Bioorthogonal Chemistry as an Innovative Synthetic Tool

Abstract

Bioorthogonal chemistry is a unique technique that allows chemical reactions to occur inside living systems, such as cells and organisms, without disturbing their natural biological processes. This paper focuses on SPAAC (Strain-Promoted Azide-Alkyne Cycloaddition), which is a metal-free click reaction. Previously, Click Chemistry required a Copper (Cu) catalyst to work. However, copper is toxic to living cells, making it unsafe for use in humans or animals. SPAAC solved this problem by removing the need for copper. Instead, it uses the concept of 'Ring Strain.' While normal alkynes are straight, SPAAC uses a bent ring called Cyclooctyne. The bond angle in this ring is forced to bend, creating stored energy. This 'strain' energy forces the reaction to happen automatically and quickly with Azides. Because it is safe for living things (biocompatible), SPAAC is widely used today for Live Cell Imaging to visualize sugars on cancer cells and for Targeted Drug Delivery to activate drugs specifically at tumor sites.