A general and atom-efficient continuous-flow approach to prepare amines, amides and imines via reactive N-chloramines.

Chloramines are an important class of reagents, providing a convenient source of chlorine or electrophilic nitrogen. However, the instability of these compounds is a problem which makes their isolation and handling difficult. To overcome these hazards, a continuous-flow approach is reported which generates and immediately reacts N-chloramines directly, avoiding purification and isolation steps. 2-Chloramines were produced from the reaction of styrenes with N-alkyl-N-sulfonyl-N-chloramines, whilst N-alkyl or N,N'-dialkyl-N-chloramines reacted with anisaldehyde in the presence of t-BuO2H oxidant to afford amides. Primary and secondary imines were produced under continuous conditions from the reaction of N-chloramines with base, with one example subsequently reduced under asymmetric conditions to produce a chiral amine in 94% ee.

Highly Productive Oxidative Biocatalysis in Continuous Flow by Enhancing the Aqueous Equilibrium Solubility of Oxygen.

We report a simple, mild, and synthetically clean approach to accelerate the rate of enzymatic oxidation reactions by a factor of up to 100 when compared to conventional batch gas/liquid systems. Biocatalytic decomposition of H2 O2 is used to produce a soluble source of O2 directly in reaction media, thereby enabling the concentration of aqueous O2 to be increased beyond equilibrium solubility under safe and practical conditions. To best exploit this method, a novel flow reactor was developed to maximize productivity (g product L-1 h-1 ). This scalable benchtop method provides a distinct advantage over conventional bio-oxidation in that no pressurized gas or specialist equipment is employed. The method is general across different oxidase enzymes and compatible with a variety of functional groups. These results culminate in record space-time yields for bio-oxidation.

A Straightforward Electrochemical Approach to Imine- and Amine-bisphenolate Metal Complexes with Facile Control Over Metal Oxidation State.

Synthetic methods to prepare organometallic and coordination compounds such as Schiff-base complexes are diverse, with the route chosen being dependent upon many factors such as metal-ligand combination and metal oxidation state. In this work we have shown that electrochemical methodology can be employed to synthesize a variety of metal-salen/salan complexes which comprise diverse metal-ligand combinations and oxidation states. Broad application has been demonstrated through the preparation of 34 complexes under mild and ambient conditions. Unprecedented control over metal oxidation state (M(II/III/IV) where M=Fe, Mn) is presented by simple modification of reaction conditions. Along this route, a general protocol-switch is described which allows access to analytically pure Fe(II/III)-salen complexes. Tuning electrochemical potential, selective metalation of a Mn/Ni alloy is also presented which exclusively delivers Mn(II/IV)-salen complexes in high yield.

Solid-state structure, solution-state behaviour and catalytic activity of electronically divergent C,N-chelating palladium-N-heterocyclic carbene complexes.

A family of electronically diverse pyridyl- and picolyl-substituted imidazolium salts have been prepared and coordinated to palladium in a single step, to deliver a variety of palladium(ii)-N-heterocyclic carbene (NHC) complexes. Neutral Pd(NHC)X2, cationic [Pd(NHC)2X]X and dicationic [Pd(NHC)2]X2-type complexes have been isolated and fully characterised, with single-crystal X-ray analysis revealing a variety of coordination environments around the palladium centres. The pre-formed complexes have been employed in a model Suzuki-Miyaura cross-coupling reaction to yield a sterically congested tetra-ortho-substituted biaryl product, showcasing turnover numbers comparable to Pd-PEPPSI-IPr catalyst.

Activation and deactivation of a robust immobilized Cp*Ir-transfer hydrogenation catalyst: a multielement in situ X-ray absorption spectroscopy study.

A highly robust immobilized [Cp*IrCl2]2 precatalyst on Wang resin for transfer hydrogenation, which can be recycled up to 30 times, was studied using a novel combination of X-ray absorption spectroscopy (XAS) at Ir L3-edge, Cl K-edge, and K K-edge. These culminate in in situ XAS experiments that link structural changes of the Ir complex with its catalytic activity and its deactivation. Mercury poisoning and "hot filtration" experiments ruled out leached Ir as the active catalyst. Spectroscopic evidence indicates the exchange of one chloride ligand with an alkoxide to generate the active precatalyst. The exchange of the second chloride ligand, however, leads to a potassium alkoxide-iridate species as the deactivated form of this immobilized catalyst. These findings could be widely applicable to the many homogeneous transfer hydrogenation catalysts with Cp*IrCl substructure.

σ-Alkenyl endo-palladacycle formation via regiospecific functionalisation of an unreactive NHC-tethered C(sp(2))-H bond.

An unusual cyclometallation reaction at palladium is described, which proceeds via C-H functionalisation of a vinylic C(sp(2))-H bond tethered to an NHC ligand. The energetic balance between palladacycle formation and bis-NHC complexation has been found to be very subtle.

Electrochemical flow-reactor for expedient synthesis of copper-N-heterocyclic carbene complexes.

An electrochemical flow-cell for highly efficient and selective generation of Cu(I)-N-heterocyclic carbene complexes under neutral and ambient conditions is reported. The feasibility of the flow-cell is demonstrated through the electrochemical synthesis of [Cu(IMes)Cl] and subsequent in situ flow directly into hydrosilylation reactions, with equal efficiency to the purified catalyst.

Relating chemical and biological diversity space: a tunable system for efficient gene transfection.

Polyethyleneimine (PEI), a well-established nonviral transfection reagent, was combinatorially modified with varying proportions of methyl, benzyl, and n-dodecyl groups to create a library of 435 derivatized polymers. Screening of this library for transfection, DNA binding, and toxicity allows systematic correlation of the biological properties of our polymers to their derivatizations. Combinations of derivatizations bring about a 100-fold variation in transfection efficiency between library members. The best PEI derivatives exhibit increases in transfection efficiency of more than 80-fold over unmodified PEI (up to 28+/-7 % of cells transfected) and rival commercial reagents such as Lipofectamine 2000 (21+/-10 %) and JetPEI (32+/-5.0 %). In addition, we can identify compounds that are specifically tuned for efficient transfection in CHO-K1 over Ishikawa cells and vice versa, demonstrating that the approach can lead to cell-type selectivity of at least one order of magnitude. This work demonstrates that multivalent derivatization of a polymeric framework can create functional diversity substantially greater than the structural diversity of the derivatization building blocks and suggests an approach to a better understanding of the molecular underpinnings of transfection as well as their exploitation.

Project management system for structural and functional proteomics: Sesame.

A computing infrastructure (Sesame) has been designed to manage and link individual steps in complex projects. Sesame is being developed to support a large-scale structural proteomics pilot project. When complete, the system is expected to manage all steps from target selection to data-bank deposition and report writing. We report here on the design criteria of the Sesame system and on results demonstrating successful achievement of the basic goals of its architecture. The Sesame software package, which follows the client/server paradigm, consists of a framework, which supports secure interactions among the three tiers of the system (the client, server, and database tiers), and application modules that carry out specific tasks. The framework utilizes industry standards. The client tier is written in Java2 and can be accessed anywhere through the Internet. All the development on the server tier is also carried out in Java2 so as to accommodate a wide variety of computer platforms. The database tier employs a commercial database management system. Each Sesame application module consists of a simple user interface in the client tier, corresponding objects in the server tier, and relevant data stored in the centralized database. For security, access to stored data is controlled by access privileges. The system facilitates both local and remote collaborations. Because users interact with the system using Java Web Start or through a web browser, access is limited only by the availability of an Internet connection. We describe several Sesame modules that have been developed to the point where they are being utilized routinely to support steps involved in structural and functional proteomics. This software is available to parties interested in using it and assisting to guide its further development.