Mesoscale inhomogeneities in aqueous solutions of small amphiphilic molecules

Abstract

Small amphiphilic molecules, also known as hydrotropes, are too small to form micelles in aqueous solutions. However, aqueous solutions of nonionic hydrotropes show the presence of a dynamic, loose, non-covalent clustering in the water-rich region, This clustering can be viewed as "micelle-like structural fluctuations". Although these fluctuations are short ranged (approximately 1 nm) and short lived (10 ps-50 ps), they may lead to thermodynamic anomalies. In addition, many experiments on aqueous solutions of hydrotropes show the occasional presence of mesoscale (approximately 100 nm) inhomogeneities. We have combined results obtained from molecular dynamics simulations, small-angle neutron scattering, and dynamic light-scattering experiments carried out on tertiary butyl alcohol (hydrotrope)-water solutions and on tertiary butyl alcohol-water-cyclohexane (hydrophobe) solutions to elucidate the nature and structure of these inhomogeneities. We have shown that stable mesoscale inhomogeneities occur in aqueous solutions of nonionic hydrotropes only when the solution contains a third, more hydrophobic, component. Moreover, these inhomogeneities exist in ternary systems only in the concentration range where structural fluctuations and thermodynamic anomalies are observed in the binary water-hydrotrope solutions. Addition of a hydrophobe seems to stabilize the water-hydrotrope structural fluctuations, and leads to the formation of larger (mesoscopic) droplets. The structure of these mesoscopic droplets is such that they have a hydrophobe-rich core, surrounded by a hydrogen-bonded shell of water and hydrotrope molecules. These droplets can be extremely long-lived, being stable for over a year. We refer to the phenomenon of formation of mesoscopic droplets in aqueous solutions of nonionic hydrotropes containing hydrophobes, as mesoscale solubilization. This phenomenon may represent a ubiquitous feature of nonionic hydrotropes that exhibit clustering in water, and may have important practical applications in areas, such as drug delivery, where the replacement of traditional surfactants may be necessary.

Mesoscale solubilization and critical phenomena in binary and quasi-binary solutions of hydrotropes

“…It has been shown that such inhomogeneities occur in aqueous solutions of nonionic hydrotropes when the solution contains a third, more hydrophobic, component [12,13,[28][29][30][31][32]. Remarkably, these inhomogeneities (emerging in water-rich ternary systems) are only pronounced in the hydrotrope concentration range where molecular clustering and thermodynamic anomalies are observed in the original binary hydrotrope-water solutions.…”

“…In aqueous environment, hydrotropes unlike surfactants do not spontaneously self-assemble to form stable equilibrium micelles [3], although they are frequently used as "cosurfactants" to stabilize micro-emulsions [4]. However, above a certain concentration, hydrotrope solutions may exhibit dynamic, non-covalent molecular clustering that may be viewed as "micellelike" or structural fluctuations [5][6][7][8][9][10][11][12][13]. Molecular dynamics studies show that the clusters of hydrotrope molecules, hydrogen-bonded with the aqueous surrounding, are short-ranged (order of 1 nm in size) and short-lived with a lifetime of tens or hundreds picoseconds [10][11][12].…”

Microstructure and concentration fluctuations in alcohol–Toluene and alcohol-Cyclohexane binary liquids: A small angle neutron scattering study

“…This deviation can be attributed to the incomplete mixing of the distinct interacting molecules at the microscopic level even though these liquids are often macroscopically miscible [1,2,3,4]. These original features are often observed for small-chains alcohols, also denoted hydrotropes, which exhibit an amphiphilic character but are too small to form ordinary micelles in solution [5]. Recent studies have linked the structural complexity of aqueous solutions of small H-bonded molecules to the interplay between concentration fluctuations and self-aggregation, the concept of molecular emulsions being introduced by Kezic and Perera [6,7,8,9].…”

“…Water -Tert-butanol (TBA) mixture is one of the systems that are the most debated currently, being considered as the prototypical system to advance our understanding of hydrotrope solubility in aqueous solution [5,8,9,15,16,17,18,19]. Analogous interest arises from studies on non-aqueous solvent -TBA mixtures.…”

Rheological characterizations of wormlike micellar solutions containing cationic surfactant and anionic hydrotropic salt

“…Structurally similar to surfactants, hydrotropic salts can act as strong "binding" additives and reduce surface tension in an aqueous solution. A number of organic hydrotropic salts such as NaSal [Rehage and Hoffmann (1988a); Shikata et al (1987)], SHNC [Mendes et al (1997[Mendes et al ( , 1998], p-toluene sulfonate [Soltero et al (1996)], chlorobenzoate [Carver et al (1996)], and naphthalenesulfonate [Brown et al (1989)] have been studied in combination with cationic surfactants because these mixtures can reduce the charge density of surfactant micellar aggregates significantly, enhancing ion pairing and surface activity of the micelles above a minimum hydrotropic concentration (MHC), promoting growth of wormlike micelles at a much lower salt/surfactant ratio in comparison to other salts [Hatzopoulos et al (2011); Hodgdon and Kaler (2007); Lin et al (2012); Subramanian et al (2013)]. In addition, Schubert et al (2003) reported that adding the hydrotropic salt NaTosylate (0.25 wt.…”