Tris(hydroxymethyl)aminomethane-based deep eutectic solvents: physicochemical insights and antimicrobial assessment

Abstract Deep eutectic solvents (DES) are emerging as promising sustainable antimicrobial systems owing to their tuneable physicochemical properties and biocompatibility. This study reports the first synthesis and physicochemical characterisation of a series of Tris(hydroxymethyl)aminomethane (Tris)-based DES, prepared with acidic, neutral, and basic hydrogen bond donors via microwave-assisted and conventional thermal methods in quantitative yield. All formulations were characterised by FTIR spectroscopy, differential scanning calorimetry (DSC), and rheological measurements. Acid-based DES exhibited true eutectic melting behaviour with transition enthalpies of 63–81 J/g and sub-ambient melting points, while polyol- and urea-based systems displayed glass-transition-dominated profiles with markedly lower enthalpies (3.5–10.6 J/g). Viscosities at 25 °C ranged from 12.0 to 528.5 mPa.s, with acid-based formulations showing intermediate values most suitable for antimicrobial application. Antimicrobial evaluation against Pseudomonas fluorescens and Staphylococcus epidermidis demonstrated that DES-2 (Tris: citric acid: water) and DES-3 (Tris: formic acid: water) were the most active formulations, with MIC values of 2–4% (v/v) against both strains, while survival assays showed DES-2 reduced P. fluorescens viability to 31.0% ± 6.0% and S. epidermidis to 8.3% ± 5.8% relative to untreated controls ( p < 0.001). Comparison with individual parent components confirmed that antibacterial activity is enhanced within the eutectic structure, demonstrating that antimicrobial efficacy is governed by formulation-dependent physicochemical properties rather than acidity alone.