Electrode array and device for high throughput electrosynthesis

Abstract

The invention relates to an electrode array comprising two electrode assemblies and to a corresponding device for performing electrochemical synthesis. The invention further relates to the use of the device in high throughput electrochemical synthesis of chemical compounds, in particular for the purposes of chemical library synthesis and chemical reaction discovery.

Description

Technical Field

[0001] The present invention relates to an electrode array and a device for performing electrochemical synthesis (such as synthesis of chemical libraries and chemical reaction discovery). More specifically, the present invention relates to an automated device and method for high-throughput, parallel electrosynthesis of milligram quantities of chemical compounds and screening of (electro)chemical reaction parameters. Background Art

[0002] Chemical libraries are collections of chemical compounds that can be screened for the purpose of specific interaction of certain classes of compounds with a certain target, such as affinity for a binding site in drug discovery, propensity to catalyze polymerization in industrial processes, or pesticidal activity in agrochemistry.

[0003] Chemical libraries are typically designed by (organic or medicinal) chemists and cheminformatics experts, and synthesized using a combination of known organic chemistry pathways. Alternatively or additionally, the synthesis of chemical libraries can be performed by electrochemical synthesis (or "electrosynthesis"), in which the starting materials (substrates) are converted into one or more reaction products in an electrochemical cell under the influence of an applied potential or current that results in one or more redox reactions.

[0004] Electrosynthesis can offer benefits over conventional organic redox reactions in terms of the selectivity and yields obtained. Thus, electrosynthesis can be an advantageous alternative for preparing new chemical compounds or classes of chemical compounds in general.

[0005] However, the discovery of new electrochemical reactions (either for the purpose of general synthesis of new compounds or for library generation) requires the design and evaluation of suitable reaction parameters, such as the selection of electrode materials, electrolytes, current density, etc. Such screening for appropriate parameters and conditions is largely beyond the skill and practice of the average organic chemist; it typically requires designing one or several electrochemical reactors using different electrode assemblies and applying many iterations of different reaction conditions.

[0006] Electrochemical devices are known in the art, such as a miniature 24-well electrochemical reactor that employs two parallel arrays of cylindrical rods as electrodes that are held closely apart so as to fit into a miniature cell array on a substrate. The device further comprises an alignment plate, a sealing plate, a custom printed circuit board, and an 8-pin connector for connecting to four controllers configured to provide a constant current or voltage. This setup allows for screening of 4 discrete currents or 4 discrete cell voltages depending on the mode of operation. However, the device requires manual manipulation of all 48 electrodes when assembled. Furthermore, to ensure experimental reproducibility, the electrodes must be manually cleaned and / or mechanically polished after each reaction to expose the unchanged surface of the electrode material. These labor-intensive processes represent a bottleneck for high-throughput electrosynthesis and hinder scaling up this concept to a larger number of cells.

[0007] US2020 / 0384434 A1 describes a device for solid phase synthesis of polymers, wherein the growing polymer chain is individually and covalently bound to a solid support by a linker molecule. The device includes an array of individually addressable electrodes embedded in a solid support, wherein the solid support includes an integrated circuit (IC) or is composed thereof. By reversing the bias at a specific electrode in the array, the linker molecule can be selectively cleaved from the support, which allows site-selective release from the polymer chain during synthesis. In a particular embodiment, the positive anode in the array is surrounded by three, four, five, six, seven, eight, nine or more electrodes each configured as a negative cathode. In the device disclosed in US2020 / 0384434 A1, a solid support with an embedded individually addressable electrode array forms the basis of a single electrolytic cell, wherein the release of the polymer product rather than the polymerization reaction itself is caused by electrolysis. Therefore, the device is not suitable for electrochemical synthesis purposes, which typically requires a controlled application of potential or current from a single electrode (cathode-anode).

[0008] Therefore, there is an unmet need for electrode arrays and corresponding electrochemical devices for electrochemical synthesis (including high-throughput synthesis of chemical libraries and chemical reaction discovery) that are easy to manufacture, modify and maintain. More specifically, it is necessary to have an electrode array that can be manufactured in several steps and at low cost, advantageously allowing the electrode array to be a disposable item, thereby avoiding manual handling of electrodes and laborious post-reaction processing. There is a further need for electrode arrays and electrochemical devices including such arrays, wherein changes in electrode materials within the same array can be easily implemented and can withstand the current required for electrochemical synthesis. In addition, it would be desirable to obtain electrode arrays and devices that allow reactions to run in parallel with very few simple power drivers. In addition, it would be helpful to have an available electrochemical device and method for rapid synthesis, quantification and separation of a large number of chemical compounds and for screening for appropriate reaction conditions for such electrochemical synthesis. Summary of the invention

[0009] The limitations of prior art devices and methods are now overcome by the present invention, which provides components, devices and methods for high-throughput electrosynthesis of chemical compounds for the purposes of reaction discovery and library synthesis.

[0010] Therefore, in a first aspect, the present invention relates to an electrode array comprising two electrode assemblies for performing electrochemical synthesis, the electrode array comprising a plurality of planar monolithic bodies arranged on a planar substrate, wherein the bodies comprise working electrode regions and / or counter electrode regions, and wherein the bodies are arranged on the substrate to form an m×n matrix (6) of m rows and n columns of the two electrode assemblies, the matrix being formed by the working electrode regions of a first body and the counter electrode regions of a second adjacent body separated by a gap in the same column or row.

[0011] The electrode array according to the present invention comprises a planar monolithic body forming a two-electrode assembly, and these two-electrode assemblies have a thickness and shape that are particularly suitable for electrochemical synthesis. Due to the absence of a third (reference) electrode, the electrode assembly can be implemented with a simple flat design that does not require conductive traces to pass through the substrate and can be easily adapted to the specific purpose of the electrochemical reaction. In addition, in the electrode array of the present invention, the working electrode area and the counter electrode area of ​​two adjacent bodies in the same column or row can form a two-electrode assembly together. This results in the components in the column or row being connected in series, and each column or row only needs to be connected to a power supply, which allows the optimal balance between the complexity of the circuit and the number of parallel reactions (and therefore the throughput) to be achieved.

[0012] The electrode array is combined with a plurality of suitable containers containing reaction substrates and other components as required (eg, electrolytes) to form an array of electrochemical cells that can be used for a variety of electrochemical synthesis reactions.

[0013] Thus, in a second aspect, the present invention relates to an apparatus for performing electrochemical synthesis, the apparatus comprising an electrode array as defined herein and a plurality of reaction vessels, wherein each reaction vessel is configured to provide electrical contact of its contents with a single two-electrode assembly of the electrode array.

[0014] The benefit of the device of the present invention is that a large number of electrochemical transformations can be carried out in parallel with different substrates under the same conditions or under controlled varying conditions. This allows the use of the device of the present invention to generate chemical libraries in a convenient manner. In addition, the device of the present invention is particularly suitable for so-called reaction discovery by enabling rapid screening of electrochemical transformation parameters.

[0015] Therefore, in a further aspect, the invention relates to the use of a device according to the invention in the synthesis of a chemical library.

[0016] In another aspect, the invention relates to the use of a device according to the invention in chemical reaction discovery.

[0017] In another aspect, the invention relates to a method for electrochemically converting one or more reactants into a reaction product, the method comprising

[0018] - Providing an electrochemical device according to the present invention

[0019] - providing one or more reactants and optionally a solvent and / or an electrolyte to a reaction vessel

[0020] - Applying a current between a working electrode and a counter electrode of the two-electrode assembly sufficient to convert one or more reactants into reaction products. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 A photograph of an electrode array according to an embodiment of the present invention is shown.

[0022] Figure 2A A schematic diagram of a monolithic body having a working electrode region and a counter electrode region is shown.

[0023] Figure 2B A schematic diagram of two bodies forming a two-electrode assembly is shown.

[0024] Figure 2C A schematic diagram of a matrix of bodies forming part of an electrode array according to an embodiment of the invention is shown.

[0025] Figure 3A , 3B 3C respectively show a schematic diagram of an electrode array configuration according to another embodiment of the present invention, a schematic diagram of two bodies forming a two-electrode assembly according to this embodiment, and a matrix of bodies forming a part of an electrode array according to this embodiment. Figure 3D Shown is a magnified photograph of a planar host array of pyrolytic carbon produced by surface laser pyrolysis on a polyimide foil.

[0026] Figure 4 A photograph showing an array of reaction vessels according to an embodiment of the present invention is shown.

[0027] Figure 5 A photograph showing an apparatus according to an embodiment of the invention is shown.

[0028] Figure 6 A schematic diagram showing power supplies and controls for an apparatus according to an embodiment of the present invention is shown. DETAILED DESCRIPTION

[0029] The present invention is described in more detail below.

[0030] In a first aspect, the present invention relates to an electrode array comprising two electrode assemblies (6) for performing electrochemical synthesis, the electrode array comprising a plurality of planar monolithic bodies arranged on a planar substrate, wherein the bodies comprise working electrode regions and / or counter electrode regions, and wherein the bodies are arranged on the substrate to form an m×n matrix of m rows and n columns of the two electrode assemblies, the matrix being formed by the working electrode regions of a first body (3) and the counter electrode regions of a second adjacent body (3) separated by a gap in the same column or row.

[0031] In the context of the present invention, the term "planar" means having an average thickness dimension that is much smaller than its extent in the other two dimensions (i.e., its length and width dimensions). Monolithic bodies will still be considered planar even if their thickness is not constant (if it meets this condition - i.e., they may include irregularities, such as surface roughness, for example).

[0032] In the context of the present disclosure, "the subject is arranged on the substrate" should be interpreted as meaning that the subject is arranged on the surface of the substrate and is not embedded therein to any relevant extent, preferably not embedded therein at all.

[0033] The advantage provided by the electrode array as defined herein is that it has a planar monolithic body array as a basic structure, which includes a working electrode area and / or a counter electrode area, wherein adjacent bodies together can form a two-electrode assembly of a working electrode and a counter electrode. Therefore, these two-electrode assemblies are located in the same plane and parallel to the substrate, and no complex electronic wiring through the substrate is required. As used herein, the term "monolithic body" should be understood to refer to a shape consisting of one piece, in which there are substantially no or no interruptions such as grooves or holes. The term "monolithic" as used herein does not necessarily mean a single material; the body can be made of a single material or of a combination of different materials, in the latter case preferably as uniform as possible.

[0034] Typically, most monolithic bodies have both working and counter electrode regions, with only the first and / or last body forming a column or row of bodies requiring a working or counter electrode region to form a two-electrode assembly with an immediately adjacent body.

[0035] In an exemplary embodiment, the electrode array comprises a plurality of planar monolithic bodies arranged on a planar substrate, wherein each of the bodies comprises a working electrode region and a counter electrode region. In this embodiment, although not required for normal device operation, the first and last bodies forming the columns or rows of bodies comprise a working electrode region or a counter electrode region.

[0036] In another exemplary embodiment, the electrode array comprises a plurality of planar monolithic bodies arranged on a planar substrate, the first and last bodies forming columns or rows of bodies comprising working electrode regions or counter electrode regions, and the remaining bodies (i.e., those not occupying edge positions) comprising working electrode regions and counter electrode regions.

[0037] Therefore, in general, the electrode array according to the present invention comprises a plurality of two-electrode assemblies formed by adjacent and continuous bodies in a column or a row. In one embodiment, the electrode array comprises a plurality of two-electrode assemblies formed by adjacent and continuous bodies in a column. In another embodiment, the electrode array comprises a plurality of two-electrode assemblies formed by adjacent and continuous bodies in a row.

[0038] Thus, within a column of adjacent bodies, in the longitudinal direction of the column, a two-electrode assembly may be formed by the working electrode region of the first body and the counter electrode region of the second directly adjacent body. Thus, each of the two electrode assemblies includes a working electrode and a counter electrode, which are separated by a gap formed by the spacing between the two adjacent bodies. The second two-electrode assembly may in turn be formed by the working electrode region of the second body and the counter electrode region of the third directly adjacent body in the same column, and so on, thereby producing a column of two-electrode assemblies connected in series.

[0039] Alternatively, within a row of adjacent bodies, in the longitudinal direction of the row, a first two-electrode assembly may be formed by the working electrode region of the first body and the counter electrode region of the second directly adjacent body. A second two-electrode assembly may be formed by the working electrode region of the second body and the counter electrode region of the third directly adjacent body, and so on, thereby generating a row of two-electrode assemblies connected in series.

[0040] In one embodiment, at least two two-electrode assemblies in a column or row are connected in series. Preferably, substantially all or all two-electrode assemblies in a column or row are connected in series, i.e., each working electrode region and each counter electrode region of a body forms a two-electrode assembly with a directly adjacent body in the same row. In this way, each column or row of components connected in series requires only one current supply connection, which allows an optimal balance between the complexity of the circuit and the number of parallel reactions (and therefore the throughput) of the corresponding electrochemical device to be achieved.

[0041] As will be described in detail below, the monolithic body can be applied using simple, low-cost techniques such as screen printing, stencil printing, or inkjet printing. Screen printing of electrode materials on substrates is a well-known technique and provides many benefits, including high reproducibility and accuracy, and the possibility of easily changing the electrode geometry and the composition of the electrode material. Laser surface pyrolysis is another technique that can be used to manufacture the desired monolithic body, especially a pyrolytic carbon body. The following references are cited to characterize the carbon body: Merlen, A.; Buijnsters, JG; Pardanaud, CA Guide to and Review of the Use of Multiwavelength Raman Spectroscopy for Characterizing Defective Aromatic Carbon Solids: from Graphene to Amorphous Carbons [Guide to and Review of Using Multiwavelength Raman Spectroscopy to Characterize Defective Aromatic Carbon Solids: from Graphene to Amorphous Carbons]; Coatings [Coating] 2017, 7, 153.

[0042] Depending on the material choice and the application technique of the body, the electrode array may be produced at such a low cost that it may be used only once. Thus, in an embodiment, the electrode array is a single-use electrode array.

[0043] The bodies are arranged so that they form a matrix of two electrode assemblies. Preferably, the matrix is ​​a rectangular matrix. The matrix has m rows and n columns, where m and n are each non-zero integers. Thus, each row m i (where i = 1, 2, ... n) having n two-electrode assemblies and each row n j (where j=1, 2, ... m) having m two-electrode assemblies.

[0044] Therefore, the m×n matrix of m rows and n columns of the two electrode assemblies consists of the same column n j Or the same line m i The working electrode region and the counter electrode region are formed in adjacent continuous bodies.

[0045] Typically, the body forming the matrix of the two electrode assemblies is arranged so that the distances between the assemblies are substantially equal or equal. In this context, the "distance between the assemblies" may be a center-to-center distance or an edge-to-edge distance, depending on the geometry of the body and the resulting electrode assembly; i.e., for substantially symmetrical geometries, either distance would be an appropriate measure, while for asymmetrical designs, the center-to-center distance would be a more useful parameter.

[0046] In a preferred embodiment, the two electrode assemblies are arranged at substantially equal mutual distances (8), wherein the distance between the two electrode assemblies is selected such that this enables the matrix of the two electrode assemblies to form the respective bottoms of the wells of a multiwell plate having m rows and n columns. Advantageously, this allows the electrode array to be combined with laboratory equipment of standard dimensions, such as commercially available multiwell plates.

[0047] In an exemplary embodiment of the present invention, the matrix size of the electrode array and the spacing between two electrode assemblies correspond to the size and well-to-well spacing of a standard Society for Biomolecular Screening (SBS) multi-well plate (e.g., a well plate having 12 (3×4), 24 (4×6), 48 (6×8), 96 (8×12), 384 (16×24), or 1536 (32×48) wells). Thus, in an embodiment, m, n, and distance (8) correspond to those of a standard Society for Biomolecular Screening (SBS) 12 (3×4), 24 (4×6), 48 (6×8), 96 (8×12), 384 (16×24), or 1536 (32×48) well plate. In a preferred embodiment, the parameters correspond to those of a standard SBS 96-well or 384-well plate.

[0048] The monolithic body providing the working electrode area and the counter electrode area can be made of any suitable conductive material. In an exemplary embodiment, the body includes a carbon-based material, is substantially composed of or is composed of a carbon-based material. Non-limiting examples of suitable carbon-based electrode materials are graphite, expanded graphite, graphene, carbon, glassy carbon, nano-carbon and pyrolytic carbon. Depending on the deposition technique used to apply the electrode array, such as screen printing, the body can include (a small) amount of other materials, such as a binder.

[0049] The monolithic body that together forms the two electrode assemblies disclosed herein should have a thickness sufficient to withstand the current and / or current density required for the electrochemical conversion reactions envisioned for the device. Typically, the thickness of the planar single material body is in the range of 1-500 μm, preferably 10-500 μm, preferably 20-400 μm, preferably 30-300 μm, and more preferably 50-300 μm.

[0050] A coating of another conductive material can be applied to at least a portion of one or more or all of the working electrode areas in these electrode assemblies. The conductive coating applied to the working electrode area will serve as the working electrode in the corresponding electrochemical cell. As a result, the use of the conductive working electrode coating expands the scope of available electrode materials and electrode combinations (and therefore electrode potentials), and allows convenient screening of suitable electrodes and electrode combinations in reaction discovery. Therefore, in an embodiment, a plurality of two-electrode assemblies include a working electrode area at least partially provided with a conductive coating, wherein the coating serves as the working electrode of the corresponding two-electrode assembly. Examples of suitable materials that can be used for this coating alone or in combination include but are not limited to graphite, glassy carbon, boron-doped diamond, Co, Fe, W, Sn, Pb, Ag, Ta, Cr, Mn, Mo, Ti, Zr, Hf, V, Nb, Au, Pt, Zn, Ni, Al, Cu, and Mg. It will be understood that, instead of one, multiple coatings can also be applied.

[0051] It is not mandatory that all working electrodes or working electrode areas are provided with the same coating. On the contrary, an advantageous aspect of this embodiment of the invention is that a variety of different types of coatings, such as different coating compositions, can be used in a single electrode array. For example, a first column or row electrode assembly having a first coating and a second column or row electrode assembly having a second coating can be provided, wherein the first coating and the second coating are different, and optionally the same applies to the third, fourth, etc. columns or rows. Advantageously, this allows for easy screening of suitable electrode materials for the purpose of reaction discovery. Therefore, in one embodiment, different coatings are present on at least two. In another embodiment, different coatings are present on each column or row of the electrode array. In yet another embodiment, substantially all or all of the two electrode assemblies are provided with different coatings on the working electrodes or their working electrode areas.

[0052] As previously explained, within a column or row of adjacent bodies, depending on the arrangement of the electrode array, two electrode assemblies each include a working electrode and a counter electrode, which are separated by a gap formed by the spacing between two adjacent monolithic bodies. Therefore, depending on the size and shape of these adjacent bodies and their spacing, the width of the gap can vary. The gap width may affect the function of the corresponding individual electrochemical cells in the entire device; for example, a gap with a smaller gap width reduces the voltage drop across the cell, but increases the risk of a short circuit condition. Typically, the width of the gap is in the range of 0.01-10 mm, preferably 0.1-4 mm, and most preferably 0.5-2 mm.

[0053] In a second aspect, the invention relates to an apparatus for performing electrochemical synthesis, the apparatus comprising an electrode array as defined herein and a plurality of reaction vessels, wherein each reaction vessel is configured to provide electrical contact of its contents to a single two-electrode assembly of the electrode array.

[0054] The device according to the present invention combines an electrode array as disclosed herein with a plurality of suitable reaction vessels, wherein each reaction vessel allows its contents to be in electrical contact with one electrode assembly so as to form a device comprising a plurality of electrochemical cells. Thus, the electrode assemblies of the electrode array of the present invention each individually form the bottom of a single electrochemical cell.

[0055] In one embodiment, the plurality of reaction vessels are formed from a plurality of droplets, wherein each droplet is in electrical contact with an electrode assembly, and wherein each droplet contains components required for an electrochemical conversion reaction, such as one or more starting materials (substrates) and a solvent and / or an electrolyte.

[0056] In another embodiment, a plurality of reaction vessels are formed by a plate comprising a plurality of holes, wherein typically each hole individually forms the wall of a single reaction vessel, and wherein the size and spacing of the holes correspond to the size and spacing of the electrode assembly forming the corresponding bottom of the resulting electrochemical cell. Such a plate comprising a plurality of, preferably equidistant holes can be made of any material capable of holding and withstanding the effects of reactive chemicals. In an embodiment, the plate is a monolithic plate, preferably a monolithic polymer plate. In an exemplary embodiment, the monolithic plate is a 3D printed polymer plate.

[0057] Typically, each reaction vessel extends in a direction substantially perpendicular or normal to the planar substrate.

[0058] Typically, the volume of each reaction vessel in the plurality of reaction vessels is in the range of 1-3000 μL, preferably 10-1000 μL, most preferably 50-300 μL.

[0059] Advantageously, the combination of the electrode array and the reaction vessel provides an array of micro electrochemical cells. Preferably, the size and mutual spacing of these cells correspond to the size and mutual spacing of the wells of a standard Society for Biomolecular Screening (SBS) multiwell plate, allowing easy compatibility with existing laboratory equipment.

[0060] In a preferred embodiment, the size and mutual arrangement of the two electrode assemblies and the reaction vessel correspond to the size and mutual arrangement of the holes of the standard biomolecular screening association (SBS) multi-well plate. Preferably, they correspond to the standard biomolecular screening association (SBS) 12 (3×4), 24 (4×6), 48 (6×8), 96 (8×12), 384 (16×24) or 1536 (32×48) well plates, preferably those of 96 or 384 well plates.

[0061] In order to carry out electrochemical conversion, the device must be connected to a suitable current source. Therefore, in an embodiment, the device further includes one or more current supply units. In principle, any type of power supply can be used, as long as it can provide a constant current of each electrochemical cell formed by an array of two electrode assemblies and a corresponding reaction vessel. Suitable current sources are commercially available, and an example thereof is a multi-channel DC power supply available from Rohde & Schwarz HMP4000 power supply series, and technicians will be able to realize one or more of these current sources suitable for a given purpose. Electrical contacts can be provided using means known to technicians (such as alligator clips, welding, etc.). Typically, the current supply unit is configured to provide a substantially constant or constant current output within the range of 0.01mA-1000mA, preferably 0.1-20mA, most preferably 0.5-10mA.

[0062] In the device of the present invention, typically, the two electrode assemblies are composed of the same row n j Or the same line m i The working electrode area of ​​the first body and the counter electrode area of ​​the second adjacent body in the matrix array are formed; therefore, the two electrode assemblies in the column or row are respectively electrically connected in series through the continuous monolithic body. Therefore, depending on whether the columns or rows in the matrix array form a series circuit, the number of current supplies is typically equal to or less than the number of rows or columns in the electrode array. Preferably, the number of current supplies is equal to the number of rows or columns forming a series connection in the electrode array, so that each of the m×n two electrode assemblies is electrically connected.

[0063] Advantageously, the planar configuration of the electrode array and the series connection in columns or rows of the electrode assembly matrix requires that the electrical contacts for the current supply be connected only at the edges of the substrate, which greatly simplifies the manufacture, operation and maintenance of the device.

[0064] The current intensity and the duration of the current supply can be adjusted using equipment and procedures that are known to the skilled person and are commercially available or can be developed in-house.

[0065] The device as disclosed herein can be used for a variety of electrochemical applications. The device of the present invention is particularly suitable for high-throughput electrochemical conversion of suitable starting materials into target chemical compounds. Therefore, in one aspect, the present invention relates to the use of the device as disclosed herein in the electrochemical synthesis of chemical compounds. In one embodiment, the use relates to chemical library synthesis. In another embodiment, the use relates to chemical reaction discovery.

[0066] The method of the present invention is applicable to a wide range of electrochemical reactions. Non-limiting examples of reduction or oxidation reactions of organic compounds suitable for use in the method and apparatus of the present invention are electrochemical cross-coupling reactions and functional group interconversions, including (oxidative) CN / NH cross-coupling reactions, metabolite synthesis, conversion of alcohols to ketones to acids, nitrile reduction, cross-electrophile coupling, Shono oxidation, and biaryl coupling reactions.

[0067] In another aspect, the present invention provides a method for electrochemically converting one or more reactants into a reaction product, the method comprising

[0068] - providing an electrochemical device as defined herein

[0069] - providing one or more reactants and optionally a solvent and / or an electrolyte to a reaction vessel

[0070] - Applying a current between the working electrode and the counter electrode of the two-electrode assembly sufficient to convert one or more reactants into reaction products

[0071] Suitable solvents and electrolytes for electrochemical synthesis are known to the skilled person. A non-limiting example is tetrabutylammonium hydroxide (Bu 4 NOH), sodium pivalate, tetrabutylammonium tetrafluoroborate (Bu 4 NBF 4 ), ethyltriethylammonium tetrafluoroborate, tetraethylammonium tetrafluoroborate, tetraethylammonium chloride (TEAC), 1-butyl-3-methyl-imidazolium tetrafluoroborate, sodium acetate, lithium perchlorate, sodium sulfate, potassium hydroxide (KOH), sodium hydroxide (NaOH), hydrogen chloride (HCl) or sulfuric acid (H 2 SO 4 ) aqueous solutions and ionic liquids.

[0072] The reaction product is post-processed, analyzed and purified using methods and equipment known in the art. In an embodiment, the size and mutual arrangement of the two electrode assemblies and the reaction vessel correspond to the standardized porous plate obtained above, and the post-processing of the reaction product can be appropriately carried out using automatic liquid handling and sample collection. The analysis of intermediates and reaction products can be completed by known techniques (such as LC-MS, GC and NMR), and the separation of the reaction can be carried out, for example, by preparative HPLC.

[0073] Depending on the geometry of the body forming the two electrode assemblies (i.e., connected in series in rows or columns), the method can be performed row by row or column by column by electrically connecting the rows or columns to a current source. In a preferred embodiment, all rows or all columns of the electrode array matrix are connected so that all reactions are performed in parallel. Preferably, the reactions differ in one or more aspects so that different reaction products are obtained, and / or different yields are obtained, and / or optimal process conditions can be found.

[0074] Thus, in a preferred embodiment, a plurality of different electrochemical conversions are performed in parallel, wherein the electrochemical conversions differ in one or more of the following aspects:

[0075] - reactants provided to the reaction vessel

[0076] - The concentration of reactants present in the reaction vessel

[0077] -Solvent supplied to the reaction vessel

[0078] - Electrolyte supplied to the reaction vessel

[0079] - Counter electrode material

[0080] -Working electrode materials

[0081] -Working electrode coating material

[0082] -Current density

[0083] - Charge passing

[0084] In an embodiment, at least two of these electrochemical conversions are performed using different working electrode materials. This can be suitably achieved by applying a coating of a different material on the working electrode region forming the body of the respective two-electrode assembly; thus, the coating of the suitable conductive material then acts as the working electrode of each of the two-electrode assemblies involved.

[0085] Electrode arrays according to the invention may generally be prepared by generating a pattern forming two electrode assemblies on a suitable substrate material, optionally followed by application of one or more coatings on selected portions of the array, in particular on the working electrode areas of one or more of the two electrode assemblies.

[0086] Therefore, in one aspect, the present invention relates to a method for manufacturing an electrode array according to the present invention, the method comprising the following steps:

[0087] - providing a substrate;

[0088] - generating a pattern forming a two-electrode assembly on the surface of the substrate;

[0089] - Optionally, a coating is applied to at least a portion of the working electrode region of one or more of the two-electrode assemblies.

[0090] The substrate can be any non-conductive flat substrate such as glass, ceramic or polymer.

[0091] The pattern forming the two electrode assemblies can be produced, for example, by applying a suitable composition comprising electrode materials to a substrate. The composition comprising the electrode materials can be a suspension, ink or a paste comprising the electrode materials in powder form. The application of the composition comprising the electrode materials can be carried out in various ways known in the art, such as screen printing, stencil printing or inkjet printing. In an exemplary embodiment, screen printing is used, which is a low-cost technology that provides many benefits, including high reproducibility and accuracy, and the possibility of easily changing the composition of electrode geometry and electrode materials.

[0092] Therefore, in one exemplary embodiment, there is provided a method for manufacturing an electrode array according to the present invention, the method comprising the following steps:

[0093] - providing a substrate;

[0094] - providing a composition comprising an electrode material;

[0095] - applying a composition comprising an electrode material to a substrate so as to obtain a pattern forming a two-electrode assembly;

[0096] - Optionally, a coating is applied to at least a portion of the working electrode region of one or more of the two-electrode assemblies.

[0097] Another suitable method for producing a pattern forming a two-electrode assembly on a substrate material is by photothermal surface pyrolysis of a suitable carbon-based substrate material (such as polyimide foil). For example, by moving a laser beam with a defined flux and wavelength at a controlled speed on the surface of the polyimide foil, local heating and carbonization (graphitization) of the polyimide surface occurs. This allows the formation of, for example, pyrolytic carbon traces with a width of about 300 microns and a height of about 40 microns. The laser head can be mounted on an XY stage, so that any area of ​​the substrate can be patterned with carbon traces. By overlapping the pyrolytic carbon traces, a desired planar array of conductive bodies can be obtained. Advantageously, this method can be economically scaled up to a roll-to-roll method using, for example, a laser / galvanometer scanning device. Other advantages of the surface pyrolysis method for preparing electrode patterns according to the present invention are that it does not require consumables other than organic substrate materials, and due to the inherent chemical compatibility of the substrate material and the carbon traces, an electrode array with excellent chemical resistance is obtained.

[0098] Therefore, in another exemplary embodiment, there is provided a method for manufacturing an electrode array according to the present invention, the method comprising the following steps:

[0099] - providing a substrate;

[0100] - subjecting the substrate to photothermal carbonization to produce a graphitic carbon pattern forming a two-electrode assembly;

[0101] - Optionally, a coating is applied to at least a portion of the working electrode region of one or more of the two-electrode assemblies.

[0102] In this embodiment, the substrate material can be any carbon-based material that is susceptible to photothermal (eg, laser-induced) conversion to graphitic carbon, examples of which include polyimide, polydimethylsiloxane, and cellulose.

[0103] As described above, in all embodiments, optionally, a coating of another conductive material is applied to at least a portion of one or more or all of the working electrode regions of these electrode assemblies. The conductive coating applied to the working electrode region will serve as a working electrode in the corresponding electrochemical cell. Therefore, applying different coatings as working electrodes in electrode arrays and corresponding electrochemical devices allows screening of suitable electrode materials and material combinations.

[0104] Depending on the specific choice of material or combination of materials, such coatings are suitably applied using thin layer deposition techniques known in the art (such as chemical vapor deposition, spraying, electrodeposition) or printing techniques (including screen printing, stencil printing, or inkjet printing).

[0105] In order to assemble a complete electrochemical device, a suitable reaction vessel and one or more current supplies in electrical contact with the electrode assembly should be added. As explained above, a plurality of droplets (wherein each droplet is in electrical contact with an electrode assembly, and wherein each droplet contains components required for the electrochemical conversion reaction, such as one or more starting materials (substrates) and solvents and / or electrolytes) can be suitable for forming a reaction vessel. In another embodiment, a plate comprising a plurality of holes is connected to an electrode array, wherein typically each hole forms the wall of a single reaction vessel individually. In both designs, each two-electrode assembly of the electrode array is configured to form the bottom of a separate electrochemical cell, and these separate electrochemical cells form a complete electrochemical device together with one or more current supply units.

[0106] The electrode array and the plate comprising a plurality of holes can be connected by any suitable means. In one embodiment, the electrode array and the plate comprising a plurality of holes are connected by bonding with the following resin: such as epoxy resin, preferably low viscosity epoxy resin, such as epoxy resin commercialized by Huntsman Corp. with the index number Araldite RAPID or epoxy resin commercialized by Masterbond with the index number EP41S-5. In another embodiment, the electrode array and the plate comprising a plurality of holes are sealed together using a suitable frame. Combinations of such chemical and mechanical connection options are also possible.

[0107] Detailed description with drawings

[0108] Figure 1 A photograph of an electrode array 1 according to an embodiment of the present invention is shown. The 8×12 electrode array comprises 8 rows and 12 columns of planar monolithic bodies screen-printed on a glass substrate 2, wherein the working electrode regions 4 and counter electrode regions 5 of adjacent bodies 3 in a column together form a column of two electrode assemblies 6 connected in series.

[0109] Figure 2 shows the Figure 1 A schematic diagram of a portion of an electrode array is shown. Figure 2A A monolithic body 3 having a working electrode region 4 and a counter electrode region 5 is shown. Figure 2B Two adjacent monolithic bodies 3 separated by a gap 8 forming a two-electrode assembly 6 are shown. Figure 2C A schematic diagram of a matrix 7 of bodies 3 forming part of an electrode array according to an embodiment of the present invention is shown. The matrix 7 has m rows and n columns of monolithic bodies 3. For each column n i (where i=1, 2, 3, ...m), the working electrode region 4 and the counter electrode region 5 of the adjacent body 3 form two electrode assemblies 6 separated by a distance 9.

[0110] Figure 3A is a schematic diagram of an electrode array configuration according to another embodiment of the present invention, comprising a substantially rectangular monolithic body 3. Figure 3B Two monolithic bodies 3 with a working electrode region 4 and a counter electrode region 5 separated by a gap 8 are schematically represented. Figure 3C Schematically, adjacent bodies 3 are shown in a column forming a matrix 7 of two electrode assemblies 6 separated by a distance 9 from each other (edge ​​to edge or center to center). Figure 3D A magnified photograph of an array of carbon planar bodies according to this embodiment produced by surface laser pyrolysis on a polyimide foil is shown. The bodies are formed of adjacent graphitic carbon strips of about 300 microns in width and about 40 microns in height.

[0111] Figure 4A photograph of an 8×12 reaction vessel array according to an embodiment of the present invention is shown. The reaction vessel array is formed from a nylon plate comprising equidistant holes prepared by 3D printing.

[0112] Figure 5 A photograph of a device according to an embodiment of the present invention without a current supply is shown. The device includes a low viscosity epoxy resin bonded to the Figure 1 The 8x12 electrode array shown is similar to Figure 4 An 8 x 12 reaction vessel array assembly is shown.

[0113] Figure 6 A schematic diagram of an assembly 11 of power supplies and controls for an apparatus according to an embodiment of the present invention is shown. In the schematically illustrated apparatus 10, each of twelve columns comprising a series of two-electrode assemblies connected in series is connected to a common supply voltage 12 and to a 12-channel current limiter 13 connected to ground 14. The 12-channel current limiter 13 is controlled using software running on a computer 15.

[0114] Examples

[0115] The present invention will be further explained, illustrated, and described in the following examples of the system of the present invention. These examples demonstrate the utility and / or function of the present invention and help provide a complete description of the present invention. These examples are intended to be illustrative and do not limit the present invention.

[0116] Example 1.1: Device preparation including printing method

[0117] Step 1: Preparation of printing paste

[0118] A graphite-containing printing paste was prepared as follows:

[0119] PDVF (615 mg, powder, Aldrich) was added to NMP (3.49 g), and the mixture was heated to 50°C and treated with ultrasound for 12-48 h until a clear viscous solution was obtained. Graphite (2.68 g, 20 micron particle size, synthetic, Aldrich) was added and dispersed thoroughly by mechanical stirring.

[0120] Step 2: Fabrication of electrode arrays

[0121] The electrode array was fabricated by template printing (template: 0.10 mm stainless steel plate, cut by water jet to provide cutouts for the body of the 8x12 two-electrode assembly) of the graphite-containing printing paste of step 1 on a glass plate (float glass, 1 mm thick, manually cut). The array was dried in air at 80°C for 16 h to provide a planar monolithic body array for the 8x12 two-electrode assembly, with a thickness of about 0.1 mm. A photograph of the electrode array is shown in Figure 1 supply.

[0122] Step 3: Fabrication of the Orifice Plate Apparatus

[0123] A polymer plate (nylon, in-house 3D printed) comprising an 8x12 array of wells was glued on top of the electrode array obtained in step 2 using a low viscosity epoxy resin (Araldite RAPID commercialized by Huntsman Corporation) to obtain 8x12 wells configured to receive and hold the reaction mixture.

[0124] In an alternative embodiment of step 3, a polymer plate comprising an 8x12 array of wells is pressed on top of the electrode array obtained in step 2 by means of a suitable frame and gaskets to obtain 8x12 wells configured to receive and contain the reaction mixture.

[0125] Step 4: Connection of Current Supply and Controls

[0126] Three commercially available four-channel power supplies from the Rohde & Schwarz HMP4000 power supply series were used to connect twelve independently controlled current supplies with a rated current of >10 mA and a rated voltage of >64 V. The power supplies were connected to the well plate apparatus of step 3 using alligator clips that independently connected each of the 12 columns of the 8x12 electrode array. The current as well as the electrolysis time could be set individually for each column.

[0127] Example 1.2: Device preparation involving laser pyrolysis method

[0128] Step 1: Fabrication of pyrolytic carbon electrode arrays

[0129] Electrode arrays were made by laser pyrolysis of polyimide foil. A piece of polyimide foil (0.25 mm thickness, Flexiso FI 16000, Dietrich Müller GmbH) was placed in the working area of ​​a laser cutter (Xtool D1 Pro, 40 W, controlled by Lightburn software) on an aluminum plate (5 mm thickness, equipped with double-sided tape to hold the foil in place). The focus of the laser head was adjusted to -10 mm. In the Lightburn software, a CAD representation of the electrode array was drawn. The laser conditions (engraving mode, 3200 mm / min speed, 11.7% power, 0.30 mm line spacing) were set and the laser was started. After pyrolysis was completed to obtain a pyrolytic carbon electrode array, the laser focus was adjusted to 0 mm, the laser conditions were modified to cut (cutting mode, 3000 mm / min speed, 60% power, 1 time), appropriate CAD drawing was selected, and the program was started again.

[0130] Step 2: Fabrication of the well array plate

[0131] A plate including an 8x 12 hole array was produced by laser cutting. A polyamide plate (PA 6, 5 mm thickness, Maagtechnic) was placed in the working area of ​​a laser cutter (Xtool D1 Pro, 40 W, controlled by Lightburn). The focus of the laser head was adjusted to 0 mm. In the Lightburn software, a CAD representation of the hole array plate was drawn. The laser conditions (cutting mode, 400 mm / min speed, 100% power, 2 times) were set, and the laser was started. After the run, the hole array plate was deburred and sanded.

[0132] Step 3: Fabrication of the Orifice Plate Apparatus

[0133] The electrode array obtained in step 1 and the well array plate obtained in step 2 are bonded using a chemically resistant epoxy resin (Araldite RAPID commercialized by Huntsman) to obtain 8x12 wells configured to receive and hold a reaction mixture. Other epoxy resins may be used, such as the resin commercialized by Master Bond under the reference number EP41S-5.

[0134] Step 4: Connection of Current Supply and Controls

[0135] Three commercially available four-channel power supplies from the Rohde & Schwarz HMP4000 power supply series were used to connect twelve independently controlled current supplies with a rated current of >10 mA and a rated voltage of >64 V. The power supplies were connected to the well plate apparatus of step 3, independently connecting each of the 12 columns of the 8x12 electrode array. The current and electrolysis time could be set individually for each column.

[0136] Step 5: Electrodeposition of Platinum (Pt)

[0137] Prepare a solution containing chloroplatinic acid (0.043 mol / L) and H 2 SO 4 (0.020 mol / L) aqueous stock solution. To each well of the well plate device prepared above, 100 μL of the stock solution was added. The device was placed on an orbital shaker and the oscillation frequency was adjusted to 400 rpm. A constant current of 6.6 mA (30 mA / cm2) was applied for 1.6 min, resulting in Pt deposition on the cathode. The wells were filled with H 2 The resulting mixture was washed with 0.2% O and then with MeOH and allowed to dry in air at room temperature.

[0138] Example 2: Reaction Discovery

[0139]

[0140] In this experiment, the optimal electrosynthetic conditions, especially the electrode materials and solvents / electrolytes to obtain compound 3 in high yield, were investigated.

[0141] The experiments were performed in an electrochemical 96-well plate setup with an all-graphite electrode array according to the present invention, where the working electrodes of each row were coated with a thin layer (<50 μm) of the following materials:

[0142] - Row 1: [Uncoated],

[0143] - Row 2: Glassy carbon,

[0144] - Row 3: IrO 2 ,

[0145] - Row 4: RuO 2 ,

[0146] - Row 5: Pt,

[0147] - Row 6: TiO,

[0148] - Row 7: Boron-doped diamond,

[0149] - Row 8: TiN

[0150] Veratrol (1, 0.01 mmol) and 5-methoxy-1,2,3-triazole (2, 5.0 eq) were added to each well. To each well in each column of the plate, the following solvents (0.10 ml 10 ml / mmol) and electrolytes (0.5 eq) were added, respectively:

[0151] - Column 1: Methanol (MeOH), Tetrabutylammonium Hydroxide (Bu 4 NOH);

[0152] - Column 2: methanol (MeOH), sodium pivalate (NaOPiv);

[0153] - Column 3: Methanol (MeOH), Tetrabutylammonium tetrafluoroborate (Bu 4 NBF 4 );

[0154] - Column 4: Acetonitrile (MeCN), Tetrabutylammonium Hydroxide (Bu 4 NOH);

[0155] - Column 5: acetonitrile (MeCN), sodium pivalate (NaOPiv);

[0156] - Column 6: Acetonitrile (MeCN), Tetrabutylammonium tetrafluoroborate (Bu 4 NBF 4 );

[0157] - Column 7: dimethyl sulfoxide (DMSO), tetrabutylammonium hydroxide (Bu 4 NOH);

[0158] - Column 8: dimethyl sulfoxide (DMSO), sodium pivalate (NaOPiv);

[0159] - Column 9: dimethyl sulfoxide (DMSO), tetrabutylammonium tetrafluoroborate (Bu 4 NBF 4 )

[0160] - Column 10: Hexafluoroisopropanol (HFIP), Tetrabutylammonium hydroxide (Bu 4 NOH);

[0161] Column 11: hexafluoroisopropanol (HFIP), sodium pivalate (NaOPiv);

[0162] - Column 12: Hexafluoroisopropanol (HFIP), Tetrabutylammonium tetrafluoroborate (Bu 4 NBF 4 )

[0163] The current supply was connected to the electrical contacts on both sides of each column, and a current of 1.0 mA was passed for 60 min.

[0164] Characterization and quantification of the reaction product 3 were performed using methods and equipment known in the art, including NMR, GC-MS, and HPLC.

[0165] Example 3: Library preparation

[0166]

[0167] This experiment is carried out in an electrochemical 96-well plate with a full graphite electrode array. In each column of the 96-well plate, one of 12 different aryl educts 4 (0.10 mmol) is introduced. In each row of the electrochemical 96-well plate, one of 8 different azole educts 5 (0.30 mmol, 3.0 eq) is added. NaOPiv (0.5 eq) is added to all 96 holes, and MeOH (0.10 ml, 1.0 ml / mmol) is then added. The current supply is connected to the electrical contacts on both sides of each column, and a current of 10 mA is passed through 60 min.

[0168] Characterization and quantification of the reaction product 6 was performed using methods and equipment known in the art, including NMR, GC-MS, and HPLC.

Claims

1. An electrode array (1) comprising two electrode assemblies (6) for performing electrochemical synthesis, the electrode array comprising a plurality of planar monolithic bodies (3) arranged on a planar substrate (2), wherein the bodies comprise working electrode regions (4) and / or counter electrode regions (5), and wherein the bodies are arranged on the substrate (2) to form an m×n matrix (7) of m rows and n columns of the two electrode assemblies (6), the matrix consisting of n rows of the same column j Or the same line m i The working electrode region (4) of the first body (3) and the counter electrode region (5) of the second adjacent body (3) are separated by a gap (8).

2. The electrode array according to claim 1, in, The two electrode assemblies (6) are arranged at a substantially equal distance (9) from each other, wherein the distance (9) between the two electrode assemblies (6) is selected such that this enables the matrix (7) of the two electrode assemblies (6) to form the corresponding bottoms of the wells of a multi-well plate having m rows and n columns.

3. The electrode array according to claim 2, in, m, n and the distance (9) correspond to those of standard Society for Biomolecular Screening (SBS) 12 (3×4), 24 (4×6), 48 (6×8), 96 (8×12), 384 (16×24) or 1536 (32×48) well plates, preferably 96-well or 384-well plates.

4. The electrode array according to any one of claims 1 to 3, in, The planar monolithic body has a thickness in the range of 10-500 μm, preferably 20-400 μm, more preferably 30-300 μm and most preferably 50-300 μm.

5. The electrode array according to any one of claims 1 to 4, in, A plurality of the two-electrode assemblies comprise a working electrode region (4) which is at least partially provided with a conductive coating.

6. The electrode array according to claim 5, in, Different coatings are present on at least two, preferably all, of the two-electrode assemblies.

7. A device for performing electrochemical synthesis, comprising an electrode array according to any one of claims 1 to 6, and a plurality of reaction containers, in, Each of the reaction vessels is configured to provide electrical contact between its contents and a single two-electrode assembly of the electrode array.

8. The device according to claim 7, in, The plurality of reaction vessels is formed by a plate comprising a plurality of holes, preferably equidistant holes.

9. The device according to claim 7 or claim 8, in, The dimensions and mutual arrangement of the two electrode assemblies and the reaction vessels correspond to the dimensions and mutual arrangement of the wells of a standard Society for Biomolecular Screening (SBS) multiwell plate, preferably a 96-well or 384-well plate.

10. Use of the device according to any one of claims 7 to 9 in the electrochemical synthesis of chemical compounds, preferably in, The uses involve chemical library synthesis or chemical reaction discovery.

11. A method for electrochemically converting one or more reactants into a reaction product, the method comprising - Providing an electrochemical device according to any one of claims 7 to 9; - providing one or more reactants and optionally a solvent and / or an electrolyte to the reaction vessel; - applying a current between the working electrode and the counter electrode of the two-electrode assembly sufficient to convert the one or more reactants into reaction products.

12. The method according to claim 11, in, A plurality of different electrochemical transformations are performed in parallel, wherein the electrochemical transformations differ in one or more of the following aspects: - reactants provided to the reaction vessel - the concentration of reactants present in the reaction vessel -Solvent supplied to the reaction vessel -Working electrode materials -Current density -The charge passed.

13. The method according to claim 12, in, At least two of the electrochemical conversions are performed using different working electrode materials.

14. The method according to any one of claims 11-13, wherein the electrochemical conversion comprises one or more of an electrochemical cross-coupling reaction and a functional group interconversion, such as a CN / NH cross-coupling reaction, metabolite synthesis, alcohol to ketone to acid conversion, nitrile reduction, cross-electrophile coupling, Zhuangye oxidation, and a biaryl coupling reaction.

15. A method for manufacturing an electrode array according to any one of claims 1 to 6, the method The following steps are involved: - providing a substrate; - generating a pattern forming the two-electrode assembly on the surface of the substrate; - Optionally, a coating is applied to at least a portion of the working electrode area of ​​one or more of the two-electrode assemblies.

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