KMnO₄.

2.2. Kinetics

The kinetics of oxidation of L-ascorbic acid by sodium hexachloroplatinate in aqueous acid medium was studied spectrophotometrically under pseudo-first order conditions by keeping the concentration of ascorbic acid at least ten times in excess over Pt(IV) complex. The decrease of absorbance with time was monitored at 457 nm using conventional mixing technique in Systronic 2202 UV-VIS spectrophotometer equipped with a thermostatic bath for temperature control. The rate constant (𝑘_obs) was calculated from the slope of ln(𝐴_𝑡−𝐴_∞) versus 𝑡(s) plot from the relationship ln𝐴_𝑡−𝐴_∞=ln𝐴₀−𝐴_∞−𝑘_obs⋅𝑡, (1) where 𝐴₀, 𝐴_𝑡, 𝐴_∞ denote optical density of the reaction mixture at zero time, time 𝑡, and at infinity, respectively. 𝐴_∞ was measured after completion of the reaction mixture (after 24 hrs of mixing), were absorbance becomes almost constant. The correlation coefficients (𝑅²) of the plots used to determine 𝑘_obs were found to be 0.99 in most of the cases. All calculations were made on a PC using least square program.

2.3. Stoichiometry and Identification of Reaction Products

The stoichiometry for the reduction of [PtCl₆]²⁻ by ascorbic acid was determined by iodine titration method. Excess of ascorbic acid is allowed to react with fixed amount of [PtCl₆]²⁻. Titrating the ascorbic acid with iodine before and after the reaction indicates a 1 : 1 stoichiometry between Pt(IV) and L-ascorbic acid H₂ASc+PtCl₆⁻²⟶DHA+PtCl₄²⁻+2H⁺+2Cl⁻DHA=dehydroascorbate. (2) The product of redox reaction was identified as dehydroascorbate along with Pt(II). The product DHA was confirmed by ¹H NMR (see Figures 1(a) and 1(b)) and FTIR (see Figures 2(a) and 2(b)). Pt(II) was identified by UV-VIS spectra after 24 h (Figure 3(b)). Figure 1(a) shows peaks at δ4.78, 4.81, 10.68(enol), 16.77(enol) corresponding to four OH groups, δ5.0 for CH of furanone, δ3.93 corresponding to methine (CH) group in ascorbic acid, whereas Figure 1(b) shows peaks at δ4.81 and 4.78, peak at δ4.45, 4.11 corresponding to CH group in butyrolactone, and peak at δ3.90 corresponding to methine (CH). All peaks of ¹H NMR Spectra of Figure 1(b) corresponds to dehydroascorbic acid. IR spectra of Figure 2(b) show the presence of two OH groups due to the broad peaks at 3411.5 cm⁻¹ and 3526 cm⁻¹, whereas there are four OH groups in Figure 2(a) corresponding to peaks 3216 cm⁻¹, 3316 cm⁻¹, 3411.5 cm⁻¹, and 3527 cm⁻¹. In Figure 2(b), two peaks at 1675 cm⁻¹ corresponds to C–O, 1755 cm⁻¹ corresponds to C=O groups. All the IR spectra of Figure 2(b) corresponds to dehydroascorbic acid.

(a)

(b)

Figure 1 

(a) 1H NMR spectra of L-ascorbic acid. (b) 1H NMR spectra of dehydroascorbic acid.

(a)

(b)

Figure 2 

(a) IR spectra of ascorbic acid. (b) IR spectra of dehydroascorbic acid.

Figure 3 

(a) UV-VIS spectral scan of reaction mixture of L-ascorbic acid and sodium hexachloroplatinate, [H+] = 0.14 mol dm−3, 𝐼=0.5 mol dm−3 at 303 K. (1) (L-ascorbic acid) = 1.0×10−1 mol dm−3, (2) (sodium hexachloroplatinate) = 5.0×10−3 mol dm−3, (3) immediately after mixing, (4) after 15 minutes, curve (5–8) Δ𝑡=5 minutes. (b) Inset: spectra of the above reaction mixture after 24 hr.

3. Results and Discussion

L-ascorbic acid (H₂ASc) has two acidic protons (pK₁ = 4.04 and pK₂ = 11.34) [18] and is a strong reducing agent (𝐸⁰=0.390 V NHE) in aqueous solutions. The electron transfer reaction between PtCl₆ ²⁻ and L-ascorbic acid was investigated by changing (L-ascorbic acid) in the range 0.05 to 0.3 mol dm⁻³ at [H⁺] = 0.14 mol dm⁻³ and 𝐼=0.5 mol dm⁻³. Temperature variation was carried out in the range 293 K to 308 K. The UV-VIS spectral scan (see Figure 3(a)) of the reaction mixture was over the wavelength range 350≤𝜆(nm)≤600. Gradual decrease of absorbance with time was observed without the formation of isosbestic point and without shifting of 𝜆_max (maximum wavelength) indicating the fact that there is no formation of intermediate species. After a long interval of time (after 24 h), the peak at 457 nm disappeared completely and two new peaks (see Figure 3(b)) at 341 nm and 389 nm appeared corresponding to square plannar Pt(II) complex. In this redox process, octahedral Pt(IV) is reduced to square plannar Pt(II). Therefore this reaction is better classified as reductive elimination reaction [19]. IR and ¹H NMR spectra showed the formation of dehydroascorbate along with Pt(II). Similar product was reported by others [20–22] for the reaction between Pt(IV) and different reductants. Plots of pseudo-first order rate constant (𝑘_obs) versus [H₂ASc]_total were linear with zero intercept (see Figure 4). The fact indicates no reverse electron transfer reaction. The redox reaction follows the second order rate law given by (3) −𝑑[Pt(IV)]𝑑𝑡=𝑘_obs[Pt(IV)]=𝑘H₂ASc[Pt(IV)]_total𝑘_obs=𝑘[H₂ASc]_total, (3)(4) where 𝑘 denotes second order rate constant. We arrive at the reaction shown in (4) H₂ASc⇌HASc⁻+H⁺pk₁()=4.04PtIV+HASc−−−−^−𝑘−→Pt(II)+DHA (5) The second-order rate constant (𝑘) for reduction of Pt(IV) was calculated using (4) by plotting 𝑘_obs versus [H₂ASc] as collected in Table 1 at four different temperatures from 293 K to 308 K. 𝑘 data were used to calculate activation parameters as ΔH^‡=11.88±1.31 kJ mol⁻¹ and ΔS^‡=−51.66±4.39 Jk mol⁻¹ (see Table 2).

Table 1 

Pseudo-first order rate constant (𝑘_obs) data at different temperatures.

Table 2 

Calculation of second order rate constant 𝑘 and activation parameters.

Figure 4 

The plot of 𝑘obs versus [H2Asc] at temperature (1) 293 K, (2) 298 K, (3) 303 K, (4) 308 K.

They are close to the reported value for similar systems [18, 19, 23]. The value of activation parameters is favorable for electron transfer reaction.

It is concluded that the redox reaction follows an outer sphere mechanism with the fact that Pt(IV) octahedral complex is substitution inert. The mechanism for reduction of Pt(IV) halide complex by biological reductant involve an attack by the reductant as a halide coordinated trans to good leaving groups forming a halide bridge activated in Pt(IV) complex which facilitates such rapid reductive elimination reaction [20, 23] (see Scheme 1).

Scheme 1 

A concerted two-electron transfer from ascorbate to Pt(IV) center leading to the release of two halide ions and formation of reaction products, Pt(II), dehydroascorbic acid are observed.

Acknowledgment

The authors are thankful to HOD Chemistry, Utkal University, for providing research facilities and also thankful to Prof. P. Mohanty (Rtd) for his help.