In the present study, selectively deuterated alkylamine ligands were prepared and subsequently used to modify the surface of porous silica. The resulting material was then reacted with either hexanoyl chloride or heptanoyl chloride to produce the corresponding alkylamide-modified surfaces. The wide-line 2 H NMR spectra of the intermediate and final materials were measured in the dry state and in the presence of both protic and aprotic solvents. The shapes of the resulting resonances are complex and are made up of spectrally broad and narrow components with widths in the restricted motion range (i.e., about 40 kHz) and widths characteristic of more motionally dynamic species. The relative contribution of the broad component is dominant in the dry state and in aprotic solvent spectra and is significantly decreased or absent in the spectra collected in polar solvents. These results can be explained via changes in the degree of interfacial hydrogen bonding between the amine and amide groups in the attached ligands and residual surface silanols.

High‐performance liquid chromatography (HPLC) is one of several separation techniques that are based on the differential migration of an analyte (solute) through a fixed medium as the result of a driving force, the eluent. In the case of HPLC, the eluent is typically either a binary or ternary mixture of solvents and the stationary phase is most often a porous adsorbent or a chemically bonded phase attached to a porous substrate. The rate of migration of an individual solute and the separation between groups of solutes are governed by their interactions with the stationary phase. Thus, the optimization of an HPLC method involves the selection/adjustment of the physical and chemical parameters which control the rate of migration of the solute in such a fashion that baseline resolution is obtained between it and other co‐analytes or interfering compounds within the mixture. In doing this, given a series of closely related compounds, it is important to identify structural differences between solutes and to maximize the interactions with the stationary phase arising from them. This article considers the important physical and chemical aspects of the solute, eluent, and stationary phase in terms of chemical equilibria, solute structure, eluent conditions, operational parameters, and nonideal effects. Likewise, as several approaches may lead to acceptable analytical separations, other performance criteria such as simplicity, reliability, speed, and cost also are discussed in terms of arriving at the optimal method.