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Research Article Open access CC BY 4.0

Degrees of Sulfonation: Mapping the Reactivity Landscape of Acridine and Acridone

Péter Kisfaludi, Sára Spátay, Péter Huszthy, Ádám Golcs

Organics · pp. 43–43 · Published 12 Sep 2025

10.3390/org6030043

Abstract

Although sulfonated acridines and acridones are valuable scaffolds in diagnostics and materials science, to our best knowledge, there is no comprehensive study that addresses how the degree of sulfonation depends on reaction parameters. To fill this gap, we investigated the sulfonation behavior of unsubstituted acridine and acridone under classical conditions, using sulfuric acid, oleum, and chlorosulfonic acid. A factorial experimental design was applied to systematically evaluate the influence of temperature and reagent excess on the extent of sulfonation, while keeping the reaction time constant. Products were analyzed by HPLC–MS/MS to determine the degree of sulfonation and its distribution. Regioselectivity and product isolation were not addressed in this study. Our results provide a foundational dataset for controlling sulfonation level for these heterocycles and can help future synthetic applications where defined sulfonation patterns are desired.

Acridone Acridine Regioselectivity Chemistry Reagent Acridine derivatives Reactivity (psychology) Combinatorial chemistry

References (30)

  1. 1 Sharghi, 2018, An overview on recent advances in the synthesis of sulfonated organic materials, sulfonated silica materials, and sulfonated carbon materials and their catalytic applications in chemical processes [DOI]
  2. 2 Wang, 2023, Green Sulfonation [DOI]
  3. 3 Dong, 2020, Recent progress in sulfonylation via radical reaction with sodium sulfinates, sulfinic acids, sulfonyl chlorides or sulfonyl hydrazides [DOI]
  4. 4 Żamojć, K., Milaș, D., Grabowska, O., Wyrzykowski, D., Mańkowska, M., and Krzymiński, K. (2025). Insight into the intercalation of N-substituted acridine-9-amines into DNA based on spectroscopic and calorimetric analysis. Biochim. Biophys. Acta Gen. Subj., 1869. [DOI]
  5. 5 Abouelenein, M.G., Mohamed, M.B.I., Elsenety, M.M., El-Rashedy, A.A., Ghalib, S.H., Mohamed, F.A.E., and Ageeli, A.A. (2024). Facile and novel synthetic approach, molecular docking, molecular dynamics, and drug-likeness evaluation of 9-substituted acridine derivatives as dual anticancer and antimicrobial agents. Chem. Biodivers., 21. [DOI]
  6. 6 Elmusa, 2025, Synthesis, characterization and in silico studies of some pyrazolo-acridine hybrid compounds as antimicrobial agents [DOI]
  7. 7 Osuna, 1988, New antiparasitic agents: III. Comparison between trypanocidal activities of some acridine derivatives against Trypanosoma cruzi in vitro [DOI]
  8. 8 Pordel, 2024, Recent advances in the synthesis and optical applications of acridine-based hybrid fluorescent dyes [DOI]
  9. 9 He, 2025, Exploring acridine-quinolinium conjugates as near-infrared photosensitizers for the amyloid-β photo-oxidation [DOI]
  10. 10 Hirao, 2019, Redox/pH dual stimuli-responsive acridine spiropyran [DOI]
  11. 11 Baranyai, 2019, An acridone-based fluorescent chemosensor for cationic and anionic species, and its application for molecular logic operations [DOI]
  12. 12 Chan, Y.C., Li, C.Y., Lai, C.W., Wu, M.W., Tseng, H.J., and Chang, C.C. (2020). Synthesis and application in cell imaging of acridone derivatives. Appl. Sci., 10. [DOI]
  13. 13 Miguel, 2020, Orthogonal cell polarity imaging by multiparametric fluorescence microscopy [DOI]
  14. 14 Matsumura, 1935, Sulfonation of acridone [DOI]
  15. 15 Pereira, 2019, A comprehensive spectral, photophysical and electrochemical study of synthetic water-soluble acridones. A new class of pH and polarity sensitive fluorescent probes [DOI]
  16. 16 (2002). Amersham Biosciences UK Limited. Acridone Derivatives as Labels for Fluorescence Detection of Target Materials. (Application No. WO2002099424A2), International Patent.
  17. 17 (2020). Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. Sulfonated 2(7)-Aminoacridone and 1-Aminopyrene Dyes and Their Use as Fluorescent Tags, in Particular for Carbohydrate Analysis. (Application No. WO2020151804A1), International Patent.
  18. 18 Cotton, G. (2004). Site-Specific Labeling of Proteins Using Acridone and Quinacridone Lifetime Dyes. (US20040023409A1), U.S. Patent.
  19. 19 Xia, 2024, Dual-modal aptasensor based on multifunctional acridone derivative for rapid detection of exosomal proteins and cancer diagnosis [DOI]
  20. 20 Zhang, 2005, Synthesis and application of biacridine DNA probe
  21. 21 Hammler, 2020, Fluorescently labelled ATP analogues for direct monitoring of ubiquitin activation [DOI]
  22. 22 (2013). Xerox Corporation. Five Member Ring Stabilizers for Quinacridone-Type Pigments in Solid Ink. (US20120140001A1), U.S. Patent.
  23. 23 Markovich, 2013, Sulfonation of 10-carboxymethylene-9-acridanone under thermal and microwave conditions. Comparison of kinetic parameters [DOI]
  24. 24 Bisballe, 2020, What is the best strategy for water-soluble fluorescence dyes?—A case study using long fluorescence lifetime DAOTA dyes [DOI]
  25. 25 (2019). PerkinElmer Health Sciences, Inc. Preparation of NIR to SWIR Fluorescent Compounds for Imaging and Detection. (Application No. WO2019067180A1), International Patent.
  26. 26 MGI Tech Co., Ltd., and Wuhan MGI Tech Co., Ltd. (2024). Fluorescent Dye, Synthesis Therefor and Use Thereof. (Application No. WO2024240051A1), International Patent.
  27. 27 Poh, 1996, No distinction between host and guest—The case of cyclodextrins complexing with disodium 1,8-disulfonato-3,4,5,6-acridinetetracarboxylic acid [DOI]
  28. 28 Segura, 2006, Acridone heterocycles as fluorescent sensors for anions [DOI]
  29. 29 Le, 2020, Synthesis, thermal, optical and electrochemical properties of acridone and thioxanthone based push-pull molecules [DOI]
  30. 30 Kumar, 2012, Acridine: A versatile heterocyclic nucleus

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