Organic synthesis in a modular robotic system driven by a chemical programming language.

The synthesis of complex organic compounds is largely a manual process that is often incompletely documented. To address these shortcomings, we developed an abstraction that maps commonly reported methodological instructions into discrete steps amenable to automation. These unit operations were implemented in a modular robotic platform by using a chemical programming language that formalizes and controls the assembly of the molecules. We validated the concept by directing the automated system to synthesize three pharmaceutical compounds, diphenhydramine hydrochloride, rufinamide, and sildenafil, without any human intervention. Yields and purities of products and intermediates were comparable to or better than those achieved manually. The syntheses are captured as digital code that can be published, versioned, and transferred flexibly between platforms with no modification, thereby greatly enhancing reproducibility and reliable access to complex molecules.

Branch-Like Iron Nitride and Carbide Magnetic Fibres Using an Electrospinning Technique.

Fe3 N and Fe3 C nanocomposites have a wide range of applications thanks to their ceramic nature, magnetic properties, conductivity and catalytic activity, just to cite some. In many fields optimal performances are ensured by crystallinity, homogeneity and hierarchical organization. In the present paper, crystalline, magnetic and well-defined nanofibres of iron nitride and iron carbide/carbon nanocomposite with tunable composition and size were prepared via electrospinning. The starting polymeric material was directly electrospun into fibres and then calcined, leading to a highly homogeneous final product of nanoparticles along the fibres (both outside and inside). A mechanistic study was undertaken and here discussed. The magnetic properties of the as-prepared nanofibres were also studied. The as-prepared final fibre mat composite material can serve as active catalyst, for example, in oxygen reduction reaction (where nanofibres outperformed mere nanoparticles), it can serve as functional support for classical catalytic processes or, thanks to its magnetic properties, can be applied in magnetic-field assisted separation or as magneto-active membranes.

A metamorphic inorganic framework that can be switched between eight single-crystalline states.

The design of highly flexible framework materials requires organic linkers, whereas inorganic materials are more robust but inflexible. Here, by using linkable inorganic rings made up of tungsten oxide (P8W48O184) building blocks, we synthesized an inorganic single crystal material that can undergo at least eight different crystal-to-crystal transformations, with gigantic crystal volume contraction and expansion changes ranging from -2,170 to +1,720 Å3 with no reduction in crystallinity. Not only does this material undergo the largest single crystal-to-single crystal volume transformation thus far reported (to the best of our knowledge), the system also shows conformational flexibility while maintaining robustness over several cycles in the reversible uptake and release of guest molecules switching the crystal between different metamorphic states. This material combines the robustness of inorganic materials with the flexibility of organic frameworks, thereby challenging the notion that flexible materials with robustness are mutually exclusive.

Shrink wrapping redox-active crystals of polyoxometalate open frameworks with organic polymers via crystal induced polymerisation.

We report examples of crystal surface modification of polyoxometalate open frameworks whereby the use of pyrrole or aniline as monomers leads to the formation of the corresponding polymers via an oxidative polymerization process initiated by the redox active POM scaffolds. Guest-exchange experiments demonstrate that the polymers can finely tune the guest exchange rate and their structural integrity is retained after the surface modifications. In addition, the formation of polyoxometalate-based self-fabricating tubes by the dissolution of Keggin-based network crystals were also modulated by the polymers, allowing a new type of hybrid inorganic polymer with an organic coating to be fabricated.

3D printing of versatile reactionware for chemical synthesis.

In recent decades, 3D printing (also known as additive manufacturing) techniques have moved beyond their traditional applications in the fields of industrial manufacturing and prototyping to increasingly find roles in scientific research contexts, such as synthetic chemistry. We present a general approach for the production of bespoke chemical reactors, termed reactionware, using two different approaches to extrusion-based 3D printing. This protocol describes the printing of an inert polypropylene (PP) architecture with the concurrent printing of soft material catalyst composites, using two different 3D printer setups. The steps of the PROCEDURE describe the design and preparation of a 3D digital model of the desired reactionware device and the preparation of this model for use with fused deposition modeling (FDM) type 3D printers. The protocol then further describes the preparation of composite catalyst-silicone materials for incorporation into the 3D-printed device and the steps required to fabricate a reactionware device. This combined approach allows versatility in the design and use of reactionware based on the specific needs of the experimental user. To illustrate this, we present a detailed procedure for the production of one such reactionware device that will result in the production of a sealed reactor capable of effecting a multistep organic synthesis. Depending on the design time of the 3D model, and including time for curing and drying of materials, this procedure can be completed in ∼3 d.

The digital code driven autonomous synthesis of ibuprofen automated in a 3D-printer-based robot.

An automated synthesis robot was constructed by modifying an open source 3D printing platform. The resulting automated system was used to 3D print reaction vessels (reactionware) of differing internal volumes using polypropylene feedstock via a fused deposition modeling 3D printing approach and subsequently make use of these fabricated vessels to synthesize the nonsteroidal anti-inflammatory drug ibuprofen via a consecutive one-pot three-step approach. The synthesis of ibuprofen could be achieved on different scales simply by adjusting the parameters in the robot control software. The software for controlling the synthesis robot was written in the python programming language and hard-coded for the synthesis of ibuprofen by the method described, opening possibilities for the sharing of validated synthetic 'programs' which can run on similar low cost, user-constructed robotic platforms towards an 'open-source' regime in the area of chemical synthesis.

Synthesis of phase pure praseodymium barium copper iron oxide.

The control of crystallization of praseodymium barium copper iron oxide, an intermediate temperature solid oxide fuel cell cathode material, has been demonstrated for the first time using a biotemplated sol-gel synthesis technique. The results obtained showed significant improvement in purity, synthesis time, surface area and simplicity over that previously reported.

A new general synthetic strategy for phase-pure complex functional materials.

The ability of ionic liquids to solvate inorganic salts completely has to date never been employed in the synthesis of complex inorganic materials. Here, we demonstrate that complex functional oxides, even those traditionally considered extremely difficult to synthesize in bulk, such as quinternary superconductors, are produced with no impurity phases and on timescales that are much shorter than other synthetic techniques.

Well-defined synthetic polymers with a protein-like gelation behavior in water.

Homopolymers of N-acryloyl glycinamide were prepared by reversible addition-fragmentation chain transfer polymerization in water. The formed macromolecules exhibit strong polymer-polymer interactions in aqueous milieu and therefore form thermoreversible physical hydrogels in pure water, physiological buffer or cell medium.

Tuning the thickness of polymer brushes grafted from nonlinearly growing multilayer assemblies.

A new versatile method for tuning the thickness of surface-tethered polymer brushes is introduced. It is based on the combination of polyelectrolyte multilayer deposition and surface-initiated atom transfer radical polymerization. To control the thickness of the brushes, the nonlinear growth of certain polyelectrolyte multilayer systems is exploited. The method is demonstrated to work with different polyelectrolytes and different monomers. The relevance for applications is demonstrated by cell adhesion experiments on grafted thermoresponsive polymer layers with varying thickness.