Study of Catalysis Mechanism of Copper Clusters on Azide-Alkyne Cycloaddition

• Main Author: ADIPRASTYO - NIM: 20516014, BAGUS
• Format: Theses
• Language: Indonesia
• Online Access: https://digilib.itb.ac.id/gdl/view/26009
• Institution: Institut Teknologi Bandung

<p align="justify">The cycloaddition reaction between organic azide and alkyne introduced by Huisgen in 1963 yields a mixture of triazole containing 1,4 and 1,5-regioisomer. Based on researches, 1,4-regio-triazole is better for drug candidates than 1,5-regio due to its low inhibition properties toward metabolism enzyme and other drugs. Various attempts to control its regioselectivity have been reported without much success until the discovery of Cu-catalyzed Azide-Alkyne Cycloadditon (CuAAC) by Sharpless in 2001 which exclusively yields 1,4-regio-triazole. Since that, experiment procedures using various Cu-based catalysts such as Cu-sulfate, Cu-halide, Cu-acetate and copper nanoparticles have sprung up over the past decade. The aim of this study is to investigate the catalysis mechanism of copper nanoparticles represented as copper clusters in CuAAC by DFT calculation using B3LYP/LANL2DZ powered by Gaussian 09. For the first part, the copper clusters (Cu2 – Cu10) have been optimized to ensure that the proposed cluster models have been able to represent real clusters and to validate the calculation method through comparison with experiments and previous studies. The results show that the proposed clusters have been able to represent real clusters based on the optimized structures, binding energies, ionization potentials and relative stability, which qualitatively show good agreement with experiments and previous studies. The second part, the uncatalyzed and catalyzed reaction mechanism using optimized clusters (Cu2 – Cu5) are investigated by involving simple reactans of methyl azide and propyne to produce 1,4 and 1,5-dimethyl-triazole. For the cycloaddition with the absence of Cu, it shows activation barriers of 37.80 and 38.61 kcal/mol for the formation of 1,4 and 1,5-dimethyl-triazole, respectively. The relatively small difference of barrier between those two formations explains why the cycloaddition without Cu catalyst yields mixture of two regioisomers. The CuAAC catalyzed by copper clusters (Cu2 – Cu5) shows average activation barriers of 26,79 and 40,26 kcal/mol for the formation of 1,4 and 1,5-dimethyl-triazole, respectively. The presence of copper clusters not only increases the rate but also leads cycloaddition to exclusively yield 1,4-regioisomer instead of 1,5-regioisomer due to its large barrier difference between those two formation pathways. The large rate increase observed in the synthesis of triazole via CuAAC is in excellent agreement with the computed activation barriers, which are as much as 11.01 kkal/mol lower than in the corresponding uncatalyzed cycloaddition. Overall, the proposed copper clusters are able to represent the ability of copper nanoparticles catalyst and this study raises a new challenge to predict the decreasing value of activation barrier more accurately.<p align="justify">