The metalloprotein-inspired Ru complex (3) was prepared via molecular convolution from linear amphiphilic polymer poly(N-isopropyl-acrylamide-co-N-vinylimidazole) (1) and ruthenium trichloride (2). The insoluble black metalloprotein-inspired Ru complex (3) efficiently promoted the 1,3-dipolar Huisgen's reaction in aqueous medium at room temperature. The reaction process resulted in a highly regioselective product within a short reaction time. A very low catalytic loading of 172 mol ppm with respect to ruthenium was sufficient to drive the reaction process. The turnover number and turnover frequency of the catalyst reached high values of 5765 and 577 min I, respectively. Furthermore, the catalyst could be easily separated by means of simple filtration and could be recycled and reused for six consecutive runs. No significant amount of leaching of the catalyst was observed. For industrial applicability, a gram-scale reaction was also performed which resulted in good yield of the product. Hence, the present catalytic process is industrially and academically attractive because of its reusability, high efficiency, high regioselectivity, short reaction time, aqueous reaction medium, room-temperature stirring, high yield, and good functional group tolerance.