Reaction of InCl3 with various reducing agents: InCl3-NaBH4-mediated reduction of aromatic and aliphatic nitriles to primary amines

While alternative methods of preparing dichloroindium hydride (HInCl(2)) via the in situ reduction of InCl(3) using lithium amino borohydride (LAB) were explored, generation of HInCl(2) from the reduction of InCl(3) by sodium borohydride (NaBH(4)) was also re-evaluated for comparison. The reductive capability of the InCl(3)/NaBH(4) system was found to be highly dependent on the solvent used. Investigation by (11)B NMR spectroscopic analyses indicated that the reaction of InCl(3) with NaBH(4) in THF generates HInCl(2) along with borane-tetrahydrofuran (BH(3)·THF) in situ. Nitriles underwent reduction to primary amines under optimized conditions at 25 °C using 1 equiv of anhydrous InCl(3) with 3 equiv of NaBH(4) in THF. A variety of aromatic, heteroaromatic, and aliphatic nitriles were reduced to their corresponding primary amine in 70-99% isolated yields. Alkyl halide and nitrile functional groups were reduced in tandem by utilizing the reductive capabilities of both HInCl(2) and BH(3)·THF in a one-pot reaction. Finally, the selective reduction of the carbon bromine bond in the presence of nitriles was achieved by generating HInCl(2) via the reduction InCl(3) with NaBH(4) in CH(3)CN or with lithium dimethylaminoborohydride (MeLAB) in THF.     

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.     

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.     

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.     

Noncovalent control for bottom-up assembly of functional supramolecular wires

Noncovalent bonds have been used to assemble stacks of pi-electron-rich moieties at a surface, generating a pathway for charge transport. The system is comprised of a tetrathiafulvalene (TTF) derivative incorporating two amide groups which fasten the relative orientations of the electroactive moieties in the supramolecular polymer that is formed at the surface of graphite in octanoic acid. Scanning tunneling microscopy (STM) combined with molecular mechanics calculations has been used to prove the structure of the wires, and theory, corroborated with STS experiments, predicts that they are promising superstructures for charge transport.     

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.     

Combined Inhibitor Free‐Energy Landscape and Structural Analysis Reports on the Mannosidase Conformational Coordinate

Mannosidases catalyze the hydrolysis of a diverse range of polysaccharides and glycoconjugates, and the various sequence‐based mannosidase families have evolved ingenious strategies to overcome the stereoelectronic challenges of mannoside chemistry. Using a combination of computational chemistry, inhibitor design and synthesis, and X‐ray crystallography of inhibitor/enzyme complexes, it is demonstrated that mannoimidazole‐type inhibitors are energetically poised to report faithfully on mannosidase transition‐state conformation, and provide direct evidence for the conformational itinerary used by diverse mannosidases, including β‐mannanases from families GH26 and GH113. Isofagomine‐type inhibitors are poor mimics of transition‐state conformation, owing to the high energy barriers that must be crossed to attain mechanistically relevant conformations, however, these sugar‐shaped heterocycles allow the acquisition of ternary complexes that span the active site, thus providing valuable insight into active‐site residues involved in substrate recognition.