In situ monitoring of photocatalyzed isomerization reactions on a microchip flow reactor by IR-MALDI ion mobility spectrometry

Abstract

The visible-light photocatalytic E/Z isomerization of olefins can be mediated by a wide spectrum of triplet sensitizers (photocatalysts). However, the search for the most efficient photocatalysts through screenings in photo batch reactors is material and time consuming. Capillary and microchip flow reactors can accelerate this screening process. Combined with a fast analytical technique for isomer differentiation, these reactors can enable high-throughput analyses. Ion mobility (IM) spectrometry is a cost-effective technique that allows simple isomer separation and detection on the millisecond timescale. This work introduces a hyphenation method consisting of a microchip reactor and an infrared matrix-assisted laser desorption ionization (IR-MALDI) ion mobility spectrometer that has the potential for high-throughput analysis. The photocatalyzed E/Z isomerization of ethyl-3-(pyridine-3-yl)but-2-enoate (E-1) as a model substrate was chosen to demonstrate the capability of this device. Classic organic triplet sensitizers as well as Ru-, Ir-, and Cu-based complexes were tested as catalysts. The ionization efficiency of the Z-isomer is much higher at atmospheric pressure which is due to a higher proton affinity. In order to suppress proton transfer reactions by limiting the number of collisions, an IM spectrometer working at reduced pressure (max. 100 mbar) was employed. This design reduced charge transfer reactions and allowed the quantitative determination of the reaction yield in real time. Among 14 catalysts tested, four catalysts could be determined as efficient sensitizers for the E/Z isomerization of ethyl cinnamate derivative E-1. Conversion rates of up to 80% were achieved in irradiation time sequences of 10 up to 180 s. With respect to current studies found in the literature, this reduces the acquisition times from several hours to only a few minutes per scan.

Keywords: IR-MALDI; Ion mobility spectrometry; Microchip; Olefin isomerization; Photocatalysis; Photochemistry; Reaction monitoring.

Fig. 1

Scheme of the general setup consisting of the liquid flow supply unit, the flow reactor unit, a radiation source, the ion mobility (IM) spectrometer unit, and an OPO IR laser

Fig. 2

a Microchip used in this study. b Layout of chip setup in front of IM spectrometer inlet with a side view of the microfluidic chip (1), the IM spectrometer inlet (2), the LED positioned in front of the chip reactor region (3), the LED cooler (4), the counter electrode (5), the laser beam (6), a PTFE insulation plate (7), the capillary system and microchip mount including clamps (8), and a fine positioning stage (9). c In-house-built IR-MALDI IM spectrometer with heated inlet in top view, inlet (2) at the bottom-left is equivalent to (2) of panel b, the pump inlet (10), the pulsed ion inlet (11), the drift tube (12), and the faraday plate (13) as the detection element

Fig. 3

Comparison of IM spectra of 50:50 mol% E/Z mixtures of an ethyl cinnamate derivative E-1: a IR-MALDI-IM spectrum at 100 mbar and b ESI-IM spectrum at an ambient pressure. Differences in relative and absolute intensity of the isomers arise from the different charge transfer equilibria for the different techniques and pressures. In both cases, a good separation between the E- and the Z-isomer was achieved

Fig. 4

IM spectrum of the E- and Z-isomer of ethyl cinnamate derivatives E-1 and Z-1 with their drift time maxima at 5.01 ms and 4.74 ms, respectively

Fig. 5

Calibration function for E/Z isomer mixtures for the IR-MALDI-IMS setup in a semi-logarithmic plot, with R² = 0.994, n = 14. The inset shows the calibration function for linearly scaled axes. The measured yield is the signal integral Z/(Z + E) in the measured spectrum. The reference yield refers to the actual molar fraction of the Z-isomer

Fig. 6

Side and top views of the structures of the Z/E-isomers, ethyl cinnamate derivatives E-1 and Z-1 (DFT: B3LYP/6-311+G(d,p))

Fig. 7

IM peaks for an E-1 and Z-1 95:5 mol% mixture in dependence of the pressure; for the sake of clarity, only area-normalized and time-scaled (drift-time shifted and peak-width normalized) fit functions are shown

Fig. 8

IR-MALDI-IM signals of the E isomer E-1 (black) and Z-isomer Z-1 (red) recorded over reaction time of the microchip reactor

Fig. 9

IR-MALDI-IM signal of the Z-isomer (product) in dependence of the concentration of the photocatalyst used (0 to 0.8 mol%, from bottom to top with in increasing line width), in this case riboflavin L. Inset shows the maximum slope (between 150 and 200 s) and marks the minimum response time of the entire setup at 10 s with a maximum response rate of 0.9 fC/s. For a riboflavin concentration of 0.8 mol%, the irradiation was stopped at 320 s

Fig. 10

Calibration-corrected yield of the E/Z isomerization for two different radiation sources, 404 nm and 365 nm sequentially applied to the photoinduced isomerization reaction carried out in the capillary flow reactor (catalyst M, [Ir[dF(CF₃)ppy]₂(dtbbpy)]PF₆, 2 mol% in MeCN)

Fig. 11

Reaction yields of the Z-isomers from its E-isomer as starting material: a ethyl cinnamate derivative E-1 in the capillary flow reactor at 404 nm excitation (Cap 404 nm, E-1), b ethyl cinnamate derivative E-1 in the capillary flow reactor at 365 nm excitation (Cap 365 nm, E-1), c ethyl cinnamate derivative E-1 in the microchip flow reactor at 404 nm excitation (Chip 404 nm, E-1), d ethyl cinnamate derivative E-2 in the microchip flow reactor at 404 nm excitation (Chip 404 nm, E-2). Photosensitizing catalysts: A, [Ru(bpy)₃](PF₆)₂; B, [Ru(phen)₃]Cl₂; C, Rose Bengal; D, [Ru(bpz)₃](PF₆)₂; E, Mes-Arc⁺ClO₄⁻; F, 9-fluorenone; G, Eosin Y; H, [Ir(dtbbpy)(ppy)₂]PF₆; I, Rhodamine 6G; J, 4CzIPN; K, fac-Ir(ppy)₃; L, Riboflavin; M, [Ir[dF(CF₃)ppy]₂(dtbbpy)]PF₆; N, [Cu(dap)₂]Cl. The dashed line at 2.5% represents the threshold of the reaction onset and results from reference measurements, and their standard errors, containing no Z-isomer