Electrostatic catalysis of a click reaction in a microfluidic cell

Abstract

Electric fields have been highlighted as a smart reagent in nature's enzymatic machinery, as they can directly trigger or accelerate chemical processes with stereo- and regio-specificity. In enzymatic catalysis, controlled mass transport of chemical species is also key in facilitating the availability of reactants in the active reaction site. However, recent progress in developing a clean catalysis that profits from oriented electric fields is limited to theoretical and experimental studies at the single molecule level, where both the control over mass transport and scalability cannot be tested. Here, we quantify the electrostatic catalysis of a prototypical Huisgen cycloaddition in a large-area electrode surface and directly compare its performance to the conventional Cu(I) catalysis. Our custom-built microfluidic cell enhances reagent transport towards the electrified reactive interface. This continuous-flow microfluidic electrostatic reactor is an example of an electric-field driven platform where clean large-scale electrostatic catalytic processes can be efficiently implemented and regulated.

Fig. 1. Catalysis of a click reaction in a microfluidic cell.

a Schematic representation of oriented external electric-field (OEEF) in an electrostatic catalysis (top panel), and copper (Cu⁺)-catalyzed click cycloaddition (bottom panel) in a confined microfluidic channel between two gold electrodes. The azide moiety (1) is immobilized on the gold surface via thiol-gold chemistry, and the ferrocene alkyne derivative (2) is flowed continuously to avoid its depletion on the functionalized gold surface. b, c Schematic drawing showing parts of the microfluidic cell prior to its assembly (in panel b) and the assembled microfluidic cell with a section-cut in the top part to demonstrate the confined reaction area formed between two gold electrodes using a spacer (in panel c).

Fig. 2. Performance of the electrostatic catalysis.

a Cyclic voltammetry (CV) data showing effect of the applied voltage in the electrostatic catalysis, e.g., 0.5 V (grey), 0.75 V (black), 1.5 V (red), 2 V (blue), and the comparison with Cu⁺-based chemical catalysis (green). The two major peaks correspond to the oxidation-reduction of the ferrocene moieties attached to azide-terminated electrode via azide-alkyne cycloaddition. The CVs in a are obtained at a scan rate (SR) of 0.2 V s⁻¹. b Integrated charge densities from the anodic (positive) peaks of the CVs for OEEF catalysis at 0.50 V (grey dot) 0.75 V (black dot), 1.5 V (red dot) and 2 V (blue dot), and for Cu⁺-based catalysis at 0 V (green dot). Open circle is the control experiment performed under non-catalytic conditions (i.e., V_applied = 0 V and absence of Cu⁺) and the dashed orange line indicates the ideal fully covered ferrocene monolayer from the literature^,. Error bars represent the standard deviation of results obtained from n experiments (3≤ n ≤6) at each applied voltage. c Scan rate dependency (see also Supplementary Fig. 4) of the anodic and cathodic peak current densities obtained from the CV analysis of samples prepared using electrostatic catalysis at 2 V (triangles) and Cu⁺-based chemical catalysis (circles) together with the corresponding linear fits (colour coded dashed lines). d Square-wave voltammetry (SWV) of electrostatically catalysed (at 1 V applied voltage) surfaces under continuous- (solid line) and stop- (dashed line) flows in the microfluidic cell.

Fig. 3. Electrostatic catalysis kinetics.

a CVs obtained from the samples prepared under electrostatic catalysis at a bias voltage of 2 V for 10 min (black), 20 min (red), 30 min (blue), and 60 min (green) and compared to the control experiment in the absence of both electric field (V_applied = 0 V) and Cu⁺ catalysis (grey). b CVs obtained from the samples prepared under chemical Cu⁺ catalysis for 10 min (black), 20 min (red), 120 min (green) and compared to the samples prepared with electrostatic catalysis for 30 min (dashed blue) and 60 min (dashed grey). In a and b, SR represents the scan rate. c Reaction yields expressed as both ferrocene (Fc) redox charge density (left Y-axis) and Fc surface coverage (right Y-axis) as a function of time for the electrostatic catalysis conducted at 2 V bias voltage (blue solid line with circles) and Cu⁺ catalysis (green solid line with circles), and corresponding linear fits (color coded dashed lines). The dashed orange line indicates the ideal fully covered ferrocene monolayer from the literature^,.

Fig. 4. Characterization of the EDL-based OEEFs using an RC circuit model.

a Representative chronoamperometry (CA) recordings showing charging and discharging currents (black) in consecutive applied step voltages (red) between the parallel electrodes immersed in pure acetonitrile. b Exponential fits (blue and red lines) to the charging and discharging currents (grey circles) using an RC circuit as a model. c Calculated electric fields from the RC fittings corresponding to different electrode configurations: in a beaker containing pure acetonitrile and (1) two parallel bare gold electrodes (Au vs Au, black line), (2) an azide-terminated gold electrode against a bare gold electrode (functionalized vs Au, red line), (3) two parallel azide-terminated electrodes (functionalized vs functionalized, blue line), and (4), two parallel azide-terminated electrodes confined in the microfluidic cell (µ-functionalized vs functionalized, green line). Error bars represent the standard deviation for number of samples, n ≥ 3. See also Supplementary Fig. 7 for detailed schematic representations of electrochemical cell configurations used in CA measurements.

Fig. 5. Effect of OEEF and medium polarity in the electrostatic catalysis.

a Schematic representation of the OEEF lines and the alignment of the polar ethynylferrocene and azide according to their dipole moments with (left) positive (+) and (right) negative (−) applied voltage with respect to the azide-terminated working electrode. Two plausible clicked products of reaction are shown depending on polarity of the working electrode. b Most likely transition state (TS) resonance structures stabilized under opposite OEEF polarities (e.g., positive (+) and negative (−) applied voltages in left and right structures, respectively). c Cyclic voltammograms of electrostatically catalised chemical reactions using opposite voltage polarities of −0.75 V (blue) and +0.75 V (red). d Schematic diagram showing EDL formation and corresponding voltage drop in high polar (acetonitrile, left) and low polar solvents (toluene, right) respectively. e Cyclic voltammograms of samples prepared in low polar medium (toluene) under Cu⁺-based chemical catalysis (solid green line) and electrostatic catalysis at a voltage of 1.5 V (solid red line). Cyclic voltammograms presented in c and e were obtained at scan rates of 0.2 V s⁻¹ and 0.3 V s⁻¹, respectively.