Carr Research Group

Email: dai@chem.umn.edu
Phone: (612) 624-5870
Office: Smith 311
Address: Department of Chemistry, University of Minnesota, 207 Pleasant St. SE, Minneapolis, MN 55455

EDUCATION

Ph.D. candidate, Analytical Chemistry, University of Minnesota
Thesis: Understanding retention mechanisms and optimizing selectivity for basic pharmaceutical separations by reversed phase liquid chromatography

M.S., Polymer Chemistry and Physics, Nankai University, Tianjin, China, 2000

B.S., Chemistry, Nankai University, Tianjin, China, 1997

RESEARCH SUMMARY

1. Understanding Retention Mechanisms and Selectivity Optimization for Basic Pharmaceutical Separations by Reversed Phase Liquid Chromatography (RPLC)

Most of my research has been focused on understanding the details of retention mechanisms and adjusting selectivity for the separation of basic pharmaceuticals in RPLC. We have developed new theories which for the first time deal in a comprehensive fashion with both the competitive effect of added counterions (e.g., triethylamine) and the retention enhancing effect of so-called "ion pairing" anions (e.g., trifluoroacetate).
In our counterion studies, we disproved the validity of the one site model and showed that at least two types of sites must exist one of which is what we call a "hydrophobically assisted" ion-exchange site. Our model very nicely rationalizes why primary amines are stronger silanophiles than secondary or tertiary amines and why the best silanol blocking agents must have a high hydrophobicity. Perhaps more importantly our model achieves unambiguous column classification based on a quantitative measurement of the relative contribution of ion-exchange and reversed phase interactions, which overcomes the frequent confusion of column comparison based on the separation of a few model compounds. As applications of our theory, we investigated the effect of several amine mobile phase counterions on the retention and selectivity of cationic solutes on octadecyl silane bonded silica (ODS) and polybutadiene-coated zirconia (PBD-ZrO2) phases. We found that the use of different primary amine counterions with different charges and hydrophobicities enables retention adjustment of basic solutes on the PBD-ZrO2 phase. In contrast to literature indications of the behavior of older type A silica phases, on modern type B ODS phases, the effect of different types of amine counterion is much smaller. We also compared the separation of basic drugs on several ODS phases and a PBD-ZrO2 phase. We found that very large differences in the relative contributions from ion-exchange and reversed phase interactions on the two types of phases lead to quite different selectivities.
In my recent studies, we investigated the retention mechanism of basic drugs in RPLC in the presence of mobile phase anionic additives. We found that the addition of anionic additives (hexafluorophosphate, perchlorate, trifluoroacetate, and chloride) profoundly influenced the retention of basic drugs. In order to understand the mechanisms by which anionic additives influence retention in chromatography, we studied the formation of ion pairs between a number of prototypical basic drugs and the above mentioned additives by measuring the effect of additives on the electrophoretic mobility of the probe drugs using capillary electrophoresis (CE). For the first time, ion pair formation between basic drugs and anionic additives under conditions commonly used in RPLC has been confirmed independently. We then used ion pair formation constants from CE to interpret the chromatographic data. Agreement between the predicted and experimental chromatographic data under various conditions was evaluated. Under certain circumstances (e.g., pH, stationary phase, and nature of anionic additive), we conclude that the ion pair formation in the mobile phase mechanism is dominant and at other conditions it remains a significant contribution.

2. Development of Acid-Stable Hyper-Crosslinked Phases

Another project in which I made important contributions is the development of acid-stable "hyper-crosslinked" phase. We developed silica based stationary phases by using a novel Friedel-Crafts synthesis concept. Our stationary phases have much higher acidic and thermal stability than the current commercially available silica phases. The greatly enhanced acidic and thermal stability makes our phases very promising for the application of high temperature fast HPLC, fast two-dimensional HPLC, and fast gradient elution HPLC.

RECENT PUBLICATIONS

1. Jun Dai and Peter W. Carr, "The Role of Ion Pairing in Anionic Additive Effects on the Separation of Cationic Drugs in Reversed Phase Liquid Chromatography", Journal of Chromatography, A, submitted.

2. Jun Dai, Shaun D. Mendonsa, Michael T. Bowser, Charles A. Lucy, and Peter W. Carr, "Effect of Anionic Additive Type on Ion Pair Formation Constants of Basic Pharmaceuticals", Journal of Chromatography, A, submitted.

3. Jun Dai, Xiqin Yang, and Peter W. Carr, "Comparison of the Chromatography of Octadecyl Bonded Silica and Polybutadiene Coated Zirconia Phases Based on a Variegated Set of Cationic Drugs", Journal of Chromatography, A, 2003, 1005, 63-82

4. Xiqin Yang, Jun Dai, and Peter W. Carr, "The Effect of Amine Counterion Type on the Retention of Various Classes of Basic Compounds on Octadecyl Bonded Silica-Based and Polybutadiene Coated Zirconia Phases", Analytical Chemistry, 2003, 75, 3153-3160.

5. Xiqin Yang, Jun Dai, and Peter W. Carr, "An Analysis and Critical Comparison of the Reversed-Phase and Ion-Exchange Contributions to Retention on Polybutadiene Coated Zirconia and Octadecyl Silane Bonded Silica Phases", Journal of Chromatography, A, 2003, 996, 13-31.

PRESENTATIONS (*presenter)

1. Jun Dai* and Peter W. Carr, "Understanding Anionic Additive Effects in the Reversed Phase Separation of Basic Pharmaceuticals", Submitted for The Pittsburgh Conference, February 27-March 04 2005, Orlando, FL, Future Oral Presentation.

2. Jun Dai* and Peter W. Carr, "A Study of Ion-Pair Agent Effect on the Retention of Basic Compounds on Silica-Based Stationary Phase", Eastern Analytical Symposium, November 15-18 2004, Somerset, NJ, Oral Presentation.

3. Lianjia Ma*, Jun Dai, , Hao Luo, and Peter W. Carr, "Silanophilicity Study and Synthesis Optimization of Hyper-Crosslinked Phases" Eastern Analytical Symposium, November 15-18 2004, Somerset, NJ, Oral Presentation.

4. Jun Dai and Peter W. Carr*, "Use of Physico-Chemical Measurements by Capillary Electrophoresis to Explore Retention Mechanism of Organic Bases in Reversed Phase Liquid Chromatography" Chemistry Seminar at University of Pittsburgh, November 02 2004, Pittsburgh, PA, Oral Presentation.

5. Lianjia Ma, Jun Dai, Hao Luo, Xiqin Yang, Brian Trammell and Peter W. Carr*, "Devolvement of Hyper-Crosslinked Acid Stable Silica Based Phases for Protein and Peptide Separations", 28th International Symposium and Exhibit on High Performance Liquid Phase Separations and Related Techniques, June 12-18 2004, Philadelphia, PA, Oral Presentation.

6. Jun Dai*, Lianjia Ma, Brian Trammell, Marc A. Hillmyer, and Peter W. Carr, "Chromatographic Characterization of Hyper Crosslinked Reversed Phases", The Pittsburgh Conference, March 7-12 2004, Chicago, IL, Oral Presentation.

7. Xiqing Yang, Jun Dai*, and Peter W. Carr, "Comparison of Retention and Efficiency of Polybutadiene Coated Zirconia and Various Octadecyl Bonded Silica Phases Using Cationic Drugs", The Pittsburgh Conference, March 7-12 2004, Chicago, IL, Oral Presentation.

8. Brian Trammell, Lianjia Ma, Jun Dai, Hao Luo, Xiqin Yang, Marc A. Hillmyer, and Peter W. Carr*, "Surface Confined Polymer Networks Based on Orthogonal Reaction Chemistry: A Novel Approach to High Efficiency Stable Silica-Based Reversed Phase Media", The Pittsburgh Conference, March 7-12 2004, Chicago, IL, Oral Presentation.

9. Jun Dai, Xiqin Yang, Peter W. Carr, and Robert T. Moody*, "Comparison of Column Performance of Polybutadiene Coated Zirconia and Various Octadecyl Bonded Silica Phases Based on Cationic Drugs", 27th International Symposium on High Performance Liquid Phase Separations and Related Techniques, June 15-19 2003, Nice, France, Poster Presentation.

10. Jun Dai*, Xiqin Yang, and Peter W. Carr, "The Effect of Amine Counterion Type on the Retention of Basic Compounds on Octadecyl Bonded Silica Phases and Polybutadiene Coated Zirconia Phases", The Pittsburgh Conference, March 9-14 2003, Orlando, FL, Oral Presentation.

11. Xiqin Yang*, Jun Dai, and Peter W. Carr, "A Critical Comparison of Reversed-Phase and Ion-Exchange Interactions on Polybutadiene Coated Zirconia and Octadecyl Bonded Silica Phases", The Pittsburgh Conference, March 9-14 2003, Orlando, FL, Oral Presentation.

12. Jun Dai, Xiqin Yang*, and Peter W. Carr, "Mixed-Mode Retention Mechanism of Cationic Compounds on Octadecyl Bonded Silica-Based Reversed Phases", Eastern Analytical Symposium, November 18-21 2002, Somerset, NJ, Poster Presentation.

13. Xiqin Yang*, Jun Dai, and Peter W. Carr, "A Comparative Study of the Retention Characteristics of Basic Analytes on Polybutadiene-Coated Zirconia and Octadecyl-Bonded Silica Phases", Eastern Analytical Symposium, November 18-21 2002, Somerset, NJ, Poster Presentation.

14. Xiqin Yang*, Jun Dai, and Peter W. Carr, "Optimizing the Separations of Basic Compounds in Mixed-Mode Chromatography by Understanding the Role of Lewis Acidity of Zirconia Based Phases", 26th International Symposium on High Performance Liquid Phase Separations and Related Techniques, June 2-7 2002, Montreal, Canada, Poster Presentation.

15. Jun Dai*, Xiqin Yang and Peter W. Carr, "Hydrophobic and Ion-Exchange Interactions in Silica-Based RPLC Stationary Phases", Minnesota Chromatography Forum, May 16 2002, Minneapolis, MN, Oral Presentation.

16. Xiqin Yang*, Jun Dai, and Peter W. Carr, "A Comparative Study of the Retention Characteristics of Basic Analytes on Polybutadiene-Coated Zirconia and Octadecyl-Bonded Silica Phases", Minnesota Chromatography Forum, May 16 2002, Minneapolis, MN, Oral Presentation.

Modified by Hao Luo --- hluo@chem.umn.edu