The Brien research lab utilizes organometallic chemistry to help improve the anti-cancer properties of various drugs, as well as catalysis of organic reactions. We are currently working on two very different projects. The first is the synthesis and biological activity of main-group derivatives of suberoylanilide hydroxamic acid (SAHA), one of the earliest histone deacetylase inhibitors. While SAHA is a remarkable drug due in part to the fact that it can be taken orally and is active at nanomolar concentrations, it is thought to be rather unselective in its inhibition of the 18 mammalian HDAC sub-types. It has been suggested that more selective HDAC inhibitors would have the potential to be better drugs. It is our hope that main-group derivatives of SAHA will accomplish this goal.
Our second project involves the study of metal complexes of 2,6-bis-hydrazinopyridine (BHP) derivatives. Many ligands have the beta-amino (or –imino) pyridine structure, but lack the alpha-amino group. The alpha-amino group in hydrazinopyridine derivatives should strengthen the donor ability of the pyridine nitrogen. We hope to verify this by comparing the X-ray structures of several BHP derivative metal complexes with those of the known bis-pyrazolylpyridines. This could lead to new tridentate ligands, which can be useful in catalysis.
Gregory, M., Dandavati, A, Lee, M., Tzou, S., Savagian, M., Brien, K. A., Satam, V., Patil, P., Lee, M. Synthesis, cytotoxicity, and structure–activity insight of NH- and N-methyl-3,5-bis-(arylidenyl)-4-piperidones. Medicinal Chemistry Research 2013, 22, 5588-5597.
Brien, K. A., Bandi, R. K., Behera, A. K., Mishra, B. K., Majumdar, P., Satam, V., Savagian, M., Tzou, S., Lee, M., Zeller, M., Westbrook, C., Mooberry, S. L. Pati, H., Lee, M. Design, Synthesis and Cytotoxicity of Novel Chalcone Analogs Derived from 1-Cyclohexylpyrrolidin-2-one and 2,3-Dihydrobenzo[f]chromen-1-one. Archiv der Pharmazie 2012, 345, 341-‐ 348.
Babu, B., Brien, K. A., Plaunt, A., Pressler, M., Shen, H., Alger, S., Ogilvie, R., Sjoholm, R., Tzou, S., Brockway, O., Rice, T., Mackay, H., Chavda, S., Seymour, M. D., Lee, M. Synthesis and DNA Binding Properties of 1,2,3-‐Triazole-‐linked H-‐pin pyrrole-‐ and imidazole-‐ containing Polyamides Formed by the Huisgen Reaction. Heterocyclic Communications 2012, 18, 79-85.
Kou, X., Wang, X., Mendoza-Espinosa, D., Zakharov, L. N., Rheingold, A. L., Watson, W. H., Brien, K. A., Jayarathna, L. K., Hanna, T. A. Bismuth Aryloxides. Inorganic Chemistry 2009 48, 11002-11016.
Brien, K. A., Garner, C. G., Pinney, K. G. Synthesis and Characterization of 2,6-Bis-hydrazinopyridine, and its Conversion to 2,6-Bis-pyrazolylpyridines. Tetrahedron 2006, 62, 3663-3666.
Brien, K. A., Garner, C. M., Klausmeyer, K. K., Feazell, R. P. Crystal Structure of 2,6-Bis-hydrazinopyridine, its tosylate salt and 2,6‐Bis-(3,5-di-tert-butylpyrazolyl)pyridine." The Journal of Chemical Crystallography 2005, 35, 875-883.
