Mining Chromatographic Enantioseparation Data Using Matched Molecular Pair Analysis

Abstract

Abstract:We apply matched molecular pair (MMP) analysis to data from ChirBase, which contains literature reports of chromatographic enantioseparations. For the 19 chiral stationary phases we examined, we were able to identify 289 sets of pairs where there is a statistically significant and consistent difference in enantioseparation due to a small chemical change. In many cases these changes highlight enantioselectivity differences between pairs or small families of closely related molecules that have for many years been used to probe the mechanisms of chromatographic chiral recognition; for example, the comparison of N-H vs. N-Me analytes to determine the criticality of an N-H hydrogen bond in chiral molecular recognition. In other cases, statistically significant MMPs surfaced by the analysis are less familiar or somewhat puzzling, sparking a need to generate and test hypotheses to more fully understand. Consequently, mining of appropriate datasets using MMP analysis provides an important new approach for studying and understanding the process of chromatographic enantioseparation.

Turbocharging Matched Molecular Pair Analysis: Optimizing the Identification and Analysis of Pairs

“…Others have shown the value of resampling to obtain a better description of the distribution of Δ values, and the SD has been emphasized as a useful statistic previously . Elsewhere it has been asserted that the SD should decrease as more pairs are added, such that the mean value of Δ divided by the SD would be a useful statistic to emphasize influential, consistent sets of pairs, but this is in contrast to our findings on a much larger data set (Figure ), which show that the SD increases or remains the same as pairs are added. , The importance of a careful consideration of the contributors to the SD, including experimental variation and data set heterogeneity, has also been highlighted, and such considerations are doubtless at play in our observations …”

“…4 Elsewhere, it has been asserted that the SD should decrease as more pairs are added such that the mean value of ∆ divided by SD would be a useful statistic to emphasize influential, consistent sets of pairs but this is in contrast to our findings on a much larger dataset Page 20 of 34 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 ( Figure 9) which see the SD increase or remain the same as pairs are added. 48,49 The importance of a careful consideration of the contributors to SD, including experimental variation and dataset heterogeneity, has also been highlighted and such considerations are doubtless at play in our observations. 50 context.…”

Matched Molecular Pair Analysis on Large Melting Point Datasets: A Big Data Perspective

“…The assembled dataset was used to calculate matched molecular pairs (MMPs). The matched molecular pair technique has been used in the analysis of many properties . In the case of this study, the transformed part of the molecule has no more than 10 atoms, and fewer atoms than the main scaffold of the molecule .…”

Enantiomeric Mixtures in Natural Product Chemistry: Separation and Absolute Configuration Assignment

“…Hence, finding the CSP at the correct elution mode for measuring e.r . is not a trivial task and, in spite of the knowledge that some classes of compounds are well resolved in a given CSP [ 39 , 49 ], the procedure is mainly based on a trial and error approach, and requires systematic search [ 50 , 51 ]. The use of ChirBase, a database that has more than 200,000 records from the literature is helpful [ 50 , 51 ]; but so far, there is no universal predictive model for selecting a CSP for a given enantiomeric mixture [ 51 , 52 , 53 ].…”