The long term objectives of this research are to develop efficient methods for the preparation of complex, nanoscale molecules with well defined shapes and sizes, by rational design and to provide new insights and gain a better understanding of recognition phenomena and self-assembly processes.
Our specific aims are to investigate and understand host-guest interactions of self-assembled 3D molecular cages;prepare, characterize and explore the chemistry of novel, chiral 3D assemblies;explore and develop new ways of characterizing nanoscale supramolecular species;examine self-selection, self-recognition and dynamic phenomena in self-assembly;investigate hierarchical abiological self-assembly and screen for biological activity all new self-assembled supramolecular ensembles. We will use our recently developed abiological coordination driven, directional bonding approach in combination with new methodology and known analytical tools to achieve these goals. As a consequence, chemists will have conceptually new, innovative strategies for the formation of unique, complex, molecules that, in the long term, will facilitate the discovery and production of improved chemical agents and chemotherapy for the treatments of medical disorders. Moreover, also in the long run, this abiological self-assembly procedure will provide the means for the manufacturing of biomedical nanodevices (sensors for diagnostic purposes, new drug delivery systems, etc.) for the better detection and treatment of medical disorders. Likewise, the rationally designed, chiral, self-assembled molecular cages have the potential for selective substrate transformations (enzyme like catalysis) and to act as nanoreactors for unique molecular transformations. Self-assembly is at the heart of countless biological processes that all living organisms, from the simplest to humans, depend upon. Protein folding, nucleic acid assembly and tertiary structures, ribosomes, phospholipid membranes, microtubules are but representative examples of self-assembly. Insights gained from the proposed abiological self-assembly studies will be applicable to a better and more complete understanding of the complex, not well understood biological self-assembly processes, such as protein folding, that play an important role in such degenerative diseases as Alzheimers, Creutzfeldt-Jakob, and prion diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM057052-31
Application #
7575602
Study Section
Synthetic and Biological Chemistry A Study Section (SBCA)
Program Officer
Fabian, Miles
Project Start
1998-01-01
Project End
2011-01-31
Budget Start
2009-02-01
Budget End
2010-01-31
Support Year
31
Fiscal Year
2009
Total Cost
$299,000
Indirect Cost
Name
University of Utah
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
009095365
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112
Grishagin, Ivan V; Pollock, J Bryant; Kushal, Swati et al. (2014) In vivo anticancer activity of rhomboidal Pt(II) metallacycles. Proc Natl Acad Sci U S A 111:18448-53
Mishra, Anurag; Chang Lee, Seung; Kaushik, Neha et al. (2014) Self-assembled supramolecular hetero-bimetallacycles for anticancer potency by intracellular release. Chemistry 20:14410-20
Dubey, Abhishek; Mishra, Anurag; Min, Jin Wook et al. (2014) Self-Assembly of New Arene-Ruthenium Rectangles Containing Triptycene Building Block and Their Application in Fluorescent Detection of Nitro Aromatics. Inorganica Chim Acta 423:326-331
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Jung, Hyunji; Dubey, Abhishek; Koo, Hyun Jung et al. (2013) Self-assembly of ambidentate pyridyl-carboxylate ligands with octahedral ruthenium metal centers: self-selection for a single-linkage isomer and anticancer-potency studies. Chemistry 19:6709-17
Dubey, Abhishek; Min, Jin Wook; Koo, Hyun Jung et al. (2013) Anticancer potency and multidrug-resistant studies of self-assembled arene-ruthenium metallarectangles. Chemistry 19:11622-8
Vajpayee, Vaishali; Lee, Sun Mi; Park, Joeng Woo et al. (2013) Growth Inhibitory Activity of a Bis-benzimidazole-Bridged Arene Ruthenium Metalla-Rectangle and Prism. Organometallics 32:1563-1566
Cook, Timothy R; Zheng, Yao-Rong; Stang, Peter J (2013) Metal-organic frameworks and self-assembled supramolecular coordination complexes: comparing and contrasting the design, synthesis, and functionality of metal-organic materials. Chem Rev 113:734-77
Mishra, Anurag; Jung, Hyunji; Park, Jeong Woo et al. (2012) Anticancer Activity of Self-Assembled Molecular Rectangles via Arene-Ruthenium Acceptors and a New Unsymmetrical Amide Ligand. Organometallics 31:3519-3526
Chakrabarty, Rajesh; Stang, Peter J (2012) Post-assembly functionalization of organoplatinum(II) metallacycles via copper-free click chemistry. J Am Chem Soc 134:14738-41

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