Diastereoselective and enantioselective alkaline-hydrolysis of 2-aryl-1-cyclohexyl acetate: a CAL-B catalyzed deacylation/acylation tandem process

Candida antarctica lipase proved to be a particularly efficient lipase for the resolution of racemic 2-arylcyclohexyl acetate in hydrolysis reaction with Na₂CO₃ in an organic medium. The (1R,2S)-trans-2-arylcyclohexanols 2a–2d were obtained with high ee values (up to >99%) and the selectivity reached E > 200. The influence of the enol ester and the solvent on (±)-trans-2-arylcyclohexanol in the CAL-B catalyzed acylation was also studied and compared with the deacylation. The CAL-B exhibits a better affinity for the alkaline hydrolysis reaction compared with acylation with the enol esters in the same organic solvents. The best conditions were applied to resolve a stereoisomeric mixture cis/trans-2-phenyl-1-cyclohexanol and its corresponding acetate by acylation and deacylation. The obtained results show a highly enantio- and diastereoselectivity of the CAL-B during the acylation and the deacylation in favor of the trans-(R)-enantiomer product. The resolution of a mixture of cis/trans-2-arylcyclohexanols was an easy, convenient approach to provide only one stereoisomer of a mixture of four with high enantiomeric excess.     

A theoretical study on the substrate deacylation mechanism of class C beta-lactamase

The whole reaction of the deacylation of class C beta-lactamase was investigated by performing quantum chemical calculations under physiological conditions. In this study, the X-ray crystallographic structure of the inhibitor moxalactam-bound class C beta-lactamase (Patera et al. J. Am. Chem. Soc. 2000, 122, 10504-10512.) was utilized and moxalactam was changed into the substrate cefaclor. A model for quantum chemical calculations was constructed using an energy-minimized structure of the substrate-bound enzyme obtained by molecular mechanics calculation, in which the enzyme was soaked in thousands of TIP3P water molecules. It was found that the deacylation reaction consisted of two elementary processes. The first process was formation of a tetrahedral intermediate, which was initiated by the activation of catalytic water by Tyr150, and the second process was detachment of the hydroxylated substrate from the enzyme, which associated with proton transfer from the side chain of Lys67 to Ser64O(gamma). The first process is a rate-determining process, and the activation energy was estimated to be 30.47 kcal/mol from density functional theory calculations considering electron correlation (B3LYP/6-31G**). The side chain of Tyr150 was initially in a deprotonated state and was stably present in the active site of the acyl-enzyme complex, being held by Lys67 and Lys315 cooperatively.     

The mechanism for the reversible oxygen addition to heme. A theoretical CASPT2 study

By performing CASPT2 calculations, the lowest energy pathway for oxygen addition to an isolated heme center of a heme-protein is evaluated and found to be reversible (the oxyheme compound is just 14.9 kcal mol(-1) more stable than the deoxyheme + O(2) reactants, and the energy barriers to dissociation are even smaller).     

Molecular mechanisms of antibiotic resistance: QM/MM modelling of deacylation in a class A beta-lactamase

Modelling of the first step of the deacylation reaction of benzylpenicillin in the E. coli TEM1 beta-lactamase (with B3LYP/6-31G + (d)//AM1-CHARMM22 quantum mechanics/molecular mechanics methods) shows that a mechanism in which Glu166 acts as the base to deprotonate a conserved water molecule is both energetically and structurally consistent with experimental data; the results may assist the design of new antibiotics and beta-lactamase inhibitors.     

Free radical scavenging and COX-2 inhibition by simple colon metabolites of polyphenols: A theoretical approach

Free radical scavenging and inhibitory potency against cyclooxygenase-2 (COX-2) by two abundant colon metabolites of polyphenols, i.e., 3-hydroxyphenylacetic acid (3-HPAA) and 4-hydroxyphenylpropionic acid (4-HPPA) were theoretically studied. Different free radical scavenging mechanisms are investigated in water and pentyl ethanoate as a solvent. By considering electronic properties of scavenged free radicals, hydrogen atom transfer (HAT) and sequential proton loss electron transfer (SPLET) mechanisms are found to be thermodynamically probable and competitive processes in both media. The Gibbs free energy change for reaction of inactivation of free radicals indicates 3-HPAA and 4-HPPA as potent scavengers. Their reactivity toward free radicals was predicted to decrease as follows: hydroxyl >> alkoxyls > phenoxyl ≈ peroxyls >> superoxide. Shown free radical scavenging potency of 3-HPAA and 4-HPPA along with their high μM concentration produced by microbial colon degradation of polyphenols could enable at least in situ inactivation of free radicals. Docking analysis with structural forms of 3-HPAA and 4-HPPA indicates dianionic ligands as potent inhibitors of COX-2, an inducible enzyme involved in colon carcinogenesis. Obtained results suggest that suppressing levels of free radicals and COX-2 could be achieved by 3-HPAA and 4-HPPA indicating that these compounds may contribute to reduced risk of colon cancer development.     

A theoretical study of the mechanism for the homogeneous catalytic reversible dehydrogenation-hydrogenation of nitrogen heterocycles

A mechanism for the dehydrogenation reaction of 1,2,3,4-tetrahydroquinoline to quinoline derivatives, catalyzed by a Cp*Ir complex containing a 2-pyridonate ligand, is proposed and supported by theoretical calculations at the B3LYP level. The proposed mechanism involves two stages which are all thermodynamically unfavorable (endothermic by 36.3 kcal mol(-1) and 18.4 kcal mol(-1), respectively). The apparent activation energies of the first and second stages of the reaction are 30.8 kcal mol(-1) and 34.0 kcal mol(-1), respectively, and are considered overestimates of the entropy change of reaction. Owing to a decrease in the oxidative ability of iridium(III) coordinated to large electronegative nitrogen and chlorine, ligand promoted hydrogen abstraction is crucial at both stages of dehydrogenation, in which the oxidation state of iridium(III) does not change, and the ligand 2-pyridonate is converted to 2-hydroxypyridine. Cp*Ir(C(5)NH(4)OH)ClH, an important intermediate, releases hydrogen through an energy barrier of 23.5 kcal mol(-1).     

A method for C2 acylation of 1,3-indandiones

The 1,3-indandione scaffold is an important structural motif used in the preparation of a large number of industrial chemical and pharmaceutical compounds. However, few approaches allow for the direct C2 acylation on these building blocks. A method was developed using DMAP and EDCI, which is mild in reactivity, covers a diverse range of carboxylic acid acylating agents, is compatible with electron releasing and withdrawing substituents on the 1,3-indandione partner, and performs well in a polar aprotic solvent (for solubility reasons) This method cleanly afforded twenty five different products in yields of 32–96%.     

A facile and efficient method for the selective deacylation of N-arylacetamides and 2-chloro-N-arylacetamides catalyzed by SOCl2

Thionyl chloride efficiently and selectively promoted the deacylation of N-arylacetamides and 2-chloro-N-arylacetamides, under anhydrous conditions, without effecting the ester group, aminosulfonyl group, or benzyloxyamide group. This method, which has been successfully applied to a variety of substrates including different N-arylacetamides and 2-chloro-N-arylacetamides, has the attractive advantages of inexpensive reagents, satisfactory selectivity, excellent yields, short reaction time, and convenient workup. This new method can probably be used to selectively deacylate between aromatic amides and alkyl amides.     

A new method for the acylation of pyrroles

N-Tosylpyrroles can be very efficiently converted into the corresponding 2-acylpyrroles by reaction with carboxylic acids and trifluoroacetic anhydride; little or none of the isomeric 3-acyl derivatives are formed.     

A macrothermodynamic approach to the limit of reversible capillary condensation

The threshold of reversible capillary condensation is a well-defined thermodynamic property, as evidenced by corresponding states treatment of literature and experimental data on the lowest closure point of the hysteresis loop in capillary condensation-evaporation cycles for several adsorbates. The nonhysteretical filling of small mesopores presents the properties of a first-order phase transition, confirming that the limit of condensation reversibility does not coincide with the pore critical point. The enthalpy of reversible capillary condensation can be calculated by a Clausius-Clapeyron approach and is consistently larger than the condensation heat in unconfined conditions. Calorimetric data on the capillary condensation of tert-butyl alcohol in MCM-41 silica confirm a 20% increase of condensation heat in small mesopores. This enthalpic advantage makes easier the overcoming of the adhesion forces by the capillary forces and justifies the disappearing of the hysteresis loop.     

H2 adsorption on Fe/ZSM-5 zeolite: a theoretical approach

The hydrogen reduction of the red-ox Fe/ZSM-5 zeolite is an essential step for catalyst preparation. In this letter, various adsorption modes of the H(2) molecules on the Fe(III)/ZSM-5 zeolite were first explored by density functional theory, with their exact configurations provided. The adsorption energies revealed that the two configurations with Fe(III) at the sextet states are the main ones, consistent with the results of inelastic neutron scattering (INS) experiments. On such basis, the vibrational and orbital analyses were made, which will be valuable for the future studies on the Fe/ZSM-5 systems.     

Redistribution in combinatorial synthesis. A theoretical approach

In modified versions of the split-mix method, the conventional solid support resin was replaced by labeled macroscopic support units in order to produce individual compounds in multi milligram quantities while the high productivity of the original procedure is preserved. Recently it has also been shown that tagging the units is unnecessary. Omission of the tags is possible if (i) the unlabeled support units are arranged into spatially ordered groups and the relative spatial arrangement of the units is maintained during the chemical reactions (ii) the support units are redistributed between the reaction steps according to a predetermined pattern permitted by the combinatorial redistribution rule and (iii) the sorting process is simulated by a computer that can trace the synthetic history of each support unit. Different kinds of solid support units, formation of spatially ordered groups, sorting devices and basic redistribution patterns (serial, semi-parallel and parallel) are discussed. It is also shown that particularly the semi-parallel and the parallel redistribution assure fast sorting.     

A theoretical approach for accurate predictions of the enthalpies of formation of carotenes

A computational approach has been designed for accurately determining enthalpies of formation (ΔH(f)) for the carotene species. This approach, named correlation corrected atomization (CCAZ), is based on the concept of bond and group additivity, and is applied along with density functional theory (DFT). Corrections to the deficiencies in DFT were divided into 1,2-, 1,3-, and 1,4- atomic interactions, which were determined by comparisons with the G3 data of the training set. When comparing predictions from CCAZ combined with two different DFT methods (B3LYP and MPWB1K), fairly accurate prediction is expected. In contrast, DFT using the atomization and isodesmic schemes resulted in poor predictions of ΔH(f). The equivalent methods, atomic equivalent (AEQ) and group equivalent (GEQ) provide improved predictions; however, the accuracies are lower than that of CCAZ.     

A theoretical approach to the kinetics of polymer degradation in solution

After main-chain scission in a polymer, the frequency of encounter between segments in the different fragments is related to the separating process between the fragments. The relationship obtained shows that the separating time is proportional to M ^½, where M is the molecular weight, when the excluded volume disappears. When good solvent is used, the half-time for the separation is obtained as τ_½ = const. M ^0.16–0.22, which is approximated to the experimental data obtained previously (τ_½ = const. M ^0.34 and τ_½ = const. M ^0.22) for the degradations of polyisobutene and poly(phenyl vinyl ketone), respectively. The increase of the half-time with increasing coil density can be explained by the excluded volume. The inverse proportionality of the diffusion of segments to solvent viscosity explains the proportionality of the half-time to microviscosity. The above separating process reverses the reaction between polymer radicals. From their dependence on the chain length, τ_½/k_D = const. M ^½ (where k_D is the specific rate for the reaction), is estimated. Such an approximation holds, regardless of the type of solvent.     

A theoretical investigation of the CH2+ di-cation

The reported observation of CH²⁺ ions, with a lifetime of a few microseconds formed as a result of charge-stripping of CH⁺ ions, is examined critically. A number of possible explanations of the observation as an experimental artifact are examined, and found wanting. Ab initio calculations of potential energy curves for CH²⁺ show that the repulsive curves correlating with C⁺ + H⁺ are seriously perturbed by bound states of the same symmetry which correlate with C²⁺ + H. The resultant potential curve for the ²Σ⁺ ground state has a slight dip whose depth has an uncertainty of a few tenths of an eV. It is shown that, while the dip in this potential curve cannot support any vibrational levels, scaling of the curve within the limits imposed by the uncertainties can yield such a metastable state, and hence can provide a self-consistent explanation of the experimental observations.     

A theoretical approach to the solvent extraction of metal chelates

A simplified theory for the solvent extraction of metal chelates is presented. Factors which are taken into account include the metal ion, the chelating reagent, aqueous complexing agents, adduct-forming substances, the organic solvent, temperature, rates of extraction, and other effects. Equations are developed for estimating the stoichiometries and the association constants of the involved species.     

MoO2Cl2 as a novel catalyst for Friedel-Crafts acylation and sulfonylation

The use of MoO₂Cl₂ as a novel catalyst for Friedel-Crafts acylation and sulfonylation is described. A series of aromatic ketones and sulfones were prepared in moderate to good yields using acyl chloride or sulfonyl chloride in the presence of MoO₂Cl₂ (20 mol %), under solvent-free conditions.