Kinetics and mechanism of the substitution of tetrachloroaurate(III) by L-Glutamine

Shen Shigang, Hao Zenghua, Shi Hongmei, Song Changying
(College of Chemistry and Environmental Science, Hebei Uinversity, Baoding 071002, Hebei Province, China)

Abstract The kinetics of substitution of tetrachloroaurate (III) by L-Glutamine has been spectrophotometrically studied in acid medium. Under pseudo-first-order conditions ([R]0>>[Au(III)]0) is first order in [Au(III)]0 and a fractional order in [R]0. Both H+ and Cl ions retard the reaction. The kobs is independent of ionic strength ¦Ì. A substitution reaction mechanism is proposed, the reaction of Au (III) with R includes two parts, the first phase is a preequilibration, which takes place between the cationic and the zwitterion species of R with AuCl4, and forms an intermediate complex AuCl3RH. The second phase this unstable intermediate AuCl3RH slowly decomposes to give a half-cyclic Au (III) complex that appears to be unreactive, it be conformed as the rate determining reaction. The rate limiting constant k, and its thermodynamic parameters are also reported (which: the L-Glutamine= R, the cationic of L-Glutamine = RH2+ and the zwitterion of L-Glutamine = RH).
Keywords Tetrachloroaurate (III); L-Glutamine; Substitution; Kinetics and mechanism

    The chemistry of gold complexes is important from a biological and medicinal point of view Au (III) is isoelectronic and isostructural to platinum (II) [1, 2], therefore, its complexes have long been evaluated as potential anticancer agents due to the structural similarity to platinum-based drugs [3]. The hydrolysis of AuCl4 has been studied by several investigators and the existence of different Au (III) species has been suggested [4, 5]. Au (III) is a low spin d8 centre which forms square-planar complexes. With a lowly acid medium, Au (III) as an oxidant is of interest as it may behave either as a one- or two-electron transfer oxidant. But the high acid medium of the Au (III) complexes limits the number of nucleophiles can be investigated without complications from substitution reaction [4-6]. However, chloride complexes of Au (III) are thermodynamically stable in aqueous solutions and also labile [7-12]. It is therefore ideal candidates for a fundamental study involving kinetic [13-17]. The kinetics of the oxidation of Glycolaldehyde [8], Sugars [18], O-phenylenediamine [19], Oxalic acid [20], Hydrazoic [21] by Au (III) have already been reported in recent times.
    The present investigation on the substitution of Au (III) by L-Glutamine in perchloric acid medium was carried out in order to throw light upon the reactivity of L-Glutamine towards Au (III), Since AuCl4 gets partially hydrolysed [3-5] and it is difficult to keep [H+] constant when change the substrate concentrations at lower acidities, but the reactions are too slow to be studied in a highly acidic medium ([H+]>0.1mol dm-3), the kinetics of the reaction have been monitored in perchloric acid medium where the reaction occurs at ameasurable rate. Furthermore, the result is very interesting, because it is very different from with the mechanism as reported for several analogous systems [15-17]. The meaning is that the reaction of Au (III) with L-Glutamine is a substitution reaction which is dominant from the tracked datas, furthermore, no kinetic data are available in the literature on the substitution of amino acids by Au (III).
    2.1 Chemicals and solutions
    L-Glutamine was obtained from guo yao ji tuan Chemical Reagent Company. NaAuCl4 was purchased from Alfa Aesar. NaCl, NaClO4 and HClO4 were obtained either from Beijing Chemical Reagent Company (Beijing, China) or from Tianjin Chemical Reagent (Tianjin, China). All the above reagents were of either analytical grade or reagent grade and used as received. All solutions were prepared with doubly distilled water.
    2.2. Spectral and kinetic measurements
    Electronic spectral recordings and kinetic measurements were performed on a UV¨Cvisible spectrophotometer (TU-1901, Beijing Puxi, Inc.,Beijing, People’s Republic of China), and quartz cells with a 1.00 cm optical pathlength were used. The spectrophotometer was equipped with a cell compartment which was thermostated by a thermostat (BG-chiller E10, Baijing Biotect Inc., Beijing Beijing, China). Temperature of solutions in cells can be controlled to ¡À0.2¡æ when cells are put in the compartment. Two reaction solutions, one containing known concentrations of NaAuCl4¡¢HClO4¡¢NaCl, and the other containing desired concentrations of R and NaClO4, were thermostated for at least 20 min before mixing each other. The function of NaClO4 was to adjust the ionic strength (m) in the reaction solutions. The HClO4 was used to adjust the pH. Pseudo first-order reaction conditions were fulfilled by making [R]0 ¡Ý 100[Au(III)]0. Kinetic traces were followed at 313 nm by the same spectrophotometer mentioned above. Time-resolved spectra for a typical reaction between Au (III) and R are displayed in (Fig. 1); no apparent shift of the absorption peak around 313 nm indicated that concentrations of any reaction intermediates in the reaction course could be very low.

Fig. 1 Time-resolved spectra for reaction between Au (III) and R at 298.2 K. [Au (III)]0=1.00¡Á10-4mol·L-1, [R]0 =5.00¡Á10-2mol·L-1, [H+]=2.00¡Á10-3mol·L-1, [Cl]=2.60¡Á10-2mol·L-1 and m=0.30 mol·L-1.

2.3. Product analysis
The reaction mixture (concentration of each reactant being twenty times that under kinetic condition) was allowed to stand for two hours, and then distilled, the distillate being collected in a closed container. Then the distillate was treated with a small amount of gallic acid and a few drops of conc H2SO4 and heated on a water bath, these is mostly nothing appeared [22], indicating no presence of RCHO.
In another experiment, The reaction mixture containing 25% (V/V) acrylonitrile was allowed to stand for two hours under the protection of nitrogen gas, these is mostly nothing appeared, No polymerization of acrylonitrile was observed, showed that there is no free radical intermediate appeared.

    3.1 Kinetic
    3.1.1 Reaction orders

    The rates were measured under pseudo first-order conditions ([R]0 >> 100 [Au (III) ]0) at constant ionic strength (¦Ì=0.3mol L-1) by monitoring the changes at 313 nm. Plots of Ln[£¨A0– A¡Þ£©/£¨At-A¡Þ£©]versus reaction time were linear and pass through the origin under these conditions (Fig. 2), suggesting that the reaction is first order in [Au(III)]0, where At and A¡Þ refer to absorbance at time t and infinity, respectively (Eqn. 1).
    Pseudo-first-order rate constants kobs were calculated from slopes of these linear. Values of kobs, representing an average of three repeated runs, are generally reproducible to ¡À5% within standard deviations.

    Fig. 2 Ln [(A0– A¡Þ)/ (At-A¡Þ)]vs reaction time t at different temperatures. [Au (III)]0=1.00¡Á10-4mol·L-1, [R]0 =5.00¡Á10-2mol·L-1, [H+]=2.00¡Á10-3mol·L-1, [Cl]=2.60¡Á10-2mol·L-1 and ¦Ì=0.30 mol·L-1.

3.1.2 Rate dependence on [R]0
Through the variation in the initial concentration of R at constant [Au (III)]0, [H+], [Cl] and ¦Ì, respectively, it can be known that kobs increased with the increasing of [R]0, and the plots kobs -1 vs [R]0-1 are linear with positive intercepts (Fig. 3). This indicated a rapid equilibrium was formed between the Au (III) and R[20, 21] at pH =2.70.

Fig. 3 The plots of kobs-1 vs [R]0-1 at different temperatures. [Au (III)]0=1.00¡Á10-4mol·L-1, [H+]=2.00¡Á10-3mol·L-1, [Cl]=2.60¡Á10-2mol·L-1 and ¦Ì=0.30 mol·L-1.

3.1.3 Rate dependence on [H+]
The rate of the reaction was studied at different pH values (1.90-3.00) using perchloric acid .The value of kobs was found to increase with an increase in pH. The plot of kobs-1 vs [H+] gave a straight line with a positive slope and positive intercept. (Fig. 4).

Fig. 4 The plots of 1/kobs vs [H+] at different temperatures. [Au (III)]0=1.00¡Á10-4mol·L-1, [R]0 =5.00¡Á10-2 mol·L-1, [Cl]=2.60¡Á10-2 mol·L-1 and ¦Ì=0.30 mol·L-1.

3.1.4 Rate dependence on [Cl]
The reaction was studied at different temperatures at different [Cl] varied by the addition of NaCl. The value of kobs was found to decrease with an increase of [Cl]. The plot of kobs-1 vs [Cl] is linear with a positive slope and positive intercept (Fig. 5).

Fig. 5 The plots of kobs-1 vs [Cl] at different temperatures. [Au (III)]0=1.00¡Á10-4mol·L-1, [R]0=5.00¡Á10-2mol·L-1, [H+]=2.00¡Á10-3mol·L-1 and ¦Ì=0.30mol·L-1.

3.1.4 Rate dependence on ionic strength m
The effect of ionic strength was studied by varying the NaClO4 concentration in the reaction medium. The ionic strength ¦Ì of the reaction medium was varied from 0.10 to 0.53 M. It was found that varied ionic strength did not show any effect on the rate of reaction (Table 1).

Table 1. The effect of the ionic strength on the rate of the reaction at 298.2 K

ClO4/(mol·L-1) 0.10 0.20 0.30 0.40 0.53
m/ (mol·L-1) 0.23 0.33 0.43 0.53 0.63
103kobs (s) 2.09 2.09 2.07 2.19 2.16

[Au (III)]0=1.00¡Á10-4mol·L-1,[R]0=5.00¡Á10-2mol·L-1,[H+]=2.00¡Á10-3mol·L-1and [Cl]=2.60¡Á10-2 mol·L-1.

3.2 Discussion
3.2.1 Protolytic equilibria
The ionization of L-glutamine occurs as:



It may be noted that most of the experiments were carried out at a pH of 2.70, where [RH2+]: [RH] is 1:3.38, the equilibrium (2). Sadler et al. studied [3] the authors proposed a reaction mechanism with the involvement of the cationic and the zwitterion species of R. It is evident that the concentration of R is too small to be considered as a reaction species. It may be noted that at the above mentioned pH, the cationic and the zwitterion species will be present as a mainly species evidently from the pKa value of R [23]. Therefore, two species are most likely to be present as the predominant and effective substituting species under the conditions of the experiment.
The ionization of Au (III) occurs at 298 K as below:
Khy=9.5¡Á10-6 (4)
Ka=0.25 (5)
Tetrachloroaurate (III) AuCl4 ion exists in equilibrium with other Au (III) species as shown in the equilibrium (4, 5). The equilibrium (4) is helpful in explaining the rate retardation by Cl ions on the assumption that AuCl4 ion is much more than AuCl3(H2O). Similarly, the equilibrium (5) can explain the retardation of the rate by H+ ions by considering AuCl3(OH) is larger than AuCl3(H2O)[8]. Thus under the experimental conditions and utilizing the literature values of Khy and Ka at 298 K, the ratio of concentration of the different Au (III) species are found to be [AuCl4]: [AuCl3(H2O)] is 2736:1, that the equilibrium (5) can be neglected. It may be proposed that AuCl4¨C is the predominant and effective Au (III) species [21].
3.2.2 Mechanism prevails
Based on the kinetic results and analysis, a straightforward reaction mechanism is proposed as below:

From the proposed reaction mechanism, it is known that the reaction of Au (III) with R includes two phases, the first phase is a preequilibration, it is quite plausible that the reaction takes place between the cationic and the zwitterion species of the R with AuCl4 in the equilibrium (6 and 7), and each molecule of RH2+ and RH consume a molecule of AuCl4¨C respectively, and form an intermediate complex AuCl3RH. It is different from the reported reaction mechanism involvement of the two oxidizing species in the Au (III)-induced oxidation of amino acids by Pratik K. Sen [22] and Vimal Soni [20]. The second phase, this unstable intermediate AuCl3RH slowly decomposes to give a half-cyclic Au (III) complex in the reaction (8). Once formed, the chelate half-cyclic Au (III) appears to be unreactive. Several authors have also reported [3, 24] the formation of an unreactive half-cyclic Au (III) intermediate complex in the substitution of organic substrates by Au (III).
Consideration of the equilibriums (2) and (3) suggests that [RH2+] and [R]0 are given by the (Eqn. 9 and 10):

According to the equilibriums (6) and (7), [AuCl4¨C] concerned two parts:

Add two parts of [AuCl4¨C] in the (Eqn. 11) get that the concentration total of AuCl4¨C:

From the (Eqn. 13), get that the total of [Au (III)]0 involves [AuCl4¨C] and [AuCl3RH],

Take the (Eqn. 9, 10 and 13) into  and Simplificated, the substitution of the values of [AuCl3RH] from the (Eqn. 6 and 7) can show as fllowed the (Eqn.14):
Under the pseudo first-order condition, the rate law derived from the disappearance of the total concentration of Au (III) in terms of reactions (6-8) is given by (Eqn. 1). It can be expressed as:
Unite (Eqn. 1). we can get the expression of kobs as the (Eqn. 17)
The equation (17), which is the derived rate law, can be expressed by the equation (18-20)

The equation (18-20) is consistent with the linear plots with intercepts shown in Fig. 3 (kobs-1 vs [R]o-1), Fig. 4 (kobs-1 vs [H+]) and Fig. 5 (kobs-1 vs [Cl]).The agreement between the equation (18-20) and the results justifies the proposed mechanism.The values of k at different temperatures were calculated from the intercepts of kobs-1 vs [R]o-1, kobs-1 vs [H+] and kobs-1vs [Cl] in different ways, and these have been found to tally basely with each other.
3.2.3 Tthermodynamic parameters
From the intercepts of the linear plot of kobs-1 vs [R]0-1, the values of k at different temperature were evaluated. The plot of log (k/T) vs (1/T) [18] was found to be linear (r=0.997) and from the slope of this plot, the overall enthalpy of activation (DH¡Ù) followed by the overall entropy of activations (DS¡Ù) were calculated using the relation (Eqn. 21) [8, 20]. Rate constants and activation parameters are listed in Table 3.

Table 3
. The values of k at the different temperatures.and the respective values of the thermodynamic parameters.

T/K 293.2 298.2 303.2 308.2 Activation parameters(298.2K )
103k/(L·mol-1 s-1£© 4.20 5.21 6.25 7.39 Ea = 30.43kJ·mol-1
DH¡Ù = 27.95kJ·mol-1
DS¡Ù = -194.92 J·K-1·mol-1

3.3 Conclusion
In conclusion, a nucleophilic substitution reaction occurred between amino acids and Au (III) complexes under the reaction conditions. The cationic and the zwitterionic species of R react with Au (III) to give a half-cyclic compound in the pH range 1.8-3.0. AuCl4 is more labile than the corresponding aqua forms, AuCl3H2O, as expected. The reaction is a first order in [Au (III)]0, a fractional order in [R]0 and negative fractional order with respect to H+ and Cl. The kobs is independent of ionic strength m. Therefore, it is an unambiguous indication that a different mechanism involving some selected L-glutamine species are presently involved.
3.4 Acknowledgement
Financial support of this work in part by a grant from the Natural Science Foudation of Hebei Province (B2006000962) is gratefully acknowledged.