Elemental mapping of half-sandwich azopyridine osmium arene complexes in cancer cells

Abstract

Nanofocused synchrotron X-ray fluorescence and inductively coupled plasma-mass spectrometry provide insights into time-dependent ligand exchange reactions of organo-osmium anticancer complexes in cancer cells. Created with Biorender.com.

Single-Cell Chemistry of Photoactivatable Platinum Anticancer Complexes

“…Synchrotron-XRF can be used to investigate the biodistribution of the heavy metal components of metallodrugs in cancer cells (in addition to endogenous biological elements). The use of synchrotron-XRF for the analysis of metal anticancer complexes in vitro and ex vivo (e.g., in tissue from xenograft models) has been reported for platinum, − ruthenium, , iridium, and osmium − anticancer agents, among others. Notably, cryo-XRF is emerging at various beamlines for the analysis of frozen-hydrated cells or tissues close to their native state, including ID16A (ESRF, Grenoble) and 9-ID-B (APS, Illinois) …”

Os(ii) complexes for catalytic anticancer therapy: recent update

“…Recently, 16 electron Os(II) complexes have been demonstrated as potent catalytic cancer drug candidates. [46][47][48] Os(II), being kinetically more inert than the corresponding secondrow transition metal ions, such as Ru(II), is more suitable to deliver the active catalyst directly to the cells. 49 In this direction, Sadler et al have recently reported a few interesting half sandwich sixteen electron Os(II) transfer hydrogenation catalysts to achieve in-cell pyruvate and quinone reduction as a novel anticancer mechanism.…”

“…49 In this direction, Sadler et al have recently reported a few interesting half sandwich sixteen electron Os(II) transfer hydrogenation catalysts to achieve in-cell pyruvate and quinone reduction as a novel anticancer mechanism. [46][47][48]50 It is important to note here that pyruvate is involved in many metabolic pathways, particularly in the Krebs cycle to produce energy. 51,52 Thus, any disturbance in pyruvate metabolism would lead to metabolic dysfunction and might ultimately cause cell death.…”

“…Aside from the conventional chemotherapeutic drugs, redoxactive drug molecules which can effectively disturb the redox balance in cancer cells by elevating the intracellular ROS level have drawn attention due to their selective cytotoxicity at the desired tumor site. 10,11,18,69 Many transition metal-based prodrugs have been reported to produce ROS in cancer cells, 48 From the X-ray absorption spectroscopy (XAS) and DFT calculations, it was evident that the anticancer mechanism of these complexes involves an azo-bond (NQN) centred catalytic reaction. 48 The NQN bond in the complexes reacted with GSH, facilitating the release of X.…”

“…10,11,18,69 Many transition metal-based prodrugs have been reported to produce ROS in cancer cells, 48 From the X-ray absorption spectroscopy (XAS) and DFT calculations, it was evident that the anticancer mechanism of these complexes involves an azo-bond (NQN) centred catalytic reaction. 48 The NQN bond in the complexes reacted with GSH, facilitating the release of X. 48 So, the activity of these complexes was found to be largely dependent on the lability of the Os-X bond.…”