From Earth to the Cosmos: How Hydrogen Bonds Shape Life

They used to call me Dr. Hydrogen Bond. Back in the day, my research focused on studying the intermolecular interactions in biological molecules, like DNA and proteins. Of all the non-covalent interactions, such as π-π stacking, anion-π, and the like, the strongest one that holds the structure of DNA together is the good ol’ hydrogen bond. Now, it turns out, hydrogen bonds might just be the secret ingredient of life. I’m talking beyond Earth, beyond humans, beyond anything we can even imagine. In previous stories, we’ve learned that hydrogen forms 380.000 years after the Big Bang, and that molecular hydrogen, H2, is the quintessential playground for quantum chemistry. But today, we’re going to explore a whole new side of this little atom – its role in biological systems. Get ready, this is going to be a long journey from the immensity of stars to the tiny quantum effects of proton transfer. Let’s go.

Hydrogen Bond cartoon - Hydrogen bonds and Life
This is the hydrogen bond picture I taped to the door of my office at the Freie Universität Berlin.

Is There Life Out There?

Picture this: You’re standing on the beach craning your neck to catch a glimpse of the Orion belt. Betelgeuse is blazing away up there like a cosmic nightlight, and the Pleiades are chilling in the Taurus constellation. You’re staring at those little pinpricks of light, and a thought pops into your head: could there be life in all that vastness?

What if there’s a planet, orbiting one of those distant stars, where the trees are blue, the seas are yellow, and a bunch of friendly bug-eyed giants live their lives? And what if they’re looking back at you, at our own sun, a mere speck of light in the expanse of space, wondering too if there’s any life beyond their own world?

I know there are folks like Enrico Fermi who might argue that we’re alone in the universe (it is a joke, man – check this). But let me hit you with a fact: we’ve already discovered thousands of exoplanets. That’s right! To be specific: 5322 at the time of writing. Knowing this, Frank Drake must have departed happy.

But hold onto your hats, because here’s where it gets even more jaw-dropping. According to data from Kepler and other planet-hunting telescopes, astronomers estimate there could be anywhere from 300 million to 40 billion Earth-like worlds only in the Milky Way.

My virtual friend Sean M. Carroll might contend that it doesn’t matter how frequent exoplanets are, if the probability of life is very, very, very small – in other words, if one of the coefficients in the Drake equation is negligible – we wouldn’t have extraterrestrial life, let alone friendly bug-eyed giants.

But I chose to dream.

Can you imagine what they look like? Do they do physics? Do they love? Do they have two eyes, DNA, proteins, hydrogen bonds?

Drake equation - Hydrogen bonds and Life
© NASA – Exoplanet Exploration – The Drake Equation

The Laws of Chemistry Are Universal

Before we dig into the role of hydrogen bonds for life here, there, and everywhere, let me clarify one thing, so we’re on the same page: Chemistry doesn’t care about where you are in the universe. Whether you’re taking it easy here on Earth, partying in Andromeda, or exploring some far-off corner of the galaxy, no matter where you go, under the right conditions, a spark will always ignite a passionate exothermic love between hydrogen and oxygen to give water.

Chemistry is universal.

To be nitpicky and more accurate: the properties of chemical bonds are the same everywhere in the universe.

Take a moment to let that sink in. The fact that something as fundamental as chemistry is the same no matter where you are in the cosmos has some pretty deep philosophical implications. But hey, we’ll save that for another time.

The fact that chemistry is universal is the foundation of Vladilo and Hassanali’s scientific article: Hydrogen Bonds and Life in the Universe. Let’s dig into their work to understand together what chemistry terrestrial and extraterrestrial living things need to survive.

Hydrogen bonds in DNA nucleobases - Hydrogen bonds and Life
The nucleobases of DNA form the double helix via relatively strong hydrogen bonds: Adenine binds Thymine and Guanine binds Cytosine. For the latter, using quantum chemical calculations, I’ve estimated the hydrogen bond strength to be 22.47 kcal/mol (vs. experimental value of 21.00 kcal/mol). Image Credit: Cell Biology By The Numbers.

Hydrogen Bonds Shape Life: Genetic and Catalytic Molecular Machines

We tend to think of life as these complex beings like plants and animals, but if we really break it down, it is all about chemistry. Life is the constant interplay of molecular machines that allow living things to exist and defeat entropy, at least for a little while.

These molecular machines primarily perform genetic and catalytic tasks.

Genetic tasks are all about sharing information. This information is encoded in a specific sequence of chemical groups, which allows it to be passed down from one generation to the next. Here on Earth, we use nucleic acids like RNA and DNA to do this.

Catalytic tasks revolve around lowering the energy barriers of chemical reactions. In other words, these molecular machines, just like proteins here on Earth, make reactions happen at temperatures that are suitable for life. This is key because it allows molecules to be synthesized or recycled, which is essential for life to keep on trucking.

I’ve always thought of proteins as the unsung heroes of the molecular world. These little workers run around tirelessly to keep life going, but they also know how to take a break and enjoy the simple things.

Like a walk on a microtubule:

Kinesin protein - Hydrogen bonds and Life
Meet the kinesin protein, walking along microtubule filaments, powered by the hydrolysis of ATP. Image Credit – The Inner Life of the Cell

Hydrogen Bonds and the Chemical Hierarchy of Life

Our genetic and catalytic molecular machines can take all sorts of wild forms and shapes – You’ve got your linear, your ring-shaped, and your funky 3D structures. But here’s the thing – for these molecular machines to do their job properly, they need a hierarchical chemical bond structure:

– Intra-chain structural bonds – To be structurally stable
Covalent bonds will keep the machines holding together atoms by atoms. Covalent bonds are strong, directional, and have a high dissociation energy. They are difficult to break – you do not want your molecular machine to fall apart under a little bit of stress.

Inter-chain pairing interactions – To hold parts of the molecular machines together
To achieve this, directional, weaker than covalent, non-invasive bonds are required. Of all non-covalent interactions, hydrogen bonding is the most promising candidate. It combines electrostatic with contributions from covalent and van der Waals forces, making it ideal for chain pairing.

Interactions for intermolecular recognition – To talk to one another
For these molecular machines to interact, van der Waals forces are too weak and lack directionality. Another candidate may be halogen bonding, but the limited cosmic abundance of halogen elements relative to hydrogen (between 10−6.5 to 10−10.5) makes it less favorable. Hydrogen bonds are best suited for molecular machines to talk to one another.

Human apoptosome (PDB code: 3J2T) – Rocking protein structure

Hydrogen Bonds: The Secret Ingredient of Life

Finally, we get to the point. Hydrogen bonds.

Hydrogen bonds aren’t your typical bond. No, no, no. This is a primarily electrostatic force of attraction between a hydrogen and an electronegative atom bearing a lone pair of electrons, such as nitrogen, oxygen, fluorine. It can occur between separate molecules or among parts of the same molecule. It’s responsible for holding materials together, like paper and felted wool, and for causing wet sheets of paper to stick together. Hydrogen bonds contribute significantly to the stability and function of proteins, our catalytics molecular machines, and nucleic acids, our genetic molecular machines.

The strength of a hydrogen bond depends on a few bits and bobs – the geometry, the environment, and the specific donor and acceptor atoms. It can roughly range from 0.5 to 40 kcal/mol. This makes it (much) stronger than van der Waals interactions, but weaker than covalent bonds.

If you’re not already convinced, let me give you a few more reasons to consider hydrogen bonds as the secret ingredient of life on Earth and beyond:

  • Hydrogen bonds are extremely versatile and can provide a spectrum of strengths and lengths with a change of molecular environment.
  • The strength of hydrogen bonds can easily be fine-tuned by solvent effects.
  • Hydrogen bonding is sensitive to nuclear quantum effects due to the low mass of the proton. This makes the so-called proton transfer accessible. Proton transfer would be a whole other book, but here it suffices to say that: it is central to biological processes.
  • Hydrogen bonding is essential for a variety of quantum-based molecular mechanism such as charge transfer, which lay the foundation for building the fluctuating, dynamical systems that characterize life.

Hydrogen Bonds and The Molecular Medium of Life

Now that we know a bit more about hydrogen bonds, let’s consider the following. Our molecular machines performing genetic and catalytic tasks cannot survive in the void of space. They need a friendly molecular medium to thrive.

Such a molecular medium provides a structural support that helps our little workers get where they need to go. And once they’re there, the molecular medium needs to keep them in place so they can do their job.

Now, the best kind of medium is something that’s pretty fluid and made of small molecules. It has to be easy for the molecular machines to move around and big molecules would just get in the way.

So, what makes a molecule suitable for the role of medium of life?

Again, it all comes down (or almost) to hydrogen-bonding capabilities.

Molecular structures of water, methane, and ammonia – Generated with QuantistryLab

Take methane, for example. It’s got four wimpy donors (C-H) but no acceptors, so it can only sustain weak hydrogen bonds. This raises the question of whether a biochemistry based on liquid methane is even feasible. Sorry Saturn lovers – it won’t be easy living on the ring planet.

Ammonia is a bit of a mixed bag – it has three donors (N-H) and only one acceptors (the lone electron pair on the nitrogen atom, :N). This allows ammonia to create a groovy 1D hydrogen-bond network: N-HN-HN-H. Now, the bad news is, if you try to connect a biomolecule to one of the NH3, you would totally crash the hydrogen-bond party and limit critical chemical phenomena, such as cooperativity and polarization. Hypothetical biochemistries based on liquid ammonia would be a bit shaky.

And then, my friends, we have water: the queen of the hydrogen bond realm. With its dual hydrogen-bond donor-acceptor powers (the oxygen atom has two lone electron pairs), water reigns supreme as the ultimate molecular medium of life. Its 3D hydrogen-bond network serves as a roadmap for directional links with biomolecules. Plus, it can mediate molecular recognition of chemical groups, at least in life as we know it on Earth. Besides: water is everywhere

The bottom line?

To explore the potential for life beyond our planet, it’s vital to dig into the nitty-gritty of the constituent molecules that make up a molecular medium. In this regard, these hydrogen-bonding criteria come in handy as they provide a valuable guide for predicting suitable candidates capable of sustaining life.

Hydrogen Bonds in water - Hydrogen bonds and Life
3D hydrogen-bond network in water. Fun fact: this is the background image of my Linkedin profile – I’ve created it with VMD

A final personal touch

Now, you might be thinking: “But Arturo, the universe is vast beyond comprehension. How likely is it that life exists in more than one place?”

To that, I say, “Have faith, my friend.”

I believe life has emerged numerous times, in countless corners of this wacky cosmos. And when we finally make contact with our friendly bug-eyed pals from across the galaxy, we’ll be blown away by Nature’s ingenuity.

Nature can be unpredictable. And yet, she’s not without her quirks and patterns.

One such pattern, as we have learned from Vladilo and Hassanali’s work, may be in the ability, the necessity even, of forming hydrogen bonds. From the structure of DNA to the functioning of proteins and the unique properties of water, these tiny, versatile hydrogen bonds may be one essential ingredient that holds the key to the potential for life beyond our terrestrial home.

Yes, I am a fan. They didn’t call me Dr. Hydrogen Bond for nothing.

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Arturo Robertazzi - Me, my room. My books.