Kinetics and mechanism of the oxidation of methionine by quinolinium chlorochromate

Transcription

1 J. Serb. Chem. Soc. 70 (2) (2005) UDC :531.3: JSCS 3257 Original scientific paper Kinetics and mechanism of the oxidation of methionine by quinolinium chlorochromate M. PANDEESWARAN, BINCY JOHN, D. S. BHUVANESHWARI AND K. P. ELANGO * Departmant of Chemistry, Gandhigram Rural Institute (Deemed University) Gandhigram , India ( drkpelango@rediffmail.com) (Received 14 April, revised 16 July 2004) Abstract: The oxidation of methionine by quinolinium chlorochromate (QCC) has been studied, in the presence of chloroacetic acid, and in water acetic acid mixtures of varying mole fractions. The reaction is first order with respect to methionine, QCC and acid. The reaction rates were determined at three different temperatures (25, 35 and 45 C) and the activation parameters were computed. The reaction rate increased with increasing mole fraction of acetic acid in the mixture and specific solvent solvent solute interactions were found to predominate (81 %). A solvation model and a suitable mechanism for the reaction are postulated. Keywords: kinetics, oxidation, mechanism, methionine. INTRODUCTION Extensive studies on the mechanism of the oxidation of methionine (Met) by several oxidants have been reported. 1 3 This sulphur containing essential amino acid is reported to behave differently, in comparison to other amino acids, towards many oxidants. This may well be due to the presence of an electron-rich sulphur centre, which is easily oxidisable. Quinolinium chlorochromate (QCC) is a mild and selective oxidant. 4 A search of the literature showed that there seems to be very few reports using QCC. 5 8 In this article, the kinetics and mechanism of the oxidation of methionine by QCC in aqueous acetic acid mixtures of varying mole fractions are reported, with the view to understand the utility of solvent variation studies in the understanding of the mechanism of this biologically important amino acid because it may reveal the mechanism of amino acid metabolism. EXPERIMENTAL Methionine (Met) (Merck) was used as supplied. QCC was prepared by the reported method 4 and its purity was checked by iodometric assay. Monochloroacetic acid was used as a source of hydrogen ions. Acetic acid was purified by the standard method. * Author for correspondence. 145

2 146 PANDEESWARAN et al. Kinetic measurements. The reaction was studied under pseudo-first-order conditions by keeping an excess of the substrate over the oxidant. The solvent was pure water unless stated otherwise. The reactions were studied at constant temperature ( C) in the presence of chloroacetic acid ( M) and were followed up to 80 % completion by monitoring iodometrically the decrease in QCC. Pseudo-first-order rate constants, k obs, were evaluated from the linear plots of (r 2 > 0.98) log QCC against time. Duplicate kinetic runs showed that the rate constants are reproducible to within 3 %. The specific rate constant, k 2, were computed from the relation: k 2 = k obs / Met. Stoichiometry and product analysis. The stoichiometry of the reaction was determined by performing the experiment under the conditions of QCC > Met. The disappearance of QCC was monitored until constant titre values were obtained. Me S R + O 2 CrClOQuH Me S(O) R + OCrClOQuH Product analysis was carried out under kinetic conditions. The oxidation of Met resulted in the formation of the corresponding sulphoxide. The sulphoxide was determined by a reported method. 9 The yield of sulphoxide was 86 4%. RESULTS AND DISCUSSION The reactions were first order with respect to QCC. Furthermore, the values of k obs were independent of the initial concentration of QCC (Table I). The reaction rate increases linearly with increasing concentration of Met. The order of the reaction with respect to Met is also one. The reaction is catalysed by hydrogen ions and the order with respect to H + is one. Therefore, the rate law can be represented as: d QCC /dt = k Met QCC H + The oxidation of Met in an atmosphere of nitrogen failed to induce the polymerization of acrylonitrile. Furthermore, the rate of oxidation decreased with the addition of Mn(II). Therefore, a one-electron oxidation, giving rise to free radicals is unlikely. The rate constants for the oxidation of Met at 25, 35 and 45 C (at Met = M; QCC = Mand H + = M) are , and s 1, respectively. The activation parameters were calculated as: H # = kj mol 1, S # = 183 3Jmol 1 K 1 and G # = kj mol 1. These activation parameters are comparable with those for the oxidation of Met by other halochromates. 1 The influence of solvent on the rate of oxidation of methionine by QCC was studied in water organic solvent mixtures of different mole fractions of organic co-solvent viz. acetic acid. The results in Table II indicate that the rate constants (k 2 ) are remarkably sensitive to the composition of the mixed solvent. The rate constants increase with increasing mole fraction of acetic acid in the mixture. The influence of the relative permittivity of a medium on the rate can be described by the equation of Laidler and Eyring. 10 Aplotoflogk 2 versus 1/ r is linear (r = 0.969, sd = 0.09, = 0.29) with a positive slope. The solvent effect was also analysed using the Grunwald Winstein equation. 11 Aplotoflogk 2 versus Y in water acetic acid mixtures is linear (r = 0.896, sd = 0.18, = 0.51) with a nega-

3 METHIONINE OXIDATION 147 tive slope which indicates a S N 2 type transition state. Such a transition state will be more stabilized with increasing organic solvent content of the medium and hence the rate of the oxidation will increase. The statistical results indicate that the correlation between log k 2 and the macroscopic solvent parameters, such as relative permittivity and ionizing power, is poor. That is, no single solvent parameter can completely explain the solvent effect on the reactivity. TABLE I. Rate constants for the oxidation of methionine by QCC in water at C 10 2 [Met] M 10 3 [QCC] M 10[Acid] M 10 4 k obs s a a contained 5-4 M Mn(II) From idealized theories, the solvent relative permittivity is often predicted to serve as a quantitative measure of solvent polarity. However, this approach is often inadequate since these theories regard solvents as a non-structured continuum, not composed of individual solvent molecules with their own solvent solvent interactions. Additionally, they do not take into account specific solute solvent interactions, such as hydrogen bonding and electron pair donor electron pair acceptor interactions, which often play a dominating role in solute solvent interactions. No single macroscopic physical parameter could possibly account for the multitude of solute solvent interactions on the molecular microscopic level. Thus, bulk solvent properties, such as relative permittivity and ionizing power, can only poorly de-

4 148 PANDEESWARAN et al. scribe the microenvironment around the reacting species, which governs the stability of the transition state and hence the rate of the reaction. Hence, there have been a variety of attempts to quantify different aspects of solvent polarity and then use the resultant parameters to interpret solvent effects on reactivity through multiple regression. Various treatments for the above solvent solvent solute interactions based on linear solvation energy relationships (LSER) have been developed. 12 TABLE II. Effect of added acetic acid on the oxidation of methionine by QCC at C, Met = M, QCC = Mand H + = M Mole fraction of AcOH k 2 /dm 3 mol -1 s The effects of solvent on reactivity may be understood from the stand point of specific solvation effects and non-specific solvation effects. This kind of dual dependency of the reactivity on the solvent composition is illustrated by the Kamlet Taft solvatochromic comparison method. 13 This method may be used to unravel, quantify, correlate and rationalize multiple interacting solvent effects on reactivity. Thus, the rate data were correlated with the solvatochromic parameters in the form of the following Linear Solvation Energy Relationship (LSER). log k = A 0 + s * + a + b where * is an index of the solvent dipolarity/polarizability, which measures the ability of a solvent to stabilize a charge or a dipole by virtue of its dielectric effect, is the solvent HBD (hydrogen bond donor) acidity, is the HBA (hydrogen bond acceptor) basicity of the solvent in a solute to solvent hydrogen bond and A 0 is the regression value of the solute property in the reference solvent cyclohexane. The regression coefficients s, a and b measure the relative susceptibilities of the solvent dependent solute property log k 2 to the indicated solvent parameter. The solvatochromic parameters employed in the present study were taken from the literature. 14 The rate of oxidation in the studied solvent mixtures show good correlations with solvent via the above LSER. The correlation results obtained are as follows: log k 2 = 7.47( 3.71) 2.88( 0.19) * ( 1.95) ( (N =8,R 2 = 0.988, sd = 0.06, = 0.19, P =31%,P =50%,P * =19%) Such a good correlation, with an explained variance of ca. 99 % in the H 2 O AcOH mixtures, indicates the existence of non-specific and specific solvent solute interactions. From the values of the regression coefficients, the contribution of each parameter (P x ), on a percentage basis, to the reactivity were calculated. 6,7 The observation of this systematic multiple regression analysis leads to the following preliminary conclusions. i) In water acetic acid mixtures, the rate of the

5 METHIONINE OXIDATION 149 reaction is strongly influenced by specific solute solvent interactions, as indicated by the percentage contributions of the parameters and. ii) The positive signs of the coefficients of the and terms suggest that the specific interactions between the transition state and the solvent, through HBD and HBA properties, are greater than those between the reactants and the solvent. iii) The contribution of the solvent HBA basicity to the total solvent effect is predominant. Since acetic acid is an amphiprotic solvent, increasing its mole fraction in the solvent mixture stabilizes the transition state through better solvation and consequently increases the rate of oxidation. iv) The solvent dipolarity/polarizability * plays a very minor role. The negative sign of the coefficient of this term suggests that the reactants are solvated to a greater extent by the solvent mixture than is the transition state. Considering these points, the solvation model for the oxidation of methionine by QCC in water acetic acid mixtures can be represnted as: dipolarity/ HBD (31 %) and polarizability HBA (50 %) interactions (19 %) interactions Reactants Transition state Products Further, a dynamic exchange of solvent molecules between the solvation shell of the transition state and the bulk exists. 15 As the organic co-solvent concentration increases in the mixture, more and more organic solvent molecules are introduced into the solvation shell. As the mole fraction of the organic co-solvent in the mixture increases, the transition state is stabilized, to a greater extent, through HBD/HBA solute solvent interactions and, consequently, the rate of the reaction increases. Mechanism Under the experimental conditions employed in the present study, methionine is oxidized to the sulphoxide stage only. Based on the above kinetic observations, i.e. first order dependence on Met, QCC and acid, the following mechanism is proposed for the reaction. The linear increase in rate with acidity suggests the involvement of protonated QCC in the rate-determining step. In the first step QCC becomes protonated. The protonated QCC attacks the substrate, in a slow step, to form a complex, which subsequently decomposes to give the products in a fast step. The proposed scheme envisages an oxygen atom transfer from the oxidant and that is in agreement with earlier observations. The electrophilic attack on the sulphide-sulphur can be viewed as an S N 2 reaction. An S N 2 like transition state is supported by the observed solvent effect.

6 150 PANDEESWARAN et al. K QCC + H + QCCH + k Met + QCCH + slow Complex fast Complex Products CONCLUSION The oxidation of methionine by QCC is first order with respect to Met, QCC and Acid. Under the experimental conditions, methionine is oxidized to the sulphoxide stage only. The entropy of activation is negative, suggesting the formation of a complex is a slow step. The reaction is highly influenced by the amount and nature of the organic co-solvent added to the mixture. Linear and multiple regression analysis may be used to separate and quantify the specific and non-specific solvational effects on the oxidation of methionine by QCC. Using the above method, the significance of the various solvent solvent solute interactions on the reactivity has been established. From the regression coefficients, information on the solvent reactant and the solvent transition state interactions was obtained and solvation models are proposed. IZVOD KINETIKA I MEHANIZAM OKSIDACIJE METIONINA HINOLINIJUM-HLOROHROMATOM M. PANDEESWARAN, BINCY JOHN, D. S. BHUVANESHWARI i K. P. ELANGO Departmant of Chemistry, Gandhigram Rural Institute (Deemed University) Gandhigram , India Prou~avana je oksidacija metionina hinolinijum-hlorohromatom (QCC) u prisustvu hlorsir}etne kiseline i u sme{ama voda sir}etna kiselina razli~itih molskih udela. Reakcija je prvog reda u odnosu na metionin, QCC i kiselinu. Odre ene su brzine reakcije na tri razli~ite temperature (25, 35 i 45 C) i izra~unati parametri aktivacije. Brzina reakcije se pove}ava pove}awem molskog udela sir}etne kiseline u sme{i i na eno je da su specifi~ne rastvara~ rastvara~ rastvorak interakcije dominantne (81 %). Predlo`en je model solvatacije i odgovaraju}i mehanizam reakcije. (Primqeno 14. aprila, revidirano 16. jula 2004) REFERENCES 1. A. Goyal, S. Kothari, Indian J. Chem. 42B (2003) V.Sharma,P.K.Sharma,K.K.Banerji,Indian J. Chem. 36A (1997) 418

7 METHIONINE OXIDATION V.Sharma,P.K.Sharma,K.K.Banerji,J. Indian Chem. Soc. 74 (1997) R. Srinivasan, C. V. Ramesh, W. Madhulatha, K. Balasubramanian, Indian J. Chem. 35B (1996) G. Fatima Jeyanthi, G. Vijayakumar, K. P. Elango, J. Serb. Chem. Soc. 67 (2002) G. Fatima Jeyanthi, K. P. Elango, Int. J. Chem. Kinet. 35 (2003) S. Saravanakanna, K. P. Elango, Int. J. Chem. Kinet. 34 (2002) J. R. C. Ramya Vijayakumari, K. P. Elango, J. Indian Chem. Soc. 79 (2002) S.Goel,S.Kothari,K.K.Banerji,J. Chem. Res. (M) (1996) E.S.Amis,J.F.Hinton,Solvent Effect of Chemical Phenomena, vol.1,academicpress,new York, A.H.Fainberg,S.Winstein,J. Am. Chem. Soc. 78 (1956) C. Reichardt, Solvents and Solvent Effects in Organic Chemistry, VCH, Weinheim, M. J. Kamlet, J. M. Abboud, M. H. Abraham, R. W. Taft, J. Org. Chem. 48 (1983) Y. Marcus, J. Chem. Soc. Perkin Trans 2 (1994) Y. Marcus, Ion Solvation, Wiley, New York, 1985.