Chromatography Forum

Why HPLC analytical columns are not available in Odd number of carbon atoms like C3, C5, C7 and only comes in even numbers of carbon atoms like C2, C8, C18 etc...

There's no reason in principal why odd-numbered carbon compounds could not be used to make HPLC columns.
I expect the reason they're not is biological. If you check, you'll find that there are very few fatty acids of biological origin with odd numbers of carbons, and most of the exceptions are short-chain fatty acids. If I recall my biochemistry correctly, this is because the biological pathways for synthesizing such acids involve addition of two-carbon moieties.
Since such acids and their metabolites represent the cheapest available source of linear carbon chains, it follows that only even-carbon-number HPLC columns would be available.

First RP column was a C18. Why? Just by accident. The modification reagent was availabel on the market, pure and not so expensive. It could be also C17, or C19. If you have a very good resolution on a C18, but a long runtime, you can do the separation on a C8 what will shorten the runtime by 50%. Some compounds are retarded very long on a C18 modified surface, that was the reason why C8, C4 and also C1 was developed. A lot was found by trial and error.

I have a Zorbax C3 column. The only time I would prefer it over a C4 is when recovery is an issue. Even then, hard to say how much it helps. For basic analytes, I would be silanol content has a greater impact on recovery than alkyl chain length...

I have a Zorbax C3 column. The only time I would prefer it over a C4 is when recovery is an issue. Even then, hard to say how much it helps. For basic analytes, I would be silanol content has a greater impact on recovery than alkyl chain length...

So, as per our discussion; the reason behind not having stationary phase of odd Carbon chain length in HPLC columns is merely of commercial availability and not of chromatographic application.

First RP column was a C18. Why? Just by accident. The modification reagent was availabel on the market, pure and not so expensive. It could be also C17, or C19. If you have a very good resolution on a C18, but a long runtime, you can do the separation on a C8 what will shorten the runtime by 50%. Some compounds are retarded very long on a C18 modified surface, that was the reason why C8, C4 and also C1 was developed. A lot was found by trial and error.

So, as per our discussion; the reason behind not having stationary phase of odd Carbon chain length in HPLC columns is merely of commercial availability and not of chromatographic application.

Shantaram,

I will provide what I hope is a slightly different perspective on your question and suggest how you can use the few available odd-numbered phases, when they might be of benefit.

Historically, the primary reason for the vast number of even-numbered bonded phases is the availability of the even-numbered (especialy C18) bonding silanes, since you can't make a bonded phase column unless the reagents are available. (I think the C18 was available form other fields and was the first silane to be readily available to people making bonded phases.) The silane chemistry was easiest with the even-numbered silanes, the creators wanted something that used partioning rather than adsorbtion, and availability drove the market place from then.

Once you get past some chain length, I suggest about C6 or C8, the difference between successive bonded phases becomes less and less. Stating it another way, the differences in partitioning between a C12 and a C14 is much less different than the differences between a C4 and a C6. Since we are trying to maximize differences in selectivity for our analytes, the minor differences become only important in special circumstances or molecular families, such as the C12 phase or the C30 phase, which in my memory is special for Vitamin D type separations. If you search the vendor information on the specialty phases, you will find guidance on the types of compounds that they find separate best on the less common phases, which may lead you to try new analytes for which YOU see a logical connection, even if the vendor did not think of them.

The last factor in my mind is less recognized but critical in only a few classes of separations. This again goes back to the differences in partitioning bahavior of the bonded phase. If we think of the bonded phase as a homologous series, we are aware that the behavior of a homologous series is most consistent between the higher members of the series, in parallel with the discussion mentioned above. [Look at the boiling points of even and odd hydrocarbons, or the hexane miscibility of a homologous series of alcohols, from C1 up.] The C1 phase is an anomolus "reversed phase" sorbent, just as methanol is an anomolous alcohol. The level of alkane shielding of the silica surface is very small and the phase does not behave like a normal reversed-phase column, but with less partitioning or retention. It may have very good uses, but chromatographers have not identiied and shared the uses much. The higher odd-numbered phases C3, C5, etc) become less anomalous but still have different properties and partition differently than their even counterparts, in parallel with the hydrocarbon BP analogy.

Remembering that the goal of the separation process is to maximize the selectivity between our analytes and the bonded phase, the differences will become most marked when the analyte is itself more sensitive to the phase differences or shows markedly different partitioning bahavior between the phases. I encountered this in evaluation of the separation of the impurities of nitroglycerin. We were able to explore the separation on a variety of phases from C18 down and found that moving to a C5 created unique (and very positive) selectivity differences that were not achievable on either C4 or C6 phases. If you are workiing with small molecules with "odd-number" character, then explore the C5 versus C6 to see if you get improved separation. I would have tried a C3 phase at the time, but could not find a commercial supplier at the time. C5 is currently available from at least two vendors and continues to have a steady, if small, number of special applications where it works better than the corresponding C4 or C6.

I may have provided more informaiton than you needed, but I hope I have stimulated your thinking and that of others to try some of the shorter chain phases (incuding phenyl or C6phenyl) to see how much different they can be.

Good hunting!