The IA version is more stable toward the various typical chromatography solvents. However, is the resolution (column selectivity) affected by the immobilization process?
According to the information from Daicel, "... there may be some small selectivity differences between the immobilized and coated support. These effects may be positive or negative, but are unimportant when compared to the far greater stability of the CSP to solvents, and to the possible improvement of separations through the exploitation of the wide range of solvents that may be used with these columns".
What is "unimportant" for Daicel, might be important for you though; in practice, however, when employing any column with the chiral stationary phase to separate enantiomers, the trial and errors approach is what eventually people use regardless of the column type. No one can predict with complete certainty which column will work for a particular separation, but having a much wider choice of different solvents for a mobile phase is a big advantage of the columns with the immobilized chiral selector.
Yes, I am aware of what Daicel (and their vendors) write, and I agree that every separation requires individual treatment/development. However, even with hydrocarbon/IPA as the solvent you get quite a bit of polarity/solubility range, and we have learned how to work with the AD/AD-H stationary phases with success, at various scales. However, the IA descriptions so far are good, hence the title question, which translates into: are the results really as good as they might otherwise be, or is there a bit of a hype caused by the "immobilized separator phase" concept.
In many similar situations in my past there has been a trade-off, like it or not :) ...
You are right, there is always a trade-off. I think it is impossible to predict which column will be better for your particular case. Try both (or as many as available) if you can !
I should also add that we quite often found the hydrocarbon-IPA mixture to be quite limiting in what you can try, especially considering that the amount of IPA you can add to the mobile phase is limited as well (because of the column stability and increased mobile phase viscosity). Additionally, the solubility of your sample in hexane/IPA is sometimes an issue.
Regarding the use of Daicel brand chiral columns and clone columns sold by others (original supplier: Chiral Technologies), here are some comments that I hope you find useful.
As an expert in chiral method development (HPLC and SFC) I can tell you from a practical perspective (as someone who uses these column all of the time) that the covalently bound versions are much LESS effective at resolving and separating apart racemates in general. Yes, the covalently bound phase itself is much more stable. The selectivity lose resulting from the covalently bound coated phase has resulted in vastly different and inferior selectivity profiles for these columns. The coated phases, while more fragile, are far superior at resolving chiral compounds apart. This is a disappointing result, but one that demonstrates how critical it is to have the maximum amount of exposed selector available to the sample for them to work. Based on decades of testing these columns we can also confirm that you need to use the full size analytical columns (4.6 x 250mm), not shorter chiral columns. The shorter columns simply do not have enough material inside to provide the wide selectivity you need to separate many chiral racemates. IMHO, Use of shorter (sometimes called "scouting columns") is a huge waste of money and time as you will miss finding methods which resolve your samples due to their being an insufficient amount of the chiral selector available.
Additionally, with great caution and experience, the coated phases can be used at much higher pressures than indicated by the manufacturer AND more importantly, with a wide array of solvent combinations including RP mode too. Columns such as the OD, OJ, AD and AS love alcohols, but mixtures (esp 50/50 with Hexane or Heptane) do tend to shed some of the coating off which results in long equilibration times. One of the best general purpose mobile phases for these columns is pure ethanol! Many compounds can be separated with this simple isocratic solution. 2-Butanol, Methanol, IPA/HEX, also work very well too. Simple methods are always preferred. *One thing that most users of these columns (both the covalently bound and coated versions) do not always appreciate is that if abused, their selectivity changes (the column's, not the users!). The use of mobile phase additives (e.g. TFA, DEA, TEA...) often permanently changes the surface chemistry of the columns so label them as such and do not use them for neutral applications. If you are screening samples to find methods, then ideally you will have a set of three labeled versions of each column type for this purpose (Neutral, Basic and Acidic). Failure to analyze samples in this manner may result in missed "hits" and/or the development of methods which can not be reproduced.
Okay, William, thanks. Like you, I am very much focused on logical choices and accuracy in chiral chromatography applications. I originated this thread some time ago when I was pondering an IA (covalently bound) column, but ended up buying a big (500 x 50 mm) ChiralPak AD column, and that proved to be an excellent decision. This thing separates everything! :) . I am very gentle to it, and wash it thoroughly after use. I also agree with you about the better performance of longer chiral analytical columns vs the shorter versions. Thanks again.