Electrode arrays and devices for high-throughput electrosynthesis

Abstract

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

Description

[Technical Field]

[0001] The present invention relates to electrode arrays and devices for use in performing electrochemical synthesis, such as the synthesis of chemical libraries and chemical reaction discovery. More specifically, the present invention relates to automation-compatible devices and methods for high-throughput parallel electrosynthesis of milligram quantities of compounds and screening of (electro)chemical reaction parameters. [Background technology]

[0002] A chemical library is a collection of compounds that can be used to screen a particular class of compounds for specific interactions with a particular target, such as affinity for a binding site in drug discovery, tendency to catalyze polymerization in industrial processes, or pesticidal activity in agrochemical chemistry.

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

[0004] Electrosynthesis may offer advantages over conventional organic redox reactions in terms of the selectivity and yields that can be obtained, and therefore, in general, electrosynthesis may be an advantageous alternative for the preparation of novel compounds or classes of compounds.

[0005] However, the discovery of novel electrochemical reactions for the general synthesis of new compounds or library generation requires the design and evaluation of appropriate reaction parameters, such as electrode materials, electrolytes, current densities, etc. Such screening for suitable parameters and conditions is well beyond the technical and practical scope of the average organic chemist and typically requires the design of one or several electrochemical reactors using different electrode assemblies and numerous iterations of various reaction conditions.

[0006] For example, electrochemical devices such as a microscale 24-well electrochemical reactor using an array of two parallel cylindrical rods as electrodes, held closely spaced to fit an array of microscale cells in a base plate, are known in the art. The device further includes an alignment plate, a sealing plate, a custom printed circuit board, and an 8-pin connector for connecting to four controllers configured to provide constant current or constant voltage. This setup allows for the screening of four discrete currents or four discrete cell voltages, depending on the mode of operation. However, the device requires manual handling of all 48 electrodes during assembly. Furthermore, to ensure experimental reproducibility, the electrodes must be manually cleaned and / or mechanically polished after each reaction to expose the unaltered surface of the electrode material. These labor-intensive processes represent a bottleneck in high-throughput electrosynthesis, preventing this concept from being scaled up to larger numbers of cells.

[0007] U.S. Patent Application Publication No. 2020 / 0384434 describes a device used in the solid-phase synthesis of polymers, in which growing polymer chains are individually and covalently attached to a solid support via linker molecules. The device includes an array of individually addressable electrodes embedded in a solid support, which may comprise or consist of an integrated circuit (IC). By reversing the bias at specific electrodes in the array, linker molecules can be selectively cleaved from the support, thereby allowing site-selective release from the polymer chains during synthesis. In certain embodiments, the positive electrode in the array includes three, four, five, six, seven, eight, nine, or more electrodes, each configured as a negative electrode. In the device disclosed in U.S. Patent Application Publication No. 2020 / 0384434, the solid support with the embedded array of individually addressable electrodes forms the basis of a single electrolytic cell, and electrolysis effects the release of the polymer product, rather than the polymerization reaction itself. As such, the device is not suitable for electrochemical synthesis purposes, which typically require the controlled application of potential or current from a single electrode (cathode-anode) pair.

[0008] Thus, there exists a heretofore unmet need for electrode arrays and corresponding electrochemical devices for use in electrochemical synthesis, including high-throughput synthesis of chemical libraries and chemical reaction discovery, that are easy to manufacture, modify, and maintain. More specifically, there is a need to have electrode arrays that can be manufactured in a few steps and at low cost, and that can advantageously be disposable items, thus avoiding manual handling and tedious post-processing of the electrodes. Furthermore, there is a need for electrode arrays and electrochemical devices including such arrays that allow for easy changing of electrode materials within the same array and that can withstand the currents required for electrochemical synthesis. In addition, it would be desirable to have access to electrode arrays and devices that allow reactions to be performed in parallel with a small number of simple power drivers. Furthermore, it would be beneficial to have electrochemical devices and methods available for the rapid synthesis, quantification, and isolation of large quantities of compounds, as well as for screening suitable reaction conditions for such electrochemical synthesis. Summary of the Invention [Means for solving the problem]

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

[0010] Thus, in a first aspect, the present invention relates to an electrode array comprising a two-electrode assembly for use in performing electrochemical synthesis, said electrode array comprising a plurality of planar monolithic bodies arranged on a planar substrate, said monolithic bodies comprising a working electrode area and / or a counter electrode area, said monolithic bodies arranged on the substrate and forming an m×n matrix (6) of m rows and n columns of two-electrode assemblies formed by the working electrode area of ​​a first monolithic body and the counter electrode area of ​​an adjacent second monolithic body in the same column or the same row, separated by a gap.

[0011] The electrode array of the present invention includes planar monolithic bodies forming a two-electrode assembly with a thickness and shape particularly suitable for electrochemical synthesis. By not having a third (reference) electrode, the electrode assembly does not require conductive traces to pass through the substrate and can be realized with a simple, flat design that can be easily adapted to the specific purpose of the electrochemical reaction. Furthermore, in the electrode array of the present invention, the working and counter electrode regions of two adjacent monolithic bodies in the same column or row may together form a two-electrode assembly. This allows the assemblies in the column or row to be connected in series, requiring only one power supply per column or row, achieving an optimal balance between the complexity of the electrical circuitry and the number of parallel reactions (and therefore throughput).

[0012] The electrode array is combined with a number of suitable containers containing other required components, such as reaction substrate and electrolyte, 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 a device for performing electrochemical synthesis comprising an electrode array as defined herein and a plurality of reaction vessels, each of the reaction vessels configured to bring its contents into electrical contact with a single two-electrode assembly of the electrode array.

[0014] An advantage of the device of the present invention is that multiple electrochemical transformations can be performed in parallel with different substrates under the same conditions or under various controlled conditions. This makes it possible to use the device of the present invention to efficiently create chemical libraries. Furthermore, 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 present 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 the discovery of chemical reactions.

[0017] In a further aspect, the present invention provides a method for electrochemically converting one or more reactants to a reaction product, comprising: - providing an electrochemical device according to the invention; - providing one or more reactants, and optionally a solvent and / or an electrolyte, to a reaction vessel; - applying a current between the working and counter electrodes of a two-electrode assembly sufficient to convert one or more reactants into reaction products; The present invention relates to a method comprising: [Brief explanation of the drawings]

[0018] [Figure 1] 1 shows a photograph of an electrode array according to one embodiment of the present invention. [Figure 2A] 1 shows a schematic diagram of a monolithic body having a working electrode area and a counter electrode area. [Figure 2B] 1 shows a schematic diagram of two monolithic bodies forming a two-electrode assembly. [Figure 2C] 1 shows a schematic diagram of a matrix of monolithic bodies forming part of an electrode array according to an embodiment of the present invention; [Figure 3A-3C] 1A and 1B show schematic diagrams of an electrode array configuration according to another embodiment of the present invention, two monolithic bodies forming a two-electrode assembly according to this embodiment, and a matrix of monolithic bodies forming part of an electrode array according to this embodiment, respectively. [Figure 3D] 1 shows a close-up photograph of an array of pyrolytic carbon flat bodies fabricated by surface laser pyrolysis on a polyimide foil. [Figure 4] 1 shows a photograph of an array of reaction vessels according to one embodiment of the present invention. [Figure 5] 1 shows a photograph of a device according to one embodiment of the present invention. [Figure 6] FIG. 1 shows a power and control schematic for a device according to one embodiment of the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0019] The invention is described in more detail below.

[0020] In a first aspect, the present invention relates to an electrode array comprising a two-electrode assembly (6) for use in performing electrochemical synthesis, said electrode array comprising a plurality of planar monolithic bodies arranged on a planar substrate, said monolithic bodies comprising a working electrode area and / or a counter electrode area, said monolithic bodies arranged on the substrate and forming an m×n matrix of m rows and n columns of two-electrode assemblies formed by the working electrode area of ​​a first monolithic body (3) and the counter electrode area of ​​an adjacent second monolithic body (3) in the same column or the same row, separated by a gap.

[0021] In the context of the present invention, the term "planar" means that the average thickness dimension is substantially less than the range of the other two dimensions, namely, its length and width dimensions. A monolithic body is still considered to be planar if it meets this condition, even if its thickness is not constant. That is, the monolithic body may contain irregularities, such as surface roughness."

[0022] In the context of the present disclosure, "a monolithic body disposed on a substrate" should be taken to mean that the monolithic body is disposed on the surface of the substrate and is not embedded to any relevant degree, and preferably not embedded at all.

[0023] An electrode array, as defined herein, has as its basic structure an array of planar monolithic bodies containing working and / or counter electrode regions, with the advantage that adjacent monolithic bodies can be joined together to form two-electrode assemblies of working and counter electrodes. These two-electrode assemblies are thus in the same plane and parallel to the substrate, eliminating the need for complex electronic wiring through the substrate. As used herein, the term "monolithic body" should be understood to refer to a shape made of one piece, substantially free of or without interruptions such as grooves or holes within the shape. The term "monolithic" as used herein does not necessarily mean a single material; the body may be made of a single material or a composition of different materials, preferably as homogeneous as possible.

[0024] Typically, the majority of the monolithic bodies will have both a working electrode area and a counter electrode area, with only the first and / or last monolithic body forming a column or row needing only a working electrode area or a counter electrode area to form a two-electrode assembly with the immediately adjacent monolithic body.

[0025] In an exemplary embodiment, the electrode array comprises a plurality of planar monolithic bodies disposed on a planar substrate, each of said monolithic bodies comprising a working electrode region and a counter electrode region, In this embodiment, the first and last monolithic bodies forming a column or row comprise both a working electrode region and a counter electrode region, although this is not required for proper device operation.

[0026] In another exemplary embodiment, the electrode array includes a plurality of planar monolithic bodies arranged on a planar substrate, the first and last monolithic bodies forming a column or row including a working electrode region or a counter electrode region, and the remaining monolithic bodies (i.e., those not taking edge positions) including working and counter electrode regions.

[0027] Thus, in general, an electrode array according to the present invention comprises a plurality of two-electrode assemblies formed by adjacent, contiguous monolithic bodies in a column or row. In one embodiment, the electrode array comprises a plurality of two-electrode assemblies formed by adjacent, contiguous monolithic bodies in a column. In another embodiment, the electrode array comprises a plurality of two-electrode assemblies formed by adjacent, contiguous monolithic bodies in a row.

[0028] Thus, within a row of adjacent monolithic bodies, a two-electrode assembly can be formed along the length of the row by the working electrode region of a first monolithic body and the counter electrode region of a second immediately adjacent monolithic body. Each two-electrode assembly thus includes a working electrode and a counter electrode separated by a gap formed by the spacing between the two adjacent monolithic bodies. A second two-electrode assembly can then be formed by the working electrode region of the second monolithic body and the counter electrode region of a third immediately adjacent monolithic body in the same row, and so on, forming a row of serially connected two-electrode assemblies.

[0029] Alternatively, within a row of adjacent monolithic bodies, along the length of the row, a first two-electrode assembly may be formed by the working electrode region of the first monolithic body and the counter electrode region of the immediately adjacent second monolithic body, a second two-electrode assembly may be formed by the working electrode region of the second monolithic body and the counter electrode region of the immediately adjacent third monolithic body, and so on, forming a string of serially connected two-electrode assemblies.

[0030] In one embodiment, at least two two-electrode assemblies in a column or row are connected in series. Preferably, substantially all or all of the 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 monolithic body forms a two-electrode assembly with an immediately adjacent monolithic body in the same row. In this way, only one current supply connection is required for each column or row of serially connected assemblies, which makes it possible to achieve an optimal balance between the complexity of the electrical circuit of the corresponding electrochemical device and the number of parallel reactions (and therefore the throughput).

[0031] As described in detail herein below, monolithic bodies can be applied using simple, low-cost techniques such as screen printing, stencil printing, or inkjet printing. Screen printing of electrode materials onto substrates is a well-known technique and offers many advantages, such as high reproducibility and precision, as well as the ability to easily modify the electrode shape and electrode material composition. Laser surface pyrolysis is another technique that can be used to produce desired monolithic bodies, particularly monolithic bodies made of pyrolytic carbon. For the properties of carbon monolithic bodies, the following references are cited: Merlen, A.; Buijnsters, JG; Pardanaud, C. From Graphene to Amorphous Carbons; Coatings 2017, 7, 153.

[0032] Depending on the material selection and application technique of the monolithic body, the electrode array can be manufactured at low cost for single use only, and therefore in one embodiment the electrode array is a disposable electrode array.

[0033] The monolithic bodies are arranged to 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 a non-zero integer. Thus, each m i (i=1, 2...) row has n two-electrode assemblies, and each n jA (j=1, 2...) column has m two-electrode assemblies.

[0034] Therefore, an m × n matrix consisting of m rows and n columns of two-electrode assemblies has the same n j column or same m i The working and counter electrode regions are formed by adjacent continuous monolithic bodies in rows.

[0035] Generally, the monolithic bodies forming the matrix of two electrode assemblies are arranged so that the distance between the assemblies is substantially equal or equal. In this specification, the "distance between the assemblies" can be the center-to-center distance or the edge-to-edge distance, depending on the geometry of the monolithic bodies and the resulting electrode assemblies. That is, for substantially symmetrical geometries, either distance is an appropriate measure, while for asymmetrical designs, the center-to-center distance is the more suitable parameter to use.

[0036] In a preferred embodiment, the two electrode assemblies are positioned at substantially equal distances (8) from one another, the distance between the two electrode assemblies being selected so that a matrix of two electrode assemblies can form each bottom of a well of a multiwell plate having m rows and n columns, advantageously allowing the electrode array to be combined with standard sized laboratory equipment such as commercially available multiwell plates.

[0037] In an exemplary embodiment of the invention, the matrix dimensions of the electrode array and the spacing between two electrode assemblies correspond to the dimensions and well-to-well spacing of a standard Society for Biomolecular Screening (SBS) multiwell plate, such as a well plate having 12 (3 x 4), 24 (4 x 8), 96 (8 x 6), 48 (6 x 12), 384 (16 x 24), or 1536 (32 x 48) wells. Thus, in one embodiment, m, n, and distance (8) correspond to those of a standard Society for Biomolecular Screening (SBS) 12 (3 x 4), 24 (4 x 8), 96 (8 x 6), 48 (6 x 12), 384 (16 x 24), or 1536 (32 x 48)-well plate. In a preferred embodiment, the parameters correspond to those of a standard SBS 96- or 384-well plate.

[0038] The monolithic body providing the working and counter electrode regions can be made of any suitable conductive material. In exemplary embodiments, the monolithic body comprises, consists essentially of, or consists of a carbon-based material. Non-limiting examples of suitable carbon-based electrode materials are graphite, expanded graphite, graphene, carbon, glassy carbon, nanocarbon, and pyrolytic carbon. Depending on the deposition technique (e.g., screen printing) used to apply the electrode array, the monolithic body may contain (minor amounts of) other materials, such as binders.

[0039] The monolithic bodies that together form the two-electrode assemblies disclosed herein should be thick enough to withstand the current and / or current density required for the electrochemical conversion reactions envisioned in the device. Typically, the thickness of a planar monolithic body made of a single material ranges from 1 to 500 μm, preferably 10 to 500 μm, preferably 20 to 400 μm, preferably 30 to 300 μm, and more preferably 50 to 300 μm.

[0040] A coating of another conductive material can be applied to at least a portion of one, more, or all of the working electrode regions of an electrode assembly. The conductive coating provided on the working electrode region functions as the working electrode in the corresponding electrochemical cell. As a result, the use of a conductive working electrode coating expands the range of available electrode materials and electrode combinations (and therefore electrode potentials) and enables efficient screening of suitable electrodes and electrode combinations for reaction discovery. Thus, in one embodiment, multiple two-electrode assemblies include working electrode regions at least partially provided with a conductive coating layer, which functions as the working electrode of the corresponding two-electrode assembly. Examples of suitable materials that can be used alone or in combination for such coating layers 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 multiple layers of coatings, rather than just one layer, can also be applied.

[0041] It is not necessary for all working electrodes or working electrode regions to have the same coating. Rather, an advantageous aspect of this embodiment of the invention is that multiple different types of coatings, e.g., different coating compositions, can be used within a single electrode array. For example, a first column or row of electrode assemblies can have a first coating, a second column or row of electrode assemblies can have a second coating (where the first and second coatings are different), and optionally, the same for the third, fourth, etc. columns or rows. Advantageously, this allows for easy screening of suitable electrode materials for reaction discovery purposes. Thus, in one embodiment, there are different coating layers on at least two. In another embodiment, there is a different coating layer on each column or row of the electrode array. In yet another embodiment, substantially all or all two-electrode assemblies have different coatings on their working electrodes or working electrode regions.

[0042] As previously mentioned, within a column or row of adjacent monolithic bodies, depending on the layout of the electrode array, each two-electrode assembly includes a working electrode and a counter electrode separated by a gap formed by the spacing between two adjacent monolithic bodies. Therefore, depending on the size and shape of these adjacent monolithic bodies and their spacing, the width of this gap can vary. This gap width can affect the function of the corresponding individual electrochemical cell in the overall device; for example, a smaller gap width reduces the voltage drop across the cell but increases the risk of a short-circuit condition. Typically, the gap width ranges from 0.01 to 10 mm, preferably from 0.1 to 4 mm, and most preferably from 0.5 to 2 mm.

[0043] In a second aspect, the present invention relates to a device for performing electrochemical synthesis comprising an electrode array as defined herein and a plurality of reaction vessels, each of the reaction vessels configured to bring its contents into electrical contact with a single two-electrode assembly of the electrode array.

[0044] A device according to the invention combines an electrode array as disclosed herein with a plurality of suitable reaction vessels, each reaction vessel having its contents in electrical contact with one electrode assembly, to form a device containing multiple electrochemical cells, such that each electrode assembly of an electrode array of the invention individually forms the base of a single electrochemical cell.

[0045] In one embodiment, the multiple reaction vessels are formed by multiple droplets, each droplet in electrical contact with one electrode assembly, and each droplet containing components necessary for the electrochemical conversion reaction, such as one or more starting materials (substrates) and solvents and / or electrolytes.

[0046] In another embodiment, the multiple reaction vessels are formed by a plate containing multiple holes, typically each hole forming an individual wall of a single reaction vessel, with the dimensions and spacing of the holes corresponding to the dimensions and spacing of the electrode assemblies forming the respective bottoms of the resulting electrochemical cells. Such a plate containing multiple, preferably equidistant, holes can be made of any material capable of retaining and withstanding the effects of reactive chemicals. In one 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.

[0047] Typically, each reaction vessel extends in a direction that is substantially perpendicular or perpendicular to the planar substrate.

[0048] Typically, the volume of each of the multiple reaction vessels is in the range of 1 to 3000 μL, preferably 10 to 1000 μL, and most preferably 50 to 300 μL.

[0049] Advantageously, the combination of the electrode array and reaction vessel provides an array of miniature electrochemical cells, preferably with dimensions and spacing that correspond to the dimensions of the wells of a standard Society for Biomolecular Screening (SBS) multiwell plate, and therefore can be easily adapted to existing laboratory equipment.

[0050] In a preferred embodiment, the dimensions and mutual arrangement of the two-electrode assembly and the reaction vessel correspond to those of the wells of a standard Society for Biomolecular Screening (SBS) multiwell plate. Preferably, they correspond to those of a standard Society for Biomolecular Screening (SBS) 12 (3 x 4), 24 (4 x 8), 96 (8 x 6), 48 (6 x 12), 384 (16 x 24) or 1536 (32 x 48)-well plate, preferably a 96 or 384-well plate.

[0051] To carry out electrochemical conversion, the device must be connected to an appropriate current source. Therefore, in one 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 is capable of supplying a constant current through each of the electrochemical cells formed by the array of two-electrode assemblies and the corresponding reaction vessels. Suitable current sources are commercially available, an example of which is the multi-channel DC power supply available from the Rohde & Schwarz HMP4000 power supply series; those skilled in the art will be able to implement one or more of these current sources appropriate for a given purpose. Electrical contacts can be established using means known to those skilled in the art, such as alligator clips, soldering, etc. Typically, the current supply units are configured to provide a substantially constant or constant current output in the range of 0.01 mA to 1000 mA, preferably 0.1 to 20 mA, and most preferably 0.5 to 10 mA.

[0052] In the device of the present invention, typically, two electrode assemblies are arranged in the same row n j Or the same line m i In the electrode array, a working electrode region of a first monolithic body and a counter electrode region of an adjacent second monolithic body are formed, such that each two-electrode assembly in a column or row is electrically connected in series through the successive monolithic bodies. Thus, the number of current supplies is typically equal to or less than the number of rows or columns of the electrode array, depending on whether the columns or rows of the matrix array form a series circuit. Preferably, the number of current supplies is equal to the number of rows or columns forming a series connection in the electrode array, such that each of the m×n two-electrode assemblies is electrically connected.

[0053] Advantageously, the planar configuration of the electrode array and the serial connection in columns or rows of the electrode assembly matrix require that electrical contacts for current supply be connected only at the edges of the substrate, which greatly simplifies the manufacture, operation and maintenance of the device.

[0054] The current intensity and duration of current delivery can be adjusted using equipment and procedures known to those skilled in the art and can be commercially available or developed in-house.

[0055] The devices disclosed herein can be used in a variety of electrochemical applications. The devices of the present invention are particularly suitable for the high-throughput electrochemical conversion of suitable starting materials to compounds of interest. Thus, in one aspect, the present invention relates to the use of the devices disclosed herein in the electrochemical synthesis of compounds. In one embodiment, the use includes chemical library synthesis. In another embodiment, the use includes chemical reaction discovery.

[0056] The methods of the present invention are applicable to a wide range of electrochemical reactions. Non-limiting examples of reduction or oxidation reactions of organic compounds suitable for use with the methods and devices of the present invention include electrochemical cross-coupling reactions and functional group interconversions, such as (oxidative) CN / NH cross-coupling reactions, metabolite synthesis, alcohol to ketone to acid conversion, nitrile reduction, cross electrophilic coupling, Shono oxidation, and biaryl coupling reactions.

[0057] In a further aspect, the present invention provides a method for electrochemically converting one or more reactants to a reaction product, comprising: - providing an electrochemical device as defined herein; - providing one or more reactants, and optionally a solvent and / or an electrolyte, to a reaction vessel; - applying a current between the working and counter electrodes of a two-electrode assembly sufficient to convert one or more reactants into reaction products; The present invention provides a method comprising:

[0058] Solvents and electrolytes suitable for electrochemical synthesis are known to those skilled in the art. Non-limiting examples include tetrabutylammonium hydroxide (BuNOH), sodium pivalate, tetrabutylammonium tetrafluoroborate (BuNBF), ethyltriethylammonium tetrafluoroborate, tetraethylammonium tetrafluoroborate, tetraethylammonium chloride (TEAC), 1-butyl-3-methylimidazolium tetrafluoroborate, sodium acetate, lithium perchlorate, sodium sulfate, potassium hydroxide (KOH), sodium hydroxide (NaOH), aqueous solutions of hydrogen chloride (HCl) or sulfuric acid (HSO), and ionic liquids.

[0059] The reaction products are worked up, analyzed, and purified using methods and equipment known in the art. In one embodiment, the dimensions and relative arrangement of the two-electrode assembly and the reaction vessel correspond to the standardized multi-well plate derived above, and workup of the reaction products can be conveniently performed using automated liquid handling and sample collection. Analysis of intermediates and reaction products can be performed by known techniques such as LC-MS, GC, and NMR, and isolation of reactants can be performed, for example, by preparative HPLC.

[0060] Depending on the geometry of the monolithic body forming the two-electrode assembly (i.e., connected in series by 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 preferred embodiments, all rows or all columns of the electrode array matrix are connected and all reactions are performed in parallel. Preferably, the reactions differ in one or more respects so that different reaction products are obtained and / or different yields are obtained and / or optimal process conditions can be discovered.

[0061] Thus, in a preferred embodiment, multiple different electrochemical transformations are performed in parallel, the electrochemical transformations differing in one or more of the following ways: - reactants provided in the reaction vessel - Concentration of reactants present in the reaction vessel - Solvent provided to the reaction vessel - Electrolyte provided in the reaction vessel - Counter electrode material - Working electrode material - Working electrode coating material - current density - Passing charge

[0062] In one embodiment, at least two of the electrochemical conversions are carried out using different working electrode materials, which may be conveniently achieved by providing a coating of a different material on the working electrode region of the monolithic body forming the corresponding two-electrode assembly, said coating of a suitable conductive material then serving as the working electrode of each associated two-electrode assembly.

[0063] Electrode arrays according to the present invention can generally be fabricated by forming a pattern forming two-electrode assemblies on a suitable substrate material, and then optionally providing one or more coating layers over selected portions of the array, particularly the working electrode regions of one or more two-electrode assemblies.

[0064] Thus, in one aspect, the present invention provides a method for manufacturing an electrode array according to the present invention, comprising the steps of: - providing a substrate; - forming a pattern on a surface of a substrate to form a two-electrode assembly; - optionally providing a coating layer on at least a portion of the working electrode area of ​​one or more two-electrode assemblies; The present invention relates to a method comprising:

[0065] The substrate can be any non-conductive flat substrate such as glass, ceramic, or polymer.

[0066] The pattern forming the two-electrode assembly can be created, for example, by applying a suitable composition containing the electrode material onto the substrate. The composition containing the electrode material can be a suspension, ink, or paste containing the electrode material in powder form. The application of the composition containing the electrode material can be performed by various methods 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 technique that offers many advantages, such as high reproducibility and precision, and the ability to easily change the electrode shape and electrode material composition.

[0067] Thus, in an exemplary embodiment, there is provided a method of manufacturing an electrode array according to the present invention, comprising the steps of: - providing a substrate; - providing a composition comprising an electrode material; - applying a composition comprising an electrode material onto a substrate to obtain a pattern forming a two-electrode assembly; - optionally providing a coating layer on at least a portion of the working electrode area of ​​one or more two-electrode assemblies; The present invention relates to a method comprising:

[0068] Another suitable method for forming a pattern on a substrate material to form a two-electrode assembly is by photothermal surface pyrolysis of a suitable carbon-based substrate material, such as polyimide foil. For example, a laser beam with a defined fluence and wavelength is moved over the surface of the polyimide foil at a controlled speed, resulting in localized heating and carbonization (graphitization) of the polyimide surface. This allows the formation of pyrolytic carbon traces, e.g., approximately 300 microns wide and 40 microns high. The laser head can be mounted on an XY table, allowing carbon traces to be patterned over any region of the substrate. By overlapping the pyrolytic carbon traces, the desired planar array of conductive monoliths can be obtained. Advantageously, this process can be economically scaled up to a roll-to-roll process, for example, using a laser / galvo scanning device. Other advantages of the surface pyrolysis method for fabricating electrode patterns according to the present invention are that it requires no consumables other than the organic substrate material and results in electrode arrays with excellent chemical resistance due to the inherent chemical compatibility between the substrate material and the carbon traces.

[0069] Thus, in another exemplary embodiment, there is provided a method of manufacturing an electrode array according to the present invention, comprising the steps of: - providing a substrate; - subjecting the substrate to photothermal carbonization to form a graphitic carbon pattern that forms a two-electrode assembly; - optionally providing a coating layer on at least a portion of the working electrode area of ​​one or more two-electrode assemblies; The present invention relates to a method comprising:

[0070] In this embodiment, the substrate material can be any carbon-based material that is susceptible to photothermal, such as laser-induced conversion to graphitic carbon, examples of which include polyimide, polydimethylsiloxane, and cellulose.

[0071] As described above, in all embodiments, a coating layer of another conductive material is optionally provided on at least a portion of the working electrode region of one or more or all of the electrode assemblies. The conductive coating on the working electrode region functions as the working electrode in the corresponding electrochemical cell. Therefore, providing a different coating layer as the working electrode in the electrode array and corresponding electrochemical device allows for screening of suitable electrode materials and material combinations.

[0072] Depending on the particular choice of material or combination of materials, such coating layers are suitably applied by thin layer deposition techniques known in the art, such as chemical vapor deposition, spray coating, electrodeposition, or printing techniques, including screen printing, stencil printing, or inkjet printing.

[0073] To assemble a complete electrochemical device, a suitable reaction vessel and one or more current supplies in electrical contact with the electrode assemblies are required. As described above, multiple droplets, each in electrical contact with one electrode assembly and each containing components necessary for the electrochemical conversion reaction, such as one or more starting materials (substrates) and solvents and / or electrolytes, can suitably form a reaction vessel. In another embodiment, a plate containing multiple holes, typically each hole individually forming the wall of a single reaction vessel, is connected to the electrode array. In both designs, each two-electrode assembly of the electrode array is configured to form the bottom of an individual electrochemical cell, which, together with one or more current supplies, forms a complete electrochemical device.

[0074] The electrode array and the plate containing multiple holes can be connected by any suitable means. In one embodiment, the electrode array and the plate containing multiple holes are bonded together with a resin, such as an epoxy resin, preferably a low viscosity epoxy resin, such as the epoxy resin commercially available from Huntsman Corp. under the trade name Araldite Rapid or the epoxy resin commercially available from Masterbond under the trade name EP41S-5. In another embodiment, the electrode array and the plate containing multiple holes are sealed together using a suitable frame. A combination of such chemical and mechanical connection options is also possible.

[0075] Detailed Description of the Drawings Figure 1 shows a photograph of an electrode array 1 according to one embodiment of the present invention. The 8x12 electrode array comprises 8 rows and 12 columns of planar monolithic bodies screen printed on a glass substrate 2, with the working electrode region 4 and counter electrode region 5 of adjacent monolithic bodies 3 within a column together forming a row of two-electrode assemblies 6 arranged in series.

[0076] Figure 2 shows a schematic diagram of a portion of the electrode array shown in Figure 1. Figure 2A represents a monolithic body 3 having a working electrode area 4 and a counter electrode area 5. Figure 2B shows two adjacent monolithic bodies 3 separated by a gap 8, forming a two-electrode assembly 6. Figure 2C shows a schematic diagram of a matrix 7 of monolithic bodies 3 forming part of an electrode array according to one embodiment of the present invention. The matrix 7 has m rows and n columns of monolithic bodies 3. Each column n i For (i=1, 2, 3, . . . m), the working electrode area 4 and the counter electrode area 5 of adjacent monolithic bodies 3 form a two-electrode assembly 6 separated by a distance 9 .

[0077] Figure 3A is a schematic diagram of an electrode array configuration according to another embodiment of the invention, including a substantially rectangular monolithic body 3. Figure 3B schematically represents two monolithic bodies 3 having working and counter electrode regions 4 and 5 separated by a gap 8. Figure 3C schematically represents adjacent monolithic bodies 3 in a row, forming a matrix 7 of two-electrode assemblies 6 separated by a mutual (edge-to-edge or center-to-center) distance 9. Figure 3D shows a close-up photograph of an array of carbon planar monolithic bodies according to this embodiment, fabricated by surface laser pyrolysis on a polyimide foil. The monolithic bodies are formed from adjacent strips of graphitic carbon about 300 microns wide and have a height of about 40 microns.

[0078] Figure 4 shows a photograph of an 8x12 array of reaction vessels according to one embodiment of the present invention, formed by 3D printing a nylon plate containing equidistant holes.

[0079] Figure 5 shows a photograph of a device, excluding the current supply, according to one embodiment of the present invention, which includes an 8x12 electrode array, as shown in Figure 1, combined with an 8x12 array of reaction vessels, as shown in Figure 4, bonded together using low viscosity epoxy.

[0080] 6 shows a schematic diagram of a power and control assembly 11 for a device according to one embodiment of the present invention. In this schematic device 10, each of 12 strings 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. [Example]

[0081] The present invention is further explained, illustrated, and described in the following examples of the system of the present invention. The examples serve to demonstrate the utility and / or functionality of the present invention and to provide a complete description of the present invention. The examples are intended to illustrate, but not to limit, the present invention.

[0082] Example 1.1: Preparation of a device involving a printing method Step 1: Preparation of printing paste A graphite-containing printing paste was prepared as follows: PDVF (615 mg, powder, Aldrich) was added to NMP (3.49 g), and the mixture was heated to 50 °C and sonicated for 12–48 h until a clear, viscous solution was obtained. Graphite (2.68 g, particle size 20 microns, synthesized, Aldrich) was added and thoroughly dispersed by mechanical stirring.

[0083] Step 2: Fabrication of electrode array Electrode arrays were fabricated by stencil printing (stencil: 0.10 mm stainless steel sheet, providing monolithic cutouts that were cut with a water jet to yield 8 × 12 two-electrode assemblies) the graphite-containing printing paste from step 1 onto a glass plate (float glass, 1 mm thick, hand-cut). The arrays were dried in air at 80 °C for 16 hours to yield flat monolithic arrays for 8 × 12 two-electrode assemblies with a thickness of approximately 0.1 mm. A photograph of the electrode array is provided as Figure 1.

[0084] Step 3: Fabrication of well plate devices A polymer plate (nylon, 3D printed in-house) containing an array of 8 × 12 holes was bonded on top of the electrode array obtained in step 2 using low viscosity epoxy resin (Araldite RAPID, commercially available from Huntsman Corp), resulting in 8 × 12 wells configured to receive and hold reaction mixtures.

[0085] In an alternative embodiment of step 3, a polymer plate containing an array of 8 x 12 holes is pressed onto the electrode array obtained in step 2 with a suitable frame and gasket to obtain 8 x 12 wells configured to receive and hold reaction mixtures.

[0086] Step 4: Connecting the power supply and control units Three commercially available 4-channel power supplies from the Rohde & Schwarz HMP4000 power supply series were used to connect 12 independently controlled current supplies with current ratings >10 mA and voltage ratings >64 V. The power supplies were connected to the well plate device in step 3 using alligator clips that independently connected each of the 12 columns of the 8 x 12 electrode array. The current, as well as the electrolysis time, could be set individually for each column.

[0087] Example 1.2: Device preparation involving laser pyrolysis Step 1: Fabrication of pyrolytic carbon electrode array Electrode arrays were fabricated by laser pyrolysis of polyimide foil. A piece of polyimide foil (0.25 mm thick, Flexiso 16000, Dietrich Mueller GmbH) was placed on an aluminum plate (5 mm thick, with double-sided tape to hold the foil in place) within the working area of ​​a laser cutter (Xtool D1 Pro, 40 W, controlled by Lightburn software). The laser head focus was adjusted to -10 mm. A CAD representation of the electrode array was then drawn in Lightburn software. The laser conditions were set (engraving mode, speed 3200 mm / min, power 11.7%, line spacing 0.30 mm) and the laser was started. After pyrolysis was completed and the pyrolytic carbon electrode array was obtained, the laser focus was adjusted to 0 mm, the laser conditions were changed to cutting mode (cutting mode, speed 3000 mm / min, power 60%, 1 pass), the appropriate CAD drawing was selected, and the program was restarted.

[0088] Step 2: Fabrication of a hole array plate A plate containing an 8 × 12 hole array was fabricated by laser cutting. A polyamide plate (PA6, 5 mm thick, 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. A CAD representation of the hole array plate was drawn in the Lightburn software. The laser conditions (cutting mode, speed 400 mm / min, power 100%, 2 passes) were set, and the laser was started. After the run, the hole array plate was deburred and polished.

[0089] Step 3: Fabrication of well plate device The electrode array from step 1 and the well array plate from step 2 were bonded together using a chemically resistant epoxy resin (Araldite RAPID, commercially available from Huntsman Corp.) to provide 8 x 12 wells configured to receive and hold the reaction mixture. Other epoxy resins can be used, such as the resin commercially available from Masterbond under the trade name EP41S.

[0090] Step 4: Connecting the power supply and control units Three commercially available 4-channel power supplies from the Rohde & Schwarz HMP4000 power supply series were used to connect 12 independently controlled current sources with current ratings >10 mA and voltage ratings >64 V. The power supplies were connected to the well plate device in step 3, which independently connected each of the 12 columns of the 8 x 12 electrode array. The current, as well as the electrolysis time, could be set individually for each column.

[0091] Step 5: Platinum (Pt) electrodeposition An aqueous stock solution containing chloroplatinic acid (0.043 mol / L) and H2SO4 (0.020 mol / L) was prepared. 100 μL of the stock solution was added to each well of the well-plate device prepared above. The device was placed on an orbital shaker and the shaking frequency was adjusted to 400 rpm. A constant current of 6.6 mA (30 mA / cm2) was applied for 1.6 minutes, depositing Pt onto the cathode. The wells were rinsed with HO, followed by MeOH, and then dried in air at room temperature.

[0092] Example 2: Reaction Discovery [ka] In this experiment, we investigated the optimal electrosynthetic conditions, particularly the electrode material and solvent / electrolyte, to obtain compound 3 in high yield.

[0093] The experiments were carried out in an electrochemical 96-well plate device according to the invention with an all-graphite electrode array, where the working electrodes in each row are coated with a thin layer (<50 μm) of the following material: - 1st row: [No coating], - 2nd row: glassy carbon, - 3rd row: IrO2, - 4th line: RUO2, - Line 5: Pt, - Row 6: TiO, - 7th row: boron-doped diamond, - Line 8: TiN

[0094] Veratrole (1, 0.01 mmol) and 5-methoxy-1,2,3-triazole (2, 5.0 equivalents) are added to each well. To each well of each row of the plate, the following solvents (0.10 ml 10 ml / mmol) and electrolytes (0.5 equivalents) are added, respectively: - 1st column: methanol (MeOH), tetrabutylammonium hydroxide (Bu4NOH); - 2nd column: methanol (MeOH), sodium pivalate (NaOPiv); - 3rd column: methanol (MeOH), tetrabutylammonium tetrafluoroborate (Bu4NBF4); - 4th column: acetonitrile (MeCN), tetrabutylammonium hydroxide (Bu4NOH); - 5th column: acetonitrile (MeCN), sodium pivalate (NaOPiv); - 6th column: acetonitrile (MeCN), tetrabutylammonium tetrafluoroborate (Bu4NBF4); - Column 7: dimethyl sulfoxide (DMSO), tetrabutylammonium hydroxide (Bu4NOH); - Column 8: dimethyl sulfoxide (DMSO), sodium pivalate (NaOPiv); - Column 9: Dimethyl sulfoxide (DMSO), Tetrabutylammonium tetrafluoroborate (Bu4NBF4) - Column 10: hexafluoroisopropanol (HFIP), tetrabutylammonium hydroxide (Bu4NOH); Column 11:: hexafluoroisopropanol (HFIP), sodium pivalate (NaOPiv); - Column 12: Hexafluoroisopropanol (HFIP), tetrabutylammonium tetrafluoroborate (Bu4NBF4)

[0095] A current supply is connected to the electrical contacts on both sides of each row, and a current of 1.0 mA is applied for 60 minutes.

[0096] Characterization and quantification of reaction product 3 is carried out using methods and equipment known in the art, including NMR, GC-MS, and HPLC.

[0097] Example 3: Library preparation [ka] This experiment was performed in an electrochemical 96-well plate equipped with an array of all-graphite electrodes. Each column of the 96-well plate was charged with one of 12 different aryl educts 4 (0.10 mmol). Each row of the electrochemical 96-well plate was charged with one of eight different azole educts 5 (0.30 mmol, 3.0 equiv.). NaOPiv (0.5 equiv.) was added to all 96 wells, followed by MeOH (0.10 ml, 1.0 ml / mmol). A current supply was connected to the electrical contacts on both sides of each column, and a 10 mA current was applied for 60 minutes.

[0098] Characterization and quantification of the reaction product 6 is carried out using methods and equipment known in the art, including NMR, GC-MS, and HPLC.

Claims

1. An electrode array (1) comprising a two-electrode assembly (6) for use in performing electrochemical synthesis, said electrode array comprising a plurality of planar monolithic bodies (3) arranged on a planar substrate (2), said monolithic bodies comprising a working electrode area (4) and / or a counter electrode area (5), said monolithic bodies arranged in the same row n on said substrate (2) and separated by gaps (8). j Or the same line m i The electrode array forms an m×n matrix (7) of m rows and n columns of two-electrode assemblies (6) formed by the working electrode region (4) of a first monolithic body (3) and the counter electrode region (5) of an adjacent second monolithic body (3).

2. 2. The electrode array of claim 1, wherein the two-electrode assemblies (6) are arranged at substantially equal distances (9) from one another, and the distance (9) between the two-electrode assemblies (6) is selected so that a matrix (7) of the two-electrode assemblies (6) can form each bottom of a well of a multiwell plate having m rows and n columns.

3. 3. The electrode array of claim 2, wherein m, n and the distance (9) correspond to those of a standard Society for Biomolecular Screening (SBS) 12 (3x4), 24 (4x8), 48 (8x6), 96 (6x12), 384 (16x24) or 1536 (32x48)-well plate, preferably a 96-well plate or a 384-well plate.

4. 4. An electrode array according to any one of claims 1 to 3, wherein the thickness of the planar monolithic body is in the range of 10 to 500 μm, preferably 20 to 400 μm, more preferably 30 to 300 μm, most preferably 50 to 300 μm.

5. 5. The electrode array according to any one of claims 1 to 4, wherein a plurality of said two-electrode assemblies comprises a working electrode region (4) at least partly provided with a conductive coating layer.

6. 6. The electrode array of claim 5, wherein different coating layers are present on at least two, and preferably all, of the two-electrode assemblies.

7. 7. A device for performing electrochemical synthesis comprising the electrode array of any one of claims 1 to 6 and a plurality of reaction vessels, each of the reaction vessels configured to bring its contents into electrical contact with a single two-electrode assembly of the electrode array.

8. 8. The device of claim 7, wherein the plurality of reaction vessels is formed by a plate containing a plurality of holes, preferably equidistant holes.

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

10. Use of a device according to any one of claims 7 to 9 in the electrochemical synthesis of compounds, preferably said use comprising chemical library synthesis or chemical reaction discovery.

11. 1. A method for electrochemically converting one or more reactants to a reaction product, 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 said 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; A method comprising:

12. A plurality of different electrochemical transformations are carried out in parallel, the electrochemical transformations being characterized by: - reactants provided in said reaction vessel - the reactant concentrations present in said reaction vessel; - Solvent provided in the reaction vessel - Working electrode material - Current density - Passing charge The method of claim 11 , wherein the two or more of the following are different:

13. The method of claim 12 , wherein at least two of the electrochemical transformations are performed using different working electrode materials.

14. 14. The method of any one of claims 11 to 13, wherein the electrochemical transformation comprises one or more of electrochemical cross-coupling reactions and functional group interconversions, such as C-N / N-H cross-coupling reactions, metabolite synthesis, alcohol to ketone to acid conversion, nitrile reduction, cross electrophilic coupling, Shono oxidation, and biaryl coupling reactions.

15. A method for manufacturing an electrode array according to any one of claims 1 to 6, comprising the steps of: providing a substrate; - forming a pattern on the surface of said substrate to form said two-electrode assembly; - optionally providing a coating layer on at least a portion of the working electrode area of ​​one or more of said two-electrode assemblies; A method comprising:

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