The broad long term objectives of this research are: (1) to develop efficient, new methods for the preparation of complex nanoscale molecules with well-defined shapes and sizes, by rational design, using abiological self- assembly;(2) to provide insights and gain a better understanding of molecular recognition phenomena and self-assembly processes;(3) to develop abiological self-assembly as a platform for novel biomedical applications. [Our specific goals are to: (a) examine encapsulation and host-guest interactions of small drug- like organic molecules, as well as the encapsulation of three diverse, widely-used commercially-available cancer drugs (fluorouracil, cyclophosphamide, doxorubicin);(b) study protein and enzyme encapsulation by pre-designed self-assembled metallacages;(c) develop targeted drug delivery methodologies via self- assembled metallacages and the multivalent display of peptidic (and other) integrin antagonists.] We will use abiological, coordination-driven and our """"""""directional bonding"""""""" approach to achieve these aims. This methodology allows for the rapid, pre-designed, (rational) self-assembly of nanoscale systems with well- defined shapes and sizes, due to metal d-orbital involvement that allows dative, metal-ligand bonds to be highly directional. Moreover, coordination kinetics can be modulated to engage in self-repair to achieve thermodynamic control of the desired, pre-designed super structures. 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 and 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. If the aims of this application are achieved, biomedical researchers will have new tools and entirely new approaches for the formation of large, nanoscale, complex molecules with unique properties that will complement and enhance classical covalent synthetic methods. As a consequence, in the long term, these approaches will facilitate the discovery and production of improved chemical agents and chemotherapy for the treatment and possible prevention of medical disorders.
If the aims of this application are achieved, biomedical researchers will have new tools and entirely new approaches for the formation of large, nanoscale, complex molecules with unique properties that will complement and enhance classical covalent synthetic methods. As a consequence, in the long term, these approaches will facilitate the discovery and production of improved chemical agents and chemotherapy for the treatment and possible prevention of medical disorders and in particular. Additionally, in the future, innovative transfection systems and possible gene-regulation may evolve from these discoveries.
|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|
|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|
|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|
|Cook, Timothy R; Vajpayee, Vaishali; Lee, Min Hyung et al. (2013) Biomedical and biochemical applications of self-assembled metallacycles and metallacages. Acc Chem Res 46:2464-74|
|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|
|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|
|Mishra, Anurag; Vajpayee, Vaishali; Kim, Hyunuk et al. (2012) Self-assembled metalla-bowls for selective sensing of multi-carboxylate anions. Dalton Trans 41:1195-201|
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