The thermodynamic driving forces (defined as the enthalpy changes or redox potentials in this work) of the 18 phenothiazines and their analogues, phenoxazine, N-methyl-dihydrophenazine, 9H-thioxanthene, 9H-xanthene and 9,10-dihydro- N-methylacridine, to release hydride, hydrogen atom, proton, and electron in acetonitrile, the thermodynamic driving forces of the radical cations of the phenothiazines and the analogues to release hydrogen atom, proton, and electron in acetonitrile, and the thermodynamic driving forces of the cations of the phenothiazines with two positive charges and their analogues to release proton in acetonitrile were estimated by using experimental methods. The effect of the remote substituents on the 11 determined thermodynamic driving forces were examined according to Brown's substituent parameters; the results show that the values of the 11 thermodynamic driving forces all are linearly dependent on the sum of Brown substituent parameters (sigma +) with very good correlation coefficients, which indicates that for any one- or multisubstituted at para- and/or meta-position phenothiazines and their various reaction intermediates, the 11 thermodynamic driving forces all can be easily and safely estimated from the corresponding Brown substituent parameters (sigma +). The relative effective charges on the center nitrogen atom in phenothiazines and their various reaction intermediates were estimated from the related Hammett-type linear free-energy relationships, which can be used to efficiently measure the electrophilicity, nucleophilicity, and dimerizing ability of the corresponding reaction intermediates of phenothiazines and their analogues. All the information disclosed in this work could not only supply a gap of the chemical thermodynamics on the mutual conversions between phenothiazines and their various reaction intermediates in solution but also strongly promote the fast development of the chemistry and application of phenothiazines and their analogues.

A protocol was developed for the solution-phase synthesis of multigram amounts of two 9-fluorenylmethoxycarbonyl (Fmoc)-protected tetraproline peptides. These tetraproline peptides were then attached to amino derivatized silica gel. The replacement of the Fmoc group with the trimethylacetyl group lead to two tetraproline chiral stationary phases (CSPs). A comparison of the chromatographic behavior of these two solution-phase-synthesized tetraproline CSPs with that prepared by stepwise solid-phase synthesis revealed that all three had similar chromatographic performance for resolving 53 model analytes. This suggests that the solution-phase synthesis of oligoprolines, which allows for the specific benefits of good batch reproducibility, selector homogeneity, and possibly low cost, is a feasible alternative to the solid-phase synthesis of oligoproline CSPs.

The chromatographic chiral resolution of two new series of racemic 4-substituted-1,4-dihydropyridine derivatives was studied on a commercial Chiralpak AD-H column. Analytes without 5,5-dimethyl substituents (1-15) are more efficiently resolved than analytes with 5,5-dimethyl groups (16-30). The AD-H column discriminated between enantiomers through both hydrogen bonding attractions and π-π interactions. This interpretation is in accord with plots of the logarithm of separation factors, log(α), versus σ (Hammett-Swain substituent parameter) and σ(+) (Brown substituent constant) plots. By elucidating the effects of the remote substituents on these chiral separations, it was shown that the influence of π-π interaction forces increase when steric bulk effects act to decrease the hydrogen bonding attractive forces on the AD-H column.

Eight diproline chiral stationary phases with different end-capping groups were prepared and evaluated for the enantio-selective resolution of 41 racemic analytes. The end-capping group on the N-terminal of the peptide proved to be important as the chiral separation efficiency was decreased significantly without it. In general, increasing steric bulkiness near the N-terminal of diproline increases the enantio-selectivity. Electronic structures of the end-capping groups are also important. One stationary phase with an adamantanecarbonyl capping group was found to provide both higher average separation and resolution factors than our previous leader. Three other stationary phases with 2-methylpropanoyl, cyclopropanecarbonyl and cyclobutanecarbonyl end capping groups were found to provide comparable average separation factor but higher resolution factors than our previous leader.

The chromatographic chiral resolution of 4-aryl-1,4-dihydropyridines (1-32), 4-aryl-2-thioxo-1,2,3,4-tetrahydropyrimidines (33-38), and 4-aryl-2-oxo-1,2,3,4-tetrahydropyrimidines (39-41) was studied on a tetraproline-immobilized chiral column synthesized in our lab. This tetraproline chiral stationary phase can resolve most of these compounds. The 4-aryl-2-thioxo-1,2,3,4-tetrahydropyrimidines (33-38) and 4-aryl-2-oxo-1,2,3,4-tetrahydropyrimidines (39-41) were more efficiently resolved than the racemic 4-aryl-1,4-dihydropyridines on the tetraproline chiralstationary phase. Analytes with 5,5-dimethyl groups (39-41) were less efficiently resolved than analytes without 5,5-dimethyl substituents (1-16). The 4-aryl-2-oxo-1,2,3,4-tetrahydropyrimidines (39-41) without a sulfur atom were much more efficiently resolved than 4-aryl-2-thioxo-1,2,3,4-tetrahydropyrimidines (33-38). No obvious electronic effects on the resolution of any of these analytes (1-41) were observed on the tetraproline chiral stationary phase. The tetraproline chiral stationary phase separated enantiomers mainly via hydrogen bonding interactions.