When Sugars Get Wet. A Comprehensive Study of the Behavior of Water on the Surface of Oligosaccharides Sai Kumar Ramadugu, † Ying-Hua Chung, † Junchao Xia, and Claudio J. Margulis* Department of Chemistry, UniVersity of Iowa, Iowa City, Iowa 52246 ReceiVed: May 27, 2009 In this article, we characterize the behavior of water on the surface of a diverse group of carbohydrates and attempt to determine the role of saccharide size, linkage, and branching as well as secondary structure on the dynamics and structure of water at the surface. In order to better understand the similarities and differences in the behavior of the solvent on the carbohydrate surface, we explore residence times, rotational correlation functions, local solvent occupancy numbers, and diffusivities. We find that due to the differences in secondary structure water residence times are longer and translational and rotational dynamics are retarded when in contact with wide helices and branched sugars. In the case of extended helices and smaller oligosaccharides, water dynamics is faster and less hindered. This indicates that branching, the type of linkage between monomers, and the anomeric configuration all play a major role in determining the structure and dynamics of water on the surface of carbohydrates. 1. Introduction Carbohydrates are an important class of biomolecules that can be found free in the cytoplasm, decorating the surface of proteins and as parts of glycolipids. They are involved in cell adhesion, immune responses, protein trafficking, and signal processing. Understanding the structure and function of oli- gosaccharides is very important because these molecules are exquisite biological recognition agents. This uniqueness stems from the large number of chiral centers, the presence of branching, and their conformational variability. As an example, in diseased states, glycans are expressed differently and act as biomarkers in cancer, AIDS, and rheumatoid arthritis. 1-4 Dashnau et al. showed that the orientation of hydroxyl groups in axial and/or equatorial positions in aldohexopyranoses affects the water structuring in the first hydration shell. Aldohexopy- ranoses such as -glucose, -mannose, and -galactose have hydrophobic and hydrophilic hydration sites that play a role in aromatic interaction during carbohydrate-protein recognition. 5,6 Resonance two photon ionization and ultraviolet and infrared ion-dip spectroscopy of hydrated mono- and disaccharides have shown that water on the surface of carbohydrates helps these biomolecules achieve the conformations that are recognized by proteins; i.e., water is not a mute spectrator, but it actively participates in molecular recognition events 7 (see ref 7 and citations therein). In contrast with the large amount of informa- tion available for the role of water in contact with proteins and nucleic acids, no comprehensive study of the role of water on the surface of glycans is available. This is perhaps because of the topological complexity of sugars. It is therefore of crucial interest 8,9 to shed light on the water structure patterns and the diffusive dynamics on the surface of carbohydrates as a function of the key elements present in carbohydrates but absent in proteins such as branching, linkage pattern, and anomeric configuration. 10-12 Several experimental and theoretical studies have reported on the behavior of water at the interface with carbohydrates. Because of the complexity of these systems, most of these studies have been carried out on monosaccharides, disaccharides, or small model oligosaccharides. Kirchner and Woods have performed high-level quantum and molecular dynamics simula- tions and have shown that the conformational preferences for the 1 f 6 linkage are correctly reproduced only in the presence of water. 13 In exploring the role of water in the vicinity of simple monosaccharides such as R-D-glucopyranose and R-D-xylopy- ranose, Leroux et al. observed that the hydroxyl groups of the monosaccharide units align in such a way that they form hydrogen bonds with water instead of intramolecular hydrogen bonds. 14 Consistent with these computational predictions, recent depolarized Rayleigh scattering (DRS) and low-frequency Raman spectroscopy experiments performed on an aqueous glucose solution by Paolantioni et al. showed that a solute with the ability to have multiple hydrogen bonds disrupts the tetrahedral geometry of water in its first hydration shell. The loss of hydrogen bonding between water molecules is compen- sated by sugar-water hydrogen bonds, leading to the denser water environment around the sugar. 15 Lee et al. have shown that disaccharides such as sucrose and trehalose disrupt not only the tetrahedral geometry of water in their vicinity but also its translational and rotational dynamics. The dynamics on the surface of these dissaccha- rides is much slower than that on the surface of glucose. 16 Liu et al. have shown that R,R-trehalose imposes a strong anisotropic structuring of solvent that extends up to three solvation shells away from the sugar due to the formation of water mediated H-bonds. In computational studies, the self- diffusion coefficient of water in 87 µM R,R-trehalose solution was found to be 20% smaller than that in neat water simulations. 17 Englesen et al. studied the disaccharides maltose, sucrose, and trehalose in dilute aqueous solutions. The H-bonding pattern, the solvent residence times, and the solvent density around these disaccharides were observed in simulation to be different. Water surrounding trehalose displayed the longest residence times and was clearly more structured than in the vicinity of maltose and sucrose. 18,19 * To whom correspondence should be addressed. † Equal contributions. J. Phys. Chem. B 2009, 113, 11003–11015 11003 10.1021/jp904981v CCC: $40.75  2009 American Chemical Society Published on Web 07/09/2009