Posts Tagged ‘zwitterion’

The dipole moments of highly polar molecules: glycine zwitterion.

Saturday, December 24th, 2016

The previous posts produced discussion about the dipole moments of highly polar molecules. Here to produce some reference points for further discussion I look at the dipole moment of glycine, the classic zwitterion (an internal ion-pair).

Dielectric relaxation studies of glycine–water mixtures yield values that range from 15.7D[1] to 11.9D[2] although these have to be derived using various approximations and assumptions for up to 4 independent Debye processes. Before proceeding to calculations, I looked at the properties of ionized amino acids in the solid state, using the following search query for the Cambridge structure database (CSD). 

The distance measures hydrogen bonds to the carboxylate oxygens and the torsion their orientation. The O…H hydrogen bond distances vary between 1.7-1.85Ã…, which are short. The orientation of the hydrogen bond can be to the in-plane oxygen “σ-lone pair” (torsion 0 or 180°) and also an out-of-plane ~Ï€ form (torsion ~60-90°).

In aqueous solution, it is normally assumed that glycine sustains five such strong H-bonds (three to the H3N+ group and two[3] to the carboxylate anion), forming a polarised “salt bridge” across the ion-pair. Two model types were subjected to calculation using ωB97XD/Def2-TZVPP/SCRF=water. Aqueous glycine without any added explicit water molecules yields a dipole moment of 12.9D (DOI: 10.14469/hpc/2000), which is within the range noted above.‡

The solvated form is shown below, in one specific conformation of the three studied (ωB97XD/Def2-TZVPP/SCRF=water). The calculated O…H hydrogen bond lengths fall into the range revealed from crystal structures. The calculated dipole moments range from 12.6 (DOI: 10.14469/hpc/2007), 15.3 (DOI: 10.14469/hpc/2006) and 14.9D (DOI: 10.14469/hpc/2005), which is a modest increase over the model with no explicit water molecules. The actual dipole is of course a Boltzmann average over these and other as yet unexplored conformations, as well as other values for the number of water molecules.

Given the difficulties in interpreting the dipole moment of a complex Debye system such as hydrated glycine, the agreement between the limited range of solvated models and the measured values seems reasonable, and provides at least some measure of “calibration” for the polar molecules commented on previously.

‡Optimized with the solvent field on. If a vacuum model is used, the proton transfers from the N to the O.

References

  1. M.W. Aaron, and E.H. Grant, "Dielectric relaxation of glycine in water", Transactions of the Faraday Society, vol. 59, pp. 85, 1963. https://doi.org/10.1039/tf9635900085
  2. T. Sato, R. Buchner, Å. Fernandez, A. Chiba, and W. Kunz, "Dielectric relaxation spectroscopy of aqueous amino acid solutions: dynamics and interactions in aqueous glycine", Journal of Molecular Liquids, vol. 117, pp. 93-98, 2005. https://doi.org/10.1016/j.molliq.2004.08.001
  3. T. Shikata, "Dielectric Relaxation Behavior of Glycine Betaine in Aqueous Solution", The Journal of Physical Chemistry A, vol. 106, pp. 7664-7670, 2002. https://doi.org/10.1021/jp020957j

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Some fun with no-go areas of chemistry: cyclobutadiene.

Sunday, September 18th, 2011

Organic chemistry has some no-go areas, where few molecules dare venture. One of them is described by a concept known as anti-aromaticity. Whereas aromatic molecules are favoured species, their anti-equivalent is avoided. I previously illustrated this (Hückel rule) with cyclopropenium anion. Now I take a look at cyclobutadiene, for which the π-system is said to be iso-electronic (where two electrons in a double bond have replaced the carbanion lone pair).

Geometric distortions available to square cyclobutadiene

The scheme above starts with a square geometry for the cyclobutadiene. This is strongly anti-aromatic, and the molecule will strive to reduce this by indulging in a geometrical distortion. The conventional distortive mechanism is into an R or rectangular geometry, where two of the C-C bonds get shorter and two longer. The trouble with this mode is that is does not actually prevent the π-π overlaps which made it anti-aromatic in the first place, it just reduces the effect. Thus rectangular cyclobutadiene is still a very very reactive and unstable molecule. So here I suggest another distortion mode, shown above as the ZW, or zwitterionic form. This converts the species into a combination of an allylic carbocation and a secondary carbanion. The latter would be expected to pyramidalize, thus reducing those pesky π-π overlaps. I am unaware of such a ZW-mode ever having been previously explored.

Any student of organic chemistry will be very familiar with how to go about stabilising either a carbocation or a carbanion. We need to do this, since another guiding tenet of organic chemistry is to try to avoid charge separation whenever possible (another almost no-go area). I am going to pull a surprise by evaluating the following model for this post.

Stabilization model for cyclobutadiene

  1. Firstly, two methyl groups have been placed at the carbocationic centres to stabilise the positive charge. Tertiary carbocations are of course well known to be more stable than secondary ones (I should state that methoxy groups in the same position would stabilise even more, but that is for another post).
  2. The carbanion could itself be stabilised with an electron withdrawing substituent (say CN) but here I am going to stabilise it with hydrogen bonding to a guanidinium cation. This has just the right shape to form two unusual hydrogen bonds from the N-H to either of the carbanionic lone pairs we might wish to promote (dashed lines above).
  3. Finally, we are going to simulate this in water as a solvent, in order to stabilize the zwitterion. One zwitterion that DOES form is of course that from the amino acid glycine, but it only forms when placed in water (and life as we know it would not be possible if amino acids did not do this).
The results are thus. The R distorted form does come out the most stable (ωB97XD/6-311G(d,p)/SCRF=water). An unsymmetrical ZW form (forming just one C…H-N hydrogen bond) is 11.2 kcal/mol higher in free energy, whilst a symmetrical form (as shown above, forming two C…H-N hydrogen bonds) is only 8.5 kcal/mol higher in free energy. It turns out that the R form of the 1,3-dimethylcyclobutadiene is itself stabilised by hydrogen bonding to the guanidinium cation. These hydrogen bonds form to the centre of the shortened C=C alkene bonds rather than being directed at an atom (Ï€-facial bonding). In contrast, the ZW forms sustain hydrogen bonds directly to the carbons. To explore these unusual features, click on any of the three thumbnails below.
R form ZW-u form ZW-s form

CBD R form. Click for 3D

Zwitterionic form. Click for 3D.

Zwitterionic symmetric form. Click for 3D

Where have the electrons gone in e.g. the symmetric ZW system? An ELF analysis tells us. The two ELF basins labelled with green arrows contain 1.2 electrons each. The basins corresponding to the 4-ring are labelled with magenta arrows. Put simply, 2.4 electrons have fled the ring, and associated themselves instead with the N-H…C hydrogen bonds. By removing ~2 electrons from an anti-aromatic ring, one converts it into an aromatic one (4n => 4n+2)!

ELF analysis. Click for 3D

We have learned that the highly reactive alkene bonds in R-distorted cyclobutadiene can be reasonable hydrogen bond donors, but that an alternative distortion into a zwitterionic form can be stabilised by forming an even stronger hydrogen bond to the forming carbanion. A symmetric form of this latter is unusual, since it still sustains four equal C-C bond lengths, but anti-aromaticity is now avoided by pyramidalising two of the carbons and hydrogen bonding to them both. As I noted earlier, these isomers of cyclobutadiene have not hitherto been proposed, and they do seem good candidates for experimental investigations.

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