Amorphous Phases, and the Fragile to Strong Transition

Water undergoes a “fragile to strong” dynamic crossover. The definition of “fragile” was introduced by C. Austen Angell; it concerns the viscosity of a liquid, as it approaches the glass transition. “Strong” liquids show Arrhenius behavior for viscosity and have an extended transition, while “fragile” liquids show non-Arrhenius behavior, and a relatively rapid transition to the glassy state. Water is one of the molecules showing such behavior.

There are also changes in the types of vibrational excitations that the different phases can support. At the lowest temperatures, the vibrations are largely local, while at higher temperatures longer wavelength vibrations, stretching over more of the crystal, become important. Proteins may not function below about 225 K, as the water is effectively too cold to move; the water exists in a glassy state, so the proteins are also trapped. Around 228 K, a network of hydrogen bonds can form, allowing longer wavelength vibrations; the low temperature localized vibrations may be similar to those in confined water, where the water is also restricted to local connections, but no long range network is possible.

It is not entirely clear that this is a phase transition, as it may be partly out of equilibrium, and the free energy change is not necessarily zero at the crossover. However, it does occur at a fixed temperature, so it does behave like a phase transition in that respect. The transition has been studied by simulations and modeling, by differential scattering calorimetry, X-ray diffraction, by NMR, and by neutron scattering; while these are not the only studies on this phenomenon, these are sufficient to demonstrate that it exists. It is sometimes important in biological systems, and is likely to be found in confined water, rather than bulk. Not all forms of confinement are biological, but there is no doubt that it is important in determining the vibrations in biological molecules, which do not function at temperatures below the transition.

Chapter 15: Epologue

Chapter 15: Epilogue

We began with an extremely brief history of how science reached its present point. Over the next 13 chapters, we reviewed the physics and chemistry of water in its interactions with proteins, nucleic acids, and lipids. Water turns out to be ubiquitous in any biological system, validating, at least in part, the comment from the Star Trek alien with which we began, calling humans “ugly bags of mostly water.” Animals and plants and fungi and bacteria all have internal surfaces that are in contact with water; prokaryotes also have external surfaces that are in contact with water. The functions of proteins are now known to include water as a part of their structure, or, if structure is defined differently, part of the immediate environment of the molecules, which helps determine the function of the protein; proteins that transport protons are critical for several functions, and proton transport almost always requires water as a part of the path.

We have gone through some of the physics of hydration of ions, as well as hydration of the larger species of biomolecules. We discussed some common themes in the way water interacts with hydrophilic and hydrophobic solutes. In the Conclusions, we summarized the ways in which it was possible to understand these interactions, as of 2023. However, we made it clear that this could not be the end of the story. The Conclusions not only tried to pull together the strands of the story as it stands now, but made it clear that the story is but half told—if that.

The questions we will be able to answer as we make further advances in both experimental and theoretical/computational techniques will show how the water participates in essentially all biological functions. Sometimes this involves actual chemical bonds, or their formation. Often, considering hydrogen bonds, it may be more like partial bonds. The hydrogen bond networks formed by water are a fairly unique property. Although water is not the only substance with hydrogen bonds, water appears to be alone in being able to both donate and accept two hydrogen bonds, leading to networks that other substances cannot produce. This has profound effects on the actions of biomolecules. Right now, we can make a rather good estimate of the strength and other properties of hydrogen bonds; however, we see that hydrogen bonds vary considerably, and that in turn makes the properties of the proteins that are responsible for most biological functions, as well as the properties of nucleic acids, difficult to compute or simulate very accurately. Networks of hydrogen bonds are only beginning to be investigated at a serious level.