Enzyme dynamics and tunneling enhanced by compression in the hydrogen abstraction catalyzed by soybean lipoxygenase-1

A fully microscopical simulation of the rate-limiting hydrogen abstraction catalyzed by soybean lipoxygenase-1 (SLO-1) has been carried out. This enzyme exhibits the largest, and weakly temperature dependent, experimental H/D kinetic isotope effect (KIE) reported for a biological system. The theoretical model used here includes the complete enzyme with a solvation shell of water molecules, the Fe(III)-OH- cofactor, and the linoleic acid substrate. We have used a hybrid QM(PM3/d-SRP)/MM method to describe the potential energy surface of the whole system, and the ensemble-averaged variational transition-state theory with multidimensional tunneling (EA-VTST/MT) to calculate the rate constant and the primary KIE. The computational results show that the compression of the wild-type active site enzyme results in the huge contribution of tunneling (99%) to the rate of the hydrogen abstraction. Importantly, the active site becomes more flexible in the Ile553Ala mutant reactant complex simulation (for which a markedly temperature dependent KIE has been experimentally determined), thus justifying the proposed key role of the gating promoting mode in the reaction catalyzed by SLO-1. Finally, the results indicate that the calculated KIE for the wild-type enzyme has an important dependence on the barrier width.     

Intramolecular ene reaction of 1,6-fullerenynes: a new synthesis of allenes

[Structure: see text] Thermal treatment of 1,6-fullerenynes bearing an alkyl group on the terminal carbon of the alkyne moiety leads quantitatively to new allenes through a reaction mechanism involving an intramolecular ene process. This reaction outcome is in contrast to that recently found for free terminal alkynes which form cyclobutene derivatives through a [2+2] cyclization mechanism.     

Understanding the differences in photochemical properties of substituted aminopyrimidines

The luminescent patterns of several members of the aminopyrimidine family are very different, showing not fluorescence at all, only a fluorescence band, normal or anomalous, or dual fluorescence, depending on the substituents and on the environment (gas phase vs. polar solvents). In this work, we study the lowest excited states of several members of this family that exhibit different fluorescence patterns to try to explain their photochemistry and to understand the effect of the substituents and the environment. We have found that several excited states (local excited (LE), charge transfer (CT) and n _N?C??* states) have minima on the lowest excited potential energy surface (S₁), being their relative energy the determinant factor of the luminescent behavior. If the more stable S₁ minima are of n _N?C??* character, a non-radiative deexcitation channel is the most efficient and the system shows no fluorescence. If the CT and/or LE states are the most stable, the non-radiative deactivation channel is not accessible and the system fluoresces. The relative energies of the CT and LE minima (affected by substituents and by the presence of a polar solvent) and the different magnitude of the oscillator strength for the radiative transition to the ground state determine which emission is more efficient, giving place to normal, anomalous or dual fluorescence. The study has been carried out by CASSCF/CASPT2 computations, including the solvent effect by means of the PCM model.     

On the ionization state of the substrate in the active site of glutamate racemase. A QM/MM study about the importance of being zwitterionic

Computer simulations on a QM/MM potential energy surface have been carried out to gain insights into the catalytic mechanism of glutamate racemase (MurI). Understanding such a mechanism is a challenging task from the chemical point of view because it involves the deprotonation of a low acidic proton by a relatively weak base to give a carbanionic intermediate. First, we have examined the dependency of the kinetics and thermodynamics of the racemization process catalyzed by MurI on the ionization state of the substrate (glutamate) main chain. Second, we have employed an energy decomposition procedure to study the medium effect on the enzyme-substrate electrostatic and polarization interactions along the reaction. Importantly, the present theoretical results quantitatively support the mechanistic proposal by Rios et al. [J. Am. Chem. Soc. 2000, 122, 9373-9385] for the PLP-independent amino acid racemases.     

Redox-controlled molecular flipper based on a chiral Cu complex

A molecular bipaddled flipper based on a tetradentate chiral Cu complex has been designed. The paddling motion of this unprecedented molecular-scale machine can be controlled by reversible oxidation of the metal center. Kinetic and computational (density functional theory) analyses provide a detailed picture of the flipper motion at the molecular scale, rationalize the switching role of the metal-ion oxidation state, and pose the basis for the fine-tuning of the dynamic motion of this new class of molecular-scale devices.