The Shape of Water

Understanding the Hydrophobic Effect

Although it seems quite abstract, the interactions of molecules and atoms on a microscopic level often have profound effects on the macroscopic properties of materials and life itself. BIOVIA Solvation Chemistry provides the scientific link to understand these connections between microscopic, molecular interactions and industry-relevant experimental properties of liquids such as solubilities, vapor pressures, partition coefficients and many more. Exemplarily, in this blog post, we want to discuss the anomalous hydrophobic effect of water on a molecular level and its implications on industrial applications and life on Earth in general.

The phenomenon known as the hydrophobic effect, originating from the Greek words ύδωρ (ydor, water) and φόβος (phobos, fear), describes how molecules that “fear” water, tend to come together to avoid interacting with it. This effect explains, why oil and water do not mix but form separate phases, or why some compounds are better soluble in water than others.

It is not just dry textbook knowledge, but a concept fundamental to the existence of life on our planet, serving as a key driver behind biological processes such as the formation of cells and the folding of proteins in active or inactive structures. Proteins are essential building blocks of our body, consisting of chains of amino acids. In many cases, proteins only function properly when they are in a certain folded state, a state that is typically achieved within a specific range of temperatures. Among other factors, increased temperatures can lead to the denaturation of proteins, rendering them inactive. This process can be easily observed when e.g. boiling an egg, where egg albumen turns into a white, opaque substance upon denaturation of proteins (mostly ovalbumin) above 60°C. Also at lower temperatures, proteins can undergo reversible unfolding, a process known as cold denaturation. This behavior is directly linked to the temperature sensitivity of the hydrophobic effect and in order to understand it, we need to investigate the hydrophobicity of water itself.

The Surprising Hydrophobicity of Water

It might sound surprising, but water itself can be hydrophobic, at least to a certain degree.

Water molecules can be arranged in specific shapes or clusters. Here, molecules are connected by, what chemists call, a hydrogen bond. In water, this special type of bond occurs between a hydrogen atom and the oxygen atom of another water molecule. Since water has two hydrogen atoms and each oxygen atom can accommodate two hydrogen-bonds, complex networks can be formed, that stabilize different shapes of water clusters. Interestingly, the surface of these clusters has different properties than the surface of individual water molecules.

The picture shows the charge density surface of water and a cluster of water molecules connected by hydrogen bonds, easily computed with BIOVIA Turbomole Blue and red areas denote surface areas with large positive or negative screening charge densities, whereas green areas denote small screening charge densities close to zero. Generally, as a direct consequence of Coulomb’s law, opposing charges attract each other. Therefore, compounds with large positive or negative screening charge densities, prefer to be in contact with compounds of matching opposing screening charge densities. Compounds with a lot of nonpolar surface area (green) prefer other nonpolar compounds. As can be seen, water itself has quite a lot of positive and negative screening charge densities (blue, red). In contrast to this, the cluster structure, has more neutral area with small screening charge densities. For this reason, these clusters partly behave like a nonpolar hydrophobic substance.

Therefore, at low temperatures, when these clusters become more stable, surface properties of water change. Water itself becomes increasingly hydrophobic and in turn, hydrophobic molecules become more soluble in water. When the temperature increases, the clusters break apart and the solubility of hydrophobic molecules decreases. At even higher temperatures, other thermodynamic effects increase the solubility again, leading to a minimum in solubility, that is typically found somewhere in the range of 20 to 80 °C, i.e. near room and body temperature.

The accurate assessment of this temperature dependence is of importance in many applications, ranging from the solubility of additives in oil processing or carbon capture applications, to computation of partition coefficients of active pharmaceutical ingredients.

Advancing Innovation with BIOVIA COSMOtherm

BIOVIA COSMOtherm allows to simulate the temperature dependent hydrophobic effect of water in an efficient and accurate way, as is shown in a recent publication by M. P. Andersson and M. Richter

The picture shows the temperature dependent solubility of hexanol and benzaldehyde in water. Since both compounds are rather hydrophobic, the solubility is generally quite small, but simulation and experiment clearly show a minimum of solubility around 290 K (17 °C) for benzaldehyde and 320 K (47 °C) for hexanol. With BIOVIA COSMOtherm the temperature dependent solubility of any compound in water can be easily assessed out-of-the-box, including anomalies like the hydrophobic effect of water. This ability allows performing large-scale in-silico screenings of molecular properties with high accuracy that complement experimental efforts, speed-up innovation and reduce time-to-market for our customers.

Learn more about BIOVIA COSMO RS.

References

1. Andersson, M.P. & Richter, M. (2024). Comment on: The shape of water – how cluster formation explains the hydrophobic effect. J. Mol. Liq., 409, 125465 https://doi.org/10.1016/j.molliq.2024.125465

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