Issue 21, 2024

Understanding structural isomerism in organoiridium picolinamidate complexes and its consequences on reactivity and biological properties

Abstract

Organoiridium picolinamidate complexes are promising for intracellular applications because of their biocompatibility, activity in living systems, and ease of derivatization. To shield their metal centers from inhibition by biological nucleophiles (e.g., glutathione), attempts were made to increase the steric bulk of the supporting N-(2,6-R2-phenyl)picolinamidate ligand. It was found that when R = H (Ir1) or methyl (Ir2), the ligand adopts N,N′-coordination to iridium, whereas when R = isopropyl (Ir3) or phenyl (Ir4), N,O-coordination was observed. Based on experimental measurements and density functional theory calculations, it was revealed that the carbon chemical shift of the C(O)NR group can be used as a diagnostic handle to distinguish between the N,N′- and N,O-isomers in solution. Computational studies indicate that the former is favored thermodynamically but the latter is preferred when the R group is overly bulky. Complexes Ir1–Ir4 exhibit differences in lipophilicity, cellular uptake, cytotoxicity, and the propensity to generate reactive oxygen species in living cells. Reaction studies showed that Ir1/Ir2 are more efficient than Ir3/Ir4 in promoting the reduction of aldehydes to alcohols via transfer hydrogenation but both isomer types were susceptible to catalyst poisoning by glutathione. This work has led to new insights into structural isomerism in organoiridium picolinamidate complexes and suggests that steric tuning alone is insufficient to protect the Ir center from poisoning by biological nucleophiles.

Graphical abstract: Understanding structural isomerism in organoiridium picolinamidate complexes and its consequences on reactivity and biological properties

Supplementary files

Article information

Article type
Research Article
Submitted
01 aug 2024
Accepted
11 sep 2024
First published
13 sep 2024

Inorg. Chem. Front., 2024,11, 7407-7415

Understanding structural isomerism in organoiridium picolinamidate complexes and its consequences on reactivity and biological properties

H. D. Nguyen, C. J. Laconsay, R. D. Jana, T. Ganguly, S. T. Hoang, K. Kaushal, J. I. Wu and L. H. Do, Inorg. Chem. Front., 2024, 11, 7407 DOI: 10.1039/D4QI01955E

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