Spectral Graph Analyses of Water Hydrogen-BondingNetwork and Osmolyte Aggregate Structures in Osmolyte–WaterSolutions.

Recently, it was shown that the spectralgraph theory is exceptionallyuseful for understanding not only morphological structural differencesin ion aggregates but also similarities between an ion network anda water H-bonding network in highly concentrated salt solutions. Here,we present spectral graph analysis results on osmolyte aggregatesand water H-bonding network structures in aqueous renal osmolyte solutions.The quantitative analyses of the adjacency matrices that are graph-theoreticalrepresentations of aggregates of osmolyte molecules and water H-bondstructures provide the ensemble average eigenvalue spectra and degreedistribution. We show that urea molecules form quite different morphologicalstructures compared to other protecting renal osmolyte molecules inwater, particularly sorbitol and trimethylglycine, which are well-knownprotecting osmolytes, and at high concentrations exhibit a strongpropensity to form morphological structures that are graph-theoreticallysimilar to that of the water H-bond network. Conversely, urea molecules,even at similarly high concentrations, form separated clusters insteadof extended osmolyte–osmolyte networks. This difference inmorphological structure of osmolyte–osmolyte aggregates betweenprotecting and destabilizing osmolytes is considered to be an importantobservation that led us to propose a hypothesis on the osmolyte aggregategrowth mechanism via either osmolyte network formation or segregatedosmolyte cluster formation. We anticipate that the present spectralgraph analyses of osmolyte aggregate structures and their interplaywith the water H-bond network structure in highly concentrated renalosmolyte solutions could provide important information on the osmolyteeffects of not only water structures but also protein stability inbiologically relevant osmolyte solutions. [ABSTRACT FROM AUTHOR]