Progress in Reaction Kinetics and Mechanism

The pH range for Compound I formation of horseradish peroxidase (2.5 to 11) is the largest for any known enzyme reaction. A key part of the reaction is proton transfer from hydrogen peroxide to distal His42. This proton is retained to complete formation of a water leaving group as the ferryl porphyrin π-cation radical is formed. How can the imidazolium side chain of His42 retain a proton at very high pH? And how can it give up the proton when required at very low pH? The answer is rearrangement of electronic charge through Electron Density Circuits (EDCs) in the protein matrix. An increase of at least 9 pK_a units, which occurs on the imidazole side chain of His42 as the Compound I reactive intermediate is formed, is facilitated by an EDC. A reverse EDC facilitates proton transfer to form the water leaving group. The pathway of the EDC involves the heme, its propionate side chains, Arg41, and His42. The occurrence of EDCs in chymotrypsin reactions reinforces the nucleophilic attack, and the subsequent electron and proton transfers. They also can shift pK_a values. The catalytic triad of chymotrypsin is Ser195, His57, and Asp102. The currently accepted one-proton transfer mechanism involves Ser195 and His57, with Asp102 being regarded as too acidic to accept a proton. A comparatively small shift in the pK_a value of Asp102 is all that is required to make it a proton acceptor from His57 so a two-proton mechanism may occur.

Second-order rate constants (k₁) have been measured spectrophotometrically for reactions of 2,4,6-tris(trifluoromethanesulfonyl)anisole 1 with 4-X-substituted anilines (X = OH, OCH₃, CH₃, H, I and Cl) 2a–f in dimethyl sulfoxide (DMSO) at 25 °C. The Hammett plot is nonlinear, i.e. the anilines having an electron-donating substituent exhibit positive deviations from the log k₁ versus correlation. The Hammett plot consists of two intersecting straight lines, i.e. ρ=– 1.40 for electron-withdrawing substituents (X = I and Cl) while ρ=– 3.26 for electron-donating substituents (X = OH, OCH₃ and CH₃). The Brønsted-type plot is also nonlinear with a change in slope from a small value (β_nuc=0.50) to a large value (β_nuc = 1.29 at pK_a=4.58). This change could be interpreted in terms of a change in mechanism from a polar S_NAr process to a single electron transfer. On the other hand, the experimental data show that the rate constants (k₁) values exhibit good correlation with the oxidation potentials (E°) of the aniline nucleophiles and are consistent with the suggested mechanism.

Four symmetrical bis-Schiff bases with either benzo-10-aza-crown ether or morpholino pendants and their Mn(III) and Co(II) complexes have been employed as models for hydrolase enzymes by studying the kinetics of their hydrolysis reactions with p-nitrophenyl picolinate (PNPP) in buffered CTAB micellar solution. A kinetic model of PNPP cleavage catalysed by these complexes is proposed. The effects of complex structures and reaction temperature on the rate of PNPP hydrolysis have been examined. All four complexes exhibit higher catalytic activity in the buffered CTAB micellar solution and the rate increases with pH of the buffer at 25 °C. The complexes containing two crown ether group exhibit higher catalytic activities than their crown-free analogues, and the catalytic activity of the phenyl-bridged Schiff base complex is larger than that of the ethyl-bridged Schiff base complex for the same substituents and metal. The catalytic activity of the manganese(III) complex exceeds that of the cobalt(II) complex in catalysing hydrolysis of PNPP under the same ligand.

The microscopic features of binary solvent systems formed by molecular solvents (methanol, ethanol, 2-methylpropan-2-ol, water, pyridine, acetonitrile, 1-propanol, 2-propanol, dimethylformamide) and the ionic liquid ([bmim]BF₄) as cosolvent were used to select mixed solvents with particular characteristics. Molecular-microscopic solvent parameters corresponding to these binary mixtures were utilised to study the kinetics of the nucleophilic substitution reaction between 2-chloro-3,5-dinitropyridine and aniline to investigate and compare the effects of the solvents on a model chemical reaction. For these mixtures, the solvation behaviour is dominated by both the dipolarity/polarisability and hydrogen bonding interactions of the media. In these solutions, the rate constants of the reaction decrease with the mole fraction of ionic liquid.

Theoretical studies of the Claisen and thio-Claisen allylic (3,3-sigmatropic) rearrangements and decomposition reactions of allyl formate (1) and allyl dithioformate (2), have been performed using density functional theory (DFT) and B3LYP and MPW1PW91 methods with a 6-31++G^** basis set. Of these DFT, the values for activation parameters obtained with the B3LYP/6-31++G^** method are in good agreement with the available experimental data. Transition states optimised at the B3LYP/6-31++G^** level of theory were used for calculating the nucleus-independent chemical shift (NICS). Our results indicate that the magnitudes of the aromatic characters of the transition states are not in agreement with the activation energies and therefore these reactions are not controlled by aromaticity, but are controlled kinetically by the aromaticity of the transition states.

The mechanism of the cycloaddition reaction between singlet state unsaturated silylene dichlorosilylenesilylene [Cl₂Si = Si:] and ethylene, which generates a silicic bis-heterocyclic compound, has been investigated with the CCSD(T)// MP2/6-31G^* method. The calculations show that the dominant reaction pathway consists of three steps. (I) The 3p unoccupied orbital of the Si atom in dichlorosilylenesilylene [Cl₂Si = Si:] (R1) and the π-orbital of ethylene (R2) firstly form a π → p donor–acceptor bond, which makes the two reactants generate a three-membered cyclic intermediates (INT) through a barrier-free exothermic reaction of 127.7 kJ mol⁻¹. (II) INT then isomerises to a four-membered cyclic silylene (P1) by the ring-expansion effect, which is via a transition state (TS1) with an energy barrier of 6.4 kJ mol⁻¹. (III) sp³ hybridisation of the Si atom finally makes P1 react directly with ethylene to form a silicic bis-heterocyclic compound (P2) without any intermediates and transition states, and this step is also a barrier-free exothermic reaction of 138.6 kJ mol⁻¹.

A theoretical study of the kinetics and mechanism of the intramolecular cycloaddition of 1,2,3-triazolo-1,4-benzoxazine was performed using DFT methods at the B3LYP level of theory with 6-311++G(d,p) basis set at 298.15 K and 310.15 K. Equilibrium molecular geometries and harmonic vibrational frequencies of the reactant, transition state and product were calculated. The solvent effect on the kinetic and thermodynamic parameters of the reaction were investigated. The calculated rate constants and activation thermodynamic parameters showed good agreement with experimental results. These calculations indicated that the reaction proceeds through a synchronous concerted mechanism.

The mechanism of the cycloaddition reaction between singlet state silylene germylidene (H₂Si = Ge:) and ethene has been investigated with the CCSD(T)//MP2/6-31G^* method; from the potential energy profile, we predict that the reaction has one dominant reaction pathway. This dominant pathway has the two reactants firstly forming a Si-heterocyclic four-membered ring germylene (INT1) through a [2 + 2] cycloaddition reaction. Due to the sp³ hybridisation of the Ge: atom in INT1, the latter further combines with ethene to form a bis-heterocyclic product containing Si and Ge (P2).

Using field induced surface photovoltage spectroscopy (FISPS) and photocatalysis, the effect of non-current field induction on photocatalysis has been studied. Enhancement has been observed for the photocatalytic oxidation of organic compounds (phenol as a model molecule) with TiO₂ film electrodes under non-current field. With this technique, photocatalysis displays an efficient, power-saving and stable performance. The FISPS technique has been developed to explain some of the experimental observations. It is concluded that the effect of non-current field induction on photocatalysis is mainly due more efficient charge separation resulting in an increase in surface photovoltage.

This article focuses on the drug–drug interaction between acetaminophen (also known as paracetamol) and β-lactam antibiotics (amoxicillin, ampicillin and penicillin) studied by means of cyclic voltammetry and controlled potential coulometry. The results indicate a drug–drug interaction between N-acetyl-p-benzoquinone-imine (NAPQI) derived from the anodic oxidation of acetaminophen and β-lactam antibiotics. Also the cyclic voltammetric data were analysed by digital simulation to measure the observed homogeneous rate constants (k_obs) of the reaction of NAPQI with β-lactam antibiotics. The calculated k_obs for the reaction between NAPQI and β-lactam antibiotics was found to vary in the order k_obs^amoxicillin = k_obs^ampicillin>k_obs^penicillinat biological pH.