Exploitation of the enantioselectivity space of coated amylose tris(3,5-dimethylphenylcarbamate) in mixtures of 2-propanol and acetonitrile.

Chiral stationary phases (CSPs) with coated amylose tris(3,5-dimethylphenylcarbamate) (ADMPC) selector have long been recognized for their excellent chiral recognition ability in liquid chromatography. The conformational versatility behind this feature is the source of their known hysteretic behavior, which has been previously observed in polar organic (PO) mode eluents containing 2-propanol (IPA). Mixtures of IPA and acetonitrile (MeCN), a typical PO mode eluent system, have not been examined in this aspect yet, even though hysteresis is promising for finding unique unexplored enantioselectivities. Not only was the hysteresis detectable on ADMPC using mixtures of IPA and MeCN, but it was the typical behavior in a diverse set of test compounds. The difference in the retention time of the same analyte under conditions which only differed in the eluent history on the column can go up to 20-fold. The assumed hindered conformational changes of the selector were reflected in retention drift at certain eluent compositions. On the two sides of the transitions, distinct, useful states of the selector were detected. A series of IPA - MeCN compositions with defined pretreatment was selected and recommended as an extension of the preliminary, first choice method screening set that used only alcohols. The incorporation of a solvent possessing substantially different characteristics enhances the potential in practical applications, while keeping the technical simplicity. Stability and robustness of the additional states of the CSP were characterized. The examined columns of different brands shared the observed behavior. Kinetic stability of a column state is adequate for successful application. The evaluated states of ADMPC provide multiple enantiorecognition potential by using mixtures of IPA and MeCN also considering the pretreatment of the column. Unprecedented double and triple elution order reversals along the composition range supported the versatility of the available states. Our findings further enhance the usefulness of ADMPC-containing CSPs. We provide instructions for the application of the widespread chiral selector in common eluent mixtures to avoid pitfalls regarding reproducibility and robustness.

A protocol to replace dedication to either normal phase or polar organic mode for chiral stationary phases containing amylose tris(3,5-dimethylphenylcarbamate).

Alteration of the enantiorecognition ability of polysaccharide-based chiral columns in the shipping normal phase (NP) eluent after exposition to polar organic (PO) mode eluents can be conceived as an incomplete hysteresis cycle. Non-standard solvents provide a solution to overcome this issue with immobilized stationary phases, but a procedure was missing so far to regenerate coated stationary phases from the altered state. Recent results with alcohol mixtures within the PO mode showed that an appropriate order of standard solvents may also be suitable to complete hysteresis. Using an analogous approach, a simple protocol was established to regenerate the original NP retentions on various stationary phases containing amylose tris(3,5-dimethylphenylcarbamate) (ADMPC) chiral selector after the change induced by flushing with 2-propanol or ethanol. The members of a chemically diverse compound set indicated that alterations in retentions and selectivities using different brands and types of ADMPC-based stationary phases can be quite different, but the recovery of the original state was very good for all of them. The proposed protocol eliminates the need of the costly dedication of a chiral column with ADMPC selector to either NP or PO mode. Furthermore, the limits of the alcohol content in the mobile phase compositions where the system is free of hysteresis were determined.

Experimental and computational study of BF3-catalyzed transformations of ortho-(pivaloylaminomethyl)benzaldehydes: an unexpected difference from TFA catalysis.

Previously, we have studied the trifluoroacetic acid (TFA)-catalyzed rearrangements of unsubstituted and alkoxy-substituted ortho-(pivaloylaminomethyl)benzaldehydes and revealed the formation of rearranged, regioisomeric aldehydes along with dimer-like products ("TFA dimers"). In the present study, related reactions of ortho-(pivaloylaminomethyl)benzaldehydes are described with the difference that boron trifluoride diethyl etherate (BF3·OEt2) is used as the catalyst. Although in these reactions the formation of the same "TFA dimers" can be observed after a couple of hours reaction time, during further stirring these are transformed into a new dimer-like keto compound ("BF3 dimer") that gradually becomes the main product. Apart from this, an oxoindene-type by-product is also formed. The new products are characterized by detailed NMR studies and two of them also by single-crystal X-ray diffraction. DFT calculations support the mechanism proposed for the transformations and explain the differences observed in the product distribution.

Utilization of the hysteresis phenomenon for chiral high-performance liquid chromatographic method selection in polar organic mode.

Polysaccharide-based chiral stationary phases (CSPs) are outstandingly suitable to play a key role in chiral HPLC method selection strategies, since they provide high success rates. One reason for this ability is that they adopt a diversity of higher order structures in various eluents, resulting in versatile chiral environments. A potential to extend this versatility further was expected and examined in the present study, based on the recently discovered hysteretic behavior of a widely used chiral selector (CS), amylose tris(3,5-dimethylphenylcarbamate). The hindered transitions of its structure, which are behind the history dependence of its separation ability, were used as a tool to identify distinct states of the chiral selector in order to exploit an extended selectivity space. The identification was carried out using a single diagnostic compound, as opposed to the common approach where testing a library of compounds is required. Eluent mixtures consisting of 2-propanol and either methanol or ethanol were scrutinized in terms of stability and robustness of the observed retentions. The solvent mixtures that were eligible for practical application in these respects were used to construct a screening sequence, including identical compositions combined with different column pretreatment. The gain achievable by using the proposed sequence was then evaluated using 15 enantiomer pairs with focus on resolution, enantiomer elution order and chemoselectivity.

Hysteresis of retention and enantioselectivity on amylose tris(3,5-dimethylphenylcarbamate) chiral stationary phases in mixtures of 2-propanol and methanol.

Seemingly identical chromatographic conditions result in drastically different enantioseparations on amylose tris(3,5-dimethylphenylcarbamate) (ADMPC) columns in mixtures of 2-propanol and methanol. Selectivities of structurally diverse enantiomer pairs depend on the direction from which the composition of the eluent is approached. An alteration in the structure of the chiral stationary phase (CSP) is the only realistic reason behind the dissimilar selectivities in the same eluent. History-dependent retention and recognition mechanisms are indicated by van't Hoff plots and even by a reversal of the enantiomer elution order. The most notable observation is the easy access to markedly different states of the CSP in the same solvent mixture by a short pretreatment with 2-propanol in one case and with methanol in the other, while the transition between the two states is hindered enough to ensure long-term stability for both. Repeatability strongly depends on the composition of the eluent and it is key to utilization and also to rationalization of the phenomenon. From a theoretical point of view, this so-called hysteretic behavior poses another challenge to consider when modeling chiral interactions.