Whelks

Fig. 5. The stmcture of the chiral selector in the Whelk-O-1 chiral stationary phase.

Recently, two examples of the separation of enantiomers using CCC have been published (Fig. 1-2). The complete enantiomeric separation of commercial d,l-kynurenine (2) with bovine serum albumin (BSA) as a chiral selector in an aqueous-aqueous polymer phase system was achieved within 3.5 h [128]. Moreover, the chiral resolution of 100 mg of an estrogen receptor partial agonist (7-DMO, 3) was performed using a sulfated (3-cyclodextrin [129, 130], while previous attempts with unsubstituted cyclodextrin were not successful [124]. The same authors described the partial resolution of a glucose-6-phosphatase inhibitor (4) with a Whelk-0 derivative as chiral selector (5) [129]. 

This technique has been used to track conceivable enantiophores of the Whelk-0 1 CSP ((3R,4S)-4-(3,5-dinitrobenzamido)-3-[3-(dimethylsilyloxy)propyl ]-l,2,3,4-tetrahydrophenanthrene) which was prepared in 1992 by Pirkle and Welch [22]. As seen in Fig. 4-7, a Whelk enantiophore should contain two ore more of the following molecular properties ... 

The four queries were examined against a list of samples tested on Whelk CSP that constitutes our search domain. Search results are summarized in Table 4-3. Of the 616 3D structures in this database list, 370 fit at least one of the query (one sample may fit more than one query) and 335 are given as resolved according to chromatographic data or information reported in the field comment. Query 2 retrieved the largest number of compounds with a high percentage of resolved samples in the hit list. While the number of hits retrieved with Query 1 is lower, this query provided a similar proportion of resolved samples (93 %). 

Table 4-3. Search results from CHIRBASE 3D with enantiophore queries built from the Whelk CSP.

Fig. 4-12. Similarity maps of Crownpak CR, Whelk-O 1 and Chiralcel OD. L luminance value of the image.

To demonstrate the excellent correlation (r- = 0.99) between the luminance of the images and molecular diversity, we plotted the luminance values of the map versus the mean similarity values of data sets (Fig. 4-13). From this plot, a scoring scheme for the classification of CSPs from specific to broad application range can be well established Crownpak CR > Pirkle DNBPG > Whelk > Chiralpak AD > Chiralcel OD. 

Whelk-0 1 and Pirkle DNBPG have appreciable differences in terms of application range. This is not surprising since Pirkle DNBPG often requires a prior derivatization of solutes to achieve a separation. This also confirms the atypical character of Whelk-0 1 compared to other Pirkle-like CSPs. 

A quick inspection of similarity maps in Fig. 4-14, allows one to see at once that Chiralcel OD and Whelk-0 1 molecule sets contain notable structural differences, whereas AGP and OVM data sets contain much more structurally related molecules. 

The purpose of this study is only intended to illustrate and evaluate the decision tree approach for CSP prediction using as attributes the 166 molecular keys publicly available in ISIS. This assay was carried out a CHIRBASE file of 3000 molecular structures corresponding to a list of samples resolved with an a value superior to 1.8. For each solute, we have picked in CHIRBASE the traded CSP providing the highest enantioselectivity. This procedure leads to a total selection of 18 CSPs commercially available under the following names Chiralpak AD [28], Chiral-AGP [40], Chiralpak AS [28], Resolvosil BSA-7 [41], Chiral-CBH [40], CTA-I (microcrystalline cellulose triacetate) [42], Chirobiotic T [43], Crownpak CR(-i-) [28], Cyclobond I [43], DNB-Leucine covalent [29], DNB-Phenylglycine covalent [29], Chiralcel OB [28], Chiralcel OD [28], Chiralcel OJ [28], Chiralpak OT(-i-) [28], Ultron-ES-OVM [44], Whelk-0 1 [29], (/ ,/ )-(3-Gem 1 [29]. 

Whelk-0 1 well predominates the aromatic samples bearing an axial chirality created by a C-N bond. 

A new brush-type CSP, the Whelk-0 1, was used by Blum et al. for the analytical and preparative-scale separations of racemic pharmaceutical compounds, including verapamil and ketoprofen. A comparison of LC and SFC revealed the superiority of SFC in terms of efficiency and speed of method development [50]. The Whelk-0 1 selector and its homologues have also been incorporated into polysiloxanes. The resulting polymers were coated on silica and thermally immobilized. Higher efficiencies were observed when these CSPs were used with sub- and supercritical fluids as eluents, and a greater number of compounds were resolved in SFC compared to LC. Compounds such as flurbiprofen, warfarin, and benzoin were enantioresolved with a modified CO, eluent [37]. 

Cause imposex in dog whelks and a variety of other effects on other mollusks... 

TBTs also cause inhibition of the P450 of monooxygenases. In fish and in the common whelk, TBT causes conversion of P450s to the inactive P420 form (Pent et al. 1998, Mensink 1997). In fish, inactivation was also found with TPT, and was related to the inhibition of ethoxy resorufin deethylase activity (EROD) activity. In these studies, organotin compounds were found both as substrates and deactivators of the hemeprotein (cf. the interaction of organophosphates with B-type esterases). 

Returning to the question of endocrine disruption, it is now known that over 100 species of gastropods worldwide suffer from a condition described as imposex, the development of male characteristics by females. It has already been established for some species (e.g., dog whelk) that TBT is the cause of this, and it is suspected that organotin compounds account for most cases of imposex worldwide (Matthiessen and Gibbs 1998). Some examples of masculinization of female gastropods caused by tributyltin are given in Table 8.4. 

Dog whelk (Nucella lapillus) Sting whelk (Ocenebra erinacea) Common whelk (Buccinum undatum)... 

TBT causes imposex Development of penis blocks oviduct Similar effect to that observed in dog whelk Also causes imposex... 

Tributyltin compounds used as antifouling agents on boats have had serious toxic effects upon many mollusks, including populations of oysters and dog whelks. Females of the latter species developed a condition known as imposex, which rendered them infertile and caused local extinction of the population in shallow coastal waters. Imposex provides the basis for a valuable biomarker assay. 

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