Click reaction or copper‐assisted azide–alkyne cycloaddition (CuAAC) reaction can conveniently synthesize desired organic molecules or functionalize biological macromolecules. In many cases, trace amounts of residual copper from the reaction mixture are not trivial to remove when the exhaustive purification step is avoided to fulfill the essential criteria of a click reaction. It is often detrimental, particularly for biochemical applications or when it involves biological macromolecules. Herein, we have reported the synthesis of a new type of copper (I) complex as a smart catalyst for click reaction, which can be separated from the reaction mixture very easily by the slight elevation of temperature, thanks to its thermoresponsive behavior. The click reactions using a thermoresponsive catalyst were first studied in an aqueous medium using various organic molecules containing alkyne and azide functional groups. Later, the strategy was extended to biological macromolecules like collagen.

The Front Cover illustrates the click reaction using a thermoresponsive copper (I) catalyst, typically on a biological macromolecule. The responsive behavior of the catalyst allows the click reaction to be effectively performed under ambient temperature (represented by a blue path) and its removal/recovery after completion of the reaction at slightly elevated temperature (represented by a red path). The cover was designed with the help of Mr. R. T. Birla Sheyara of PST Department of CSIR‐CLRI. More information can be found in the Research Article by D. Samanta et al.