Extraordinary chiral discrimination in inclusion gas chromatography. Thermodynamics of enantioselectivity between a racemic perfluorodiether and a modified γ-cyclodextrin

The enantiomers of the perfluorodiether “compound B” [2-(fluoromethoxy)-3-methoxy-1,1,1,3,3-pentafluoropropane], a decomposition product of the inhalational anesthetic sevoflurane [2-(fluoromethoxy)-1,1,1,3,3,3-hexafluoropropane], were separated by gas chromatography on octakis(3-O-butanoyl-2,6-di-O-n-pentyl)-γ-cyclodextrin (Lipodex E), dissolved in polysiloxane PS 255 (30% w/w), with an unexpectedly high separation factor of =10.6 at 26 °C. Using the concept of the retention increment R′, non-enantioselective and enantioselective contributions to retention were separated and thus reliable thermodynamic parameters of enantioselectivity, i.e. −Δ_S,R(ΔG)=5.7 (0.05) kJ/mol at 303 K, −Δ_S,R(ΔH)=20.1 (0.64) kJ/mol, Δ_S,R(ΔS)=−47.4 (2.0) J/K mol and T_isoenant=424 (30) K or 150 °C, were determined by temperature-dependent measurements. The enantiomeric bias represents the largest values ever measured in enantioselective gas chromatography. An equation is presented which allows calculation of the non-enantioselective contributions to retention from measurements at two arbitrary concentrations of Lipodex E in polysiloxane. Surprisingly, the enantioselectivity is greatly reduced when employing the β-cyclodextrin analogue and breaks down completely with the -cyclodextrin analogue of Lipodex E.     

Determination of interconversion barriers by dynamic gas chromatography: epimerization of chalcogran

The four stereoisomers of chalcogran 1 ((2RS,SRS)-2-ethyl-1,6-di-oxaspiro[4.4]nonane), the principal component of the aggregation pheromone of the bark beetle pityogenes chalcographus, are prone to interconversion at the spiro center (C5). During diastereo- and enantioselective dynamic gas chromatography (DGC), epimerization of 1 gives rise to two independent interconversion peak profiles, each featuring a plateau between the peaks of the interconverting epimers. To determine the rate constants of epimerization by dynamic gas chromatography (DGC), equations to simulate the complex elution profiles were derived, using the theoretical plate model and the stochastic model of the chromatographic process. The Eyring activation parameters of the experimental interconversion profiles, between 70 and 120 C in the presence of the chiral stationary phase (CSP) Chirasil-beta-Dex, were then determined by computer-aided simulation with the aid of the new program Chrom-Win: (2R,5R)-1: deltaG(++) (298.15 K) = 108.0 +/-0.5 kJ mol(-1), deltaH(++) = 47.1+/-0.2 kJ mol(-1), deltaS(++) = -204+/-6 JK(-1) mol(-1): (2R,5S)-1: deltaG(++) (298.15 K) = 108.5+/-0.5 kJ mol(-1), deltaH(++) = 45.8+/-0.2 kJ mol(-1), deltaS(++) = -210 +/-6 J K mol(-1); (2S,5S)-1: deltaG(++) (298.15 K)= 108.1+/-0.5 kJ mol(-1), deltaH(++) = 49.3+/-0.3 kJ mol(-1), deltaS(++) = -197+/-8 J K(-1) mol(-1); (2S,5R)-1: deltaG(++) (298.15 K)=108.6+/-0.5 kJ mol(-1), deltaH(++) = 48.0+/-0.3 kJ mol(-1), deltaS(++) = -203+/-8 J K(-1) mol(-1). The thermodynamic Gibbs free energy of the E/Z equilibrium of the epimers was determined by the stopped-flow multidimensional gas chromatographic technique: deltaG(E/Z) (298.15 K)= -0.5 kJ mol(-1), deltaH(E/Z) = 1.4 kJ mol(-1) and deltaS(E/Z) = 6.3 J K(-1) mol(-1). An interconversion pathway proceeding through ring-opening and formation of a zwitterion and an enol ether/alcohol intermediate of 1 is proposed.     

3,3'-Bis(trisarylsilyl)-substituted binaphtholate rare earth metal catalysts for asymmetric hydroamination

Chiral 3,3'-bis(trisarylsilyl)-substituted binaphtholate rare earth metal complexes (R)-[Ln{Binol-SiAr3}(o-C6H4CH2NMe2)(Me2NCH2Ph)] (Ln = Sc, Lu, Y; Binol-SiAr3 = 3,3'-bis(trisarylsilyl)-2,2'-dihydroxy-1,1'-binaphthyl; Ar = Ph (2-Ln), 3,5-xylyl (3-Ln)) and (R)-[La{Binol-Si(3,5-xylyl)3}{E(SiMe3)2}(THF)2] (E = CH (4a), N (4b)) are accessible via facile arene, alkane, and amine elimination. They are efficient catalysts for the asymmetric hydroamination/cyclization of aminoalkenes, giving TOF of up to 840 h(-1) at 25 degrees C for 2,2-diphenyl-pent-4-enylamine (5c) using (R)-2-Y. Enantioselectivities of up to 95% ee were achieved in the cyclization of 5c with (R)-2-Sc. The reactions show apparently zero-order rate dependence on substrate concentration and first-order rate dependence on catalyst concentration, but rates depend on total amine concentrations. Activation parameters for the cyclization of pent-4-enylamine using (R)-2-Y (deltaH(S)(double dagger) = 57.4(0.8) kJ mol(-1) and deltaS(S)(double dagger) = -102(3) J K(-1) mol(-1); deltaH(R)(double dagger) = 61.5(0.7) kJ mol(-1) and deltaS(R)(double dagger) = -103(3) J K(-1) mol(-1)) indicate a highly organized transition state. The binaphtholate catalysts were also applied to the kinetic resolution of chiral alpha-substituted aminoalkenes with resolution factors f of up to 19. The 2,5-disubstituted aminopentenes were formed in 7:1 to > or = 50:1 trans diastereoselectivity, depending on the size of the alpha-substituent of the aminoalkene. Rate studies with (S)-1-phenyl-pent-4-enylamine ((S)-15e) gave the activation parameters for the matching (deltaH(double dagger) = 52.2(2.8) kJ mol(-1), deltaS(double dagger) = -127(8) J K(-1) mol(-1) using (S)-2-Y) and mismatching (deltaH(double dagger) = 57.7(1.3) kJ mol(-1), deltaS(double dagger) = -126(4) J K(-1) mol(-1) using (R)-2-Y) substrate/catalyst combination. The absolute configuration of the Mosher amide of (2S)-2-methyl-4,4-diphenyl-pyrrolidine and (2R)-methyl-(5S)-phenyl-pyrrolidinium chloride, prepared from (S)-15e, were determined by crystallographic analysis. Catalyst (R)-4a showed activity in the anti-Markovnikov addition of n-propylamine to styrene.     

Integration of catalysis and analysis is the key: rapid and precise investigation of the catalytic asymmetric Gosteli-Claisen rearrangement

The kinetics of the Cu(II)(bisoxazoline)-catalyzed diastereo- and enantioselective Gosteli-Claisen rearrangement of 2-alkoxycarbonyl-substituted allyl vinyl ethers has been investigated by enantioselective on-column reaction gas chromatography (ocRGC). Enantioselective ocRGC integrates (stereoselective) catalysis and enantioselective chromatography in a single microcapillary, which is installed in a GC-MS for direct analysis of conversion and selectivity. Thus, this technique allows direct differentiation of thermal and stereoselectively catalyzed reaction pathways and determination of activation parameters and selectivities of the individual reaction pathways starting from stereoisomeric reactants with high precision. Two modes of operation of enantioselective ocRGC are presented to investigate noncatalyzed, i.e., conversion of isopropyl-2-(allyloxy)but-2Z-enoate 1 to isopropyl-3R,S-methyl-2-oxy-hex-5-enoate (±)-2 and the [Cu{(R,R)-Ph-box}](SbF(6))(2)-catalyzed Gosteli-Claisen rearrangement, i.e., conversion of isopropyl-2-(but-2'E-en-1-yloxy)but-2Z-enoate (E,Z)-3 to isopropyl-3S,4S-dimethyl-2-oxy-hex-5-enoate 4b. Eyring activation parameters have been determined by temperature-dependent measurements: Uncatalyzed rearrangement of 1 to (±)-2 gives ΔG(?) (298 K) = 114.1 ± 0.2 kJ·mol(-1), ΔH(?) = 101.1 ± 1.9 kJ·mol(-1), and ΔS(?) = -44 ± 5 J·(K·mol)(-1), and catalyzed rearrangement of (E,Z)-3 to 4b gives ΔG(?)(298 K) = 101.1 ± 0.3 kJ·mol(-1), ΔH(?) = 106.1 ± 6.6 kJ·mol(-1), and ΔS(?) = 17 ± 19 J·(K·mol)(-1).     

Practice and theory of enantioselective complexation gas chromatography

The practice and theory of enantioselective complexation GC is comprehensively reviewed for the first time. A multitude of racemic oxygen-, nitrogen- and sulfur-containing selectands can be separated without prior derivatization into enantiomers by complexation GC on optically active metal(II) bis[3-(perfluoroacyl)-(1R)-camphorate] selectors. Peak inversion is obtained when the selectors with opposite configuration are employed. Applications pertain to chiral analysis in asymmetric synthesis, enzymatic reactions, pheromone and flavour chemistry. Although the use of enantioselective complexation GC has diminished recently with the advent of modified cyclodextrins in enantioselective GC, the inherent principles of enantiorecognition together with other enantioselective phenomena can be elucidated easily by complexation GC. Using the concept of the retention-increment R' which allows the distinction between non-enantioselective and enantioselective contributions to retention, concise thermodynamic parameters of enantioselectivity - deltaD,L(deltaG) are accessible. The enantiomerization of configurationally labile enantiomers can be investigated and quantified by complexation GC. Four distinct enantioselective processes and four different coalescence phenomena have been discerned in complexation GC.     

d-orbital effects on stereochemical non-rigidity: twisted Ti(IV) intramolecular dynamics

The isomerization dynamics of tris-catecholate complexes have been investigated by variable-temperature NMR methods, demonstrating that the intramolecular racemization of Delta and Lambda enantiomers of d0 Ti(IV) is facile and faster than that of d10 Ga(III) and Ge(IV) analogues. Activation parameters for the racemization of K2[Ti2(3)] (H(2)2 = 2,3-dihydroxy-N,N'-diisopropylterephthalamide) were determined from line shape analysis of 1H NMR spectra [methanol-d4: deltaH++ = 47(1) kJ/mol; deltaS++ = -34(4) J/mol K; deltaG++(298) = 57(3) kJ/mol; DMF-d7: deltaH++ = 55(1) kJ/mol; deltaS++ = -16(4) J/mol K; deltaG++(298) = 59(3) kJ/mol; D2O (pD* = 8.6, 20% MeOD): deltaH++ = 48(3) kJ/mol; deltaS++ = -28(10) J/mol K; deltaG++(298) = 56(3) kJ/mol]. The study of K2[Ti4(3)] (H(2)4 = 2,3-dihydroxy-N-tert-butyl-N'-benzylterephthalamide) reveals two distinct isomerization processes: faster racemization of mer-[Ti4(3)]2- by way of a Bailar twist mechanism (D3h transition state) [T(c) approximately 242 K, methanol-d4], and a slower merright harpoon over left harpoonfac [Ti4(3)]2- isomerization by way of a Ray-Dutt mechanism (C2v transition state) [T(c) approximately 281 K, methanol-d4]. The solution behavior of the Ti(IV) complexes mirrors that reported previously for analogous Ga(III) complexes, while that of analogous Ge(IV) complexes was too inert to be detected by 1H NMR up to 400 K. These experimental findings are augmented by DFT calculations of the ML3 ground states and Bailar and Ray-Dutt transition states, which correctly predict the relative kinetic barriers of complexes of the three metal ions, in addition to faithfully reproducing the ground-state structures. Orbital calculations support the conclusion that participation of the Ti(IV) d orbitals in ligand bonding contributes to the greater stabilization of the prismatic Ti(IV) transition states.     

Solvation properties of N-substituted cis and trans amides are not identical: significant enthalpy and entropy changes are revealed by the use of variable temperature 1H NMR in aqueous and chloroform solutions and ab initio calculations

The cis/trans conformational equilibrium of N-methyl formamide (NMF) and the sterically hindered tert-butylformamide (TBF) was investigated by the use of variable temperature gradient 1H NMR in aqueous solution and in the low dielectric constant and solvation ability solvent CDCl3 and various levels of first principles calculations. The trans isomer of NMF in aqueous solution is enthalpically favored relative to the cis (deltaH(o) = -5.79 +/- 0.18 kJ mol(-1)) with entropy differences at 298 K (298 x deltaS(o) = -0.23 +/- 0.17 kJ mol(-1)) playing a minor role. The experimental value of the enthalpy difference strongly decreases (deltaH(o) = -1.72 +/- 0.06 kJ mol(-1)), and the contribution of entropy at 298 K (298 x deltaS(o) = -1.87 +/- 0.06 kJ mol(-1)) increases in the case of the sterically hindered tert-butylformamide. The trans isomer of NMF in CDCl3 solution is enthalpically favored relative to the cis (deltaH(o) = -3.71 +/- 0.17 kJ mol(-1)) with entropy differences at 298 K (298 x deltaS(o) = 1.02 +/- 0.19 kJ mol(-1)) playing a minor role. In the sterically hindered tert-butylformamide, the trans isomer is enthalpically disfavored (deltaH(o) = 1.60 +/- 0.09 kJ mol(-1)) but is entropically favored (298 x deltaS(o) = 1.71 +/- 0.10 kJ mol(-1)). The results are compared with literature data of model peptides. It is concluded that, in amide bonds at 298 K and in the absence of strongly stabilizing sequence-specific inter-residue interactions involving side chains, the free energy difference of the cis/trans isomers and both the enthalpy and entropy contributions are strongly dependent on the N-alkyl substitution and the solvent. The significant decreasing enthalpic benefit of the trans isomer in CDCl3 compared to that in H2O, in the case of NMF and TBF, is partially offset by an adverse entropy contribution. This is in agreement with the general phenomenon of enthalpy versus entropy compensation. B3LY/6-311++G** and MP2/6-311++G** quantum chemical calculations confirm the stability orders of isomers and the deltaG decrease in going from water to CHCl3 as solvent. However, the absolute calculated values, especially for TBF, deviate significantly from the experimental values. Consideration of the solvent effects via the PCM approach on NMF x H2O and TBF x H2O supermolecules improves the agreement with the experimental results for TBF isomers, but not for NMF.     

Gold(I) heteroatom-substituted imido complexes. Amino nitrene loss from

The heteroatom-substituted imido complexes [(LAu)3(mu-NX)]+ (X = NR2, R = Ph, Me, Bz; X = OH, Cl; L = a phosphine) have been prepared from the reactions of NH2X with [(LAu)3(mu-O)]+. Thermally unstable [(LAu)3(mu-NNMe2)]+ (L = P(p-XC6H4)3, X = H, F, Me, Cl, MeO) decompose to the gold cluster [LAu]6(2+) and tetramethyltetrazene Me2NN=NNMe2. The decomposition is first-order overall with a rate constant that increases with increasing pKa of the phosphine ligand. Activation parameters for the decomposition are deltaH(not equal to) = 99(4) kJ/mol and deltaS(not equal to) = 18.5(5) J/K.mol for L = PPh3 and deltaH(not equal to) = 78(3) kJ/mol and deltaS(not equal to) = -47(2) J/K.mol for L = P(p-MeOC6H4)3. The decomposition of analogous [(LAu)3(mu-NNBz2)]+ produces bibenzyl, indicative of the release of free amino nitrene Bz2NN.     

Platinum(II) and palladium(II) complexes of bisphosphine ligands bearing o-N,N-dimethylanilinyl substituents: a hint of catalytic olefin hydration

Platinum(II) and palladium(II) complexes of the potentially hexadentate P,N-donor ligand family Ar2P-X-PAr2 (X = (CH2)2 [dmape], cyclic-C5H8 [dmapcp]; Ar = o-N,N-dimethylanilinyl) are described. In CH2Cl2, the dmape complexes exist as equilibrium mixtures of MCl2(P,P'-dmape) and [MCl(P,P',N-dmape)]Cl isomers (M = Pd, Pt), governed by deltaH(o) = -19 +/- 4 kJ mol(-1) and deltaS(o) = -100 +/- 30 J mol(-1) K(-1) for M = Pt, and deltaH(o) = -11 +/- 7 kJ mol(-1) and deltaS(o) = -60 +/- 20 J mol(-1) K(-1) for M = Pd. The water-soluble dmapcp complexes exist solely in the [MCl(P,P',N-dmapcp)]Cl form, but the free and coordinated anilinyl rings in these complexes are in slow diastereoselective exchange. X-ray crystal structures for MCl2(P,P'-dmape) (M = Pd, Pt), and the [PdCl(P,P',N-dmape)]+ and [PtCl(P,P',N-dmapcp)]+ cations, are presented. Some of the complexes show marginal activity in water for the catalyzed hydration of maleic to malic acid, giving about 6-7% conversion in 24 h at 100 degrees C and substrate:catalyst loadings of 100:1. Attempts to synthesize a PdCl(P,P',N-dmapm)+ species led instead to isolation of [Pd(mu-Cl)(P,P'-dmapm)]2[PF6]2 (dmapm = Ar2PCH2Ar2).     

Structural and thermodynamic investigations of an unusual enantiomeric separation: Lipodex E and compound B

Compound B (1,1,3,3,3-pentafluoro-2-fluoromethoxy-1-methoxypropane) can be separated by gas chromatography with an extraordinary chiral separation factor on a column coated with Lipodex E (octakis(3-O-butanoyl-2,6-di-O-n-pentyl)-γ-cyclodextrin). The enantioselectivity is greatly reduced when employing the β-cyclodextrin analogue. To further investigate the background of this unusual separation, the complexation between ‘compound B’ and Lipodex E (octakis(3-O-butanoyl-2,6-di-O-n-pentyl)-γ-cyclodextrin) and heptakis(3-O-butanoyl-2,6-di-O-n-pentyl)-β-cyclodextrin were studied by NMR. Association constants of the interaction of the two enantiomers of compound B with Lipodex E and its β-cyclodextrin analogue were determined by NMR chemical shift titration and showed a large difference corroborating earlier GC results. Heteronuclear NOE measurements proved that inclusion complex formation is taking place with compound B situated inside the cavity of the cyclodextrin moiety. Differences between the inclusion complex structures and their connection to association constants are discussed.     

Optimized and validated initial-rate method for the determination of perindopril erbumine in tablets

A simple and sensitive kinetic spectrophotometric method for the determination of perindopril in pharmaceutical preparations is described. The method is based on the interaction of drug with 1-chloro-2,4-dinitrobenzene (CDNB) in dimethylsulfoxide (DMSO) at 40+/-1 degrees C. The reaction is followed spectrophotometrically by measuring the rate of change of the absorbance at 420 nm. Under the optimized experimental conditions, the calibration curve showed a linear relationship over the concentration range of 20-140 microg/ml. The activation parameter such as E(a), deltaH*, deltaS* and deltaG* for this reaction were calculated and found to be 27.31 kJ/mol, 24.69 kJ/mol, -138.84 J/K/mol and 61.50 kJ/mol, respectively. The method has been successfully applied to the determination of perindopril in commercial dosage forms. Statistical comparison of the results with the Abdellatef's spectrophotometric method shows excellent agreement and indicates no significant difference between the methods compared in terms of accuracy and precision.     

Interplay of Twisting and Folding in Overcrowded Heteromerous Bistricyclic Aromatic Enes

Fluorenylidenexanthenes 5-7 were synthesized by 2-fold extrusion diazo-thione couplings. 7 exhibited yellow crystals and purple (560 nm) solutions. (1)H NMR of 5 and 7 indicated subtle equilibria twisted (t) right harpoon over left harpoon anti-folded (a) major/minor conformations. (13)C DNMR of 6 gave DeltaG(c)(double dagger)(enantiomerization/inversion) = 26.5 kJ/mol and DeltaG(c)(double dagger)(E,Z-topomerization) = 82.0 kJ/mol. PM3 calculations of 5 revealed minima a, t, ts (twisted/syn-folded), DeltaDeltaH(f) degrees = 0.0, 14.1, 15.6 kJ/mol, and transition states [t-ts], [a-ts], [t( perpendicular)], [a-a], DeltaDeltaH(f) degrees = 16.3, 17.4, 82.2, 99.3 kJ/mol.     

Syntheses, structural determinations of [Ru(ROCS2)2(PPh3)2](+/0) pairs, and kinetic analyses of thermal reactions involving transient trans-[Ru(iPrOCS2)2(PPh3)2] species (ROCS2(-) = ethyl- or isopropyldithiocarbonate and PPh3 = triphenylphosphine)

Controlled-potential electrochemical oxidation of cis-[Ru(ROCS2)2(PPh3)2] (R = Et, iPr) yielded corresponding Ru(III) complexes, and the crystal structures of cis-[Ru(ROCS2)2(PPh3)2] and trans-[Ru(ROCS2)2(PPh3)2](PF6) were determined. Both pairs of complexes exhibited almost identical coordination structures. The Ru-P distances in trans-[Ru(III)(ROCS2)2(PPh3)2](PF6) [2.436(3)-2.443(3) A] were significantly longer than those in cis-[Ru(II)(ROCS2)2(PPh3)2] [2.306(1)-2.315(2) A]: the smaller ionic radius of Ru(III) than that of Ru(II) stabilizes the trans conformation for the Ru(III) complex due to the steric requirement of bulky phosphine ligands while mutual trans influence by the phosphine ligands induces significant elongation of the Ru(III)-P bonds. Cyclic voltammograms of the cis-[Ru(ROCS2)2(PPh3)2] and trans-[Ru(ROCS2)2(PPh3)2]+ complexes in dichloromethane solution exhibited typical dual redox signals corresponding to the cis-[Ru(ROCS2)2(PPh3)2](+/0) (ca. +0.15 and +0.10 V vs ferrocenium/ferrocene couple for R = Et and iPr, respectively) and to trans-[Ru(ROCS2)2(PPh3)2](+/0) (-0.05 and -0.15 V vs ferrocenium/ferrocene for R = Et and iPr, respectively) couples. Analyses on the basis of the Nicholson and Shain's method revealed that the thermal disappearance rate of transient trans-[Ru(ROCS2)2(PPh3)2] was dependent on the concentration of PPh3 in the bulk: the rate constant for the intramolecular isomerization reaction of trans-[Ru(iPrOCS2)2(PPh3)2] was determined as 0.338 +/- 0.004 s(-1) at 298.3 K (deltaH* = 41.8 +/- 1.5 kJ mol(-1) and deltaS* = -114 +/- 7 J mol(-1) K(-1)), while the dissociation rate constant of coordinated PPh3 from the trans-[Ru(iPrOCS2)2(PPh3)2] species was estimated as 0.113 +/- 0.008 s(-1) at 298.3 K (deltaH* = 97.6 +/- 0.8 kJ mol(-1) and deltaS* = 64 +/- 3 J mol(-1) K(-1)), by monitoring the EC reaction (electrode reaction followed by chemical processes) at different concentrations of PPh3 in the bulk. It was found that the trans to cis isomerization reaction takes place via the partial dissociation of iPrOCS2(-) from Ru(II), contrary to the previous claim that it takes place by the twist mechanism.     

Synthesis, structure, and reactivity of O-donor Ir(III) complexes: C-H activation studies with benzene

Various new thermally air- and water-stable alkyl and aryl analogues of (acac-O,O)2Ir(R)(L), R-Ir-L (acac-O,O = kappa2-O,O-acetylacetonate, -Ir- is the trans-(acac-O,O)2Ir(III) motif, R = CH3, C2H5, Ph, PhCH2CH2, L = Py) have been synthesized using the dinuclear complex [Ir(mu-acac-O,O,C3)-(acac-O,O)(acac-C3)]2, [acac-C-Ir]2, or acac-C-Ir-H2O. The dinuclear Ir (III) complexes, [Ir(mu-acac-O,O,C3)-(acac-O,O)(R)]2 (R = alkyl), show fluxional behavior with a five-coordinate, 16 electron complex by a dissociative pathway. The pyridine adducts, R-Ir-Py, undergo degenerate Py exchange via a dissociative mechanism with activation parameters for Ph-Ir-Py (deltaH++ = 22.8 +/- 0.5 kcal/mol; deltaS++ = 8.4 +/- 1.6 eu; deltaG++298 K) = 20.3 +/- 1.0 kcal/mol) and CH3-Ir-Py (deltaH++ = 19.9 +/- 1.4 kcal/mol; deltaS++ = 4.4 +/- 5.5 eu; deltaG++298 K) = 18.6 +/- 0.5 kcal/mol). The trans complex, Ph-Ir-Py, undergoes quantitatively trans-cis isomerization to generate cis-Ph-Ir-Py on heating. All the R-Ir-Py complexes undergo quantitative, intermolecular CH activation reactions with benzene to generate Ph-Ir-Py and RH. The activation parameters (deltaS++ =11.5 +/- 3.0 eu; deltaH++ = 41.1 +/- 1.1 kcal/mol; deltaG++298 K = 37.7 +/- 1.0 kcal/mol) for CH activation were obtained using CH3-Ir-Py as starting material at a constant ratio of [Py]/[C6D6] = 0.045. Overall the CH activation reaction with R-Ir-Py has been shown to proceed via four key steps: (A) pre-equilibrium loss of pyridine that generates a trans-five-coordinate, square pyramidal intermediate; (B) unimolecular, isomerization of the trans-five-coordinate to generate a cis-five-coordinate intermediate, cis-R-Ir- square; (C) rate-determining coordination of this species to benzene to generate a discrete benzene complex, cis-R-Ir-PhH; and (D) rapid C-H cleavage. Kinetic isotope effects on the CH activation with mixtures of C6H6/C6D6 (KIE = 1) and with 1,3,5-C6H3D3 (KIE approximately 3.2 at 110 degrees C) are consistent with this reaction mechanism.     

Kinetics and mechanism of hydrolysis of a model phosphate diester by [Cu(Me3tacn)(OH2)2]2+ (Me3tacn = 1,4,7-trimethyl-1,4,7-triazacyclononane)

The kinetics of hydrolysis of bis(p-nitrophenyl)phosphate (BNPP) by [Cu(Me3tacn)(OH2)2]2+ has been studied by spectrophotometrical monitoring of the release of the p-nitrophenylate ion from BNPP. The reaction was followed for up to 8000 min at constant BNPP concentration (15 microM) and ionic strength (0.15 M) and variable concentration of complex (1.0-7.5 mM) and temperature (42.5-65.0 degrees C). Biphasic kinetic traces were observed, indicating that the complex promotes the cleavage of BNPP to NPP [(p-nitrophenyl)phosphate] and then cleavage of the latter to phosphate, the two processes differing in rate by 50-100-fold. Analysis of the more amenable cleavage of BNPP revealed that the rate of BNPP cleavage is among the highest measured for mononuclear copper(II) complexes and is slightly higher than that reported for the close analogue [Cu(iPr3tacn)(OH2)2]2+. Detailed analysis required the determination of the pKa for [Cu(Me3tacn)(OH2)2]2+ and the constant for the dimerization of the conjugate base to [(Me3tacn)Cu(OH)2Cu(Me3tacn)]2+ (Kdim). Thermodynamic parameters derived from spectrophotometric pH titration and the analysis of the kinetic data were in reasonable agreement. Second-order rate constants for cleavage of BNPP by [Cu(Me3tacn)(OH2)(OH)]+ and associated activation parameters were obtained from initial rate analysis (k = 0.065 M(-1) s(-1) at 50.0 degrees C, deltaH = 56+/-6 kJ mol(-1), deltaS = -95+/-18 J K(-1) mol(-1)) and biphasic kinetic analysis (k = 0.14 M(-1) s(-1) at 50.0 degrees C, deltaH = 55+/-6 kJ mol(-1), deltaS = -92+/-20 J K(-1) mol(-1)). The negative entropy of activation is consistent with a concerted mechanism with considerable associative character. The complex was found to catalyze the cleavage of BNPP with turnover rates of up to 1 per day. Although these turnover rates can be considered low from an application point of view, the ability of the complexes to catalyze phosphate ester cleavage is clearly demonstrated.     

Highly enantioselective kinetic resolution of primary alcohols of the type Ph-X-CH(CH3)-CH2OH by Pseudomonas cepacia lipase: effect of acyl chain length and solvent

Although lipase from Pseudomonas cepacia (PCL) shows high enantioselectivity towards many secondary alcohols, it usually exhibits only low to moderate enantioselectivity towards primary alcohols. To increase this enantioselectivity, we optimised the reaction conditions for the PCL-catalysed hydrolysis of esters of three chiral primary alcohols: 2-methyl-3-phenyl-1-propanol 1, 2-phenoxy-1-propanol 2 and solketal 3. The enantioselectivity towards 1-acetate increased from E=16 to 38 upon changing the solvent from ethyl ether/phosphate buffer to 30% n-propanol in phosphate buffer and increased again to E ≥190 upon changing the substrate from 1-acetate to 1-heptanoate. The same changes increased the enantioselectivity towards alcohol 2 from E=17 to 70, but did not significantly increase the enantioselectivity towards alcohol 3. The best solvent was similar to the solvent used to crystallise the open form of PCL and likely stabilises the open form of PCL. This stabilisation may increase the enantioselectivity by removing kinetic contributions from a non-enantioselective lid-opening step. We determined the kinetic contribution of the lid-opening step by measuring the interfacial activation of PCL. The activation energy for the PCL-catalysed hydrolysis of ethyl acetate was at least 2.6 kcal/mol lower in the presence of a water–organic solvent interface.     

Synthesis of deuterium-labeled cryptophane-A and investigation of Xe@cryptophane complexation dynamics by 1D-EXSY-NMR experiments

We present the synthesis of a series of deuterated cryptophanes 2-6 by a slightly modified procedure used for cryptophane-A. We show that for [Xe@cryptophane] complexes the use of variable-temperature one-dimensional 129Xe magnetization transfer (1D-EX-SY) allows the measurement of exchange rates. From these data the decomplexation activation energy Ea has been estimated to be 37.5+/-2 kJ mol(-1). The decomplexation activation enthalpy, deltaH(++) = 35.5+/-2 kJ mol(-1), and entropy, deltaS(++) = -60+/-5 J mol(-1) K(-1), have also been calculated. The calculated negative activation entropy suggests that the activated complex associated with decomplexation is conformationally more strained than the complex in its ground state.     

Enantioselective complexation of chiral propylene oxide by an enantiopure water-soluble cryptophane

ECD and NMR experiments show that the complexation of propylene oxide (PrO) within the cavity of an enantiopure water-soluble cryptophane 1 in NaOH solution is enantioselective and that the (R)-PrO@PP-1 diastereomer is more stable than the (S)-PrO@PP-1 diastereomer with a free energy difference of 1.7 kJ/mol. This result has been confirmed by molecular dynamics (MD) and ab initio calculations. The enantioselectivity is preserved in LiOH and KOH solutions even though the binding constants decrease, whereas PrO is not complexed in CsOH solution.     

Thermal decomposition of trimethylgallium Ga(CH3)3: a shock-tube study and first-principles calculations

The thermal decomposition of Ga(CH3)3 has been studied both experimentally in shock-heated gases and theoretically within an ab-initio framework. Experiments for pressures ranging from 0.3 to 4 bar were performed in a shock tube equipped with atomic resonance absorption spectroscopy (ARAS) for Ga atoms at 403.3 nm. Time-resolved measurements of Ga atom concentrations were conducted behind incident waves as well as behind reflected shock waves at temperatures between 1210 and 1630 K. The temporal variation in Ga-atom concentration was described by a reaction mechanism involving the successive abstraction of methyl radicals from Ga(CH3)3 (R1), Ga(CH3)2 (R2), and GaCH3 (R3), respectively, where the last reaction is the rate-limiting step leading to Ga-atom formation. The rate constant of this reaction (R3) was deduced from a simulation of the measured Ga-atom concentration profiles using thermochemical data from ab-initio calculations for the reactions R1 and R2 as input. The Rice-Ramsperger-Kassel-Marcus (RRKM) method including variational transition state theory was applied for reaction R3 assuming a loose transition state. Structural parameters and vibrational frequencies of the reactant and transition state required for the RRKM calculations were obtained from first-principles simulations. The energy barrier E3(0) of reaction R3, which is the most sensitive parameter in the calculation, was adjusted until the RRKM rate constant matched the experimental one and was found to be E(0) = 288 kJ/mol. This value is in a good agreement with the corresponding ab-initio value of 266 kJ/mol. The rate constant of reaction R3 was found to be k 3/(cm(3) mol(-1)s(-1)) = 2.34 x 10(11) exp[-23330(K/ T)].     

Mechanistic insight into the activity of tyrosinase from variable-temperature studies in an aqueous/organic solvent

The activity of mushroom tyrosinase towards a representative series of phenolic and diphenolic substrates structurally related to tyrosine has been investigated in a mixed solvent of 34.4% methanol-glycerol (7:1, v/v) and 65.6% (v/v) aqueous 50 mM Hepes buffer at pH 6.8 at various temperatures. The kinetic activation parameters controlling the enzymatic reactions and the thermodynamic parameters associated with the process of substrate binding to the enzyme active species have been deduced from the temperature variation of the kcat and KM parameters. The activation free energy is dominated by the enthalpic term, the value of which lies in the relatively narrow range of 61+/-9 kJ mol(-1) irrespective of substrate or reaction type (monophenolase or diphenolase). The activation entropies are small and generally negative and contribute no more than 10% to the activation free energy. The substrate binding parameters are characterized by large and negative enthalpy and entropy contributions, which are typically dictated by polar protein-substrate interactions. The substrate 4-hydroxyphenylpropionic acid exhibits a strikingly anomalous temperature dependence of the enzymatic oxidation rate, with deltaH(double dagger) approximately = 150 kJ mol(-1) and deltaS(double dagger) approximately = 280 J K(-1) mol(-1), due to the fact that it can competitively bind to the enzyme through the phenol group, like the other substrates, or the carboxylate group, like carboxylic acid inhibitors. A kinetic model that takes into account the dual substrate/inhibitor nature of this compound enables rationalization of this anomalous behavior.