Research Project
10201920
PROJECT SUMMARY The detection of new microbe strains together with drug resistant bacteria require innovative advances in chemical synthesis and biology to ensure prompt development of new therapeutic molecules. These molecules are typically built from versatile building block. Ideally, these molecular fragments should be obtained from readily available and diverse starting materials. The long-term goal of the proposed work is two-fold; first, to give undergraduate students the opportunity to perform hands-on research, aiming to enhance their planning, executing, and analysis skills. Second, to improve our research environment by utilizing FGCU facilities and equipment to examine new, more efficient routes to access valuable small molecules via assessment of a new class of heterobimetallic complexes as catalysts versus their ligandless counterparts. This approach is innovative as it combines the power of two transition metals (e.g., Pd-Ag or Pd-Cu) with a new class of pincer- like ligands to functionalize readily available starting materials and to construct diverse structural motifs, making heavy use of benign reagents, namely water and air. The rationale for this proposed work is based on the recent demonstrated reactivity of heterobimetallic catalysts by the PI (see the research strategy section). The first aim of this proposal is to design, synthesize, and fully elucidate the structure and reactivity of several heterobimetallic complexes, together with DFT calculations of catalyst-substrate interactions. The second aim is to evaluate our new complexes with or without organic ligands. The direct conversion of alkyl halides into enals/enones, a novel functional group interconversion discovered in our group, will be used as the screening transformation. The third aim will examine and evaluate the catalytic activity of the proposed heterobimetallic complexes versus their ligand-free equivalents in the direct conversion of alkynes into enones. Overall results obtained from all three aims will help elucidate important mechanistic aspects of our new catalytic systems and employment of these new strategies to the expedite synthesis of natural products. The following expected outcomes are foreseen: First, this research program will give a training platform to undergraduate students in catalysis and synthesis of pharmacological relevant molecules. Second, to provide much easier access to small molecules required to synthesize therapeutic agents used to treat human illnesses. Thus, expanding the current organic toolkit. Third, this work will reduce significantly the number of synthetic steps required, while simultaneously giving access to new synthetic bond disconnections and unique reactivity. Fourth, the approach described is both more cost efficient and more environmentally friendly than current synthetic approaches employed in synthesis of key intermediates. These outcomes are expected to have a significant positive impact towards the careers of all undergraduate students involved and drug discovery. The ability to more efficiently assemble complex pharmaceuticals targets will benefit human health.
