Photocatalytic α-Tertiary Amine Synthesis via C−H Alkylation of Unmasked Primary Amines

A practical, catalytic entry to α,α,α-trisubstituted (α-tertiary) primary amines by C−H functionalisation has long been recognised as a critical gap in the synthetic toolbox. We report a simple and scalable solution to this problem that does not require any in situ protection of the amino group and proceeds with 100 % atom-economy. Our strategy, which uses an organic photocatalyst in combination with azide ion as a hydrogen atom transfer (HAT) catalyst, provides a direct synthesis of α-tertiary amines, or their corresponding γ-lactams. We anticipate that this methodology will inspire new retrosynthetic disconnections for substituted amine derivatives in organic synthesis, and particularly for challenging α-tertiary primary amines.     

Self-immobilization of Recombinant Caulobacter crescentus and Its Application in Removal of Cadmium from Water

Microbial biofilms can be valuable in many biotechnological applications, including bioremediation. We have previously constructed a recombinant strain of Caulobacter crescentus JS4022/p723-6H by inserting a hexahistidine peptide to a permissive site of the host surface layer (S-layer) protein RsaA. This engineered strain is highly effective in removal of cadmium from water as free cells. In this communication, we examined the biofilms formed by self-immobilized JS4022/p723-6H and evaluated their ability to retrieve cadmium from contaminated water samples. According to light and electron microscopic observations, JS4022/p723-6H cells developed a uniform monolayer biofilm on borosilicate surfaces through their intrinsic appendage, a stalk with an adhesive holdfast. The density of the biofilms reached a maximum after 48 h of incubation and was not affected by exposure to at least 1 ppm cadmium. When 0.4 ppm Cd(II) was added to the growth medium, immobilized JS4022/p723-6H removed 76.9% of the total metal, whereas the control strain only removed 13.5%. When a water sample collected from Lake Erie was spiked with various amounts of CdCl₂, immobilized JS4022/p723-6H was able to sequester 44～51% of the total metal, compared to 37～42% accumulated by the control strain. By combining two powerful techniques, cell surface display and self-immobilization, we achieved complete separation of dissolved heavy metals from contaminated water in a single step. This study laid down the foundation to cost-effectively construct large-scale bioreactors with high efficiency and specificity to retrieve environmental contaminants from water.     

Catalytic proficiency of ubiquitin conjugation enzymes: balancing pK(a) suppression, entropy, and electrostatics

Biological organisms orchestrate coordinated responses to external stimuli through temporal fluctuations in protein-protein interaction networks using molecular mechanisms such as the synthesis and recognition of polyubiquitin (polyUb) chains on signaling adaptor proteins. One of the pivotal chemical steps in ubiquitination involves reaction of a lysine amino group with a thioester group on an activated E2, or ubiquitin conjugation enzyme, to form an amide bond between Ub and a target protein. In this study, we demonstrate a nominal 14-fold range for the rate of the chemical step, k(cat), catalyzed by different E2 enzymes using non-steady-state, single-turnover assays. However, the observed range for k(cat) is as large as ～100-fold for steady-state, single-turnover assays. Biochemical assays were used in combination with measurement of the underlying protein-protein interaction kinetics using NMR line-shape and ZZ-exchange analyses to determine the rate of polyUb chain synthesis catalyzed by the heterodimeric E2 enzyme Ubc13-Mms2. Modest variations in substrate affinity and k(cat) can achieve functional diversity in E2 mechanism, thereby influencing the biological outcomes of polyubiquitination. E2 enzymes achieve reaction rate enhancements through electrostatic effects such as suppression of substrate lysine pK(a) and stabilization of transition states by the preorganized, polar enzyme active site as well as the entropic effects of binding. Importantly, modestly proficient enzymes such as E2s maintain the ability to tune reaction rates; this may confer a biological advantage for achieving specificity in the diverse cellular roles for which these enzymes are involved.     

Practical synthesis of a renin inhibitor via a diastereoselective Dieckmann cyclization

A scalable synthesis of a potent renin inhibitor (1) is described. The absolute stereochemistry is set via an unprecedented diastereoselective Dieckmann cyclization directed by a remote chiral protecting group. This transformation enables preparation of chiral 1,3-[3.3.1]-diazabicyclononenes by desymmetrization of alkyl-esters, with selectivities ranging from 4 to 17:1.     

Interplay between cationic and neutral species in the rhodium-catalyzed hydroaminomethylation reaction

The reactivity of [Rh(CO)(2){(R,R)-Ph-BPE}]BF(4) (2) toward amine, CO and/or H(2) was examined by high-pressure NMR and IR spectroscopy. The two cationic pentacoordinated species [Rh(CO)(3) {(R,R)-Ph-BPE}]BF(4) (4) and [Rh(CO)(2)(NHC(5)H(10)){(R,R)-Ph-BPE}]BF(4) (8) were identified. The transformation of 2 into the neutral complex [RhH(CO)(2){(R,R)-Ph-BPE}] (3) under hydroaminomethylation conditions (CO/H(2), amine) was investigated. The full mechanisms related to the formation of 3, 4 and 8 starting from 2 are supported by DFT calculations. In particular, the pathway from 2 to 3 revealed the deprotonation by the amine of the dihydride species [Rh(H)(2)(CO)(2){(R,R)-Ph-BPE}]BF(4) (6), resulting from the oxidative addition of H(2) on 2.     

Continuous-wave wavelength conversion for high-power applications using an external cavity diamond Raman laser

We demonstrate continuous-wave (cw) operation of a diamond Raman laser at 1240 nm in an external cavity configuration. The output power increased linearly with pump power with a 49.7% slope efficiency and reached 10.1 W at the maximum available pump power of 31 W. The combination of resonator design with diamond provides a novel approach to power-scalable cw wavelength and beam conversion.     

Bistable surface anchoring and hysteresis of pitch jumps in a planar cholesteric liquid crystal

The relationship between bistable surface anchoring and the pitch jump process is examined for a planar cholesteric liquid crystal. Introducing a high-order, azimuthal surface anchoring potential into a simple model to describe a cholesteric, we derive an expression for the director twist as the natural pitch of the liquid crystal is allowed to vary. Writing the energy in terms of the surface twist, we are able to determine the twists which minimize the total energy of the system. We demonstrate how a pitch jump is related to an energy exchange from one branch of metastable states to another. We then discuss how the co-existence of energy minima and their associated solution branches may help explain the thermal hysteresis observed experimentally in cholesterics in the neighbourhood of a pitch jump. The presence of a higher-order surface energy term can expand the range of anchoring strengths in which pitch jumps are possible. We also investigate the influence of bidirectional surface anchoring on the behaviour of the total energy. Intermediate quarter-turn pitch jumps can occur, depending on the relative strength of the high-order anchoring term, and these can have a significant effect on the system hysteresis.     

An investigation of gold adsorption from a binary mixture with selective mesoporous silica adsorbents

Gold-selective adsorbents were prepared from mesoporous MCM-41 silica by grafting organic amine groups (i.e., RNH2, R2NH, and R3N; R=propyl). NH2-MCM-41, NRH-MCM-41, and NR2-MCM-41 displayed strong affinity for gold and at 1 mmol/g loading adsorbed 0.40, 0.33, and 0.20 mmol/g of gold. Copper and nickel were not adsorbed on these adsorbents. Grafting surface chemical moieties introduces heterogeneity on an otherwise uniform MCM-41 pore surface and metal adsorption is best described by the Freundlich adsorption model. A series of binary adsorption equilibrium studies with NH2-MCM-41 containing 2.2 mmol RNH2/g shows that NH2-MCM-41 adsorbs only gold from solutions containing copper and nickel with an adsorption capacity of 0.6 mol of Au/mol of RNH2 (1.1 mmol of Au/g of NH2-MCM-41). Copper and nickel were not adsorbed by NH2-MCM-41 regardless of the solution concentration, composition, and pH (i.e., 2 to 4) in the presence of gold. The LeVan and Vermeulen adsorption model based on a single component Freundlich isotherm and corrected for the anion effect accurately predicted the binary adsorptions. The adsorbed gold was completely recovered by a simple acid wash and the recovered gold solution is 99% pure. The regenerated NH2-MCM-41 remained 100% selective for gold removal and exhibited the same adsorption capacity even after several uses.