Bioorthogonal Activation of Dual Catalytic and Anti-Cancer Activities of Organogold(I) Complexes in Living Systems, a joint research paper by Doctor Cao Bei, Lecturer in  General Education from the School of Humanity and Social Sciences (HSS), CUHK-Shenzhen, and a research team from Sun Yat-sen University, was published at the prime chemistry journal Angewandte Chemie International Edition.

Her research has developed an approach to modulate the bioreactive activity of gold complex using palladium-induced bioorthogonal reactions to achieve targeted inhibition of cancer cells. This is the first application of bioorthogonal reactions in the related fields, and will be a powerful stimulus for further development of metal complexes in related biological fields. As the co-first author of the paper, Dr. Cao Bei uses theoretical calculations to elucidate the reaction path for such an approach, laying a theoretical basis for the optimal design of this new orthogonal reaction.

About the Research

As an important alternative to traditional platinum-based anticancer drugs that may have intrinsic or acquired resistance, Au (I) anticancer drugs boast great potential due to their low toxic side effects and unique mechanism of action. Such classification also has significant application value in the field of biocatalysis. However, due to the existence of off-target sulfhydryl compounds competing for binding in vivo, the application of Au(I) complexes in cells and in vivo is greatly limited.

The team has reported a new bioorthogonal activation approach by employing Pd(II)‐triggered transmetallation reactions to conditionally activate the bio-reactivity of NHC‐Au(I)‐phenylacetylide complexes (e.g., 1a ) in vitro and in vivo. In this way, it is possible to avoid the competitive binding of Au(I) complexes and off-target sulfhydryl compounds in vivo, and to reduce the toxic side effects.

In this work, Dr. Bei Cao uses Density-functional theory (DFT), a computational quantum mechanical modelling method, to model and calculate the key mechanism of the path of transmetallation reactions. The results show that there are gold-palladium interactions in the transmetallation reactions, which greatly reduces the reaction energy barrier. And in comparison, the same gold(I) complex combined with off-target sulfhydryl compounds in vivo has a much higher reaction energy barrier than that of the gold-palladium transmetallation reactions. The results have provided key theoretical support for the further optimization of the screening of palladium reagents in this project. Noteworthy, the theoretical calculations of the paper were greatly supported by the Warshel Institute for Computational Biology, CUHK-Shenzhen in terms of hardware.

The results of this study were highly regarded by the reviewers of Angew. Chem. Int. Ed. as an important advance in the field of gold-containing drugs. The reviewers consider the study as a solid and innovative paper that demonstrates well the intracellular reactivity of gold complexes with good pharmacological properties activated in a controlled manner.

About the Author

Doctor CAO, Bei

Lecturer in General Education

HSS, CUHK-Shenzhen