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As a young scientist, I was told by my instructors that water was the “universal solvent.” Then, a few years later, that statement got a contingency — apparently, this was mostly just the case in life science. For a vast number of chemicals that are hydrophobic, water is more or less the enemy. I have seen my inorganic, organometallic colleagues working in glove boxes trying to keep out water as much as possible.

When I began to submerge myself in biochemistry studies, I was amazed at how important water is to the function of biological molecules.  For example, proteins often fold so that their hydrophobic interiors are buried away from the contents of the cell, which are water-based. These very structures dictate the function of those proteins and can lead to enzyme active sites, vast intracellular architectures and compartmentalization.

So, we have the intricate workings of our cells, organs and tissues able to produce sight, hearing, motion, thought, language and all our critical activities. Each of these activities can be traced back, at least in part, to proteins whose functions are directly affected by their structure, which, in turn, is influenced by water.

I can think of a time or two that relates the power of water and its importance in biology and biochemistry to my own life.

The final step

During the first moments in my research group in graduate school, I was converting alpha amino acids (the type found in nature) to beta-3-amino acids. At that time, foldamers (non-natural folded oligomers) were a burgeoning field. My first tasks were to synthesize a library of beta-amino acids using the alpha versions as starting materials, then use these as building blocks in a long chain to make artificial peptides with nonnatural backbones. Each synthesis required two steps: the Arndt-Eistert homologation and the Wolff rearrangement.

Danielle Guarracino

Guarracino and her grad school labmates used specialized “funky glassware” like this to generate potentially explosive diazomethane gas that they then had to let condense and drip into their activated compound.

As a first-year graduate student, I felt like a big shot performing these named reactions and creating compounds that had never been studied before. The coolest, and most dangerous, part was when we generated diazomethane (note: potentially explosive) gas as part of the process using specialized funky glassware, let it condense and add, dropwise, to our activated compound, and hoped the blast shield could contain any mishaps. We never had a single explosion, even when building construction work was shaking the floors.

How does this relate to water? In the final step of this multistep reaction (shown in the picture), a single molecule of water had the most important role — to make the new C-terminus of the new beta-amino acid and get it in its final format that gave it its amino acid characteristics (mechanism shown under the full reaction, provided). A highly reactive carbene intermediate primed the reaction so that water could slide in and make the molecule a stable beta amino acid ready for use in a peptide.

At this ending step, all the potentially explosive steps, then the separations and purifications culminated as we added this one, simple molecule to bring it home — finishing days of work.

We were so careful through the preceding steps to use dry glassware and try to keep water away; all our work would have been quenched by any significant quantity of water. But in this last stage, toss in some water and we’re finished.

At times, it felt a bit anticlimactic to end my syntheses this way, but such is the power of the water molecule. Indispensable, even as a single-molecule synthetic agent.

Danielle Guarracino

The two steps required by each synthesis Danielle Guarracino performed as a first-year graduate student: the Arndt-Eistert homologation and the Wolff rearrangement.

A contributing factor

Water is important to my life as a biochemistry professor in another, more personal way. In my sixth year of teaching, I was approaching the last week of biochemistry class for the spring semester, ready for the student group presentations about oxidative phosphorylation, when I was suddenly taken ill with a stuck kidney stone.

/Wikimedia Common

For Guarracino, a kidney stone like this one reinforced the importance of drinking water.

After hospitalization, surgery and a stent, I learned my lesson about proper hydration. While there are many reasons stones can form, I knew that, at least in part, dehydration contributed. I am generally bad about keeping up drinking water, and I had recently begun exercising again without increasing any fluid intake.

Did this impact my professional life as a biochemistry professor? Yes. And I have spoken to my classes about the benefits of water ever since.

Whether I’m using water in the lab for a critical synthetic step or drinking it before going into the lab to perform said critical step, water has such universal importance.

Not bad for a bent tetrahedral molecule with extensive hydrogen bonding.