| Click chemistry is a type of reaction in which products can be formed instantly in nontoxic solvents like water. The products should be easy to be purified with non-chromatography methods, and if there are side products, they can only be inoffensive byproducts. The reaction of aldehydes or ketones with an alpha-effect amine to form a hydrazone is one of the early types of click reactions. Alpha-effect amines can be hydrazine, hydrazide, or other amine-nitrogen or amine-oxygen containing molecules. However, the optimal condition for this reaction is between pH 2-5, which is far beyond physiological pH. In our group, we found that aromatic aldehydes or ketones that possess a boronic acid substituent ortho- to the carbonyl react extremely fast with alpha-effect amines in dilute, neutral aqueous solutions. The product is a boron-containing heterocycle such as a 2,3,1-diazaborine or a related heterocycle. We have discovered that in general reactions of this type occur under physiologically compatible conditions; for example, using water as the medium and mixing the two components. The purification method can be as simple as a gravity filtration. Products of the reaction are compatible with biological requirements. These results well match the definition to click chemistry. If a hydrazide has an amino group present at the alpha carbon, that rate of the reaction is faster and structure seems more stable than in its absence. My focus on this new click chemistry consists of two parts: 1) the elucidation of the structure of products formed between different types of ortho-formylphenyl boronic acids and four types of alpha-effect amine through a series of NMR characterizations; 2) synthesis of ortho-formylphenylboronic acid containing fluorophores as potential bioorthogonal labeling reagents. |
