Revealing the Influence of Secondary Metals on Redox-Active Palladium Complexes

Incorporation of redox-inactive metals into redox-active complexes and catalysts attracts attention for engendering new reactivity modes, but this strategy has not been extensively investigated beyond the first-row of the transition metals. Here, the isolation and characterization of the first series of heterobimetallic complexes of palladium with mono-, di-, and tri-valent redox-inactive metal ions are reported. A Reinhoudt-type heteroditopic ligand with a salen-derived [N2,O2] binding site for Pd and a crown-ether-derived [O6] site has been used to prepare isolable adducts of the Lewis acidic redox-inactive metal ions (Mn+). Comprehensive data from single-crystal X-ray diffraction analysis reveal distinctive trends in the structural properties of the heterobimetallic species, including an uncommon dependence of the Pd•••M distance on Lewis acidity. The reorganization energy associated with reduction of the heterobimetallic species is strongly modulated by Lewis acidity, with the slowest heterogeneous electron transfer kinetics associated with the strongest incorporated Lewis acids. This hitherto unexplored reorganization energy penalty for electron transfer contrasts with prior thermodynamic studies, revealing that kinetic parameters should be considered in studies of reactivity involving heterobimetallic species.

Mechanistic Insights Expatiating the Redox-Active-Metal-Mediated Neuronal Degeneration in Parkinson’s Disease

Parkinson’s disease (PD) is a complicated and incapacitating neurodegenerative malady that emanates following the dopaminergic (DArgic) nerve cell deprivation in the substantia nigra pars compacta (SN-PC). The etiopathogenesis of PD is still abstruse. Howbeit, PD is hypothesized to be precipitated by an amalgamation of genetic mutations and exposure to environmental toxins. The aggregation of α-synucelin within the Lewy bodies (LBs), escalated oxidative stress (OS), autophagy-lysosome system impairment, ubiquitin-proteasome system (UPS) impairment, mitochondrial abnormality, programmed cell death, and neuroinflammation are regarded as imperative events that actively participate in PD pathogenesis. The central nervous system (CNS) relies heavily on redox-active metals, particularly iron (Fe) and copper (Cu), in order to modulate pivotal operations, for instance, myelin generation, synthesis of neurotransmitters, synaptic signaling, and conveyance of oxygen (O2). The duo, namely, Fe and Cu, following their inordinate exposure, are viable of permeating across the blood–brain barrier (BBB) and moving inside the brain, thereby culminating in the escalated OS (through a reactive oxygen species (ROS)-reliant pathway), α-synuclein aggregation within the LBs, and lipid peroxidation, which consequently results in the destruction of DArgic nerve cells and facilitates PD emanation. This review delineates the metabolism of Fe and Cu in the CNS, their role and disrupted balance in PD. An in-depth investigation was carried out by utilizing the existing publications obtained from prestigious medical databases employing particular keywords mentioned in the current paper. Moreover, we also focus on decoding the role of metal complexes and chelators in PD treatment. Conclusively, metal chelators hold the aptitude to elicit the scavenging of mobile/fluctuating metal ions, which in turn culminates in the suppression of ROS generation, and thereby prelude the evolution of PD.

Lewis Acid-Assisted Reduction of Nitrite to Nitric and Nitrous Oxide via the Elusive Nitrite Radical Dianion

Reduction of nitrite anions [NO2]- takes place in a myriad of environments such as in the soil as part of the biogeochemical nitrogen cycle as well as in acidified nuclear waste. Nitrite reduction typically takes place within the coordination sphere of a redox active transition metal. Lewis acid coordination, however, can dramatically modify the reduction potential of this polyoxoanion to allow for reduction under non-aqueous conditions (-0.74 V vs. NHE). This strategy enables the isolation of a borane-capped nitrite dianion [NO2]2- along with its spectroscopic study consistent with reduction to the N(II) oxidation state. Protonation of the nitrite dianion results in facile loss of nitric oxide (NO) while reaction of the nitrite dianion with nitric oxide results in disproportionation to nitrous oxide (N2O) and nitrite, connecting three redox levels in the global nitrogen cycle.

In Vitro Anticancer Screening and Preliminary Mechanistic Study of A-Ring Substituted Anthraquinone Derivatives

Anthraquinone derivatives exhibit various biological activities, e.g., antifungal, antibacterial and in vitro antiviral activities. They are naturally produced in many fungal and plant families such as Rhamnaceae or Fabaceae. Furthermore, they were found to have anticancer activity, exemplified by mitoxantrone and pixantrone, and many are well known redox-active compounds. In this study, various nature inspired synthetic anthraquinone derivatives were tested against colon, prostate, liver and cervical cancer cell lines. Most of the compounds exhibit anticancer effects against all cell lines, therefore the compounds were further studied to determine their IC50-values. Of these compounds, 1,4-bis(benzyloxy)-2,3-bis(hydroxymethyl)anthracene-9,10-dione (4) exhibited the highest cytotoxicity against PC3 cells and was chosen for a deeper look into its mechanism of action. Based on flow cytometry, the compound was proven to induce apoptosis through the activation of caspases and to demolish the ROS/RNS and NO equilibrium in the PC3 cell line. It trapped cells in the G2/M phase. Western blotting was performed for several proteins related to the effects observed. Compound 4 enhanced the production of PARP and caspase-3. Moreover, it activated the conversion of LC3A/B-I to LC3A/B-II showing that also autophagy plays a role in its mechanism of action, and it caused the phosphorylation of p70 s6 kinase.