Current research projects and general research directions

My research interests are centered on the dynamic molecular interactions at the solid-liquid interface – the fundamental basis of the most important chemical analysis method, High Performance Liquid Chromatography (HPLC). My research program includes complex physico-chemical study of static and dynamic adsorption phenomena along with broad investigation of analytical behavior of various primarily pharmaceutically active compounds. The explanation of the main analytical dependencies and components behavior in an analytical system lies in the field of physical chemistry and this is a primary goal of my research.

High Performance Liquid Chromatography (HPLC). 

On the basis of comparison of chromatographic properties and geometric parameters of a series of common adsorbents used in HPLC, we were able to show that the dominant process governing the retention in HPLC is adsorption of the analyte on the surface of a chemically modified stationary phase. At the same time dynamic adsorption studies of binary systems had shown the existence of an adsorbed layer of significant thickness, which, in fact, is acting as quasi-stationary phase for analyte partitioning. This allows us to introduce an adsorption-partitioning model for analyte retention in HPLC with binary solvents. The mathematical description of the analyte migration through the column was also derived and allows the prediction of the analyte retention on the basis of external physico-chemical parameters. Experimental verification of our theory confirmed its applicability not only for prediction of the retention of ideal nonpolar compounds, but also for complex polar and ionizible chemicals.

New physico-chemical methods for measuring the excess adsorption isotherms that we developed during this study appear to be very useful for the comparison of the commercial HPLC columns. Currently we are working on the application of these methods for the characterization of reversed-phase HPLC columns in terms of the presence of accessible residual silanoles on the surface. Another outcome of the above research project is fast and convenient method for the column void volume measurement, which was a subject for extensive research and debates during the last 20 years.

The research described above shows that HPLC is a very powerful tool for studying the physico-chemical nature of intermolecular interactions, especially important that it allows observation of minor variations in those interactions. Similarly we are using HPLC for the investigation of adsorption from solution, surface interactions, and for characterization of adsorbent geometry and surface properties. Combination of the different chromatographic techniques (RP-HPLC and GPC) together with classical adsorption studies (Low Temperature Nitrogen Adsorption) allows complete characterization of the geometry of the adsorbent in the column (total surface area, pore size, and pore volume). We also found that HPLC provides significant information about the chemically bonded layer on the adsorbent surface. We were able to show that the effective molecular volume of bonded alkyl chains in all environments (in vacuum and in the contact with the liquid phase) is equal to the molecular volume of corresponding n-alkanes in the liquid state. This is a fundamental finding, since it tells that solvation of alkyl chains bonded on the surface is absent, correspondingly absent is the partitioning of the foreign molecules into the bonded layer. Consequently, the chromatographic retention mechanism should be considered on the basis of adsorption from solutions on the surface of bonded phase.

HPLC Retention of ionizible compounds.  

Original development of the chromatographic theory of chaotropicity was done in my lab in 1999 – 2001 by my Ph.D. students Rosario LoBrutto and Tarun Patel. During the last 7 years this theory was widely accepted in chromatographic community and in 2008 we published the review of recent developments in this field.

Further experimental verification of chaotropicity theory and its applicability to the description of chromatographic behavior of wide range of ionizable analytes suggests the more complex mechanism than simple solvation – desolvation equilibrium as it was originally thought.  

Surface interactions are dependent on the nature of the solution. Different ionization states and degree of solvation show significant effects on the overall analyte retention in a chromatographic system. The primary common tool to control the analyte ionization is the eluent pH. Our study has shown that the concentration of counteranions in the solution might significantly alter the retention not only through their influence on the analyte solvation shell as was thought before, but also through direct retention of counterions on the stationary phase or in adsorbed organic layer. The ability of the counterion to interact with hydrophobic surface is dependent on the degree of delocalization if it’s electrons. The adsorption behavior of different counterions has been studied and mathematical description of the influence of the counterion adsorption isotherms on the retention of different basic analytes has been suggested and verified for different classes of basic pharmaceutical compounds. The suggested theory was able to describe the analyte behavior in all studied systems and with all used counteranions.  We also discover principal difference between methanol and acetonitrile in their effect on the counterion adsorption. Acetonitrile prone for dispersive interactions due to its 4 pi-electrons, thus being adsorbed on the adsorbent surface it tend to retain counterions with delocalized charge, while methanol does not. 

Surface area of chemically modified adsorbents.

Traditional way of reporting experimental results in any mode of chromatography is in the form of retention factor, unitless parameter which relates the analyte retention volume to the volume of the mobile phase in the column. Recently we introduce surface specific retention factor, which more realistically reflects the influence of the adsorbent surface area on the retention of analytes in the column and allow for justified comparison of the chromatographic properties of different columns

In collaboration with the research group of Prof. Alex Fadeev, we are working on the development of a new class of HPLC adsorbents based on the ordered porous silica (SBA-15). These silicas have hexagonal arrangement of nearly ideal cylindrical pores without noticeable pore connectivity (networking). This material is an ideal model for studying of the influence of molecular diffusion on the analyte retention.

Some old instrumental development on the field of static headspace