Energetic and stereochemical effects of the protein environment on substrate: a theoretical study of methylmalonyl-CoA mutase

QM/MM methods were used to study the isomerization step from (2R)-methylmalonyl-CoA to succinyl-CoA. A pathway via a "fragmentation-recombination" mechanism is ruled out on energetic grounds. For the other radicalic pathway, involving an addition recombination step, geometries and vibrational contributions have been determined, and a barrier height of 11.70 kcal/mol was found. The effect of adjacent hydrogen-donating groups was found to reduce the energy barrier by 1-2 kcal/mol each and thus to provide a significant catalytic effect for this reaction. By means of molecular dynamics studies, the stereochemistry of the methylmalonyl-CoA mutase catalyzed reaction was examined. It is shown that TYR89 is essential for maintaining stereoselectivity of the abstraction of a hydrogen in the backreaction. The subsequent selective formation of one isomer of methylmalonyl-CoA is probably due to the presence of a bulky side chain.     

Continuous flow hydroformylation of alkenes in supercritical fluid-ionic liquid biphasic systems

A process for the hydroformylation of relatively low volatility alkenes (demonstrated for 1-dodecene) in a continuous flow system is described. The catalyst is dissolved in an ionic liquid while the substrate and gaseous reagents are transported into the reactor dissolved in supercritical CO(2), which simultaneously acts as a transport vector for aldehyde products. Decompression of the fluid mixture downstream yields products which are free of both reaction solvent and catalyst. The use of rhodium complexes of triaryl phosphites leads to ligand degradation through reaction of the ionic liquid with water and subsequent attack of the released HF on the phosphite. Sodium salts of sulfonated phosphines are insufficiently soluble in the ionic liquids to obtain acceptable rates, but replacing the sodium by a cation similar to that derived from the ionic liquid, allows good solubility and activity to be obtained. The nature of the ionic liquid is very important in achieving high rates, with 1-alkyl-3-methylimidazolium bis(trifluoromethanesulfonyl)amides giving the best activity if the alkyl chain is at least C(8). Catalyst turnover frequencies as high as 500 h(-1) have been observed, with the better rates at higher substrate flow rates. Rhodium leaching into the product stream can be as low as 0.012 ppm, except at low partial pressures of CO/H(2), when it is significantly higher. Oxygen impurities in the CO(2) feed can lead to oxidation of the phosphine giving higher rates, lower selectivities to the linear aldehyde, increased alkene isomerization and greater leaching of rhodium. However, it is found that under certain process conditions, the supercritical fluid-ionic liquid (SCF-IL) system can be operated continuously for several weeks without any visible sign of catalyst degradation. Comparisons with commercial hydroformylation processes are provided.     

Structure and protonation of some indolizine derivatives studied by ab initio MO calculations

Some gauge invariant atomic orbitals-coupled-perturbed Hartree-Fock (GIAO-CPHF) calculations were performed for seven indolizine derivatives and their monoprotonated forms. Chemical shift, molecular geometry, and charge distribution data are reported for each molecule. The calculations support the results of nuclear magnetic resonance (NMR) spectroscopy measurements showing that protonation occurs preferentially at N1. The good agreement between the calculated and observed ¹³C and ¹⁵N chemical shifts show that such calculations can be used for chemical shift assignment purposes. Cation structures and probable sites for electrophilic reaction or second protonation are also discussed.     

Conformations of 1,3,3,5,7,7-Hexamethyl-1,5-diazacyclooctane and Its Bis-BH(3) Adduct. Mono- and Bis-BH(3) Adducts of Di-Tertiary Amines

A variable-temperature (1)H- and (13)C-NMR study revealed a conformational equilibrium for 1,3,3,5,7,7-hexamethyl-1,5-diazacyclooctane (4) having DeltaG() = 8.8 +/- 0.6 kcal/mol at 184 K. This activation barrier connects a major and a minor form of 4. Molecular mechanics calculations on 4 led to the conclusion that the major form is a set of twist-chair-chairs interconverting rapidly via the chair-chair and that the minor form is most likely a set of twist-boat-boats interconverting rapidly via the boat-boat. The proximity of the two nitrogen lone pairs in the major form of 4 made plausible the expectation that 4, as well as a related diamine with apposed nitrogens, 3,7-dimethyl-3,7-diazabicyclo[3.3.1]nonane (3), might bind a Lewis acid, namely BH(3), using both lone pairs simultaneously and equally. This proved not to be the case: for 3 only the bis-BH(3) adduct was found and for 4 the mono-BH(3) adduct utilized only one nitrogen lone pair. The structure of the bis-BH(3) adduct of 4 (12) was determined by X-ray crystallography to be a twist-boat-boat with BH(3)s cis. Molecular mechanics calculations on 12 were consistent with the solid state conformation found.     

NMR study of some sydnones,isosydnones, and isothiosydnones

Multinuclear¹H,¹³C,¹⁴N,¹⁵N, and¹⁷O NMR data are presented for some sydnones, isosydnones and isothiosydnones. The type of valence tautomerism shown in (Fig. 1) is not observed for the compounds studied. At high pH compounds2 and12 are found to undergo transformations. The more suitable NMR parameters are reported for establishing the structures of mesoionic compounds containing three heteroatoms in the five-membered conjugated ring. Someab initio GIAO calculations on a model structure of sydnones and related compounds have been performed.     

Continuous flow homogeneous catalysis using supercritical fluids

The continuous flow hydroformylation of 1-octene catalysed by Rh/[RMIM][Ph(2)PC(6)H(4)SO(3)](R = 1-propyl, 1-pentyl or 1-octyl) dissolved only in the steady state reaction mixture and using scCO(2) as a transport vector for both substrates and products gives rates up to 160-240 catalyst turnovers h(-1) with low rhodium leaching over a 12 h period at a total pressure of 125-140 bar.