Work of Professor Cibulka's team featured on the cover of Chemical Science journal

Professor Radek Cibulka's laboratory has long been trying to develop systems that would facilitate chemical reactions, and thus the ways how to easily synthesize some drugs or other useful substances. The prestigious journal Chemical Science has now published a new system for chemical reductions based on deprotonated flavins, derivatives of vitamin B2. The system was developed as part of a collaboration between teams from the University of Chemical Technology, Prague and Adam Mickiewicz University within LA project from Czech Science Foundation and National Science Centre (Poland).

"We feel like builders. Removing one component (a proton) from a molecule of almost colourless 3-methyllumichrome - a substance related to flavins - causes structural changes that lead to the formation of an orange flavin anion. This flavin anion is unique because its protonated form does not exist. Moreover, we used this anion as a catalyst for reductions. All you have to do is shine cyan light on it and the reduction takes place." says Radek Cibulka.

The original article

Introduction of flavin anions into photoredox catalysis: acid–base equilibria of lumichrome allow photoreductions with an anion of an elusive 10-unsubstituted isoalloxazine

Dorota Prukała, Ekaterina Zubova, Eva Svobodová, Ludmila Šimková, Naisargi Varma, Josef Chudoba, Jiří Ludvík, Gotard Burdzinski, Iwona Gulaczyk, Marek Sikorski and  Radek Cibulka

Chem. Sci., 2025,16, 11255-11263

https://doi.org/10.1039/D5SC01630D

licensed under CC-BY 3.0

Selected sections from the article follow. Formats and hyperlinks were adapted from the original.

Abstract

Flavins have been established as effective catalysts in oxidative photoredox catalysis. Conversely, their use in reductive photocatalysis remains limited, mainly due to the relatively low stability of the transient flavin radicals (semiquinones), which are used in photoreductions. The fully reduced forms of flavins are also disadvantaged in photocatalysis because they absorb light in the UV rather than in the visible region. In this work, we present a new approach for reductive flavin photocatalysis that utilises a flavin (isoalloxazine) anion derived from the elusive 10-unsubstituted 3,7,8-trimethylisoalloxazine, an unstable tautomer of 3-methyllumichrome. We found the conditions under which this isoalloxazine anion is formed by in situ deprotonation/isomerisation from the readily available 3-methyllumichrome and we subsequently used it as a photoredox catalyst in the reductive dehalogenation of activated bromoarenes and their C–P coupling reaction with trimethyl phosphite to form an arylphosphonate. Steady-state and transient absorption spectroscopy, NMR and cyclic voltammetry investigations, together with quantum chemical calculations, showed that the anion of oxidised isoalloxazine has several advantages, compared to other forms of flavins used in photoreductions, such as high stability, even in the presence of oxygen, an absorption maximum in the visible region, thereby allowing the use of excitation light between 470 and 505 nm, and a relatively long-lived singlet excited-state.

Materials and methods

Nuclear magnetic resonance (NMR) spectra were recorded in CD₃CN, DMSOd₆ , DMF-d₆, TFA-d₃ or in their mixtures on an Agilent 400-MR DDR2 (399.94 MHz for ¹H, 100.58 MHz for ¹³C), JEOL-ECZL400G (400 MHz for ¹H, 101 MHz for ¹³C), or Bruker Avance III 600 MHz (600 MHz for ¹H and 151 MHz for ¹³C) at 298 K. Data for ¹H NMR are reported as follows: chemical shift (δ ppm), multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, dd = doublet of doublets, dt = doublet of triplets, br = broad etc.), coupling constant (Hz), and integration. All NMR spectra were processed and assigned using MestreNova. High-resolution mass spectra were obtained on Q-Tof Micro (Waters), equipped with a quadrupole and time-of-flight (TOF) analyser and a multichannel plate (MCP) detector. GC-MS analysis were performed on gas chromatograph Trace Ultra (Themo Scientific) with a quadrupole mass spectrometer DSQ II (Thermo Scientific) equipped with DB-5ms capillary column (30 m x 0.25mm, film 0,25 um) or on gas chromatograph 7890 (Agilent) with an orbital trap mass spectrometer Exploris 240 (Thermo Scientific) equipped with DB-5ms capillary column (30 m x 0.25mm, film 0,25 um). SICRIT (Soft Ionization by Chemical Reaction In Transfer - Plasmion GmbH, Germany) was used in positive mode. The melting points were measured on a Boetius melting point apparatus and are not corrected. Photoredox catalysis was performed using Luxeon Star LED 470 nm (65 lm @ 700mA) with dominant peak wavelengths 460–485 nm in tempered aluminium block (for arrangement, see S3) and Luxeon Star LED 505 nm (76 lm @ 350mA) with dominant peak wavelengths 490–515 nm. UV-Vis absorption spectra were recorded on a UV-2550 spectrophotometer (Schimadzu). Steady-state emission spectra and fluorescence excitation spectra were recorded on a Jobin Yvon-SpexFluorolog 3-22 spectrofluorometer. Note that spectra were recorded using the same excitation and emission slits for uniform spectral resolution and sensitivity. Fluorescence lifetime measurements of all compounds were performed using the time-correlated single-photon counting (TCSPC) method. Decays were measured with the TCSPC Triple Illuminator as an accessory for the Fluorologs 3-22 steady-state spectrofluorometer that adds lifetime-capability in the time domain. The excitation source were NanoLED diodes (λexc = 368 nm and 389 nm) from IBH. The instrument in this hardware configuration is capable of measuring lifetimes as short as 400 ps. Deconvolution of fluorescence decay curves was performed using IBH Consultants software. The experimental uncertainties in the lifetimes are 10 %. Setup for UV-Vis transient absorption spectra measurements: The triplet states were generated and analysed using laser flash photolysis employing a nanosecond Q-switched Nd: YAG laser in combination with an optical parametric oscillator (OPO) operating at 470 nm; the laser pulse energy was kept around 0.5 mJ/pulse. The sample's solution was deoxygenated by bubbling argon for 15 min before measurements. Spectra were determined using kinetics collected between 350–700nm with a 10 nm interval. See ref.1 for details. Electrochemical measurements(cyclic voltammetry) were managed by a computer driven potentiostat PGSTAT101 (Autolab-Metrohm) using NOVA 1.11 software, for details see Chapter 5.