A computer-simulation study of hydrophobic hydration of rare gases and of methane. I. Thermodynamic and structural properties

“…This is one of the characteristics of hydrophobic hydration. 17 Here, the first hydration shell is defined as the inside of the first minimum of the radial distribution of the O number density. For each of the 1-substituted adamantane derivatives, the actual hydration pattern in the first hydration shell is not just "hydrophobic," as will be discussed below.…”

Section: ¹3mentioning

confidence: 99%

Hydration of Adamantane Skeleton: Water Assembling around Amantadine and Halo-substituted Adamantanes

Doi

Aida

2013

Chemistry Letters

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We performed Monte Carlo simulations to reveal the water distributions around adamantane derivatives. Adamantane derivatives attract water molecules, and specific water distributions are observed around the skeleton. Perfluoroadamantane attracts water more than adamantane.Adamantane (C 10 H 16 ) is a highly symmetric tricyclic aliphatic hydrocarbon that is the simplest of the diamondoids, with a dipole moment of 0 D. Adamantane is known as a valuable building block for polymers for the enhancement of their thermal stability or improvement of their physical properties.1,2 Adamantyl-bearing compounds are also used in the field of medicinal chemistry and drug development, and some of them are in clinical use.3 The adamantyl group is used to modify the water solubility and lipophilicity of an original compound that may be highly water soluble or poorly soluble. Through the incorporation of an adamantyl group into the structure, the membrane solubility can be changed to a value that may be clinically useful.The octanol/water partition coefficient, log P, 4 is used as an index of the lipophilicity of a compound and is often used to evaluate the bioavailability of candidate molecules for therapy. A positive value of log P indicates a preference of the compound for the lipid phase, and a negative value shows a preference for water. It is thought that a compound should have a reasonable value of log P to be a good candidate for a new drug. The log P value of adamantane is positive, yet lower than that of decane, which is also composed of ten carbon atoms.5 This feature affords adamantylbearing compounds with more tractable solubility properties compared to decane-substituted analogs, which may be much less soluble in water.3 Amantadine (1-aminoadamantane) is known as a blocker of the M2 channel activity of the influenza A virus, 6 and also as an antagonist against Parkinson's disease. 7 The estimated log P values of amantadine 5 and adamantane 3 are 2.22 and 4.24, respectively, indicating that the ratio of the water solubility to the lipophilicity of amantadine is roughly 100 times larger than that of adamantane.Although the water solubility of adamantane is very low, it is still slightly "soluble" in water, which is related to hydrophobic hydration.8 Previously, 9 we showed that the water molecules in the first solvent shell around adamantane are oriented in such a way that the dipole direction of water is tangential to the skeleton surface, and the hydrogen-bonding network is formed among the water molecules in the first shell as well as between the first shell and the outer shell.For the development of new drugs and materials utilizing adamantyl groups, it is necessary to estimate how attractive the adamantane skeleton is for water. To this end, we have performed Monte Carlo (MC) simulations of some adamantane derivatives surrounded by water molecules, and show how the water distribution changes by a substituent group.For the MC simulations, the molecular mechanics (MM) parameters of the solutes were created as follo...

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“…Indeed, entropy is expected to be the driving force behind most biochemical processes, ranging from protein folding and ligand/protein binding, [15][16][17] to DNA transformations and recognition 18 and hydrophobic effects. 19,20 In particular, solubility and therefore miscibility of molecules in organic liquids may be dominated by changes in entropy, [21][22][23] making accurate measures of the standard molar entropy critical to understanding solvation phenomena. We propose here a practical approach to obtain accurate thermodynamics from short MD trajectories, which we validate by predicting entropies and specific heats of 15 standard…”

Section: Introductionmentioning

confidence: 99%

Thermodynamics of liquids: standard molar entropies and heat capacities of common solvents from 2PT molecular dynamics

Pascal

Lin

Goddard

2011

Phys. Chem. Chem. Phys.

170

215

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We validate here the Two-Phase Thermodynamics (2PT) method for calculating the standard molar entropies and heat capacities of common liquids. In 2PT, the thermodynamics of the system is related to the total density of states (DoS), obtained from the Fourier Transform of the velocity autocorrelation function. For liquids this DoS is partitioned into a diffusional component modeled as diffusion of a hard sphere gas plus a solid component for which the DoS(u) -0 as u -0 as for a Debye solid. Thermodynamic observables are obtained by integrating the DoS with the appropriate weighting functions. In the 2PT method, two parameters are extracted from the DoS self-consistently to describe diffusional contributions: the fraction of diffusional modes, f, and DoS(0). This allows 2PT to be applied consistently and without re-parameterization to simulations of arbitrary liquids. We find that the absolute entropy of the liquid can be determined accurately from a single short MD trajectory (20 ps) after the system is equilibrated, making it orders of magnitude more efficient than commonly used perturbation and umbrella sampling methods. Here, we present the predicted standard molar entropies for fifteen common solvents evaluated from molecular dynamics simulations using the AMBER, GAFF, OPLS AA/L and Dreiding II forcefields. Overall, we find that all forcefields lead to good agreement with experimental and previous theoretical values for the entropy and very good agreement in the heat capacities. These results validate 2PT as a robust and efficient method for evaluating the thermodynamics of liquid phase systems. Indeed 2PT might provide a practical scheme to improve the intermolecular terms in forcefields by comparing directly to thermodynamic properties.

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A computer-simulation study of hydrophobic hydration of rare gases and of methane. I. Thermodynamic and structural properties

Cited by 162 publications

References 48 publications

CANCELLED Molecular dynamics simulations of noble gases in liquidwater: Solvati on structure, self-diffusion, and kinetic isotopeeffect

CANCELLED Molecular dynamics simulations of noble gases in liquidwater: Solvati on structure, self-diffusion, and kinetic isotopeeffect

Hydration of Adamantane Skeleton: Water Assembling around Amantadine and Halo-substituted Adamantanes

Thermodynamics of liquids: standard molar entropies and heat capacities of common solvents from 2PT molecular dynamics

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