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

1. INTRODUCTION
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. EXPERMENTAL SECTION
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–visible 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 ±0.2℃ 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 ≥ 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.

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.

Fig. 3 The plots of k_obs^-1 vs [R]₀^-1 at different temperatures. [Au (III)]₀=1.00×10^-4mol·L^-1, [H⁺]=2.00×10^-3mol·L^-1, [Cl^-]=2.60×10^-2mol·L^-1 and μ=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 k_obs was found to increase with an increase in pH. The plot of k_obs^-1 vs [H⁺] gave a straight line with a positive slope and positive intercept. (Fig. 4).

Fig. 4 The plots of 1/k_obs vs [H⁺] at different temperatures. [Au (III)]₀=1.00×10^-4mol·L^-1, [R]₀ =5.00×10^-2 mol·L^-1, [Cl^-]=2.60×10^-2 mol·L^-1 and μ=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 k_obs was found to decrease with an increase of [Cl^-]. The plot of k_obs^-1 vs [Cl^-] is linear with a positive slope and positive intercept (Fig. 5).

Fig. 5 The plots of k_obs^-1 vs [Cl^-] at different temperatures. [Au (III)]₀=1.00×10^-4mol·L^-1, [R]₀=5.00×10^-2mol·L^-1, [H⁺]=2.00×10^-3mol·L^-1 and μ=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 μ 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).

[Au (III)]₀=1.00×10^-4mol·L^-1,[R]₀=5.00×10^-2mol·L^-1,[H⁺]=2.00×10^-3mol·L^-1and [Cl^-]=2.60×10^-2 mol·L^-1.

3.2 Discussion
3.2.1 Protolytic equilibria
The ionization of L-glutamine occurs as:
    
                                           K_a1=6.76×10^-3        (2)

                                         K_a2=7.41×10^-10         (3)

    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:
K_hy=9.5×10^-6 (4)
K_a=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 K_hy and K_a 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^– 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:

(6)
(7)

(8)

    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^– 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):
(9)
(10)
According to the equilibriums (6) and (7), [AuCl₄^–] concerned two parts:
(11)
Add two parts of [AuCl₄^–] in the (Eqn. 11) get that the concentration total of AuCl₄^–:
(12)
From the (Eqn. 13), get that the total of [Au (III)]₀ involves [AuCl₄^–] and [AuCl₃RH],
(13)
Take the (Eqn. 9, 10 and 13) into (12) and Simplificated, the substitution of the values of [AuCl₃RH] from the (Eqn. 6 and 7) can show as fllowed the (Eqn.14):
(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:
(15)
(16)
Unite (Eqn. 1). we can get the expression of k_obs as the (Eqn. 17)
(17)
The equation (17), which is the derived rate law, can be expressed by the equation (18-20)
(18)
(19)
(20)
    The equation (18-20) is consistent with the linear plots with intercepts shown in Fig. 3 (k_obs^-1 vs [R]_o^-1), Fig. 4 (k_obs^-1 vs [H⁺]) and Fig. 5 (k_obs^-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 k_obs^-1 vs [R]_o^-1, k_obs^-1 vs [H⁺] and k_obs^-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 k_obs^-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^≠) followed by the overall entropy of activations (DS^≠) were calculated using the relation (Eqn. 21) ^{[8, 20]}. Rate constants and activation parameters are listed in Table 3.
(21)

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

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 k_obs 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.

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