First oxidative coupling of cyclazine heterocycle via regioselective dimerization of 1,2-dicarbomethoxy-3-phenylcycl[3.2.2]azine: Synthesis, theoretical aspects and physicochemical studies

• Published in: Dyes and pigments 2025-02, Vol.233, p.112539, Article 112539
• Main Authors: Starikov, Andrei S., Borodachev, Alexey V., Tarakanov, Pavel A., Slesarenko, Nikita A., Simonov, Sergey V., Simakov, Anton O., Istakova, Olga I., Goncharova, Olga A., Konev, Dmitry V., Pushkarev, Victor E.
• Format: Article
• Language: English
• Subjects: 1,2-Dicarbometoxy-3-phenylcycl[3.2.2]azine; Covalently linked dimers; Electrochemistry; Green fluorophores; Intermolecular oxidative coupling
• ISSN: 0143-7208
• DOI: 10.1016/j.dyepig.2024.112539

The first covalently linked dimer has been prepared for cyclazine systems by regioselective oxidative homocoupling of 1,2-dicarbomethoxy-3-phenylcycl[3.2.2]azine. The regioselectivity of this reaction at 4-position, having been confirmed by X-ray diffraction analysis and NMR spectroscopy, has been also reliably predicted within the model of average local ionization energy on the molecular surface of the starting monomer at the BP86/def2-TZVP level of theory. Due to the planar π-π interaction of the cycl[3.2.2]azine subunits, the dimer is a green fluorophore (λem = 527 nm, toluene), characterized by a bathochromic shift of the main bands in the UV–vis and fluorescence spectra relative to the monomer by 41 and 71 nm, respectively. Furthermore, the dimer demonstrates an increased fluorescence quantum yield relative to the monomer (55 % vs. 35 % in toluene), and according to the data of X-ray diffraction analysis, DFT calculations and variable temperature 1D and 2D 1H NMR spectroscopy, is characterized by hindered rotation of the S1-state-involved cycl[3.2.2]azine cores along the C4–C4′ bond axis. Such prerequisites determine good application potential of the 4-4′ coupled cycl[3.2.2]azine derivatives as turn-on fluorescent, i.e. fluorogenic probes for advanced bioimaging in living systems. Finally, unlike the monomer, the dimer shows reversibility of both one- and two-electron reduction and oxidation processes, and therefore can become the basis of both n- and p-type semiconductors. [Display omitted] •The intermolecular oxidative coupling reaction has been first carried out for cyclazine systems.•A cycl[3.2.2]azine based 4-4′ homodimer (2) was obtained regioselectively with good yields scalable to gram quantities.•Dimer 2 shows green fluorescence at 527 nm (ΦF ≈ 55%) shifted bathochromically by 71 nm relative to monomer 1.•The found hindered mutual rotation of cycl[3.2.2]azine cores in 2 is to be developed in turn-on fluorescent probes.•The reversibility of both electrochemical reduction and oxidation in 2 provides the base for n- and p-type semiconductors.