Is there a "hydrophobic effect"?

I was interested to find this 1979 PNAS paper, by Hildebrand (a chemist, I think an eminent one), criticizing the notion of “hydrophobic” molecules and moieties. Sample quotation (not selected very carefully, but there is less than a page in whole thing):

The loss of entropy when an alkane gas dissolves in water has been explained by the formation of what has been facetiously called an ‘iceberg’ around the solute molecules. Any such assumption is not tenable: the viscocities of water and carbon tetrachloride at 25C are nearly the same … If the molecules of methane were encased in ‘icebergs’ they could not diffuse 0.6 as rapidly in water as in CCl4.

It’s a followup to a 1968 article in J. Phys. Chem., I haven’t looked at that one.

The hydrophobic effect is confidently invoked in biology textbooks: to explain cell membranes, and to describe tertiary structure of proteins.

The paper has a footnote:

The publication costs of this article were defrayed in part by a page charge payment. The article must therefore be hereby marked ‘advertisement’ in accordance with 18 USC S1734 solely to indicate this fact.

Hildebrand was close to 100 years old in 1979.

Here’s a link to the paper in case anyone is curious.

In looking into this I found this paper which is very interesting! Both for the history and discussion of solvation shells.

the current view is that the degree of water ordering in the first solvation shell around a nonpolar solute is much smaller than the degree of ordering in ice. Walter Kauzmann noted that the entropy of freezing of water is 5.3 cal K-1 mol-1,whereas inserting a nonpolar solute into water costs about 20 cal K-1 mol-1, which amounts to an entropy of only 1 cal K-1 mol-1 for each of the approximately 20 waters surrounding a small nonpolar solute. He concluded that water in solvation shells around nonpolar solutes is less ordered, and different than, ice. But so far, few experiments have been able to elucidate the amount of water structuring in solvation shells

The paper then goes on to talk about how this isn’t quite accurate and that other factors besides hydrogen bonding need to be considered. I find topics like this are very poorly conveyed in biology – few students (and teachers!) have a great conception of the interplay of biological systems at a molecular level.

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Few have a great conception of the interplay of biological systems at a molecular level

I too don’t understand the world of molecules. And there are basic non-biological things, like temperature or pH, that I don’t know how to think of. A fundamental concept is “equilibrium” which is hard to pin down.

Thanks for linking to the subject-line article, here is a reciprocal link to “A view of the hydrophobic effect,” that you quoted. And (partly to experiment with the forum) I’m going to try to paste a figure from the article:


which might illustrate something about both passages. The caption is:

“Iceberg” model for the large heat capacity of transfer of nonpolar solutes into water. (A) At room temperature the water molecules surrounding a nonpolar solute adopt only a few orientations (low entropy) to avoid wasting hydrogen bonds. Most water configurations are fully hydrogen bonded (low energy). (B) In hot water, more conformations become accessible (higher entropy), but at the cost of breaking hydrogen bonds (high energy).

I’d recommend reading David S. Goodsell’s The Machinery of Life as an introductory text. He’s an amazing artist and I think communicates the rapidly moving soup that is the cell quite well.

Some passages I have highlighted:

On average, though, it will only take about a second for those two molecules to bump into each other at least once. This is truly remarkable: this means that any molecule in a typical bacterial cell, during its chaotic journey through the cell, will encounter almost every other molecule in a matter of seconds. So as you are looking at the illustrations in this book, remember that static images give only a single snapshot of this teeming molecular world. (pg 6)

Cells are amazingly crowded, typically with 25–35% of the space filled by large molecules such as proteins and nucleic acids. As you might imagine, these molecules get in the way of each other. This has two seemingly opposite affects on the function of molecules. First, larger molecules have more trouble diffusing through the cellular environment, since they are constantly blocked by neighbors. This slows the motion of each molecule, so it takes longer for two molecules to find each other. However, countering this effect, crowded environments tend to favor the association of molecules once they have found each other. Since they are constantly crowded together by neighboring molecules, they spend more time next to each other and are far more likely to find the proper orientation for interaction. This property tends to favor association of molecules into big complexes in crowded environments, rather than filling the cell with lots of separate molecules. (pg 25)

Cells live in a world of thick, viscous water, almost oblivious to gravity. When moving from place to place, most of their energy is spent trying to push through the gooey liquid, not in lifting their weight up from the ground. For example, Howard Berg presented a surprising observation in his 1976 lecture ‘‘Life at Low Reynolds Number.’’ Escherichia coli cells swim using long corkscrew-shaped flagella, which act like propellers. The cells push their way through the water, typically moving about 30 mm/s (30 mm is 10 or 15 times the length of the cell). But, when they stop turning the flagella, they don’t keep coasting along the way a ship or submarine would. Instead, the surrounding water instantly stops them in less than the diameter of a water molecule. (pg 65)

In a typical cell, 20–40% of newly synthesized proteins will be destroyed within an hour (pg 110)

I tracked down Goodsell this week. I’m grateful for the recommendation, it’s wonderful.