From antibacterial to antiscalant: repurposing N-Acetylcysteine (NAC) for green Reverse Osmosis membrane cleaning strategies.
Reverse osmosis (RO) membranes are critical for desalination and water reuse. Inorganic scaling (mostly precipitates or oxides containing Ca2+, Mg2+, Mn2+, SiOx) and biofouling, however, severely impair flux and effectively shortens the membrane lifetime. Phosphonate-based antiscalants excel at prevention but contribute to eutrophication. Even ‘green’ alternatives (e.g., polyaspartic acid, carboxymethyl inulin) often show dose-dependent limitations, incomplete biodegradability, and weaker efficacy against mixed or silica scaling. Citric acid remains the standard low-pH cleaner for CaCO₃ and metal oxide scaling due to its chelating ability. Yet, it is only moderately effective, risks promoting biofouling, and shows limited action on sulfates, phosphates, or mature biofilms.
Could thiol-containing amino acids offer a green alternative? We recently discovered that N-acetylcysteine (NAC), previously assessed by our group as effective green biocide against drinking water bacteria, is as much effective as citric acid in dissolving inorganic scaling species at concentrations 10 times lower.
This project aims to modify NAC structure, thereby changing the binding strength to di- or trivalent cations which can cause scaling or are part of inorganic fouling. We envision NAC derivatives to become a sustainable fouling prevention and/or cleaning strategy for RO membranes, targeting both inorganic fouling and bacterial growth.
Research challenges
Despite NAC’s proven thiol-mediated chelation of divalent cations, weak-acid properties (pKa COOH ≈ 3.2 enabling partial deprotonation at RO-relevant pH), and established antibacterial activity, its application as a dual antiscalant and cleaning agent for RO membranes was never explored. Current green options rarely integrate strong inorganic scale dissolution with antibacterial effects, and structure-activity relationships for enhanced performance (e.g., against silica or mixed scales) are poorly defined.
Key challenges are: (1) provide detailed understanding of NAC mechanisms based on binding affinity, solubility in water, reaction rates under varying RO conditions; (2) generate data on efficacy for sulfate/phosphate scales or mature biofilms; (3) assess the new NAC derivatives to maintain biocidal effects while improving dose-efficiency and stability against scaling. The proposed innovation is based on a physical organic chemical approach, wherein three-level derivatization of NAC is applied: (a) fine tuning of the N-acetyl side chain (i.e., changing the affinity based on proximity effects); (b) rough tuning of the thiol moiety (i.e., changing the affinity based on direct interactions), and (c) chemical programming of the carboxylic acid (protected forms for pH-, light-, temperature-, or chemically-triggered activation). The aim is to enable precise control of chelation strength, cleaning potency, and preserve multi-function (scaling/cleaning/disinfection) synergy.
Your assignment
You will design and synthesise a targeted library of NAC derivatives following three strategies: (1) fine tuning of the acetyl side group for subtle binding modulation, (2) rough tuning of the reactive thiol for enhanced ligand affinity, and (3) chemical programming of the carboxylic acid to enable triggered restoration of acidity and scale-dissolving power.
You will characterize the compounds (NMR, MS, IR) and evaluate their performance for scale inhibition both in static and dynamic experiments, using a dedicated custom-made RO simulator. The antibacterial and antifouling efficacy will be assessed against relevant drinking water bacteria and lab-grown mixed biofilms utilizing the established flow setups part of the Biofilms Theme of Wetsus. Mechanisms will be elucidated through kinetic assays and mathematical modeling established in Wong’s Research Group (University of Twente). Results will be benchmarked against citric acid and commercial antiscalants. Promising candidates will advance to pilot-scale validation with industrial partners for real-world high-recovery RO applications.
Your profile
You have a master’s degree in organic chemistry, chemical engineering, environmental engineering, or equivalent, with strong skills in organic synthesis and analytical techniques. You have affinity for membrane processes and water chemistry. You like microbiology and you wish to conduct multidisciplinary research connecting different disciplines to find answers. You are ambitious, independent, innovative, and motivated to develop sustainable solutions in collaboration with companies.
Keywords
green antiscalants; N-acetylcysteine; reverse osmosis; scale inhibition; membrane cleaning
Professor/University group/Wetsus supervisor(s)
University promotor and co-promotor: prof. Albert Wong, University of Twente, Department of Molecules and Materials; prof. Wiebe de Vos, University of Twente, Department of Membrane Science and Technology.
Wetsus daily supervisor: dr. M. Cristina Gagliano, Senior Scientist and Theme Coordinator Biofilms; Wetsus co-supervisor: dr. Ruben Halfwerk, Scientific Project Manager
Project partners: The companies connected to the Biofilms Theme of Wetsus, namely Vitens, WLN, Brabant Water and Evides.
Only applications that are complete, in English, and submitted via the application webpage before the deadline will be considered eligible.
Guidelines for applicants: https://phdpositionswetsus.eu/guide-for-applicants/
