Sustainable polyphenolate assisted hydrotropic solubilization of riboflavin

• Hydrotropic polyphenolates increase riboflavin’s water-solubility exponentially. • Polyphenolates are more efficient solubilizers for riboflavin than nicotinamide. • Aromatic polyphenolates undergo π-stacking with riboflavin’s isoalloxazine ring. • The hydrotropic effect of polyphenolates on riboflavin is enthalpically driven. The solubility of riboflavin is currently thoroughly investigated due to its importance for biological systems. Using real-life experiments and theoretical models, we study the hydrotropic performance and solubilizing mechanism of polyphenolic acid salts and derivatives for the solubilization of riboflavin. Sodium/choline polyphenolates were both identified as potent hydrotropes for riboflavin via UV–Vis-spectroscopy. Using sodium ferulate and 3,4-dimethoxycinnamate, riboflavin’s water solubility can be increased 240 and >2000 times, respectively (molar polyphenolate/riboflavin ratios ≈ 6). Thus, polyphenolates were revealed as more efficient hydrotropes for riboflavin than the usually applied hydrotrope nicotinamide. Solubilization, surface tension, and dynamic light scattering experiments ruled out the presence of larger well-defined aggregates around riboflavin. The (i) importance of the polyphenolates’ π-electron system for riboflavin’s solubilization, (ii) reversible bathochromic shifts of riboflavin’s absorbance by π-electron-rich solubilizers, (iii) mutual solubilization of riboflavin and of some aromatic sodium carboxylates, (iv) nuclear magnetic resonance (NMR) measurements, and (v) molecular dynamics confirmed π-complexation of riboflavin and aromatic carboxylates as reason for this hydrotropy. Additionally, NMR and NPT simulation indicated sodium polyphenolates to influence the ribityl chain. In water, the overall entropy of riboflavin dissolution is favorable, but in the presence of polyphenolate, the entropy of riboflavin’s dissolution is unfavorable and overcompensated by the respective enthalpy. Finally, both methods hint to a minor influence of the ribityl chain on the dissolution process. Moreover, real-life experiments and theoretical models state π-electron driven complex formation between the solute riboflavin and the hydrotropic polyphenolates.