The "like interacts with like" rule of thumb works well when there are polar and non-polar molecules that are mobile (liquid-liquid extraction, membrane vs cytosol, questions of solubility).

  • Polar molecules interact with polar molecules rather than with non-polar molecules because the interactions are stronger.
  • Non-polar molecules "hang out" with non-polar molecules because that way, they don't disrupt the stronger interactions between polar molecules.

The latter is sometimes called the hydrophobic effect when water is present as a solvent. Self-assembly of detergents into micelles, folding of proteins, formation of lipid bilayers are all rationalized by "like interacts with like".

In a previous post, the question was asked why polar molecules have lower retention times than non-polar molecules when running gas chromatography with a non-polar column. One of the answers invoked "like interacts with like" as rationalization.

I have two questions:

  1. Do polar molecules have lower retention times than non-polar molecules on a non-polar GC column (to make it comparable, the molecules should have similar boiling points)?
  2. Does the "like interacts with like" rule of thumb apply to gas chromatography, given that there are no interactions in the gas phase and there is no hydrophobic effect in the stationary phase (i.e. the non-polar stationary phase interacting with the polar analyte would not disrupt any polar-polar interactions)?

In the post I referred to, the question started with a convincing statement:

I remembering reading that the interaction between a polar molecule and non-polar molecule is stronger than the interaction between two non-polar molecules.

This would suggest non-polar molecules have the weaker interaction and elute first, even on a non-polar column.

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    $\begingroup$ I think it's helpful here to consider what the stationary phase looks like for GC. $\endgroup$ – Zhe Jan 10 '19 at 17:07
  • $\begingroup$ For open tubular columns, I found wall-coated (WCOT), support-coated (SCOT) and porous layer (PLOT). For WCOT and SCOT, the stationary phase is a liquid (at least at operating temperature), which I did not know. $\endgroup$ – Karsten Theis Jan 10 '19 at 17:22
  • $\begingroup$ Also important is the polarity of the stationary phase, right? $\endgroup$ – Zhe Jan 10 '19 at 18:27
  • $\begingroup$ Yes, the question is about a non-polar stationary phase. Like with like would suggest that non-polar analytes stick more, while priniciples of IMF suggest that polar analytes stick more (induced dipole: dipole forces vs. dispersion forces). $\endgroup$ – Karsten Theis Jan 14 '19 at 14:30
  • $\begingroup$ "I remembering reading that the interaction between a polar molecule and non-polar molecule is stronger than the interaction between two non-polar molecules." You seem to be basing your post on this statement, which looks incorrect to me. By definition, polar molecules will interact with each other via their dipoles. This means that for any non-polar molecule to interact with a polar molecule, it must be strong enough to break the polar-polar interaction. It's not, because dipole-dipole are stronger IMF. That's why non-polar will interact with each other and leave the polars to themselves. $\endgroup$ – Blaise Jan 17 '19 at 17:05

I respectfully disagree with @Quip_Boy. If you want to separate compounds based on their vapor pressures, you can just carry out a distillation, which is also based on a gradient in temperatures along the column, whereas a capillary column used in GC is kept at the same temperature all the way in an oven. So there must be something else in the process.

You are quite right citing "like interacts with like", but interaction between 2 non-polar molecules is more than escaping polar molecules (hydrophobic effect). Non-polar molecules can form an attraction because of the Van der Waals force. The Van der Waals force is weak but it can add up a carbon-carbon chain (with the necessary hydrogen atoms, of course) just like with a zipper(1).

(1) i.e. each "hook" on one side of the zipper forms a small attraction to a "hook" on the other side, but altogether, the whole zipper is very strong.

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  • $\begingroup$ I agree that non-polar molecules interact via Van der Waals force (temporary dipole). However, a polar molecule would interact with a non-polar molecule via dipole:induced dipole interactions, which are supposedly stronger. $\endgroup$ – Karsten Theis Jan 16 '19 at 15:22

For GC, the most significant factor affecting separation resolution is differences in vapor pressures, boiling points if you will, between analytes. While column phase selection, oven temperature programming, detector type and temperature, and other factors will have an effect on the efficiency of separation, IMFs are not generally important for the majority of separations. The "like interacts with like" principle does apply to GC such that in the case you describe, nonpolar analytes will spend more time interacting with the stationary phase while polar will have little to nearly zero interaction and elute first. The separation of the various nonpolar compounds will, holding all the other column conditions constant, "boil down" to varying vapor pressures.

Edited for clarification:

To begin, I think it beneficial to keep in mind that the question you pose is sufficiently clear we are dealing with polar analytes using a non-polar GC column. Regarding proprietary column selection, temperature programming, and the choice of various other method parameters, these things are necessarily important in an efficient and successful separation (generally called method development) but they do not do much to answer the principle questions asked about whether 1) polar compounds are less retained on a non-polar column, and 2) does "like with like" apply to GC. To that end, I will again address these two primary questions and then try to clarify another issue brought into the discussion that does not bear directly on answering the questions as asked.

The most direct answer to your first question is simply, yes, polar analytes do have shorter retention times than non-polar compounds when using a non-polar column because polar compounds have little interaction (partitioning) with the column's stationary phase. The polar molecules of interest have little affinity for the non-polar stationary phase, i.e. hydrophobicity. Had it been a polar stationary phase column then IMFs would be significant. You mention making things comparable by considering compounds of similar boiling points which is precisely why a ramping temperature program is most beneficial for efficiently resolving such a separation. This too, however, is a method development consideration and thus an example of the applied science of gas chromatography taking advantage of pure science principles.

Considering your second question, this, too, is most directly answered with another yes - the "like with like" concept does apply here, but as you point out, this is a rule of thumb, and as such, a conceptual aid not strict principle. The qualification about hydrophobic effects in the stationary phase you make in your wording of the question actually explains, as well as I could, what is happening. Also, as @Blaise points out, the statement with which you end your original question referencing a previous user (I [remember] reading that the interaction between a polar molecule and non-polar molecule is stronger than the interaction between two non-polar molecules.), is in error: the interaction between polar and non-polar molecules is not stronger than between two non-polar molecules. Perhaps what this person meant is the interaction between two polar molecules is stronger, and relatively much stronger, than interactions between two non-polars.

With regard to your request I clarify why IMFs are not generally important (in this case), it must be remembered that the analytes in GC are not in "pure liquid form" but, rather, in the gas phase and they are completely surrounded by inert carrier gas molecules - little chance for IMFs to be of significance. The polar molecules to be resolved do not spend a significant time partitioning into the stationary phase so they cannot form immiscible droplets as you brought up.

With respect to @SteffX, your question is about GC specifically and is not a question of what is the best separation method to use. I take your question to be about using GC (on small sample sizes, right or wrong on my part) to effect a separation for analytical purposes, not as a preparatory separation like distillation. Also, your original question(s) are with regard to gas chromatography in general and make no reference to column packing, bore, or length (other than being of a non-polar stationary phase) and I tried to answer in general terms. However, since capillary GC columns were brought into the discussion, I think it deserves clarifying that, in fact, most capillary column separations are not isothermal. Without going too deeply into something you were not asking about, it should be noted that isothermal temperature separations are a simpler and therefore preferred method development as long as you have good analyte resolution; the more common practice is to program a temperature gradient to resolve similar boiling point compounds - part of your original Question 1. Lastly, Van der Waals force(s), a subject for much definitional discussion in its own right, have little importance to your polar analytes at GC conditions, and are moot almost before the sample hits the injector.

I hope this has been helpful and, in my opinion, I think you already have a good understanding of this.

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  • $\begingroup$ Could you clarify why you say IMFs are not generally important? I'm confused because you also say the differences in vapor pressure are important, but these depend on the strength of IMFs in the pure liquid form of the analytes. Also, it seems to me that column phase selection, which you say is important, would affect IMFs between the stationary phase and the analyte. $\endgroup$ – Karsten Theis Jan 16 '19 at 15:19
  • $\begingroup$ I tried to post a reply here but I was too wordy for this section. I am editing my original answer to reflect your request. Still new here - Thanks. $\endgroup$ – Quip Boy Jan 18 '19 at 5:08

The following is based on comparing retention indices, using two main sources:

  1. Practical retention index models of OV-101, DB-1, DB-5, and DB-Wax for flavor and fragrance compounds, DOI: 10.1016/j.lwt.2007.07.007
  2. Linear retention indices in gas chromatographic analysis: a review; DOI: 10.1002/ffj.1887

Difference in retention are due to differences in interaction with the stationary phase:

When considering the average gas linear velocity as a constant throughout an analysis, the solutes should spend an identical period of time in the mobile phase to elute from the column. To this extent, only the differences in the time spent in the stationary phase are responsible for the solutes distinct retention time values.[2]

The two properties of the solute that determine time spent in the stationary phase are vapor pressure (of the solute in the stationary phase) and activity:

In general, the affinity of a solute for the stationary phase depends on its vapour pressure and the activity coefficient of the solute in that phase.[2]

To summarize, the relevant interactions are between the analyte and the stationary phase. There are no analyte:analyte interactions (not in the vapor phase and not while in solution with the stationary phase). If the stationary phase is non-polar, the retention time will be determined by non-polar:non-polar interactions in the case of a non-polar analyte, and by polar:non-polar interactions in the case of a polar analyte. The question is which of these interactions is stronger.

It is difficult to find two analytes, one polar and the other non-polar, with all other "things" being equal, to address the first part of question. Looking at retention index models based on boiling point and octanol:water partition alone1, you can compare analytes with the same boiling point and with different polarities (based on the partition coefficient).

For polar columns like DB-WAX, it is very clear that polar analytes have longer retention times, i.e. bind more tightly compared to non-polar analytes with the same boiling point.

For non-polar columns like DB-5, there is very little dependence of retention times on polarity, and the model is non-linear (highest retention time for medium polarity, lower retention times for high or low polarity).

One example of actual data is a comparison between eugenol (polar) and tetradecane (non-polar). Eugenol has a boiling point of 254 deg Celsius and a pKow of 2.73, while tetradecane has a similar boiling point of 253 deg Celsius and a pKow of 7.22. The retention index for eugenol is 1360, while that for tetradecane by definition is 1400 (14 carbon atoms). So the more polar eugenol has a slightly lower retention index compare to the non-polar tetradecane on the non-polar column. (Data from 1).

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