Our study explores the use of microwave synthesis of near-infrared (NIR) absorbing carbon quantum dots (CQDs) for cancer treatment with a particular focus on mole ratios of citric acid to urea. Current cancer therapy methods face challenges due to the lack of specificity in resulting in collateral damage to healthy tissues. CQDs, with their unique ability to bind selectively to cancer cells, present a promising avenue for targeted eradication. The CQDs employed in this study are synthesized via microwave synthesis. The process involves the dissolution of different ratios of citric acid to urea including 1:1, 1:3, 1.5, and 1:10 in nano-water, followed by microwave synthesis. Our study proves our hypothesis and showcases a correlation between CQDs and reduction in cancer cells.

Drawing from nature, biomimetic approaches in synthetic chemistry aim to replicate the precision and efficiency of enzymatic transformations by leveraging the enzymatic mechanism. Inspired by the biological activity of lysine 2,3-aminomutase, which converts lysine to beta-lysine through a radical generation and an aziridine intermediate, we wish to develop a general method for the transposition of amines in synthetic chemistry. This development would allow a facile method for beta amino acid production from readily available biological amino acids, for example. The computational exploration of the chemical system allows us to determine the principles underlying this reaction pathway. Density functional theory calculations were carried out on a variety of substrates to probe electronic effects and generate energetics diagrams. Trends found were used to accurately predict another substrate tested with the lowest barrier of reaction among those tested, validating findings.

In this presentation, we demonstrate tunable degradation and protein release in polyelectrolyte complex (PEC) hydrogels. Hydrogels are soft, porous materials formed by a three-dimensional network of interconnected polymer chains with a high capacity for water absorption. They are promising materials for protein delivery applications such as contact lenses, wound dressings, and bioadhesives, due to their moldable form and ability to encapsulate proteins. Chemical hydrogels, consisting of covalent crosslinkages, are most often used due to their mechanical strength. However, their physicochemical and mechanical properties are difficult to tune after formation. These gels typically require damaging organic solvents and UV light to crosslink, and they suffer from uncontrollable protein release. PEC hydrogels, a type of physical hydrogel, address these issues as they are formed in aqueous media through the self-assembly of triblock polyelectrolytes and have tunable mechanical properties. We present the swelling and degradation behavior of PEC hydrogels through free swelling experiments under physiological conditions as a function of polymer concentration and end-block length. Furthermore, we use BSA as a model protein to relate swelling behavior to the protein release kinetics through circular dichroism experiments. We demonstrate modulation of protein release is possible by varying polymer concentration and end-block length, showing that PEC hydrogels can act as a tunable protein delivery system in biomedical applications.

Cyclic peptides have emerged as a promising source of new medications with advantages over traditional small molecules including the ability to interact with shallow binding sites on protein surfaces, as well as having high selectivities and potencies for their protein targets. Using solid phase peptide synthesis (SPPS) and a variable solid-phase compatible dialkoxydiphenylsilane (DADPS) group, we have developed methodology that enables the production of a library of structurally diverse cyclic peptides. These cyclic peptides can be functionalized with a variety of reactive handles to facilitate the evaluation of their biological activities. Linear peptide sequences were synthesized using SPPS and comprise a C‑terminal DADPS group. Cyclization of these peptides is achieved by DADPS cleavage in 10% trifluoroacetic acid to afford a primary alcohol that can undergo a variety of intramolecular crosslinking reactions. SPPS is a robust method for synthesizing linear peptides and can incorporate a variety of amino acid residues into the peptide sequence. Addition of our recently reported, SPPS-compatible DADPS building block to the peptide is well tolerated and a number of structurally diverse peptides have been isolated. Variation in the length of the DADPS moiety enables control over the structure and size of the cyclic peptide without affecting the primary sequence. To establish our synthetic route, we first combined the DADPS building block with the synthesis of a focused set of linear and electrophile-containing peptides.

The protein alpha-synuclein (a-syn) is a factor in the pathology of many neurodegenerative diseases, including Parkinson’s disease. The disease state of a-syn arises from the oligomerization and aggregation of this protein. The search for therapies targeting a-syn pathology currently focuses on the discovery and development of small molecules that can bind to a-syn to disrupt aggregation. The molecule epigallocatechin gallate (EGCG), which is found in green tea, has been shown to disrupt a-syn aggregation. It is believed to bind to the N-terminus of a-syn. CNS-11 and CNS-11g are two other molecules which have been shown to disrupt a-syn aggregation well. CNS-11 is believed to bind to the N-terminus of a-syn, which has so far been determined using molecular dynamic simulations. My recent experiments aimed to use top-down, gas-phase mass spectrometry with electrospray ionization (MS with ESI) to confirm that EGCG, CNS-11, and CNS-11g bind to a-syn at the N-terminus. I explored whether the nature of such interactions is covalent or noncovalent by comparing binding of each under native and denatured conditions. Beta and gamma synuclein proteins, related to a-syn, have also been implicated as disrupting the aggregation process of a-syn. Moving forward, I plan to use gas-phase MS with ESI to analyze the impact of these two proteins on the aggregation of a-syn, as well as their interactions with EGCG, CNS-11, and CNS-11g, to determine similarities and differences between the binding activities of these three synucleins.