Exquisitely controlled self-assembly in water is a key modality used by Nature to build highly functional biological systems. Research in the Jayawickramarajah group involves a highly interdisciplinary effort to develop bio-inspired functional molecules capable of undergoing specific molecular recognition events. A main thrust of our research is to study water compatible, self-assembling, synthetically functionalized oligomers that address contemporary problems. We are currently focused on the following research areas.
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The Chemistry and Self-Assembly of Macrocyclic Host-DNA Conjugates. The focus of our scientific research is at the interface of supramolecular chemistry with biology and materials. In particular, we have recently pioneered the nascent field of Host-DNA conjugates. This field involves the imbrication of synthetic macrocyclic hosts with DNA sequences. Such chimeric systems can exploit the programmability and controllability of DNA with the orthogonal molecular recognition and interesting functionality of synthetic hosts leading to highly functional and dynamic assemblies (e.g., input-responsive nanomachines and biomarker triggered protein inhibitors) that thrive in aqueous environments. Robust molecular recognition in water is a critical strength since most synthetic molecular recognition systems fail in water (as a result of insolubility issues and/or competing interactions with water).
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Development of Stimuli Responsive Protein-Binders Based on DNA-Small Molecule Chimeras. This project focuses on the development of DNA-small molecule chimeras that are programmed to bind and inhibit salient protein targets only upon non-covalent activation by specific endogenous or externally introduced trigger molecules. The development of general mechanisms for the non-covalent transformation of inactive protein inhibitors into activated compounds in the presence of specific endogenous (or externally added) stimuli is envisioned to contribute to prodrug development.
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Development of Well-Defined Porphyrin Arrays in Water: Towards Photonic Nanostructures. This project concerns the development of photonic nanowires composed of self-assembled multi-porphyrins in water. In these assemblies, the individual chromophores are non p-aggregated and are placed, via molecular recognition, at well-defined positions. The generation of self-assembled multi-porphyrin containing photonic nanostructures in water is envisioned to have potential applications as synthetic light harvesting antennae, catalyst arrays, and chemo-responsive sensing materials.
As a result of our prepare-and-analyze philosophy, students in the laboratory will be versed in synthetic organic chemistry and chemical biology, as well as being proficient in a whole host of spectroscopic, microscopic, and analytical techniques.