Linear Solvation Energy Relationships (LSERs) are used to explain the congeneric behavior observed when using Micellar Electrokinetic Chromatography (MEKC) to estimate the octanol-water partition coefficient scale of solute hydrophobicity. Such studies provide useful insights about the nature of solute interactions that are responsible for the sources of congeneric relationships between MEKC retention and log Po/w. It was determined that solute dipolarity/polarizability and hydrogen-bonding character play the most important roles in the congeneric behavior observed for many surfactant systems. The individual dipolarity/polarizability and hydrogen-bonding contributions to the free energy of transfer were also investigated.

The influence of surfactant headgroups on migration behavior in micellar electrokinetic chromatography is examined. Using linear solvation energy relationships (LSER) and functional group selectivity studies, the effect of six anionic headgroups on chemical selectivity is characterized. The sodium dodecyl surfactants of the sulfate [SO4-], sulfonate [SO3-], carboxylate [CO2-], carbonyl valine [OC(O)NHCH(CH(CH3)2)CO2-], and sulfoacetate [OC(O)CH2SO3-] anions are investigated. Solute size and the hydrogen-bond-donating ability of the micellar phase play the most significant roles in solute retention in all of the surfactants studied. While solute-micelle hydrogen bonding plays a dominant role in the observed selectivity, the dipolarity and polarizability of the micellar phase also have a small influence. The results also suggest that the hydrogen-bond-accepting ability for surfactants is inversely proportional to the proton acidity (pKa) of its headgroup. The observed hydrogen-bond-donating ability and dipolarity of surfactant systems are believed to be a result of the water that resides near the micelle surface.

An efficient asymmetric synthesis of N-[(1R)-6-chloro-2,3,4,9tetrahydro-1H-carbazol-1-yl]-2-pyridinecarboxamide 1, a potential treatment for human papillomavirus infections, is described. The key step in the synthesis of this molecule is an asymmetric reductive amination directed by chiral (phenyl)ethylamines resulting in up to 96% disastereo facial selectivity. The synthesis is also highlighted by isolation of a unique 2-picolinic acid salt of (1R)-6-chloro-2,3,4,9-tetrahydro-1Hcarbazol-1-amine (13). Subsequent application of 1-propylphosphonic acid cyclic anhydride (T3P) for convenient amide formation from the two components of the salt provides the product 1 in high yield. The process research work leading to the final synthesis includes a racemic synthesis followed by resolution with chiral supercritical fluid chromatography, and an enantioselective reductive amination via chiral transfer hydrogenation catalyzed by Ru(II) complexes of N-[(1S,2S)-2amino-1,2-diphenylethyl]-1-naphthalenesulfonamide or (R)-BI-NAP. Highlighting the practicality of the synthesis, the process has been scaled up in 200-gallon reactors for delivery of multikilograms of the target compound 1 in over 99.5% enantiomeric purity.

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