Equilibrium and Redox Kinetics of Copper(II)-Thiourea Complexes

Stopped-flow spectrophotometric measurements identify and determine equilibrium data for thiourea (tu) complexes of copper(II) formed in aqueous solution. In excess Cu(II), the complex ion [Cu(tu)](2+) has a stability constant beta(1) = 2.3 +/- 0.1 M(-)(1) and molar absorptivity at 340 nm of epsilon(1) = (4.0 +/- 0.2) x 10(3) M(-)(1) cm(-)(1) at 25.0 degrees C, 2.48 mM HClO(4), and &mgr; = 464 mM (NaClO(4)). The fast reduction of Cu(II) by excess tu obeys the rate law -d[Cu(II)]/dt = k'[Cu(II)](2)[tu](7) with a value for the ninth-order rate constant k' = (1.60 +/- 0.18) x 10(14) M(-)(8) s(-)(1), which derives from a rate-determining step involving the bimolecular decomposition of two complexed Cu(II) species. Copper(II) catalyzes the reduction of hexachloroiridate(IV) by tu according to the rate law -d[IrCl(6)(2)(-)]/dt = (k(2,unc)[tu](2) + k(1,cat) [tu](5)[Cu(II)])[IrCl(6)(2)(-)]. Least-squares analysis yields values of k(2,unc) and k(1,cat) equaling 385 +/- 4 M(-)(2) s(-)(1) and (3.7 +/- 0.1) x 10(13) M(-)(6) s(-)(1), respectively, at &mgr; = 115 mM (NaClO(4)). The corresponding mechanism has a rate-determining step that involves the oxidation of [Cu(II)(tu)(5)](2+) by [IrCl(6)](2)(-) rather than the bimolecular reaction of two cupric-tu complexes.     

NMR studies of phenylbenzohydroxamic acid and kinetics of complex formation with nickel(II)

The behavior of N-phenylbenzohydroxamic acid (PBHA) in organic solvents has been investigated by (1)H and (13)C NMR spectroscopy. Measurements in acetone at different temperatures and concentrations enable one to individualized two signals, in a 20/80 area ratio, which were ascribed to partition of PBHA between two isomers, HZ (cis) and HE (trans). The dependence of the low-intensity peak on concentration and temperature strongly suggests dimer formation. Since only the HZ form can give dimers, it may be concluded that in acetone PBHA is present mainly in the HE form. (13)C NMR measurements in methanol yielded a 50/50 [HZ]/[HE] ratio. The equilibria and kinetics of complex formation in aqueous solutions between Ni(II) and PBHA were investigated by spectrophotometric and stopped-flow techniques at 25 degrees C and 0.2 M ionic strength. Two reaction paths, involving the binding of Ni(2+) to the neutral PBHA and to its anion, were observed. The rate constants of the forward and reverse steps are k(1) = (7.1 +/- 0.3) x 10(2) M(-)(1) s(-)(1) and k(-1) = (4.9 +/- 0.6) s(-)(1) for the step involving the undissociated PBHA and k(2) = (5.5 +/- 0.7) x 10(4) M(-)(1) s(-)(1) and k(-2) = (1.2 +/- 0.1) s(-)(1) for the step involving the anion. The k(2) value indicates that the PBHA anion reacts with Ni(2+) according to Eigen's mechanism and that in water the cis form prevails. The k(1) value is lower by a factor of 13 compared to the value estimated on the basis of Eigen's mechanism, suggesting that at least 90% of the neutral ligand is present in a nonreactive conformation.     

Kinetics and mechanism of ligand substitution in bis(N-alkylsalicylaldiminato)oxovanadium(IV) complexes

Conventional and stopped-flow spectrophotometry was used to to study the kinetics of ligand substitution in a number of bis(N-alkylsalicylaldiminato)oxovanadium(IV) complexes (=VO(R-X-sal)(2)) by 1,1,1- trifluoropentane-2,4-dione (=Htfpd) in acetone, according to the following reaction: VO(R-X-sal)(2) + 2Htfpd --> VO(tfpd)(2) + 2R-X-salH. The acronym R-X-salH refers to N-alkylsalicylaldimines with substituents X = H, Cl, Br, CH(3), and NO(2) in the 5-position of the salicylaldehyde ring and N-alkyl groups R = n-propyl, isopropyl, phenyl, and neopentyl. Under excess conditions ([Htfpd](0) > [VO(R-X-sal)(2)](0)), substitution by Htfpd occurs in two observable steps, as characterized by pseudo-first-order rate constants k(obsd(1)) and k(obsd(2)). Both rate constants increase linearly with [Htfpd](0) according to k(obsd(1)) = k(s(1)) + k(1)[Htfpd](0) and k(obsd(2)) = k(s(2)) + k(2)[Htfpd](0), with k(s(1)) and k(s(2)) describing small contributions of solvent-initiated pathways. Depending on the nature of R and X, second-order rate constants k(1) and k(2) lie in the range 0.098-0.87 M(-1) s(-1) (k(1)) and 0.022-0.41 M(-1) s(-1) (k(2)) at 298 K. For ligand substitution in the system VO(n-propyl-sal)(2)/Htfpd, the activation parameters DeltaH++ = 35.8 +/- 2.8 kJ mol(-1) and DeltaS++ = -146 +/- 23 J K(-1) mol(-1) (k(1)) and DeltaH++ = 40.2 +/- 1.3 kJ mol(-1) and DeltaS++ = -142 +/- 11 J K(-1) mol(-1) (k(2)) were obtained. The Lewis acidity of the complexes VO(n-propyl-X-sal)(2) with X = H, Cl, Br, CH(3), and NO(2) was quantified spectrophotometrically by determination of equilibrium constant K(py), describing the formation of the adduct VO(n-propyl-X-sal)(2).pyridine. The adduct VO(tfpd)(2).n-propyl-salH, formed as product in the system VO(n-propyl-sal)(2)/Htfpd, was characterized by its dissociation constant, K(D) = (3.30 +/- 0.10) x 10(-3) M. The mechanism suggested for the two-step substitution process is based on initial formation of the adducts VO(R-X-sal)(2).Htfpd (step 1) and VO(R-X-sal)(tfpd).Htfpd (step 2).     

Structural characterization and formation kinetics of sitting-atop (SAT) complexes of some porphyrins with copper(II) ion in aqueous acetonitrile relevant to porphyrin metalation mechanism. Structures of aquacopper(II) and cu(II)-SAT complexes as determined by XAFS spectroscopy

The formation of the sitting-atop (SAT) complexes of 5,10,15,20-tetraphenylporphyrin (H(2)tpp), 5,10,15,20-tetrakis(4-chlorophenyl)porphyrin (H(2)t(4-Clp)p), 5,10,15,20-tetramesitylporphyrin (H(2)tmp), and 2,3,7,8,12,13,17,18-octaethylporphyrin (H(2)oep) with the Cu(II) ion was spectrophotometrically confirmed in aqueous acetonitrile (AN), and the formation rates were determined as a function of the water concentration (C(W)). The decrease in the conditional first-order rate constants with the increasing C(W) was reproduced by taking into consideration the contribution of [Cu(H(2)O)(an)(5)](2+) in addition to [Cu(an)(6)](2+) to form the Cu(II)-SAT complexes. The second-order rate constants for the reaction of [Cu(an)(6)](2+) and [Cu(H(2)O)(an)(5)](2+) at 298 K were respectively determined as follows: (4.1 +/- 0.2) x 10(5) and (3.6 +/- 0.2) x 10(4) M(-1) s(-1) for H(2)tpp, (1.15 +/- 0.06) x 10(5) M(-1) s(-1) and negligible for H(2)t(4-Clp)p, and (4.8 +/- 0.3) x 10(3) and (1.3 +/- 0.3) x 10(2) M(-1) s(-1) for H(2)tmp. Since the reaction of H(2)oep was too fast to observe the reaction trace due to the dead time of 2 ms for the present stopped-flow technique, the rate constant was estimated to be greater than 1.5 x 10(6) M(-1) s(-1). According to the structure of the Cu(II)-SAT complexes determined by the fluorescent XAFS measurements, two pyrrolenine nitrogens of the meso-substituted porphyrins (H(2)tpp and H(2)tmp) bind to the Cu(II) ion with a Cu-N(pyr) distance of ca. 2.04 A, while those of the beta-pyrrole-substituted porphyrin (H(2)oep) coordinate with the corresponding bond distance of 1.97 A. The shorter distance of H(2)oep is ascribed to the flexibility of the porphyrin ring, and the much greater rate for the formation of the Cu(II)-SAT complex of H(2)oep than those for the meso-substituted porphyrins is interpreted as due to a small energetic loss at the porphyrin deformation step during the formation of the Cu(II)-SAT complex. The overall formation constants, beta(n), of [Cu(H(2)O)(n)()(an)(6)(-)(n)](2+) for the water addition in aqueous AN were spectrophotometrically determined at 298 K as follows: log(beta(1)/M(-1)) = 1.19 +/- 0.18, log(beta(2)/M(-2)) = 1.86 +/- 0.35, and log(beta(3)/M(-3)) = 2.12 +/- 0.57. The structure parameters around the Cu(II) ion in [Cu(H(2)O)(n)(an)(6-n)](2+) were determined using XAFS spectroscopy.     

A photometric study of the complexation reaction between Alizarin complexan and zinc(II), nickel(II), lead(II), cobalt(II) and copper(II)

The complexation reaction between Alizarin complexan ([3-N,N-di(carboxymethyl)aminomethyl]-1,2-dihydroxyanthraquinone; H(4)L) and zinc(II), nickel(II), lead(II), cobalt(II) and copper(II) has been studied by a spectrophotometric method. All these metal ions form 1:1 complexes with HL; 2:1 metal:ligand complex were found only for Pb(II) and Cu(II). The stability constants are (ionic strength I = 0.1, 20 degrees C): Zn(2+) + HL(3-) right harpoon over left harpoon ZnHL(-) log K +/- 3sigma(log K) = 12.19 +/- 0.09 (I = 0.5) Ni(2+) + HL(3-) right harpoon over left harpoon NiHL(-) log K +/- 3sigma(log K) = 12.23 +/- 0.21 Pb(2+) + HL(3-) right harpoon over left harpoon PbHL(-) log K +/- 3sigma(log K) = 11.69 +/- 0.06 PbHL(-) + Pb(2+) right harpoon over left harpoon Pb(2)L + H(+) log K approximately -0.8 Co(2+) + HL(3-) right harpoon over left harpoon CoHL(-) log K 3sigma(log K) = 12.25 + 0.13 Cu(2+) + HL(3-) right harpoon over left harpoon CuHL(-) log K 3sigma(log K) = 14.75 +/- 0.07 Cu(2+) + CuHL(-) right harpoon over left harpoon Cu(2)L + H(+) log K approximately 3.5 The solubility and stability of both the reagent and the complexes and the closenes of the values of the stability constants make this reagent suitable for the photometric detection of several metal ions in the eluate from an ion-exchange column.     

Electron transfer reactions between copper(II) porphyrin complexes and various oxidizing reagents in acetonitrile

Homogeneous electron transfer reactions of the Cu(II) complexes of 5,10,15,20-tetraphenylporphyrin (TPP) and 2,3,7,8,12,13,17,18-octaethylporphyrin (OEP) with various oxidizing reagents were spectrophotometrically investigated in acetonitrile. The reaction products were confirmed to be the pi-cation radicals of the corresponding Cu(II)-porphyrin complexes on the basis of the electronic spectra and the redox potentials of the complexes. The rate of the electron transfer reaction between the Cu(II)-porphyrin complex and solvated Cu(2+) was determined as a function of the water concentration under the pseudo first-order conditions where Cu(2+) is in large excess over the Cu(II)-porphyrin complex. The decrease in the pseudo first-order rate constant with increasing the water concentration was attributed to the stepwise displacement of acetonitrile in [Cu(AN)(6)](2+)(AN = acetonitrile) by water, and it was concluded that only the Cu(2+) species fully solvated by acetonitrile, [Cu(AN)(6)](2+), possesses sufficiently high redox potential for the oxidation of Cu(ii)-OEP and Cu(ii)-TPP. The reactions of the Cu(II)-porphyrin complexes with other oxidizing reagents such as [Ni(tacn)(2)](3+)(tacn = 1,4,7-triazacyclononane) and [Ru(bpy)(3)](3+)(bpy = 2,2'-bipyridine) were too fast to be followed by a conventional stopped-flow technique. Marcus cross relation for the outer-sphere electron transfer reaction was used to estimate the rate constants of the electron self-exchange reaction between Cu(II)-porphyrin and its pi-cation radical: log(k/M(-1) s(-1))= 9.5 +/- 0.5 for TPP and log(k/M(-1) s(-1))= 11.1 +/- 0.5 for OEP at 25.0 degrees C. Such large electron self-exchange rate constants are typical for the porphyrin-centered redox reactions for which very small inner- and outer-sphere reorganization energies are required.     

The nature of the intermediates in the reactions of Fe(III)- and Mn(III)-microperoxidase-8 with H(2)O(2): a rapid kinetics study

Kinetic studies were performed with microperoxidase-8 (Fe(III)MP-8), the proteolytic breakdown product of horse heart cytochrome c containing an octapeptide linked to an iron protoporphyrin IX. Mn(III) was substituted for Fe(III) in Mn(III)MP-8.The mechanism of formation of the reactive metal-oxo and metal-hydroperoxo intermediates of M(III)MP-8 upon reaction of H(2)O(2) with Fe(III)MP-8 and Mn(III)MP-8 was investigated by rapid-scan stopped-flow spectroscopy and transient EPR. Two steps (k(obs1) and k(obs2)) were observed and analyzed for the reaction of hydrogen peroxide with both catalysts. The plots of k(obs1) as function of [H(2)O(2)] at pH 8.0 and pH 9.1 for Fe(III)MP-8, and at pH 10.2 and pH 10.9 for Mn(III)MP-8, exhibit saturation kinetics, which reveal the accumulation of an intermediate. Double reciprocal plots of 1/k(obs1) as function of 1/[H(2)O(2)] at different pH values reveal a competitive effect of protons in the oxidation of M(III)MP-8. This effect of protons is confirmed by the linear dependence of 1/k(obs1) on [H(+)] showing that k(obs1) increases with the pH. The UV-visible spectra of the intermediates formed at the end of the first step (k(obs1)) exhibit a spectrum characteristic of a high-valent metal-oxo intermediate for both catalysts. Transient EPR of Mn(III)MP-8 incubated with an excess of H(2)O(2), at pH 11.5, shows the detection of a free radical signal at g approximately equal to 2 and of a resonance at g approximately equal to 4 characteristic of a Mn(IV) (S = 3/2) species. On the basis of these results, the following mechanism is proposed: (i) M(III)MP-8-OH(2) is deprotonated to M(III)MP-8-OH in a rapid preequilibrium step, with a pK(a) = 9.2 +/- 0.9 for Fe(III)MP-8 and a pK(a) = 11.2 +/- 0.3 for Mn(III)MP-8; (ii) M(III)MP-8-OH reacts with H(2)O(2) to form Compound 0, M(III)MP8-OOH, with a second-order rate constant k(1) = (1.3 +/- 0.6) x 10(6) M(-1) x s(-1) for Fe(III)MP-8 and k(1) = (1.6 +/- 0.9) x 10(5) M(-1) x s(-1) for Mn(III)MP-8; (iii) this metal-hydroperoxo intermediate is subsequently converted to a high-valent metal-oxo species, M(IV)MP-8=O, with a free radical on the peptide (R(*+)). The first-order rate constants for the cleavage of the hydroperoxo group are k(2) = 165 +/- 8 s(-1) for Fe(III)MP-8 and k(2) = 145 +/- 7 s(-1) for Mn(III)MP-8; and (iv) the proposed M(IV)MP-8=O(R(*+)) intermediate slowly decays (k(obs2)) with a rate constant of k(obs2) = 13.1 +/- 1.1 s(-)(1) for Fe(III)MP-8 and k(obs2) = 5.2 +/- 1.2 s(-1) for Mn(III)MP-8. The results show that Compound 0 is formed prior to what is analyzed as a high-valent metal-oxo peptide radical intermediate.     

Kinetic and equilibria studies of the aquation of the trinuclear platinum phase II anticancer agent [(trans-PtCl(NH(3))(2))(2)(mu-trans-Pt(NH(3))(2)(NH(2)(CH(2))(6)NH(2))(2))](4+) (BBR3464)

The hydrolysis profile of the bifunctional trinuclear phase II clinical agent [(trans-PtCl(NH(3))(2))(2)(mu-trans-Pt(NH(3))(2)(NH(2)(CH(2))(6)NH(2))(2))](4+) (BBR3464, 1) has been examined using [(1)H,(15)N] heteronuclear single quantum coherence (HSQC) 2D NMR spectroscopy. Reported are estimates of the rate and equilibrium constants for the first and second aquation steps, together with the acid dissociation constant (pK(a1) approximately equal to pK(a2) approximately equal to pK(a3)). The equilibrium constants for the aquation determined by NMR at 298 and 310 K (I = 0.1 M, pH 5.3) are similar, pK(1) = pK(2) = 3.35 +/- 0.04 and 3.42 +/- 0.04, respectively. At lower ionic strength (I = 0.015 M, pH 5.3) the values at 288, 293, and 298 K are pK(1) = pK(2) = 3.63 +/- 0.05. This indicates that the equilibrium is not strongly ionic strength or temperature dependent. The aquation and anation rate constants for the two-step aquation model at 298 K in 0.1 M NaClO(4) (pH 5.3) are k(1) = (7.1 +/- 0.2) x 10(-5) s(-1), k(-1) = 0.158 +/- 0.013 M(-1) s(-1), k(2) = (7.1 +/- 1.5) x 10(-5) s(-1), and k(-2) = 0.16 +/- 0.05 M(-1) s(-1). The rate constants in both directions increase 2-fold with an increase in temperature of 5 K, and rate constants increase with a decrease in solution ionic strength. A pK(a) value of 5.62 plus minus 0.04 was determined for the diaqua species [(trans-Pt(NH(3))(2)(OH(2)))(2)(mu-trans-Pt(NH(3))(2)(NH(2)(CH(2))(6)-NH(2))(2))](6+) (3). The speciation profile of 1 under physiological conditions is explored and suggests that the dichloro form predominates. The aquation of 1 in 15 mM phosphate was also examined. No slowing of the initial aquation was observed, but reversible reaction between aquated species and phosphate does occur.     

Kinetics of manganese(III) acetate in acetic acid: generation of Mn(III) with Co(III), Ce(IV), and dibromide radicals; reactions of Mn(III) with Mn(II), Co(II), hydrogen bromide,and alkali bromides

The reaction of cobalt(III) acetate with excess manganese(II) acetate in acetic acid occurs in two stages, since the two forms Co(IIIc) and Co(IIIs) are not rapidly equilibrated and thus react independently. The rate constants at 24.5 degrees C are kc = 37.1 +/- 0.6 L mol-1 s-1 and ks = 6.8 +/- 0.2 L mol-1 s-1 at 24.5 degrees C in glacial acetic acid. The Mn(III) produced forms a dinuclear complex with the excess of Mn(II). This was studied independently and is characterized by the rate constant (3.43 +/- 0.01) x 10(2) L mol-1 s-1 at 24.5 degrees C. A similar interaction between Mn(III) and Co(II) is substantially slower, with k = (3.73 +/- 0.05) x 10(-1) L mol-1 s-1 at 24.5 degrees C. Mn(II) is also oxidized by Ce(IV), according to the rate law -d[Ce(IV)]/dt = k[Mn(II)]2[Ce(IV)], where k = (6.0 +/- 0.2) x 10(4) L2 mol-2 s-1. The reaction between Mn(II) and HBr2., believed to be involved in the mechanism by which Mn(III) oxidizes HBr, was studied by laser photolysis; the rate constant is (1.48 +/- 0.04) x 10(8) L mol-1 s-1 at approximately 23 degrees C in HOAc. Oxidation of Co(II) by HBr2. has the rate constant (3.0 +/- 0.1) x 10(7) L mol-1 s-1. The oxidation of HBr by Mn(III) is second order with respect to [HBr]; k = (4.10 +/- 0.08) x 10(5) L2 mol-2 s-1 at 4.5 degrees C in 10% aqueous HOAc. Similar reactions with alkali metal bromides were studied; their rate constants are 17-23 times smaller. This noncomplementary reaction is believed to follow that rate law so that HBr2. and not Br. (higher in Gibbs energy by 0.3 V) can serve as the intermediate. The analysis of the reaction steps then requires that the oxidation of HBr2. to Br2 by Mn(III) be diffusion controlled, which is consistent with the driving force and seemingly minor reorganization.     

Reactivity of M(II) metal-substituted derivatives of pig purple acid phosphatase (uteroferrin) with phosphate

The Fe(II) of the binuclear Fe(II)Fe(III) active site of pig purple acid phosphatase (uteroferrin) has been replaced in turn by five M(II) ions (Mn(II), Co(II), Ni(II), Cu(II), and Zn(II)). An uptake of 1 equiv of M(II) is observed in all cases except that of Cu(II), when a second more loosely bound Cu(II) is removed by treatment with edta. The products have been characterized by different analytical procedures and by UV-vis spectrophotometry. At 25 degrees C, I = 0.100 M (NaCl), the nonenzymatic reactions with H(2)PO(4)(-) give the mu-phosphato product, and formation constants K/M(-1) show an 8-fold spread at pH 4.9 of 740 (Mn), 165 (Fe), 190 (Co), 90 (Ni), 800 (Cu), 380 (Zn). The variations in K correlate well with stability constants for the complexing of H(2)PO(4)(-) and (CH(3)O)HPO(3)(-) with M(II) hexaaqua ions. At pH 4.9 with [H(2)PO(4)(-)] > or = 3.5 mM rate constants k(obs) decrease, and an inhibition process in which a second [H(2)PO(4)(-)] coordinates to the dinuclear center is proposed. The mechanism considered accounts for most but not all of the features displayed. Thus K(1) values for the coordination of phosphate to M(II) are in the range10-60 M(-1), whereas K(2) values for the bridging of the phosphate to Fe(III) are in the narrower range 7.8-12.4. From the fits described K(i) approximately 10(3) M(-1) for the inhibition step, which is independent of the identity of M(II). Values of k(obs) decrease with increasing pH, giving pK(a) values which are close to 3.8 and independent of M(II) (Fe(II), Zn(II), Mn(II)). The acid dissociation process is assigned to Fe(III)-OH(2) to Fe(III)-OH(-), where OH(-) is less readily displaced by phosphate.     

Kinetics and mechanism of platinum-thallium bond formation: the binuclear [(CN)5Pt-Tl(CN)](-) and the trinuclear [(CN)5Pt-Tl-Pt(CN)5](3-) complex

Formation kinetics of the metal-metal bonded binuclear [(CN)(5)Pt-Tl(CN)](-) (1) and the trinuclear [(CN)(5)Pt-Tl-Pt(CN)(5)](3-) (2) complexes is studied, using the standard mix-and-measure spectrophotometric method. The overall reactions are Pt(CN)(4)(2-) + Tl(CN)(2)(+) <==> 1 and Pt(CN)(4)(2-) + [(CN)(5)Pt-Tl(CN)](-) <==> 2. The corresponding expressions for the pseudo-first-order rate constants are k(obs) = (k(1)[Tl(CN)(2)(+)] + k(-1))[Tl(CN)(2)(+)] (at Tl(CN)(2)(+) excess) and k(obs) = (k(2b)[Pt(CN)(4)(2-)] + k(-2b))[HCN] (at Pt(CN)(4)(2-) excess), and the computed parameters are k(1) = 1.04 +/- 0.02 M(-2) s(-1), k(-1) = k(1)/K(1) = 7 x 10(-5) M(-1) s(-1) and k(2b) = 0.45 +/- 0.04 M(-2) s(-1), K(2b) = 26 +/- 6 M(-1), k(-2b) = k(2b)/K(2b) = 0.017 M(-1) s(-1), respectively. Detailed kinetic models are proposed to rationalize the rate laws. Two important steps need to occur during the complex formation in both cases: (i) metal-metal bond formation and (ii) the coordination of the fifth cyanide to the platinum site in a nucleophilic addition. The main difference in the formation kinetics of the complexes is the nature of the cyanide donor in step ii. In the formation of [(CN)(5)Pt-Tl(CN)](-), Tl(CN)(2)(+) is the source of the cyanide ligand, while HCN is the cyanide donating agent in the formation of the trinuclear species. The combination of the results with previous data predict the following reactivity order for the nucleophilic agents: CN(-) > Tl(CN)(2)(+) > HCN.     

Oxidation of chlorine(III) by hypobromous acid: kinetics and mechanism

The kinetics and mechanism of the chlorine(III)-HOBr reaction were studied by the stopped-flow method under acidic conditions, pH 1.0-3.0, in 1.0 M NaClO(4) and at 25.0 degrees C. The overall redox process occurs in two consecutive steps via the formation of the BrClO(2) intermediate. The electron transfer reactions are coupled with bromine hydrolysis, the formation of the tribromide ion, and the protolytic equilibrium of chlorine(III). On the basis of simultaneous evaluation of the kinetic traces, the following rate constants were obtained for the redox steps: HClO(2) + HOBr right harpoon over left harpoon BrClO(2) + H(2)O, k(3) = (3.34 +/- 0.02) x 10(4) M(-1) s(-1), k(-3) = (3.5 +/- 1.3) x 10(3) s(-1); BrClO(2) + ClO(2)(-)<==>2ClO(2) + Br(-), k(4) = (2.9 +/- 1.0) x 10(7) M(-1) s(-1). The second step was practically irreversible under the conditions applied, and the value of k(-4) could not be determined. The equilibrium constant for the formation of BrClO(2), K(3) = 9.5 M(-1), was calculated from the kinetic results, and it was confirmed that this species is a very powerful oxidant. The redox potential was also estimated for the BrClO(2) + e(-) = Br(-) + ClO(2) reaction: epsilon(0) approximately 1.70 V.     

Kinetic study of the hexacyanoferrate (III) oxidation of dihydroxyfumaric acid in acid media

The kinetics of the hexacyanoferrate (III) oxidation of dihydroxyfumaric acid to hexacyanoferrate (II) and diketosuccinic acid was looked into within the 0.04 to 5.3 M HCl acidity range under different temperatures, ionic strengths, and solvent permittivity conditions. The kinetic effect of alkali metal ions, transition metal impurities, and substrate concentrations have also been analyzed. The observed inhibition effect brought about by addition of the reaction product, hexacyanoferrate (II), is a sign of a complex mechanism. The rate constants remained essentially unchanged up to 1 M HCl, diminished between 1.0 and 3.0 M HCl, and rose above 3.0 M HCl. Depending on the medium acidity, three mechanisms can be put forward, which involve different kinetically active forms. At low acidity, the rate-determining step involves a radical cation and both the neutral and the anion substrate forms are equally reactive ( k 1 = k 2 = 2.18 +/- 0.05 M (-1) s (-1), k -1 = 0.2 +/- 0.03). When the medium acidity is boosted, the rate-determining step involves the neutral dihydroxyfumaric acid and two hexacyanoferrate (III) forms. In the intermediate region the rate constant diminished with rising [H (+)] ( k' 1 = 0.141 +/- 0.01 and k' 2 = 6.80 +/- 0.05). Specific catalytic effect by binding of alkali metal ions to oxidant has not been observed. In all instances it was assessed that the substrate decomposition is slow compared to the redox reaction.     

Study on the transesterification of methyl aryl phosphorothioates in methanol promoted by Cd(II), Mn(II), and a synthetic Pd(II) complex

Methanol solutions containing Cd(II), Mn(II), and a palladacycle, (dimethanol bis(N,N-dimethylbenzylamine-2C,N)palladium(II) (3), are shown to promote the methanolytic transesterification of O-methyl O-4-nitrophenyl phosphorothioate (2b) at 25 °C with impressive rate accelerations of 10(6)-10(11) over the background methoxide promoted reaction. A detailed mechanistic investigation of the methanolytic cleavage of 2a-d having various leaving group aryl substitutions, and particularly the 4-nitrophenyl derivative (2b), catalyzed by Pd-complex 3 is presented. Plots of k(obs) versus palladacycle [3] demonstrate strong saturation binding to form 2b:3. Numerical fits of the kinetic data to a universal binding equation provide binding constants, K(b), and first order catalytic rate constants for the methanolysis reaction of the 2b:3 complex (k(cat)) which, when corrected for buffer effects, give corrected (k(cat)(corr)) rate constants. A sigmoidal shaped plot of log(k(cat)(corr)) versus (s)(s)pH (in methanol) for the cleavage of 2b displays a broad (s)(s)pH independent region from 5.6 ≤ (s)(s)pH ≤ 10 with a k(minimum) = (1.45 ± 0.24) × 10(-2) s(-1) and a [lyoxide] dependent wing plateauing above a kinetically determined (s)(s)pK(a) of 12.71 ± 0.17 to give a k(maximum) = 7.1 ± 1.7 s(-1). Br?nsted plots were constructed for reaction of 2a-d at (s)(s)pH 8.7 and 14.1, corresponding to reaction in the midpoints of the low and high (s)(s)pH plateaus. The Br?nsted coefficients (β(LG)) are computed as -0.01 ± 0.03 and -0.86 ± 0.004 at low and high (s)(s)pH, respectively. In the low (s)(s)pH plateau, and under conditions of saturating 3, a solvent deuterium kinetic isotope effect of k(H)/k(D) = 1.17 ± 0.08 is observed; activation parameters (ΔH(Pd)(++) = 14.0 ± 0.6 kcal/mol and ΔS(Pd)(++)= -20 ± 2 cal/mol·K) were obtained for the 3-catalyzed cleavage reaction of 2b. Possible mechanisms are discussed for the reactions catalyzed by 3 at low and high sspH. This catalytic system is shown to promote the methanolytic cleavage of O,O-dimethyl phosphorothioate in CD3OD, producing (CD3O)2P═O(S(-)) with a half time for reaction of 34 min.     

Direct oxidation of L-cysteine by [FeIII(bpy)2(CN)2]+ and [FeIII(bpy)(CN)4]-

The oxidation of L-cysteine by the outer-sphere oxidants [Fe(bpy)2(CN)2]+ and [Fe(bpy)(CN)4]- in anaerobic aqueous solution is highly susceptible to catalysis by trace amounts of copper ions. This copper catalysis is effectively inhibited with the addition of 1.0 mM dipicolinic acid for the reduction of [Fe(bpy)2(CN)2]+ and is completely suppressed with the addition of 5.0 mM EDTA (pH<9.00), 10.0 mM EDTA (9.010.0) for the reduction of [Fe(bpy)(CN)4]-. 1H NMR and UV-vis spectra show that the products of the direct (uncatalyzed) reactions are the corresponding Fe(II) complexes and, when no radical scavengers are present, L-cystine, both being formed quantitatively. The two reactions display mild kinetic inhibition by Fe(II), and the inhibition can be suppressed by the free radical scavenger PBN (N-tert-butyl-alpha-phenylnitrone). At 25 degrees C and micro=0.1 M and under conditions where inhibition by Fe(II) is insignificant, the general rate law is -d[Fe(III)]/dt=k[cysteine]tot[Fe(III)], with k={k2Ka1[H+]2+k3Ka1Ka2[H+]+k4Ka1Ka2Ka3{/}[H+]3+Ka1[H+]2+Ka1Ka2[H+]+Ka1Ka2Ka3}, where Ka1, Ka2, and Ka3 are the successive acid dissociation constants of HSCH2CH(NH3+)CO2H. For [Fe(bpy)2(CN)2]+, the kinetics over the pH range of 3-7.9 yields k2=3.4+/-0.6 M(-1) s(-1) and k3=(1.18+/-0.02)x10(6) M(-1) s(-1) (k4 is insignificant in the fitting). For [Fe(bpy)(CN)4]- over the pH range of 6.1-11.9, the rate constants are k3=(2.13+/-0.08)x10(3) M(-1) s(-1) and k4=(1.01+/-0.06)x10(4) M(-1) s(-1) (k2 is insignificant in the fitting). All three terms in the rate law are assigned to rate-limiting electron-transfer reactions in which various thiolate forms of cysteine are reactive. Applying Marcus theory, the self-exchange rate constant of the *SCH2CH(NH2)CO2-/-SCH2CH(NH2)CO2- redox couple was obtained from the oxidation of L-cysteine by [Fe(bpy)(CN)4]-, with k11=4x10(5) M(-1) s(-1). The self-exchange rate constant of the *SCH2CH(NH3+)CO2-/-SCH2CH(NH3+)CO2- redox couple was similarly obtained from the rates with both Fe(III) oxidants, a value of 6x10(6) M(-1) s(-1) for k11 being derived. Both self-exchange rate constants are quite large as is to be expected from the minimal rearrangement that follows conversion of a thiolate to a thiyl radical, and the somewhat lower self-exchange rate constant for the dianionic form of cysteine is ascribed to electrostatic repulsion.     

Formation and stability of enolates of acetamide and acetate anion: an Eigen plot for proton transfer at alpha-carbonyl carbon

Second-order rate constants were determined in D(2)O for deprotonation of acetamide, N,N-dimethylacetamide, and acetate anion by deuterioxide ion and for deprotonation of acetamide by quinuclidine. The values of k(B) = 4.8 x 10(-8) M(-1) s(-1) for deprotonation of acetamide by quinuclidine (pK(BH) = 11.5) and k(BH) = 2-5 x 10(9) M(-1) s(-1) for the encounter-limited reverse protonation of the enolate by protonated quinuclidine give pK(a)(C) = 28.4 for ionization of acetamide as a carbon acid. The limiting value of k(HOH) = 1 x 10(11) s(-1) for protonation of the enolate of acetate anion by solvent water and k(HO) = 3.5 x 10(-9) M(-1) s(-1) for deprotonation of acetate anion by HO(-) give pK(a)(C) approximately 33.5 for acetate anion. The change in the rate-limiting step from chemical proton transfer to solvent reorganization results in a downward break in the slope of the plot of log k(HO) against carbon acid pK(a) for deprotonation of a wide range of neutral alpha-carbonyl carbon acids by hydroxide ion, from -0.40 to -1.0. Good estimates are reported for the stabilization of the carbonyl group relative to the enol tautomer by electron donation from alpha-SEt, alpha-OMe, alpha-NH(2), and alpha-O(-) substituents. The alpha-NH(2) and alpha-OMe groups show similar stabilizing interactions with the carbonyl group, while the interaction of alpha-O(-) is only 3.4 kcal/mol more stabilizing than for alpha-OH. We propose that destabilization of the enolate intermediates of enzymatic reactions results in an increasing recruitment of metal ions by the enzyme to provide electrophilic catalysis of enolate formation.     

A new zinc(II) fluorophore 2-(9-anthrylmethylamino)ethyl-appended 1,4,7,10-tetraazacyclododecane

A new 2-(9-anthrylmethylamino)ethyl-appended cyclen, L(3) (1-(2-(9-anthrylmethylamino)ethyl)-1,4,7,10-tetraazacyclododecane) (cyclen = 1,4,7,10-tetraazacyclododecane), was synthesized and characterized for a new Zn(2+) chelation-enhanced fluorophore, in comparison with previously reported 9-anthrylmethylcyclen L(1) (1-(9-anthrylmethyl)-1,4,7,10-tetraazacyclododecane) and dansylamide cyclen L(2). L(3) showed protonation constants log K(a)(i)() of 10.57 +/- 0.02, 9.10 +/- 0.02, 7.15 +/- 0.02, <2, and <2. The log K(a3) value of 7.15 was assigned to the pendant 2-(9-anthrylmethylamino)ethyl on the basis of the pH-dependent (1)H NMR and fluorescence spectroscopic measurements. The potentiometric pH titration study indicated extremely stable 1:1 Zn(2+)-L(3) complexation with a stability constant log K(s)(ZnL(3)) (where K(s)(ZnL(3)) = [ZnL(3)]/[Zn(2+)][L(3)] (M(-)(1))) of 17.6 at 25 degrees C with I = 0.1 (NaNO(3)), which is translated into the much smaller apparent dissociation constant K(d) (=[Zn(2+)](free)[L(3)](free)/[ZnL(3)]) of 2 x 10(-)(11) M with respect to 5 x 10(-)(8) M for L(1) at pH 7.4. The quantum yield (Phi = 0.14) in the fluorescent emission of L(3) increased to Phi = 0.44 upon complexation with zinc(II) ion at pH 7.4 (excitation at 368 nm). The fluorescence of 5 microM L(3) at pH 7.4 linearly increased with a 0.1-5 microM concentration of zinc(II). By comparison, the fluorescent emission of the free ligand L(1) decreased upon binding to Zn(2+) (from Phi = 0.27 to Phi = 0.19) at pH 7.4 (excitation at 368 nm). The Zn(2+) complexation with L(3) occurred more rapidly (the second-order rate constant k(2) is 4.6 x 10(2) M(-)(1) s(-)(1)) at pH 7.4 than that with L(1) (k(2) = 5.6 x 10 M(-)(1) s(-)(1)) and L(2) (k(2) = 1.4 x 10(2) M(-)(1) s(-)(1)). With an additionally inserted ethylamine in the pendant group, the macrocyclic ligand L(3) is a more effective and practical zinc(II) fluorophore than L(1).     

Determination of the pKa of cyclobutanone: Brønsted correlation of the general base-catalyzed enolization in aqueous solution and the effect of ring strain

The induction of strain in carbocycles, thereby increasing the amount of s-character in the C-H bonds and the acidity of these protons, has been probed with regard to its effect on the rate constants for the enolization of cyclobutanone. The second-order rate constants for the general base-catalyzed enolization of cyclobutanone have been determined for a series of 3-substituted quinuclidine buffers in D(2)O at 25 °C, I = 1.0 M (KCl). The rate constants for enolization were determined by following the extent of deuterium incorporation (up to ～30% of the first α-proton) into the α-position, as a function of time. The observed pseudo-first-order rate constants correlated to the [basic form] of the buffer and yielded the second-order rate constants for the general base-catalyzed enolization of cyclobutanone for four tertiary amine buffers. A Br?nsted β-value of 0.59 was determined from the second-order rate constants determined. Comparison of the results for cyclobutanone to those previously reported for acetone and a 1-phenylacetone derivative, under similar conditions, indicated that the ring strain of the carbocycle appeared to have only a small effect on the general base-catalyzed rate constants for enolization. The similarity of the rate constants for the general base-catalyzed enolization of cyclobutanone to those determined for acetone allowed for an estimation of the limits of the rate constant for protonation of the enolate intermediate of cyclobutanone by the conjugate acid of 3-quinuclidinone (k(BH) = 5 × 10(8) - 2 × 10(9) M(-1) s(-1)). Combining the rate constants for deprotonation of cyclobutanone (k(B)) and protonation of the enolate of cyclobutanone (k(BH)) by 3-quinuclidinone and its conjugate acid, the pK(a) of the α-protons of cyclobutanone has been estimated to be pK(a) = 19.7-20.2.     

Stable simple enols. Self-catalyzed E/Z-isomerization of the sterically crowded 2-(m-methoxymesityl)-1,2-dimesitylethenol

(E)-2-(m-methoxymesityl)-1,2-dimesitylethenol (3a) isomerizes in the absence of a catalyst in solution to a 1.0:0.9 E/Z (3a/3b) equilibrium mixture. In CDCl3 the isomerization is first order in 3a within a run, but the plot of the rate constant k(obs) vs the changing [3a]0 in different runs is a half-parabola, indicating self-catalysis by more than one enol molecule. At 0.09 M enol, the isotope effect k(3a)/k(3a)-OD = 2.1. In the presence of 0.025-0.25 M pyridine-d5, the k(obs) vs [pyridine-d5] plot displays a bell-shaped profile. The change in the shape of the OH signals of the 3a/3b mixture at 295-430 K in C6D5NO2 was followed by DNMR. The four signals of the diastereomeric 3a/3b mixture observed at 330 K coalesce at 350 K with barriers of 18.3 and 18.4 kcal x mol(-1) due to the diastereomerization of the vinyl propellers. The resulting two signals observed at >360 K further coalesce at 425 K with a barrier of 22.9 kcal x mol(-1) due either to oxygen-to-oxygen proton exchange or to E/Z isomerization. The estimated upper limit for the rate of proton exchange of k(ex) < or = (2-4) x 10(3) M(-1) x s(-1) at 425 K between the enol molecules is sufficiently slow to be a rate-controlling step in the isomerization. A process in which several enol molecules catalyze the isomerization is suggested, and several mechanistic routes are analyzed.     

Thermodynamics and kinetics of the nickel(II)-salicylhydroxamic acid system. Phenol rotation induced by metal ion binding

The kinetics and the equilibria of Ni(II) binding to p-hydroxybenzohydroxamic acid (PHBHA) and salicylhydroxamic acid (SHA) have been investigated in an aqueous solution at 25 degrees C and I=0.2 M by the stopped-flow method. Two reaction paths involving metal binding to the neutral acid and to its anion have been observed. Concerning PHBHA, the rate constants of the forward and reverse steps are k1=(1.9+/-0.1)x10(3) M-1 s-1 and k-1=(1.1+/-0.1)x10(2) s-1 for the step involving the undissociated PHBHA and k2=(3.2+/-0.2)x10(4) M-1 s-1 and k-2=1.2+/-0.2 s-1 for the step involving the anion. Concerning SHA, the analogous rate constants are k1=(2.6+/-0.1)x10(3) M-1 s-1, k-1=(1.3+/-0.1)x10(3) s-1, k2=(5.4+/-0.2)x10(3) M-1 s-1, and k-2=6.3+/-0.5 s-1. These values indicate that metal binding to the anions of the two acids concurs with the Eigen-Wilkins mechanism and that the phenol oxygen is not involved in the chelation. Moreover, a slow effect was observed in the SHA-Ni(II) system, which has been put down to rotation of the benzene ring around the C-C bond. Quantum mechanical calculations at the B3LYP/lanL2DZ level reveal that the phenol group in the most stable form of the Ni(II) chelate is in trans position relative to the carbonyl oxygen, contrary to the free SHA structure, where the phenol and carbonyl oxygen atoms both have cis configuration. These results bear out the idea that the complex formation is coupled with phenol rotation around the C-C bond.