Effect of the adamantane derivatives structure for its retention under condition of reversed-phase high performance liquid chromatography

Abstract

The problem of establishing the relationship between the compounds structure and its properties (QSPR) is one of the most topical in modern materials science during many years. One aspect of this problem is to establish the relation "structure -chromatographic retention", the most studied for gas chrotography. The establishment of such relations for liquid chromatography is complicated by the absence of at least developed a molecular-statistical theory of adsorption even from dilute solutions and quantitative theory of waterorganic solutions in general. Interesting studies objects with respect to this issue are adamantane derivatives with important properties from a practical point of view. So the purpouse our this work was to study the effect of some adamantane derivatives structure on their chromatographic retention under condition of reverse phase high performance liquid chromatography (RP-HPLC). Chromatographic investigation was carried out with a UV spectrophotometric detector ProStar at a wavelength of 254 nm at room temperature on a silica gel sorbents, graphitized carbon -hypercarb and hypercrosslinked polystyrene. As the eluent a mixture of acetonitrile -water in isocratic condition was used. As objects of study were chosen heterocyclic and phenyl adamantane derivatives. It was observed that the major role in the physical and chemical characteristics changing, including chromatographic retention of adamantane derivatives play nature of a substituent which affects, in addition, the molecules stereochemistry. Nearly plane structure of the phenyl derivatives facilitate the better contact with the surface of adsorbents, especially carbon. For non-planar heteroaromatic compounds the relative positions of the imidazole fragment and adamantyl is important for its the interacting with polar components of the eluent. The presence of an imidazole moiety linked to a carbonyl group through adamantyl or through a methylene unit, and significantly reduces the lipophilicity increases dipole moment of the corresponding derivatives, thus enhancing their interaction with the components of the mobile phase.
It was found that the addition of the methylene bridge between the adamantyl and carbonyl leads to a substantial increase in retention (up to 80%) compared with their structural analogues with comparable values of the polarizability, lipophilicity and molecular volume -the parameters responsible for dispersion interactions. The probable cause greater retention can increase the contact area of the molecules of adamantane derivatives containing methylene unit, the surface of the sorbent. Introduction methyl into heteroaromatic moiety changes the physical and chemical parameters of the molecules corresponding adamantane derivatives and, ultimately, its chromatographic retention (these changes are incomparably large compared to the size of the radical СН3).
Replacing the OH group on the phenyl СН3 in adamantane derivatives significantly increases retention in a RP-HPLC method for the attenuation of the interaction with the polar eluent as hydroxy adamantane chromatographic behavior is determined by interaction with competing non-polar sorbent, and the possibility of hydrogen bonding between hydroxyl groups of analytes and the mobile components phase. Very important contribution to the retention makes phenyl radical. In general, according to the data obtained, the retention of the investigated adamantane derivatives varies symbatically to physico-chemical parameters responsible for the intermolecular interactions in the RP-HPLC. The main contribution to the retention of making dispersion interactions, but the specific features of used carbon and polymer sorbents reflect on sorption characteristics of adamantane derivatives so much. Thus, in particular, porous graphitized carbon is characterized by substantial retention of polar compounds (called polar effect retention) due to the interaction of analyte molecules with free electron pair or an aromatic system, and the free electrons ("electron conductivity") of hypercarb. It is assumed, moreover, that the plane sorbate molecules capable of approaching the hypercarb surface on smaller distances, which increases the interaction and increases retention. Nonplan molecules are retained on its surface, thus, to a lesser extent. The peculiarities of sorption hypercrosslinked polystyrene include a significant additional π-interactions contribution in retention which is most pronounced for sorbates with electron excess or electron deficit plan aromatic moieties, multiple bonds, vacant d-orbitals or lone pairs of electrons. Retention features of heterocyclic and phenyl adamantane derivatives under RP HPLC generally vary symbatically with physico-chemical parameters of molecules.
Despite the fact that the main contribution to the chromatographic retention of adamantane derivatives under RP HPLC making non-polar adamantyl fragment substituents change sorption characteristics of the relevant analytes at a value determined by the nature of the substituent and the nature of the sorbent. Graphitized carbon and hypercrosslinked polystyrene are very sensitive to the stereochemistry of the adamantane derivatives and the presence of substituents capable to interact with such sorbents due to specific interactions that are additional to the dispersion, which generally defined retention under RP HPLC.