Our interests center on the development of C-H bond activation reagents and catalysts for complex organic synthesis. C-H bond activation represents a chemical process of broad scientific and technological potential. The ability to transform ubiquitous but inert C-H bonds to other functional groups has far-reaching implications, ranging from oxidation of simple alkanes to the synthesis of complex organic molecules.
We are developing a program directed toward selective C-H bond functionalization of complex, multifunctional substrates. This plan represents uncharted territory as C-H functionalization has previously been achieved mostly in simple substrates. Despite significant advances in this area, most transition metal complexes capable of C-H bond activation are intolerant to functional groups and have a strong preference for the activation of aryl and other activated C-H bonds. Assuming the possibility of overcoming such constraints, novel and unique strategies for the assembly of complex organic molecules can be envisioned. General solutions to this problem will ultimately require the integration of several chemical disciplines, including organometallic chemistry, synthetic chemistry, and molecular recognition. Currently, we seek to achieve this goal via coordination-directed C-H bond activation. Thus, a suitable heteroatomic function is utilized to activate and direct a metal complex to a specific alkane region of the substrate in such a way as to prevent interference of other functional groups. This logic has been supported by our recent results. The total synthesis of the natural product rhazinilam was accomplished via selective C-H bond functionalization (see references). Recently, we have developed a catalytic system capable of selective hydroxylation of a-amino acids in water. We will continue to further develop this approach in the context of complex molecule assembly. Toward these ends we will pursue both the rational design of catalysts and high throughput screening methods.
We also focus on the development of new fluorogenic probes in order to detect chemical reactions with high sensitivity. Fluorogenic substrates are designed to change their fluorescent profile during the bond-making and -breaking events. These probes are currently used in the high throughput screening of solid-supported catalysts. Furthermore, the study of molecular interactions and chemical reactions in living cells through the use of such probes will also be pursued.
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"Fluorescent False Neurotransmitters Visualize Dopamine Release from Individual Presynaptic Terminals," Niko G. Gubernator, Hui Zhang, Roland G. W. Staal, Eugene V. Mosharov, Daniela Pereira, Minerva Yue, Vojtech Balsanek, Paul A. Vadola, Bipasha Mukherjee, Robert H. Edwards, David Sulzer, and Dalibor Sames, Science, Science Express (2009)
"C-H Bonds as Ubiquitous Functionality: A General Approach to Complex Arylated Pyrazoles via Sequential Regioselective C-Arylation and N-Alkylation Enabled by SEM-Group Transposition,” Roman Goikhman, Teresa L. Jacques, and Dalibor Sames, J. Am. Chem. Soc. 131, 3042-3048 (2009)
“C-H Bond Functionalization via Hydride Transfer: Lewis Acid Catalyzed Alkylation Reactions by Direct Intramolecular Coupling of sp3 C-H Bonds and Reactive Alkenyl Oxocarbenium Intermediates,” Kevin M. McQuaid and Dalibor Sames, J. Am. Chem. Soc. 131, 402-403 (2009)
“Imaging Induction of Cytoprotective Enzymes in Intact
Human Cells: Coumberone, a Metabolic Reporter for Human AKR1C Enzymes Reveals
Activation by Panaxytriol, an Active Component of Red Ginseng,” Marlin Halim,
Dominic J. Yee, and Dalibor Sames, J. Am. Chem. Soc. 130, 14123-14128 (2008)
“A Luminescent Sensor for Tyrosine Phosphorylation,” Matthew
S. Tremblay, Minhee Lee, and Dalibor Sames, Org. Lett. 10, 5-8 (2008)
“Harnessing Functional Plasticity of Enzymes: A Fluorogenic Probe for Imaging 17ß-HSD10 Dehydrogenase, an Enzyme Involved in Alzheimer's and Parkinson's Diseases,” Mary K. Froemming and Dalibor Sames, J. Am. Chem. Soc. 129, 14518-14522 (2007)
“Ruthenium Catalyzed Decarbonylative Arylation at sp3 Carbon Centers in Pyrrolidine and Piperidine Heterocycles,” Denis V. Gribkov, Stefan J. Pastine, Michael Schnurch, and Dalibor Sames, J. Am. Chem. Soc. 129, 11750-11755 (2007)
“Transposing Molecular Fluorescent Switches into the Near-IR: Development of Luminogenic Reporter Substrates for Redox Metabolism,” Marlin Halim, Matthew S. Tremblay, Steffen Jockusch, Nicholas J. Turro, and Dalibor Sames, J. Am. Chem. Soc. 129, 7704-7705 (2007)
“Cocktails of Tb3+ and Eu3+ Complexes: A General Platform
for the Design of Ratiometric Optical Probes,” Matthew S. Tremblay, Marlin
Halim, and Dalibor Sames, J. Am. Chem. Soc. 129, 7570-7577 (2007)
“Two-Photon Excitation of Fluorogenic Probes for Redox Metabolism: Dramatic Enhancement of Optical Contrast Ratio by Two-Photon Excitation,” Steffen Jockusch, Qingdong Zheng, Guang S. He, Haridas E. Pudavar, Dominic J. Yee, Vojtech Balsanek, Marlin Halim, Dalibor Sames, Paras N. Prasad, and Nicholas J. Turro, J. Phys. Chem. C 111, 8872-8877 (2007)
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