Sugar-based amphiphilic molecules, which contain a hydrophilic sugar headgroup and a hydrophobic segment such as an alkyl chain, can assemble in water depending on their concentration, forming hydrophobic microenvironments or organizing at interfaces. These properties are important fundamental phenomena related to detergents, emulsifiers, molecular assemblies, and the dispersion and delivery of drugs and functional molecules. However, how subtle changes in molecular structure affect aggregation and interfacial behavior remains incompletely understood. In particular, the sulfur atom linking a sugar unit to a hydrophobic chain can be oxidized from sulfide to sulfoxide and sulfone, allowing its electronic and chemical properties to be tuned while largely preserving the overall molecular framework. Although such effects have been reported in more complex sugar-based molecules, few studies have directly compared aggregation in water with surface-tension-based interfacial behavior in simple, nonionic carbohydrate amphiphiles.
A research team comprising graduate student Kanon Suzuki, Assistant Professor Takahiko Matsushita, Dr. Tetsuo Koyama, Associate Professor Ken Hatano, and Professor Koji Matsuoka from the Graduate School of Science and Engineering at Saitama University synthesized a series of S -linked octyl α-D-mannosides that share the same mannose headgroup and octyl chain but differ only in the oxidation state of the sulfur atom: sulfide, sulfoxide, and sulfone. By combining nuclear magnetic resonance (NMR) spectroscopy, single-crystal X-ray crystallography, Nile Red fluorescence measurements, surface tension measurements, dynamic light scattering (DLS), and transmission electron microscopy (TEM), the team demonstrated that the sulfur oxidation state changes the relationship between aggregation in water and interfacial behavior. The study was published in Volume 565 of the journal Carbohydrate Research on April 28, 2026.
In the study, the researchers compared three structurally matched S-linked octyl α-D-mannosides that differed only in the oxidation state of sulfur. This molecular design minimized the influence of differences in the sugar headgroup or hydrophobic chain, making it possible to directly examine how sulfur oxidation affects aggregation behavior in water. The structures of the compounds were confirmed by NMR spectroscopy, while the sulfoxide framework was further validated by single-crystal X-ray crystallography of the corresponding acetylated derivative. The formation of hydrophobic microenvironments in water was evaluated using Nile Red fluorescence measurements. All three compounds showed concentration-dependent fluorescence responses. The apparent critical aggregation concentrations were estimated to be 1.86 mM for the sulfide derivative, 2.72 mM for the sulfoxide derivative, and 1.52 mM for the sulfone derivative, indicating that the sulfur oxidation state influences the concentration at which aggregation-related behavior becomes detectable. In contrast, surface tension measurements revealed a clear breakpoint only for the sulfide derivative, at approximately 1.69 mM, consistent with classical surfactant-like behavior. For the sulfoxide and sulfone derivatives, aggregation-related fluorescence responses were observed, but no clear surface tension breakpoint was detected within the measured concentration range. DLS and TEM observations also qualitatively supported the aggregation-related features of this molecular series. Although the detailed mechanism remains to be clarified, the researchers suggest that differences in local polarity, hydration, or molecular packing around the sulfur linkage may contribute to the observed behavior. Overall, the findings show that the sulfur oxidation state not only changes the tendency of these molecules to aggregate in water but can also alter the correspondence between aggregation detected in the bulk aqueous phase and interfacial behavior detected as changes in surface tension.
“The significance of this study lies in showing that the aggregation of carbohydrate amphiphiles may be controlled not only by the type of sugar or the length of the alkyl chain, but also by a very small structural element: the oxidation state of the atom linking the sugar and hydrophobic chain,” says Professor Matsuoka and Matsushita, who led the research team. “What is particularly important is that the formation of hydrophobic microenvironments observed by Nile Red fluorescence and the interfacial activity observed by surface tension do not always arise at the same concentration. This result highlights the need to understand bulk aqueous behavior and interfacial behavior separately, rather than relying on a single measure such as the critical micelle concentration or surface activity. Demonstrating this distinction in a structurally simple, nonionic carbohydrate amphiphile provides a useful reference point before moving on to more complex functional molecules. We believe that sulfur oxidation state can serve as a new molecular design parameter for carbohydrate-based surfactants and glycan-modified nanoassemblies.”
“This study does not point directly to immediate commercialization, but over the next five to ten years, it could help guide the design of sugar-based molecular materials that assemble when needed in water while avoiding excessive activity at interfaces,” says graduate student Suzuki. “Because sugar-based amphiphilic molecules offer hydrophilicity and molecular recognition features similar to those of biomolecules, they may be useful for dispersing drugs and functional ingredients in water, stabilizing nanoparticles and emulsions, and designing surfaces for bio- and medical materials. Our findings suggest that simply changing the oxidation state of sulfur could make it possible to tune aggregation and interfacial behavior separately. In the future, this approach may contribute to the development of environmentally friendly, sugar-derived interfacial control materials whose water dispersibility, surface activity, and assembly behavior can be finely adjusted for specific purposes.”
Carbohydrate Research
Experimental study
Effect of sulfur oxidation state on aggregation-related and interfacial behavior of S-linked octyl α-d-mannosides
28-Apr-2026