The Effects of Hydrogen-Bonding Environment on the Polarization and Electronic Properties of Water Molecules M. Devereux and P. L. A. Popelier* Manchester Interdisciplinary Biocentre, UniVersity of Manchester, 131 Princess Street, Manchester M1 7DN, Great Britain ReceiVed: NoVember 29, 2006 Adequate representation of the interactions that take place between water molecules has long been a goal of force field design. A full understanding of how the molecular charge distribution of water is altered by adjacent water molecules and by the hydrogen-bonding environment is a vital step toward achieving this task. For this purpose we generated ab initio electron densities of pure water clusters and hydrated serine and tyrosine. Quantum chemical topology enabled the study of a well-defined water molecule inside these clusters, by means of its volume, energy, and multipole moments. Intra- and intermolecular charge transfer was monitored and related to the polarization of water in hydrogen-bonded networks. Our analysis affords a way to define different types of water molecules in clusters. 1. Introduction Quantifying to what extent molecules are affected by their local environment in gas-phase clusters or in condensed matter is important. For example, it has long been known that polarization and cooperative effects are needed when modeling the bulk properties of liquid water. 1,2 Much effort has been invested in the accurate determination of cluster geometries and in trying to determine the physical properties of water molecules within these clusters. Water is central to the design of many force fields, but if we wish to accurately describe the interactions between individual water molecules or with the molecules they hydrate, we must account for polarization of their electron density. Exploring the properties of molecules within clusters inevi- tably calls for a decision on how to partition a given system into its constituent molecules. Although increasingly sophisti- cated experiments and accurate quantum chemical calculations provide converging information 3-5 on molecular clusters and liquids, this convergence does not address the issue of partition- ing. This is the reason why, for example, the dipole moment of a single water molecule in pure liquid water remains a matter of debate. 6 Values can vary as much as 2.3 to 3.1 D, 7 while experimental 8 and ab initio calculations 6,9 closely agree on 1.855 D for a single water’s dipole moment in the gas phase. The ability to identify and characterize individual atoms in water clusters allows us to see changes in the charge density taking place and to use this information to reveal how the charge is redistributed throughout the molecule. Demarcation of individual molecules that are part of larger systems is not only essential to obtain insight but also matters in the design of force fields. For example, the simple point charge water force field 10 deliberately overestimates the dipole moment of a single water because it is widely accepted that its dipole moment is enhanced when in a liquid water environment. In terms of insight, there is growing evidence that proximal water in the vicinity of biological macromolecules behaves differently compared to the bulk solvent. For example, an inelastic incoherent neutron scattering study 11 suggested that one to four layers of water molecules around DNA comprise the interfacial water signal detected. In their study 12 on water molecules in clusters and ice Ih, Batista et al. employed a variety of partitioning methods to compute molecular multipole moments. The chosen methods all started from the electron density and included the molecular equivalent of the Hirshfeld partitioning technique, 13 two types of Voronoi cells, and the theory of atoms in molecules, 14-16 which we hereafter refer 17 to as quantum chemical topology (QCT). Although these methods all depart from the electron density (for a brief review of alternative nonelectron density methods, see ref 18), they provide quantitatively very different results; the magnitude of the molecular dipole moment in ice Ih ranges between 2.3 and 3.1 D. However, they all agree on the qualitative result of the molecular dipole moment in the ring hexamer being smaller than that in ice Ih. To their analysis the authors added an induction model, a common method for constructing molecular multipoles in a condensed-phase envi- ronment, using polarizabilities of the isolated molecule. Un- questionably, the success of this method depends on the (dubious) assumption that the gas-phase polarizability does not significantly differ from that in the cluster or condensed phase. 19 The current study also focuses on water clusters (but not on ice), on their own and in the presence of the amino acid serine or tyrosine. We limit the analysis to the QCT partitioning method but extend it to more than the dipole moment. The question we ask is not about the convergence of the dipole moment with cluster size but how the charge density is affected by the presence of other molecules and whether we can identify “types” of water molecule with characteristic atomic and molecular properties. This is in line with previous work where we computed, for the first time, atom types 20,21 occurring in the set of all natural amino acids (and smaller derived molecules). This work culminated in recommendations for the design or modification of protein force fields. Here we focus on molecular and atomic properties, in particular, the volume, charge, dipole, and quadrupole moments. Supermolecular * To whom correspondence should be addressed. E-mail: pla@manchester.ac.uk. 1536 J. Phys. Chem. A 2007, 111, 1536-1544 10.1021/jp067922u CCC: $37.00 © 2007 American Chemical Society Published on Web 02/06/2007