Continuous parallel ESI-MS analysis of reactions carried out in a bespoke 3D printed device

Abstract

Herein, we present an approach for the rapid, straightforward and economical preparation of a tailored reactor device using three-dimensional (3D) printing, which can be directly linked to a high-resolution electrospray ionisation mass spectrometer (ESI-MS) for real-time, in-line observations. To highlight the potential of the setup, supramolecular coordination chemistry was carried out in the device, with the product of the reactions being recorded continuously and in parallel by ESI-MS. Utilising in-house-programmed computer control, the reactant flow rates and order were carefully controlled and varied, with the changes in the pump inlets being mirrored by the recorded ESI-MS spectra.

Keywords: 3D printing; ESI-MS; continuous parallel analysis; reactionware; supramolecular chemistry.

Scheme 1

Reaction scheme for the formation of the ttop and metal-salt coordination complex (1 is [Cu(C₂₄H₂₄N₆)(NO₃)]⁺; 2 is [Ni(C₂₄H₂₄N₆)(NO₃)]⁺; 3 is [Cu₂(C₂₄H₂₄N₆)(NO₃)₂]²⁺).

Figure 1

On the left is a schematic presentation of the STL file, whilst on the right is the device with screw fittings and connected with 1/16 inch (1.6 mm) tubing. Methylene blue and rhodamine B are being pumped through the device, which allows the inner-tube path to be rendered visible. A section consisting of only methylene blue can be seen at the front, followed by a stronger purple band, which is obtained from the successful mixing of rhodamine B and methylene blue.

Figure 2

Top: A schematic overview of the device setup. The three inlets were each connected to a syringe pump, which were connected to stock solutions of the required starting materials or MeOH. The outlet is directly connected to a T-piece, where it mixes with a stream of MeOH for dilution. This is followed by the splitting step, where a PEEK microsplitter valve is used to split the stream so that only a suitable flow-rate reaches the ESI-MS. The parallel stream allows for collection of the reaction product. Bottom: Photograph of the device setup and connection to the mass spectrometer (where a = Tricontinent C-3000 syringe pumps; b = screw fittings; c = 3D printed device; d = T-piece; e = PEEK microsplitter valve).

Figure 3

ESI-MS isotope patterns of ttop + Na (square), m/z 419.2, [Cu(C₂₄H₂₄N₆)(NO₃)]⁺ (1, pentagon), m/z 521.1, and [Cu₂(C₂₄H₂₄N₆)(NO₃)₂]²⁺ (3, star), m/z 323.0, showing how an increase in flow rate from the pump containing Cu(NO₃)₂·6H₂O changes the stoichiometry of the complex from 1 ttop:1 Cu(NO₃)₂ to 1 ttop:2 Cu(NO₃)₂ (where a = MS of ttop; b = 1 ttop: 2 Cu(NO₃)₂·6H₂O; c = 1 ttop: 3 Cu(NO₃)₂·6H₂O; d = 1 ttop:5 Cu(NO₃)₂·6H₂O; e = 1 ttop:15 Cu(NO₃)₂·6(H₂O)) (for the full spectra see Supporting Information File 1).

Figure 4

Normalised intensity plotted against time showing the change in intensity of [Ni(C₂₄H₂₄N₆)(NO₃)]⁺ (2), m/z 516.1, (black) and [Cu(C₂₄H₂₄N₆)(NO₃)]⁺ (1), m/z 521.1, (red) over five pump cycles. (The dotted lines correspond to the instability in the intensity of the species due to the pumps refilling, and thus, the system is not at equilibrium).