Water molecules in the narrow cylindrical pore of a (6,6) carbon nanotube form single-file chains with their dipoles collectively oriented either up or down along the tube axis. We study the interaction of such water chains with homogeneous electric fields for finite closed and infinite periodically replicated tubes. By evaluating the grand-canonical partition function term-by-term, we show that homogeneous electric fields favor the filling of previously empty nanotubes with water from the bulk phase. A two-state description of the collective water dipole orientation in the nanotube provides an excellent approximation for the dependence of the water-chain polarization and the filling equilibrium on the electric field. The energy and entropy contributions to the free energy of filling the nanotube were determined from the temperature dependence of the occupancy probabilities. We find that the energy of transfer depends sensitively on the water-tube interaction potential, and that the entropy of one-dimensionally ordered water chains is comparable to that of bulk water. We also discuss implications for proton transfer reactions in biology.

We explore the structure and thermodynamics of water clusters confined in nonpolar cavities. By calculating the grand-canonical partition function term by term, we show that small nonpolar cavities can be filled at equilibrium with highly structured water clusters. The structural and thermodynamic properties of these encapsulated water clusters are similar to those observed experimentally in the gas phase. Water filling is highly sensitive to the size of the cavity and the strength of the interactions with the cavity wall. Water penetration into pores can thus be modulated by small changes in the polarity and structure of the cavity. Implications on water penetration into proteins are discussed.grand canonical ensemble ͉ hydrophobic interactions ͉ fullerenes ͉ free energy of transfer ͉ configurational-specific heat H ydrophobic literally means water repelling. So are nonpolar cavities hydrophobic, i.e., devoid of water? Answering this question profoundly impacts our understanding of the role of water in protein function. Although some weakly polar cavities created inside proteins by mutations were indeed found to be empty (1), recent studies using crystallography (2-4), NMR (5, 6), and simulations (7) show that water molecules may be present at least transiently. Evidence for a functional role of water in the nonpolar interior of proteins is also accumulating. Water has been implicated as the mediator for proton transfer through the nonpolar interior channels of the proton pumps cytochrome c oxidase (8) and bacteriorhodopsin (9), and the monooxygenase cytochrome P450 (10, 11), with water detected in trapped intermediates (9, 10), but empty channels in crystal structures of the resting enzymes.Water permeation of carbon nanotubes (12-14) and the dewetting of hydrophobic surfaces (15-17) have been studied recently, but the thermodynamic driving forces for water filling nonpolar cavities remain poorly understood. The loss of hydrogen-bond energy should render the transfer of a single water molecule into a nonpolar environment energetically unfavorable (18). Moreover, multiple water molecules confined into narrow spaces will form highly ordered structures, resulting in unfavorable entropies of transfer. However, mounting experimental evidence for water penetrating into weakly polar cavities in the protein interior (2-6, 9, 10, 19) suggests that this simple reasoning must be incomplete.To investigate the hydration of nonpolar cavities, we reverse the extensively studied process of nonpolar solvation in water (20, 21) and study instead the more poorly understood transfer of water into a nonpolar environment (18). We demonstrate that water can fill nonpolar cavities at ambient conditions, with entropy and ''weak'' van der Waals interactions playing a critical role, and that the strong water-hydrogen-bond interactions lead to the formation of unique water clusters similar in topology to the gas-phase structures detected spectroscopically (22-27).We study the stability and structure of water in nonpolar cavities of varyi...