Hydrogen bonding — again, again

I’ve been thinking about hydrogen bonding ever since my senior thesis in 1959. Although its’ role in the protein alpha helix had been known since ’51 and in the DNA double helix since ’53, little did we realize at the time just how important it would be for the workings of the cell. So I was lucky Dr. Schleyer put me at an IR spectrometer and had me make a bunch of compounds, to look for hydrogen bonding of OH, NH and SH to the pi electrons of the benzene ring. I had to make a few of them, which involved getting a (CH2)n chain between the benzene ring and the hydrogen donor. Just imagine the benzene as the body of a scorpion and the (CH2) groups as the length of the tail.  The SH compounds were particularly nasty, and people would look at their shoes when I’d walk into the eating club. Naturally the college yearbook screwed things up and titled my thesis “Studies in Hydrogen Bombing”, to which my parents’ friends would say — he looks like such a nice young man, why was he doing that?

At any rate I’m going to talk about a recent paper [ Science vol. 371 pp. 160 – 164 ’21 ] on the nature of the bond in the F H F – anion.  It’s going to be pretty hard core stuff with relatively little explanatory material. You’ve either been previously exposed to this stuff or you haven’t.  So this post is for the cognoscenti.  Hold on, it’s going to be wild ride.

In conventional hydrogen bonds, the donor (D) atom is separated from the Acceptor atom (A) by 2.7 Angstroms or more, and the hydrogen nucleus is found closer to A where the potential energy minimum is found.

So it looks like this D – H . .. A

The D-H bond isn’t normal, but is stretched  and weakened.  This means that it takes less energy to stretch it meaning that it absorbs infrared radiation at a lower frequency (higher wavelength) — red shift if you will. 

Such is what we were looking for and we found it comparing 

Benzene (CH2)n OH vibrations to butanol, pentanol, hexanol, etc etc. cyclohexane (CH2)n OH.

As the D – A distance shrinks there is ultimately a flat bottomed single well potential, where H becomes a confined particle (but still delocalized) betwen D and A.

The vibrations of protons in hydrogen bonds deviate markedly from the classic quantum harmonic oscillator beloved by physicists.  Here the energy levels on solving the classic H psi = E psi equation of quantum mechanics are evenly spaced (see Lancaster & Blundell “Quantum Field Theory” p. 20.)

However in real molecules, as you ascend the vibrational ladder, conventional hydrogen bonds show a decrease in the difference between energy levels (positive anharmonicity).  By contrast, when proton confinement dictates the potential shape in short hydrogen bonds (when D and A are close together, mimicking the particle in a box model in quantum mechanics) the spacing between states increases (negative anharmonicity).

The present work shows that in FHF- the proton motion is superharmonic — https://en.wikipedia.org/wiki/Subharmonic_function — which they don’t describe very well. 

When the F F distance gets below 2.4 Angstroms, covalent bonding starts to become a notable contributor to the short hydrogen bond, and the authors actually have evidence that there is overlap in FHF- between the 3s orbital of H and the 2 Pz orbitals of the donor and the acceptor atoms, yielding a stabilization of the resulting molecular orbital. 

Is that cool or what.  The bond sits right on the borderland between a covalent bond and a hydrogen bond, taking on aspects of both. 

 

Good to see Charlie’s still at it

Good to see Charlie Perrin is still pumping out papers, and interesting ones to boot.  I knew him in grad school.  He’s got to be over 80.

This one —J. Am. Chem. Soc. 141, 4103 (2019) –is about something that any undergraduate organic chemist can understand (if not the techniques he used) — keto/enol tautomerism, in which the hydrogen bounces between two oxygens, so that, given N molecules in solution, N/2  have the hydrogen bound to one oxygen and N/2 have it bound to the other.

No so in what Charlie found — a compound where the hydrogen is smack dab in the middle.  Some fancy NMR techniques were used to show this.

Hydrogen bonds are extremely subtle (which is why we don’t understand water as well as we might).  Due to the small mass of the proton it isn’t appropriate to treat the proton in hydrogen bonded systems as a classical particle.  When quantum mechanics enters, aspects such as zero point motion, quantum delocalization and tunneling come into play.  These are called quantum nuclear effects (aka Ubbelohde effects).

Was I the last to find out?

Quick ! Can you form a hydrogen bond from a carbon hybridized sp3 to an oxygen atom?

I didn’t think so, but you can. This, in spite of reading about proteins for over half a century. [ Proc. Natl. Acad. Sci. vol. 111 pp. E888 – E895 ’14 ] describes this (along with lots of references backing up the statements which follow) to such bonds forming between the transmembrane segments of membrane proteins (estimated to be 30% of all our proteins).

Whether or not they contribute to membrane stability isn’t known. Consider the alpha carbon of an amino acid. It is adjacent to a carbonyl group of an amide (electron hungry, but less so than a pure carbonyl because of resonance) and the nitrogen atom of an amide (slightly more electronegative than carbon, and probably more electron hungry because it loses part of its lone pair to resonance).

They are usually found from the alpha carbon of glycine on one helix to the carbonyl of an adjacent transmembrane helix. Glycine zippers (e.g. the G X X X G motif) have long been known in transmembrane helices. Since glycine is the smallest amino acid, having them on the same side of the helix was thought to be a way to pack adjacent helices together.

What would you consider good evidence for such a bond? Spectroscopy of model compounds with deuterium for the alpha hydrogen would be one way (it’s been done). The best evidence would be a shortened distance between the hydrogen and the carbonyl and this has been found as well.

Humbling ! !