Skip to main content

Bioconcentration potential and microbial toxicity of onium cations in photoacid generators


Despite the widespread utilization of onium salts as photoacid generators (PAGs) in semiconductor photolithography, their environmental, health, and safety (EHS) properties remain poorly understood. The present work reports the bioconcentration potential of five representative onium species (four sulfonium and one iodonium compound) by determining the octanol–water partition coefficient (POW) and lipid membrane affinity coefficient (KMA); microbial toxicity was evaluated using the bioluminescent bacterium Aliivibrio fischeri (Microtox bioassay). Four of the oniums exhibited varying degrees of hydrophobic (lipophilic) partitioning (log POW: 0.08–4.12; KMA: 1.70–5.62). A strong positive linear correlation was observed between log POW and KMA (KMA = log POW + 1.76, R2 = 0.99). The bioconcentration factors (log BCF) estimated from POW and KMA for the four oniums ranged from 0.13 to 3.67 L kg−1. Bis-(4-tert-butyl phenyl)-iodonium and triphenylsulfonium had 50% inhibitory concentrations (IC50) of 4.8 and 84.6 μM, whereas the IC50 values of the other three oniums were not determined because these values were higher than their aqueous solubility. Given the increased regulatory scrutiny regarding the use and potential health impacts from onium PAGs, this study fulfills critical knowledge gaps concerning the EHS properties of PAG oniums, enabling more comprehensive evaluation of their environmental impacts and potential risk management strategies.

Graphical abstract

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2

Data availability

All data generated or analyzed during this study are included in this published article (and its supplementary information files).


  1. Abbas M, Adil M, Ehtisham-ul-Haque S, Munir B, Yameen M, Ghaffar A, Shar GA, Tahir MA, Iqbal M (2018) Vibrio fischeri bioluminescence inhibition assay for ecotoxicity assessment: a review. Sci Total Environ 626:1295–1309

    CAS  Article  Google Scholar 

  2. Armitage JM, Arnot JA, Wania F, Mackay D (2013) Development and evaluation of a mechanistic bioconcentration model for ionogenic organic chemicals in fish. Environ Toxicol Chem 32:115–128

    CAS  Article  Google Scholar 

  3. Barrett RH, Selwyn MJ (1976) Effects of triphenylsulphonium ions on mitochondria. Inhibition of adenosine triphosphatase activity. Biochem J 156:315–322

    CAS  Article  Google Scholar 

  4. Bowman BJ, Mainzer SE, Allen KE, Slayman CW (1978) Effects of inhibitors on the plasma membrane and mitochondrial adenosine triphosphatases of Neurospora crassa. Biochimica et Biophysica Acta (BBA)-Biomembranes 512:13–28

    CAS  Article  Google Scholar 

  5. Brand S, Schlüsener MP, Albrecht D, Kunkel U, Strobel C, Grummt T, Ternes TA (2018) Quaternary (triphenyl-) phosphonium compounds: environmental behavior and toxicity. Water Res 136:207–219

    CAS  Article  Google Scholar 

  6. Chakraborty S, Massey V (2002) Reaction of reduced flavins and flavoproteins with diphenyliodonium chloride. J Biol Chem 277:41507–41516

    CAS  Article  Google Scholar 

  7. Coves J, Lebrun C, Gervasi G, Dalbon P, Fontecave M (1999) Overexpression of the FAD-binding domain of the sulphite reductase flavoprotein component from Escherichia coli and its inhibition by iodonium diphenyl chloride. Biochem J 342:465–472

    CAS  Article  Google Scholar 

  8. Dolzonek J, Cho CW, Stepnowski P, Markiewicz M, Thoming J, Stolte S (2017) Membrane partitioning of ionic liquid cations, anions and ion pairs-estimating the bioconcentration potential of organic ions. Environmental pollution (Barking, Essex : 1987) 228:378–389

    CAS  Article  Google Scholar 

  9. Engelhardt H, Müller H, Dreyer B (1984) Is there a “true” dead volume for HPLC columns? Chromatographia 19:240–245

    CAS  Article  Google Scholar 

  10. EPA (2012) Quantitative risk assessment calculations. Sustainable futures/P2 framework manual 2012 EPA-748-B12-001 13. Quantitative Risk Assessment Calculations 13:1–11

  11. Escher BI, Sigg L (2004) Chemical speciation of organics and of metals at biological interphases. IUPAC Series on Analytical and Physical Chemistry of Environmental Systems 9:205–270

  12. Escher BI, Schwarzenbach RP, Westall JC (2000) Evaluation of liposome-water partitioning of organic acids and bases. 2. Comparison of experimental determination methods. Environ Sci Technol 34:3962–3968

    CAS  Article  Google Scholar 

  13. Gerami-Nejad M, Stretton R (1981) Aspects of the antibacterial action of diphenyliodonium chloride. Microbios 30:97–107

    CAS  Google Scholar 

  14. Gobas FA (2001) Assessing bioaccumulation factors of persistent organic pollutants in aquatic food-chains, persistent organic pollutants. Springer, pp 145–165

  15. Golius A, Gorb L, Scott AM, Hill FC, Shukla M, Goins AB, Johnson DR, Leszczynski J (2016) Experimental and computational study of membrane affinity for selected energetic compounds. Chemosphere 148:322–327

    CAS  Article  Google Scholar 

  16. Hendriks AJ, Traas TP, Huijbregts MA (2005) Critical body residues linked to octanol−water partitioning, organism composition, and LC50 QSARs: meta-analysis and model. Environ Sci Technol 39:3226–3236

    CAS  Article  Google Scholar 

  17. Hirayama M (2011) The antimicrobial activity, hydrophobicity and toxicity of sulfonium compounds, and their relationship. Biocontrol Science 16:23–31

    CAS  Article  Google Scholar 

  18. Hirayama M (2012) The antimicrobial activity, toxicity and antimicrobial mechanism of a new type of tris (alkylphenyl) sulfonium. Biocontrol Science 17:27–35

    CAS  Article  Google Scholar 

  19. James R, Dindal A, Willenberg Z, Riggs K (2003) Strategic Diagnostics Inc. Microtox® Rapid Toxicity Testing System. Environmental technology verification report. ETV Advanced Monitoring Systems Center, US Environmental Protection Agency, Columbus, Ohio

  20. Kah M, Brown CD (2008) LogD: lipophilicity for ionisable compounds. Chemosphere 72:1401–1408

    CAS  Article  Google Scholar 

  21. Kuznetsova NA, Malkov GV, Gribov BG (2020) Photoacid generators. Application and current state of development. Russ Chem Rev 89:173

    CAS  Article  Google Scholar 

  22. Liao Q, Yao J, Yuan S (2006) SVM approach for predicting LogP. Mol Divers 10:301–309

    CAS  Article  Google Scholar 

  23. Loidl-Stahlhofen A, Eckert A, Hartmann T, Schöttner M (2001a) Solid-supported lipid membranes as a tool for determination of membrane affinity: high-throughput screening of a physicochemical parameter. J Pharm Sci 90:599–606

    CAS  Article  Google Scholar 

  24. Loidl-Stahlhofen A, Hartmann T, Schottner M, Rohring C, Brodowsky H, Schmitt J, Keldenich J (2001b) Multilamellar liposomes and solid-supported lipid membranes (TRANSIL): screening of lipid-water partitioning toward a high-throughput scale. Pharm Res 18:1782–1788

    CAS  Article  Google Scholar 

  25. Martin Y (1995) Exploring QSAR: hydrophobic, electronic, and steric constants. In: Hansch C, Leo A, Hoekman D (eds) American Chemical Society, Washington, DC

  26. Miyazawa T (2017) Onium salt, photoacid generator, photosensitive resin composition, and method for producing device. Google Patents

  27. Mulkiewicz E, Jastorff B, Składanowski A, Kleszczyński K, Stepnowski P (2007) Evaluation of the acute toxicity of perfluorinated carboxylic acids using eukaryotic cell lines, bacteria and enzymatic assays. Environ Toxicol Pharmacol 23:279–285

    CAS  Article  Google Scholar 

  28. Ochoa-Herrera V, Field JA, Luna-Velasco A, Sierra-Alvarez R (2016) Microbial toxicity and biodegradability of perfluorooctane sulfonate (PFOS) and shorter chain perfluoroalkyl and polyfluoroalkyl substances (PFASs). Environ Sci Process Impacts 18:1236–1246

    CAS  Article  Google Scholar 

  29. OECD (2004) Test no. 117: partition coefficient (n-octanol/water), HPLC method. OECD Guidelines for the Testing of Chemicals, Section 1: physical-chemical properties

  30. Pandey M, Singh AK, Thakare R, Talwar S, Karaulia P, Dasgupta A, Chopra S, Pandey AK (2017) Diphenyleneiodonium chloride (DPIC) displays broad-spectrum bactericidal activity. Sci Rep 7:1–8

    Article  Google Scholar 

  31. Parvez S, Venkataraman C, Mukherji S (2006) A review on advantages of implementing luminescence inhibition test (Vibrio fischeri) for acute toxicity prediction of chemicals. Environ Int 32:265–268

    CAS  Article  Google Scholar 

  32. Riganti C, Gazzano E, Polimeni M, Costamagna C, Bosia A, Ghigo D (2004) Diphenyleneiodonium inhibits the cell redox metabolism and induces oxidative stress. J Biol Chem 279:47726–47731

    CAS  Article  Google Scholar 

  33. Shiemke AK, Arp DJ, Sayavedra-Soto LA (2004) Inhibition of membrane-bound methane monooxygenase and ammonia monooxygenase by diphenyliodonium: implications for electron transfer. J Bacteriol 186:928–937

    CAS  Article  Google Scholar 

  34. Sikkema J, de Bont JA, Poolman B (1995) Mechanisms of membrane toxicity of hydrocarbons. Microbiol Rev 59:201–222

    CAS  Article  Google Scholar 

  35. Tvermoes B, Speed D (2019) Increased regulatory scrutiny of photolithography chemistries: the need for science and innovation (Conference Presentation), Advances in Patterning Materials and Processes XXXVI. International Society for Optics and Photonics, pp 1096003

  36. Wells MJ, Clark CR (1981) Liquid chromatographic elution characteristics of some solutes used to measure column void volume on C18 bonded phases. Anal Chem 53:1341–1345

    CAS  Article  Google Scholar 

  37. Zhang K, Wiseman S, Giesy JP, Martin JW (2016) Bioconcentration of dissolved organic compounds from oil sands process-affected water by medaka (Oryzias latipes): importance of partitioning to phospholipids. Environ Sci Technol 50:6574–6582

    CAS  Article  Google Scholar 

Download references


This study was funded by the Semiconductor Industry Association (SIA) and Semiconductor Research Corporation (SRC) (award # 2818.004). UA/NASA Undergraduate Internship Program is acknowledged for providing partial support for RDP.

Author information




XZN performed the experiments; coordinated the investigation processes; analyzed, interpreted, and visualized data; and wrote the manuscript. JAF interpreted data and acquired funding. RP participated to Microtox experiments and analyzed the respective data. RDP participated to the membrane affinity experiments, analyzed data, and wrote the manuscript. JC interpreted data and acquired funding. LA interpreted data and participated in LC-MS analysis. RSA interpreted data, acquired funding, wrote the manuscript, and conceptualized the investigation.

Corresponding author

Correspondence to Reyes Sierra-Alvarez.

Ethics declarations

Competing interests

The authors declare that they have no competing interests.

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Responsible editor: Philippe Garrigues

Supplementary information


(DOCX 380 kb).

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Niu, XZ., Field, J.A., Paniego, R. et al. Bioconcentration potential and microbial toxicity of onium cations in photoacid generators. Environ Sci Pollut Res 28, 8915–8921 (2021).

Download citation


  • Hydrophobicity
  • Octanol–water partition
  • Lipid membrane affinity
  • Microbial toxicity
  • Photolithography