Billion-fold acceleration of the methanolysis of paraoxon promoted by La(OTf)3 in methanol

The methanolysis of the insecticide paraoxon (2) was investigated in methanol solution containing varying [La(OTf)(3)] (OTf = (-)OS(O)(2)CF(3)) as a function of at 25 degrees C. Plots of the pseudo-first-order rate constants (k(obs)) for methanolysis as a function of [La(OTf)(3)](total) were obtained under buffered conditions from 5.15 to 10.97, and the slopes of the linear parts of these were used to determine the second-order rate constants (k(2)(obs)) for the La(3+)-catalyzed methanolysis of 2. Detailed analysis of the potentiometric titration data of La(OTf)(3) in methanol through fits to a multicomponent equilibrium mixture of dimers of general stoichiometry La(3+)(2)((-)OCH3)n, where n assumes values of 1-5, gives the equilibrium distribution of each as a function of. These data, when fit to a second expression describing k(2)(obs) in terms of a linear combination of individual rate constants k(2)(2:1), k(2)(2:2).k(2)(2:)n for the dimers, allow one to describe the overall catalytic profile in terms of the individual contributions. The most catalytically important species are the three dimers La(3+)(2)((-)OCH3)1, La(3+)(2)((-)OCH3)2, and La(3+)(2)((-)OCH3)3. The catalysis of the methanolysis of 2 is spectacular: a 2 x 10(-3) M solution of [La(3+)](total), at neutral, affords a 10(9)-fold acceleration relative to the base reaction (t(1/2) approximately 20 s at 8.2) with excellent turnover. A mechanism of the catalyzed reaction involving the La(3+)(2)((-)OCH3)2 species is proposed.     

Simple, rapid, and highly sensitive detection of diphosgene and triphosgene by spectrophotometric methods

Methods for the detection and estimation of diphosgene and triphosgene are described. These compounds are widely used phosgene precursors which produce an intensely colored purple pentamethine oxonol dye when reacted with 1,3-dimethylbarbituric acid (DBA) and pyridine (or a pyridine derivative). Two quantitative methods are described, based on either UV absorbance or fluorescence of the oxonol dye. Detection limits are ∼4 μmol/L by UV and <0.4 μmol/L by fluorescence. The third method is a test strip for the simple and rapid detection and semi-quantitative estimation of diphosgene and triphosgene, using a filter paper embedded with dimethylbarbituric acid and poly(4-vinylpyridine). Addition of a test solution to the paper causes a color change from white to light blue at low concentrations and to pink at higher concentrations of triphosgene. The test strip is useful for quick on-site detection of triphosgene and diphosgene in reaction mixtures. The test is easy to perform and provides clear signal readouts indicative of the presence of phosgene precursors. The utility of this method was demonstrated by the qualitative determination of residual triphosgene during the production of poly(bisphenol-A carbonate).     

La3+-catalyzed methanolysis of N-aryl-beta-lactams and nitrocefin

The kinetics of the La(3+)-catalyzed methanolysis of N-phenyl-beta-lactam (2) and N-p-nitrophenyl-beta-lactam (3) as well as that of nitrocefin (1) were studied at 25 degrees C under buffered conditions. In the case of 2 and 3, the observed second-order rate constants (k(2)(obs)) for catalysis plateau at pH 7.5-7.8, reaching values of 1 x 10(-)(2) and 35 x 10(-)(2) M(-)(1) s(-)(1) respectively. Potentiometric titrations of solutions of 2 x 10(-)(3) M La(OTf)(3) were analyzed in terms of a dimer model (La(3+)(2)((-)OCH(3))(n)()), where the number of methoxides varies from 1 to 5. The species responsible for catalysis in the pH range investigated contain 1-3 methoxides, the one having the highest catalytic activity being La(3+)(2)((-)OCH(3))(2), which comprises 80% of the total La(3+) forms present at its pH maximum of 8.9. The catalysis afforded by the La(3+) dimers at a neutral pH is impressive relative to the methoxide reactions: at pH 8.4 a 1 mM solution of catalyst (generated from 2 mM La(OTf)(3)) accelerated the methanolysis of 2 by approximately 2 x 10(7)-fold and 3 by approximately 5 x 10(5)-fold. As a function of metal ion concentration, the La(3+)-catalyzed methanolysis of 1 proceeds by pathways involving first one bound metal ion and then a second La(3+) leading to a plateau in the k(obs) vs [La(3+)](total) plots at all pH values. The k(max)(obs) pseudo-first-order rate constants at the plateaus, representing the spontaneous methanolysis of La(3+)(2)(1(-)) forms, has a linear dependence on [(-)OCH(3)] (slope = 0.84 +/- 0.05 if all pH values are used and 1.02 +/- 0.03 if all but the two highest pH values are used). The speciation of bound 1 at a La(3+) concentrations corresponding to that of the onset of the kinetic plateau region was approximated through potentiometric titration of the nonreactive 3,5-dinitrobenzoic acid in the presence of 2 equiv of La(OTf)(3). A total speciation diagram for all bound forms of La(3+)(2)(1(-))((-)OCH(3))(n)(), where n = 0-5, was constructed and used to determine their kinetic contributions to the overall pH vs k(max)(obs) plot under kinetic conditions. Two kinetically equivalent mechanisms were analyzed: methoxide attack on La(3+)(2)(1(-))((-)OCH(3))(n)(), n = 0-2; unimolecular decomposition of the forms La(3+)(2)(1(-))((-)OCH(3))(n)(), n = 1-3.     

Catalysis of the methanolysis of activated amides by divalent and trivalent metal ions. The effect of Zn(2+), Co(2+), and La(3+) on the methanolysis of acetylimidazole and its (NH(3))(5)Co(III) complex.

The metal ions Zn(2+), Co(2+), and La(3+) strongly catalyze the methanolysis of the activated amides acetylimidazole (1) and its ligand-exchange-inert Co(III) complex, (NH(3))(5)Co(III)-AcIm (2). Studies of the kinetics of methanolysis are performed with pH measurement and control, and the metal ions are soluble in the medium throughout the pH regions where ionization of the M(x+)(CH(3)OH)(y) occurs. Zn(2+) and Co(2+) act as Lewis acids toward 1, catalyzing attack of external methoxide on a 1:M(2+) complex at values only 100-fold lower than the diffusion limit, the k(OR) values being 5.6 x 10(7) M(-1) s(-1) and 2.5 x 10(7) M(-1) s(-1), while that for CH(3)O(-) attack on 2 is 4.69 x 10(7) M(-1) s(-1). Since neither Zn(2+) nor Co(2+) promotes the methanolysis of 2, these metals appear to be acting through transient binding to the distal N of 1, which activates the C=O of the complex to external CH(3)O(-) attack. La(3+) catalyzes the methanolysis of both 1 and 2, which occurs by a mechanism that is fundamentally different from that exhibited by Zn(2+) and Co(2+) in that the active species appears to be a bis-methoxy-bridged dimer (La(3+))(2)(CH(3)O(-))(2)(CH(3)OH)(x)() that interacts directly with the C=O unit of the substrate.     

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.     

Water-exchange study revealed unexpected substitution behavior of [(CO)2(NO)Re(H2O)3]2+ in aqueous media

The pH-dependent water-exchange rates of [(CO)2(NO)Re(H2O(cis))2(H2O(trans))]2+ (1) in aqueous media were investigated by means of 17O NMR spectroscopy at 298 K. Because of the low pK(a) value found for 1 (pK(a) = 1.4 +/- 0.3), the water-exchange rate constant k(obs)(H2O(trans/cis)) was analyzed with a two-pathway model in which k(Re)(H2O(trans/cis)) and k(ReOH)(H2O)(trans/cis)) denote the water-exchange rate constants in trans or cis position to the nitrosyl ligand on 1 and on the monohydroxo species [(CO)2(NO)Re(H2O)2(OH)]+ (2), respectively. Whereas the rate constants k(ReOH)(H2O)(trans)) and k(ReOH)(H2O)(cis)) were determined as (4.2 +/- 2) x 10(-3) s(-1) and (5.8 +/- 2) x 10(-4) s(-1), respectively, k(Re)(H2O)(trans)) and k(Re)(H2O)(cis)) were too small to be determined in the presence of the much more reactive species 2. Apart from the water exchange, an unexpectedly fast C identical with 16O --> C identical withO exchange was also observed via NMR and IR spectroscopy. It was found to proceed through 1 and 2, with rate constants k(Re)(CO) and k(ReOH)(CO) of (19 +/- 4) x 10(-3) s(-1) and (4 +/- 3) x 10(-3) s(-1), respectively. On the other hand, N identical with 16O --> N identical with *O exchange was not observed.     

Kinetics and mechanism of large rate enhancement in the alkaline hydrolysis of N'-morpholino-N-(2'-methoxyphenyl)phthalamide

The apparent second-order rate constant (k OH) for hydroxide-ion-catalyzed conversion of 1 to N-(2'-methoxyphenyl)phthalamate (4) is approximately 10(3)-fold larger than k OH for alkaline hydrolysis of N-morpholinobenzamide (2). These results are explained in terms of the reaction scheme 1 --> k(1obs) 3 --> k(2obs) 4 where 3 represents N-(2'-methoxyphenyl)phthalimide and the values of k(2obs)/k(1obs) vary from 6.0 x 10(2) to 17 x 10(2) within [NaOH] range of 5.0 x 10(-3) to 2.0 M. Pseudo-first-order rate constants (k(obs)) for alkaline hydrolysis of 1 decrease from 21.7 x 10(-3) to 15.6 x 10(-3) s(-1) with an increase in ionic strength (by NaCl) from 0.5 to 2.5 M at 0.5 M NaOH and 35 degrees C. The values of k obs, obtained for alkaline hydrolysis of 2 within [NaOH] range 1.0 x 10(-2) to 2.0 M at 35 degrees C, follow the relationship k(obs) = kOH[HO(-)] + kOH'[HO (-)] (2) with least-squares calculated values of kOH and kOH' as (6.38 +/- 0.15) x 10(-5) and (4.59 +/- 0.09) x 10(-5) M (-2) s(-1), respectively. A few kinetic runs for aqueous cleavage of 1, N'-morpholino-N-(2'-methoxyphenyl)-5-nitrophthalamide (5) and N'-morpholino-N-(2'-methoxyphenyl)-4-nitrophthalamide (6) at 35 degrees C and 0.05 M NaOH as well as 0.05 M NaOD reveal the solvent deuterium kinetic isotope effect (= k(obs) (H 2) (O)/ k(obs) (D 2 ) (O)) as 1.6 for 1, 1.9 for 5, and 1.8 for 6. Product characterization study on the cleavage of 5, 6, and N-(2'-methoxyphenyl)-4-nitrophthalimide (7) at 0.5 M NaOD in D2O solvent shows the imide-intermediate mechanism as the exclusive mechanism.     

A simple DNase model system comprising a dinuclear Zn(II) complex in methanol accelerates the cleavage of a series of methyl aryl phosphate diesters by 10(11)-10(13)

The di-Zn(II) complex of 1,3-bis[ N1, N1'-(1,5,9-triazacyclododecyl)]propane with an associated methoxide ( 3:Zn(II) 2: (-)OCH 3) was prepared and its catalysis of the methanolysis of a series of fourteen methyl aryl phosphate diesters ( 6) was studied at s (s)pH 9.8 in methanol at 25.0 +/- 0.1 degrees C. Plots of k obs vs [ 3:Zn(II) 2: (-)OCH 3] free for all members of 6 show saturation behavior from which K(M) and kcat (max) were determined. The second order rate constants for the catalyzed reactions (kcat (max)/K(M)) for each substrate are larger than the corresponding methoxide catalyzed reaction (k 2 (-OMe)) by 1.4 x 10(8) to 3 x 10 (9)-fold. The values of k cat (max) for all members of 6 are between 4 x 10(11) and 3 x 10(13) times larger than the solution reaction at s (s)pH 9.8, with the largest accelerations being given for substrates where the departing aryloxy unit contains ortho-NO 2 or C(O)OCH 3 groups. Based on the linear Br?nsted plots of k cat (max) vs s (s)pKa of the phenol, beta lg values of -0.57 and -0.34 are determined respectively for the catalyzed methanolysis of "regular" substrates that do not contain the ortho-NO 2 or C(O)OCH 3 groups, and those substrates that do. The data are consistent with a two step mechanism for the catalyzed reaction with rate limiting formation of a catalyst-coordinated phosphorane intermediate, followed by fast loss of the aryloxy leaving group. A detailed energetics calculation indicates that the catalyst binds the transition state comprising [CH 3O (-): 6], giving a hypothetical [ 3:Zn(II) 2:CH 3O (-): 6] complex, by -21.4 to -24.5 kcal/mol, with the strongest binding being for those substrates having the ortho-NO 2 or C(O)OCH 3 groups.     

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.     

Divergent pathways of C-H bond activation: reactions of (t-Bu(3)PN)(2)TiMe(2) with trimethylaluminum

The reaction of AlMe(3) with (t-Bu(3)PN)(2)TiMe(2) 1 proceeds via competitive reactions of metathesis and C-H activation leading ultimately to two Ti complexes: [(mu(2)-t-Bu(3)PN)Ti(mu-Me)(mu(4)-C)(AlMe(2))(2)](2) 2, [(t-Bu(3)PN)Ti(mu(2)-t-Bu(3)PN)(mu(3)-CH(2))(2)(AlMe(2))(2)(AlMe(3))] 3, and the byproduct (Me(2)Al)(2)(mu-CH(3))(mu-NP(t-Bu(3))) 4. X-ray structural data for 2 and 3 are reported. Compound 3 undergoes thermolysis to generate a new species [Ti(mu(2)-t-Bu(3)PN)(2)(mu(3)-CH(2))(mu(3)-CH)(AlMe(2))(3)] 5. Monitoring of the reaction of 1 with AlMe(3) by (31)P[(1)H] NMR spectroscopy revealed intermediates including (t-Bu(3)PN)TiMe(3) 6. Compound 6 was shown to react with AlMe(3) to give 2 exclusively. Kinetic studies revealed that the sequence of reactions from 6 to 2 involves an initial C-H activation that is a second-order reaction, dependent on the concentration of Ti and Al. The second-order rate constant k(1) was 3.9(5) x 10(-4) M(-1) s(-1) (DeltaH(#) = 63(2) kJ/mol, DeltaS(#) = -80(6) J/mol x K). The rate constants for the subsequent C-H activations leading to 2 were determined to be k(2) = 1.4(2) x 10(-3) s(-1) and k(3) = 7(1) x 10(-3) s(-1). Returning to the more complex reaction of 1, the rate constant for the ligand metathesis affording 4 and 6 was k(met) = 6.1(5) x 10(-5) s(-1) (DeltaH(#) = 37(3) kJ/mol, DeltaS(#) = -203(9) J/mol x K). The concurrent reaction of 1 leading to 3 was found to proceed with a rate constant of k(obs) of 6(1) x 10(-5) s(-1) (DeltaH(#) = 62(5) kJ/mol, DeltaS(#)= -118(17) J/mol x K). Using these kinetic data for these reactions, a stochastic kinetic model was used to compute the concentration profiles of the products and several intermediates with time for reactions using between 10 and 27 equivalents of AlMe(3). These models support the view that equilibrium between 1 x AlMe(3) and 1 x (AlMe(3))(2) accounts for varying product ratios with the concentration of AlMe(3). In a similar vein, similar equilibria account for the transient concentrations of 6 and an intermediate en route to 3. The implications of these reactions and kinetic and thermodynamic data for both C-H bond activation and deactivation pathways for Ti-phosphinimide olefin polymerization catalysts are considered and discussed.     

Kinetics of the reactions of chlorinated methyl radicals (CH2Cl, CHCl2, and CCl3) with NO2 in the temperature range 220-360 K

The kinetics of the reactions of chlorinated methyl radicals (CH2Cl, CHCl2, and CCl3) with NO2 have been studied in direct measurements at temperatures between 220 and 360 K using a tubular flow reactor coupled to a photoionization mass spectrometer. The radicals have been homogeneously generated at 193 or 248 nm by pulsed laser photolysis of appropriate precursors. Decays of radical concentrations have been monitored in time-resolved measurements to obtain the reaction rate coefficients under pseudo-first-order conditions with the amount of NO2 being in large excess over radical concentrations. The bimolecular rate coefficients of all three reactions are independent of the bath gas (He or N2) and pressure within the experimental range (1-6 Torr) and are found to depend on temperature as follows: k(CH2Cl + NO2) = (2.16 +/- 0.08) x 10(-11) (T/300 K)(-1.12+/-0.24) cm3 molecule(-1) s(-1) (220-363 K), k(CHCl2 + NO2) = (8.90 +/- 0.16) x 10(-12) (T/300 K)(-1.48+/-0.13) cm3 molecule(-1) s(-1) (220-363 K), and k(CCl3 + NO2) = (3.35 +/- 0.10) x 10(-12) (T/300 K)(-2.2+/-0.4) cm3 molecule(-1) s(-1) (298-363 K), with the uncertainties given as one-standard deviations. Estimated overall uncertainties in the measured bimolecular reaction rate coefficients are about +/-25%. In the reactions CH2Cl + NO2, CHCl2 + NO2, and CCl3 + NO2, the products observed are formaldehyde, CHClO, and phosgene (CCl2O), respectively. In addition, a weak signal for the HCl formation has been detected for the CHCl2 + NO2 reaction.     

Sensitive and Visual Detection of Phosgene by a TICT-Based BODIPY Dye with 8-(o-Hydroxy)aniline as the Active Site

Phosgene and its substitutes (diphosgene and triphosgene) are widely utilized as chemical industrial materials and chemical warfare agents and pose a threat to public health and environmental safety due to their extreme toxicity. Research efforts have been directed to develop selective and sensitive detection methods for phosgene and its substitutes. In this paper, we have prepared two BODIPY-based fluorescent probes, o-Pah and o-Pha, which are two isomers with different active sites, ortho-aminohydroxy (3′,4′ or 4′,3′) phenyls at meso position of BODIPY, and compared their sensing performance toward triphosgene. The probe with o-(4′-amino-3′-hydroxyl), o-Pha, exhibits better sensing performance over the o-(3′-amino-4′-hydroxyl), o-Pah, for instance, a lower limit of detection (LOD) (0.34 nm vs. 1.2 nm ), and more rapid response (10 s vs. 200 s). Furthermore, based on the above comparative studies, a red-fluorescence probe o-Phae has been constructed through extending 3,5-conjugation of o-Pha. The probe o-Phae displays rapid response (60 s), high sensitivity to triphosgene (LOD=0.88 nm ), and high selectivity for triphosgene over relevant analytes including nitric oxide. Finally, a facile test strip for phosgene was fabricated by immobilizing o-Phae in a polyethylene oxide membrane for sensitive (<2 ppm) and selective detection of phosgene in the gas phase.     

Thermodynamics, kinetics, and mechanism of the stepwise dissociation and formation of Tris(L-lysinehydroxamato)iron(III) in aqueous acid

pK(a) values for the hydroxamic acid, alpha-NH(3)(+), and epsilon-NH(3)(+) groups of L-lysinehydroxamic acid (LyHA, H(3)L(2+)) were found to be 6.87, 8.89, and 10.76, respectively, in aqueous solution (I = 0.1 M, NaClO(4)) at 25 degrees C. O,O coordination to Fe(III) by LyHA is supported by H(+) stoichiometry, UV-vis spectral shifts, and a shift in nu(CO) from 1648 to 1592 cm(-1) upon formation of mono(L-lysinehydroxamato)tetra(aquo)iron(III) (Fe(H(2)L)(H(2)O)(4)(4+)). The stepwise formation of tris(L-lysinehydroxamato)iron(III) from Fe(H(2)O)(6)(3+) and H(3)L(2+) was characterized by spectrophotometric titration, and the values for log beta(1), log beta(2), and log beta(3) are 6.80(9), 12.4(2), and 16.1(2), respectively, at 25 degrees C and I = 2.0 M (NaClO(4)). Stopped-flow spectrophotometry was used to study the proton-driven stepwise ligand dissociation kinetics of tris(L-lysinehydroxamato)iron(III) at 25 degrees C and I = 2.0 M (HClO(4)/NaClO(4)). Defining k(n) and k(-n) as the stepwise ligand dissociation and association rate constants and n as the number of bound LyHA ligands, k(3), k(-3), k(2), k(-2), k(1), and k(-1) are 3.0 x 10(4), 2.4 x 10(1), 3.9 x 10(2), 1.9 x 10(1), 1.4 x 10(-1), and 1.2 x 10(-1) M(-1) s(-1), respectively. These rate and equilibrium constants are compared with corresponding constants for Fe(III) complexes of acetohydroxamic acid (AHA) and N-methylacetohydroxamic acid (NMAHA) in the form of a linear free energy relationship. The role of electrostatics in these complexation reactions to form the highly charged Fe(LyHA)(3)(6+) species is discussed, and an interchange mechanism mediated by charge repulsion is presented. The reduction potential for tris(L-lysinehydroxamato)iron(III) is -214 mV (vs. NHE), and a comparison to other hydroxamic acid complexes of Fe(III) is made through a correlation between E(1/2) and pFe.     

Reactivity difference between diphosgene and phosgene in reaction with (2,3-anti)-3-amino-1,2-diols

In reactions of (2,3-anti)-3-amino-1,2-diols with diphosgene and phosgene and their conversion into 1,3-oxazolidin-2-ones, some differences in the stereochemistry of the reactions have been found with these two reagents. The reactions with phosgene afforded the expected cis-oxazolidinones, and in the reaction with diphosgene under the same reaction conditions, the trans-oxazolidinones were also obtained.     

Cobalt(III) complexes of [3(5)] adamanzane, 1,5,9,13-tetraazabicyclo[7.7.3]nonadecane. Report of an inert, chelate hydrogen carbonate ion

Three cobalt(III) complexes of the macrocyclic tetraamine [3(5)]adamanzane (1,5,9,13-tetraazabicyclo[7.7.3]nonadecane) were isolated as salts. The X-ray crystal structures were solved for the compounds [Co([3(5)]adz)(CO(3))]AsF(6) (1b), [Co([3(5)]adz)(HCO(3))]ZnBr(4).H(2)O (2a), and [Co([3(5)]adz)(SO(4))]AsF(6).H(2)O (3a). The coordination geometry around the cobalt(III) ion is a distorted octahedron with the inorganic ligands at cis-positions. Complex 2 is the second example of a cobalt(III) complex for which the X-ray structure shows a chelate binding mode of the hydrogen carbonate entity. The pK(a) value of the [Co([3(5)]adz)(HCO(3))](2+) ion (2) was determined spectrophotometrically to be 0.27 (25 degrees C, I = 5.0 M). The protonation appears to occur at the noncoordinated carbonyl oxygen atom of the carbonate group, with hydrogen bonding to the crystal water molecule. Evidence is presented for this oxygen atom as the site of protonation in solution as well. In 5.0 M CF(3)SO(3)H a slow reaction of the carbonato complex, quantitatively yielding the [Co([3(5)]adz)(H(2)O)(2)](3+) ion, was observed. k(obs) = 7.9(1) x 10(-)(6) s(-)(1) at 25 degrees C.     

La(3+)-Catalyzed methanolysis of hydroxypropyl-p-nitrophenyl phosphate as a model for the RNA transesterification reaction

The methanolysis of hydroxypropyl-p-nitrophenyl phosphate (HPNPP, 1) promoted by La(OTf)(3) under buffered conditions was studied in methanol as a function of pH at 25 degrees C. (31)P NMR studies at -90 degrees C indicate that there are at least three La/1 complexes formed at pH approximately 5.3 of 1:1, 2:2, and 1:2 stoichiometry. Kinetic studies of the observed pseudo-first-order rate constants for the methanolysis of 1 as a function of [La(3+)] at 4.5 < pH < 10.5 indicate there are two general pH regimes. In the low pH regime between 4.5 and 7.6, the plots of k(obs) versus [La(3+)] exhibit saturation behavior with very strong 1:1 binding, with a plateau rate constant that depends on [OCH(3)(-)]. The catalytically productive species is shown to be a 2:2 complex of La(3+) and 1, where the phosphate is proposed to be doubly activated, thereby promoting the methoxide reaction by some 4.6 x 10(10)-fold. In the high pH regime from 7.9 to 10.5, 1:1, 2:2, and 2:1 La(3+)/1 complexes are formed with the La(3+) coordinated in the form of [La(3+)(OCH(3)(-))](1,2). Throughout this pH regime at high [La(3+)], a saturation complex, (La(3+)OCH(3)(-))(2)/1, is formed that spontaneously decomposes with a rate constant of (5-10) x 10(-)(3) s(-)(1), leading to an acceleration of 10(9)-fold at pH 8.0.     

Mechanistic studies of nitric oxide reactions with water soluble iron(II), cobalt(II), and iron(III) porphyrin complexes in aqueous solutions: implications for biological activity.

The reactions of nitric oxide and carbon monoxide with water soluble iron and cobalt porphyrin complexes were investigated over the temperature range 298-318 K and the hydrostatic pressure range 0.1-250 MPa [porphyrin ligands: TPPS = tetra-meso-(4-sulfonatophenyl)porphinate and TMPS = tetra-meso-(sulfonatomesityl)porphinate]. Large and positive DeltaS(double dagger) and DeltaV(double dagger) values were observed for NO binding to and release from iron(III) complexes Fe(III)(TPPS) and Fe(III)(TMPS) consistent with a dissociative ligand exchange mechanism where the lability of coordinated water dominates the reactivity with NO. Small positive values for Delta and Delta for the fast reactions of NO with the iron(II) and cobalt(II) analogues (k(on) = 1.5 x 10(9) and 1.9 x 10(9) M(-1) s(-1) for Fe(II)(TPPS) and Co(II)(TPPS), respectively) indicate a mechanism dominated by diffusion processes in these cases. However, reaction of CO with the Fe(II) complexes (k(on) = 3.6 x 10(7) M(-1) s(-1) for Fe(II)(TPPS)) displays negative Delta and Delta values, consistent with a mechanism dominated by activation rather than diffusion terms. Measurements of NO dissociation rates from Fe(II)(TPPS)(NO) and Co(II)(TPPS)(NO) by trapping free NO gave k(off) values of 6.3 x 10(-4) s(-1) and 1.5 x 10(-4) s(-1). The respective M(II)(TPPS)(NO) formation constants calculated from k(on)/k(off) ratios were 2.4 x 10(12) and 1.3 x 10(13) M(-1), many orders of magnitude larger than that (1.1 x 10(3) M(-1)) for the reaction of Fe(III)(TPPS) with NO.     

Kinetics of Water Exchange on the Dihydroxo-Bridged Rhodium(III) Hydrolytic Dimer

()()Conventional (18)O isotopic labeling techniques have been used to measure the water exchange rates on the Rh(III) hydrolytic dimer [(H(2)O)(4)Rh(&mgr;-OH)(2)Rh(H(2)O)(4)](4+) at I = 1.0 M for 0.08 < [H(+)] < 0.8 M and temperatures between 308.1 and 323.1 K. Two distinct pathways of water exchange into the bulk solvent were observed (k(fast) and k(slow)) which are proposed to correspond to exchange of coordinated water at positions cis and trans to bridging hydroxide groups. This proposal is supported by (17)O NMR measurements which clearly showed that the two types of water ligands exchange at different rates and that the rates of exchange matched those from the (18)O labeling data. No evidence was found for the exchange of label in the bridging OH groups in either experiment. This contrasts with findings for the Cr(III) dimer. The dependence of both k(fast) and k(slow) on [H(+)] satisfied the expression k(obs) = (k(O)[H(+)](tot) +k(OH)K(a1))/([H(+)](tot) + K(a1)) which allows for the involvement of fully protonated and monodeprotonated Rh(III) dimer. The following rates and activation parameters were determined at 298 K. (i) For fully protonated dimer: k(fast) = 1.26 x 10(-)(6) s(-)(1) (DeltaH() = 119 +/- 4 kJ mol(-)(1) and DeltaS() = 41 +/- 12 J K(-)(1) mol(-)(1)) and k(slow) = 4.86 x 10(-)(7) s(-)(1) (DeltaH() = 64 +/- 9 kJ mol(-)(1) and DeltaS() = -150 +/- 30 J K(-)(1) mol(-)(1)). (ii) For monodeprotonated dimer: k(fast) = 3.44 x 10(-)(6) s(-)(1) (DeltaH() = 146 +/- 4 kJ mol(-)(1) and DeltaS() = 140 +/- 11 J K(-)(1) mol(-)(1)) and k(slow) = 2.68 x 10(-)(6) s(-)(1) (DeltaH() = 102 +/- 3 kJ mol(-)(1) and DeltaS() = -9 +/- 11 J K(-)(1) mol(-)(1)). Deprotonation of the Rh(III) dimer was found to labilize the primary coordination sphere of the metal ions and thus increase the rate of water exchange at positions cis and trans to bridging hydroxides but not to the same extent as for the Cr(III) dimer. Activation parameters and mechanisms for ligand substitution processes on the Rh(III) dimer are discussed and compared to those for other trivalent metal ions and in particular the Cr(III) dimer.     

A supramolecular receptor of diatomic molecules (O2, CO, NO) in aqueous solution

A per-O-methylated beta-cyclodextrin dimer, Py2CD, was conveniently prepared via two steps: the Williamson reaction of 3,5-bis(bromomethyl)pyridine and beta-cyclodextrin (beta-CD) yielding 2A,2'A-O-[3,5-pyridinediylbis(methylene)bis-beta-cyclodextrin (bisCD) followed by the O-methylation of all the hydroxy groups of the bisCD. Py2CD formed a very stable 1:1 complex (Fe(III)PCD) with [5,10,15,20-tetrakis(p-sulfonatophenyl)porphinato]iron(III) (Fe(III)TPPS) in aqueous solution. Fe(III)PCD was reduced with Na2S2O4 to afford the Fe (II)TPPS/Py2CD complex (Fe(II)PCD). Dioxygen was bound to Fe(II)PCD, the P(1/2)(O2) values being 42.4 +/- 1.6 and 176 +/- 3 Torr at 3 and 25 degrees C, respectively. The k(on)(O2) and k(off)(O2) values for the dioxygen binding were determined to be 1.3 x 10(7) M(-1) s(-1) and 3.8 x 10(3) s(-1), respectively, at 25 degrees C. Although the dioxygen adduct was not very stable (K(O2) = k(on)(O2)/k(off)(O2) = 3.4 x 10(3) M(-1)), no autoxidation of the dioxygen adduct of Fe(II)PCD to Fe(III)PCD was observed. These results suggest that the encapsulation of Fe (II)TPPS by Py2CD strictly inhibits not only the extrusion of dioxygen from the cyclodextrin cage but also the penetration of a water molecule into the cage. The carbon monoxide affinity of Fe(II)PCD was much higher than the dioxygen affinity; the P(1/2)(CO), k(on)(CO), k(off)(CO), and K(CO) values being (1.6 +/- 0.2) x 10(-2) Torr, 2.4 x 10(6) M(-1) s(-1), 4.8 x 10(-2) s(-1), and 5.0 x 10(7) M(-1), respectively, at 25 degrees C. Fe(II)PCD also bound nitric oxide. The rate of the dissociation of NO from (NO)Fe(II)PCD ((5.58 +/- 0.42) x 10(-5) s(-1)) was in good agreement with the maximum rate ((5.12 +/- 0.18) x 10(-5) s(-1)) of the oxidation of (NO)Fe(II)PCD to Fe(III)PCD and NO3(-), suggesting that the autoxidation of (NO)Fe(II)PCD proceeds through the ligand exchange between NO and O2 followed by the rapid reaction of (O2)Fe(II)PCD with released NO, affording Fe(II)PCD and the NO3(-) anion inside the cyclodextrin cage.     

Kinetics and Mechanism of the Reaction between Serum Albumin and Auranofin (and Its Isopropyl Analogue) in Vitro

The first detailed kinetic analysis and mechanistic interpretation of the reactions between serum albumin and the second-generation gold drug Auranofin [Et(3)PAuSATg = (triethylphosphine)(2,3,4,6-tetra-O-acetyl-1-beta-D-glucopyranosato-S-) gold(I)] and its triisopropylphosphine analogue, iPr(3)PAuSATg, in vitro are reported. The reactions were investigated using Penefsky spun columns and NMR saturation transfer methods. Under the Penefsky chromatography conditions with 0.4-0.6 mM albumin and a wide range of Et(3)PAuSATg concentrations, the reaction is biphasic. The fast phase is apparently first order in albumin with a rate constant [k(1) = 3.4 +/- 0.3 x 10(-)(2) s(-)(1)] that decreases slightly in magnitude and becomes intermediate in order at low gold concentrations, [Et(3)PAuSATg] < [AlbSH]; it accounts for approximately 95% of the Au(I) that binds. A minor, slower step [k(2) = 2.3 +/- 0.3 x 10(-)(3) s(-)(1)), which accounts for only 5% of the reaction, is also first order with respect to albumin, and zero order with respect to auranofin. For iPr(3)PAuSATg, only the first step was observed, k(1) = (1.4 +/- 0.1) x 10(-)(2) s(-)(1), and is first order in albumin and independent of the iPr(3)PAuSATg concentration. (31)P-NMR saturation transfer experiments utilizing iPr(3)PAuSATg, under equilibrium conditions, yielded second-order rate constants for both the forward (1.2 x 10(2) M(-)(1) s(-)(1)) and the reverse (3.9 x 10(1) M(-)(1) s(-)(1)) directions. A multistep mechanism involving a conformationally altered albumin species was developed. Albumin domain IA opens with concomitant Cys-34 rearrangement, allowing facile gold binding and exchange, and then closes. In conjunction with the steady-state approximation, this mechanism accounts for the different reaction orders observed under the two set of conditions. The rate-determining conformational change of albumin governs the reaction as monitored by the Penefsky columns. Rapid second order exchange of R(3)PAuSATg at the exposed Cys-34 residue is observed under the NMR conditions. The mechanism predicts that under physiological conditions where [Et(3)PAuSATg] is 10-25 &mgr;M, the reaction will be second order and rapid with a rate constant of 8 +/- 2 x 10(2) M(-)(1) s(-)(1). The Penefsky spun columns revealed a previously unreported and novel binding mechanism, association of auranofin in the pocket of albumin-disulfide species, which was confirmed by Hummel-Dreyer gel chromatographic techniques under equilibrium conditions. This albumin-auranofin complex (AlbSSR-Et(3)PAuSATg) is weakly bound and readily dissociates during conventional gel exclusion chromatography.