Preparation and Evaluation of a Ferrocenediamide Bridge bis (β-Cyclodextrin)-Bonded Chiral Stationary Phase for HPLC

Ferrocene is a stable metallocene complex with aromatic high-electron π-conjugated system and sandwich structures. We first prepared and characterized a novel ferrocenediamide bridged bis (β-cyclodextrin) chiral stationary phase (FeCDP) to explore its chiral separation function. Its HPLC performance was systematically evaluated by basic, acidic, amphoteric and neutral chiral probes, including triazoles, profens, flavanones, amino acids and β-blocker drugs in reversed-phase and polar organic modes, respectively. The results showed that FeCDP successfully resolved 44 kinds of tested analytes ( R s = 0.66–4.38), of which 36 were completely separated ( R s ≥ 1.5). The best resolutions of different types, such as hexaconazole, ketoprofen, 3'-hydroxyflavanone, phenylalanine and arotinolol on FeCDP were reached at 3.06, 1.90, 4.38, 1.89 and 2.12 in a short time, respectively. Especially, FeCDP could completely resolve imazalil ( R s = 1.97), ketoprofen ( R s = 1.90), dansylated arginine (Dns-Arg, R s = 1.50), pindolol ( R s = 1.42), bevantolol ( R s = 1.41), which were very difficult to be resolved on the conventional CDCSPs. However, under optimal condition, the ordinary CDCSP could only separate 19 analytes with low resolutions ( R s = 0.29–1.27). Compared with the reported similar stationary phases, the HPLC performance of FeCDP was also further improved. Based on the above comparison results, the satisfactory enantioselectivity of FeCDP may be mainly due to the fact that the “ pseudo -cavity” composed of two CDs and a ferrocene diamide, could provide cooperative inclusion for analytes. Meanwhile, the large π-conjugated ferrocenediamide bridging group could also provide hydrogen bonding, π–π stacking, dipole–dipole and hydrophobic interactions, which may promote the chiral recognition effect of FeCDP. Bridge CD-CSP was a versatile chiral separation material in drugs analysis. Graphical Abstract