New Study Unveils Cobalt(III) Reaction Mechanism with Nitriles, Opening Pathways for Drug Development

Abstract
The intrinsic relationship between spin states and reactivity in peroxocobalt(III) complexes was investigated, specifically focusing on the influence of steric modulation on supporting ligands. Together with the previously reported [CoIII(TBDAP)(O2)]+ (2Tb), which exhibits spin crossover characteristics, two peroxocobalt(III) complexes, [CoIII(MDAP)(O2)]+ (2Me) and [CoIII(ADDAP)(O2)]+ (2Ad), bearing pyridinophane ligands with distinct N-substituents such as methyl and adamantyl groups, were synthesized and characterized. By manipulating the steric bulkiness of the N-substituents, control of spin states in peroxocobalt(III) complexes was demonstrated through various physicochemical analyses. Notably, 2Ad oxidized the nitriles to generate hydroximatocobalt(III) complexes, while 2Me displayed an inability for such oxidation reactions. Furthermore, both 2Ad and 2Tb exhibited similarities in spectroscopic and geometric features, demonstrating spin crossover behavior between S = 0 and S = 1. The steric bulkiness of the adamantyl and tert-butyl group on the axial amines was attributed to inducing a weak ligand field on the cobalt(III) center. Thus, 2Ad and 2Tb are an S = 1 state under the reaction conditions. In contrast, the less bulky methyl group on the amines of 2Me resulted in an S = 0 state. The redox potential of the peroxocobalt(III) complexes was also influenced by the ligand field arising from the steric bulkiness of the N-substituents in the order of 2Me (−0.01 V) < 2Tb (0.29 V) = 2Ad (0.29 V). Theoretical calculations using DFT supported the experimental observations, providing insights into the electronic structure and emphasizing the importance of the spin state of peroxocobalt(III) complexes in nitrile activation.

A research team, led by Professor Jaeheung Cho from the Department of Chemistry at UNIST has unveiled the reaction mechanism of cobalt(III)-based metal complexes with nitrile substances, paving the way for potential new drug development.

In this study, the team investigated the mechanism of nitrile activation in biomimetic compounds utilizing cobalt(III), highlighting the significant impact of metal spin states on reaction activity. Their findings demonstrate that even small modifications to metal properties can profoundly influence the speed and outcomes of chemical reactions.

Figure 1. Schematic image, illustrating the overall research.

To examine how nitriles interact with cobalt compounds, the researchers employed a structure known as the ‘Macrocyclic Pyridinophane System,’ which enables adjustments in cobalt compound structures. Notably, compounds featuring larger adamantyl groups demonstrated enhanced nitrile activation reactions.

In contrast, compounds with smaller methyl groups showed no reactivity. This difference is attributed to changes in the metal’s spin states, which depend on the size of the functional group, resulting in distinct reactivity profiles.

Nitriles are widely used in pharmaceuticals and pesticides but often present challenges in reactivity. The team confirmed that cobalt(III)-peroxo species can react with nitriles at room temperature to form a specific compound, which shows promise as a potential anticancer agent.

“We successfully synthesized cobalt(III)-peroxo species with varying spin states by modifying the three-dimensional configuration of the ligands, revealing a close relationship with nitrile reactivity,” said first author Seonghan Kim. Professor Cho added, “Controlling the spin state of cobalt(III)-peroxo species is of significant academic importance and could pave the way for new developments in metal catalysts.”

This collaborative research involved Professor Jana Roithová from Radboud University in the Netherlands and Professor Sunggi Lee from DGIST. The findings, supported by the National Research Foundation of Korea (NRF), the Ministry of Science and ICT (MSIT), and the Ministry of Trade, Industry and Energy (MOTIE), were published online in the Journal of the American Chemical Society (JACS) on July 20, 2024.

Journal Reference
Seonghan Kim, Yuri Lee, Guilherme L. Tripodi, et al., “Controlling Reactivity through Spin Manipulation: Steric Bulkiness of Peroxocobalt(III) ComplexesArticle link copied!,” JACS, (2024).