Tri-Manganese(III) Salen-Based Cryptands: A Metal Cooperative Antioxidant Strategy that Overcomes Ischemic Stroke Damage In Vivo

Abstract

Oxidative stress is one of the hallmarks of ischemic stroke. Catalase-based (CAT) biomimetic complexes are emerging as promising therapeutic candidates that are expected to act as neuroprotectants for ischemic stroke by decreasing the damaging effects from H2O2. Unfortunately, these molecules result in the unwanted production of the harmful hydroxyl radical, HO•. Here, we report a series of salen-based tri-manganese (Mn­(III)) metallocryptands (1–3) that function as catalase biomimetics. These cage-like molecules contain a unique “active site” with three Mn centers in close proximity, an arrangement designed to facilitate metal cooperativity for the effective dismutation of H2O2 with minimal HO• production. In fact, significantly greater oxygen production is seen for 1–3 as compared to the monomeric Mn­(Salen) complex, 1c. The most promising system, 1, was studied in further detail and found to confer a greater therapeutic benefit both in vitro and in vivo than the monomeric control system, 1c, as evident from inter alia studies involving a rat model of ischemic stroke damage and supporting histological analyses. We thus believe that metallocryptand 1 and its analogues represent a new and seemingly promising strategy for treating oxidative stress related disorders.

Introduction of a trinuclear manganese(iii) catalyst on the surface of magnetic cellulose as an eco-benign, efficient and reusable novel heterogeneous catalyst for the multi-component synthesis of new derivatives of xanthene

“…[41][42][43] Trinuclear catalyst Mn could be better alternatives for greener production of xanthene derivatives because they can provide a large surface terrain as the catalytic patronage for catalyzing organic reactions. 44,45 To the best of our knowledge, no such trinuclear catalyst based on magnetic nano-ber cellulose has been used so far to prepare these derivatives making this approach a novel one for such synthesis. In this work, we synthesized a manganese trinuclear catalyst using a mechanical method using nanober cellulose as a substrate and a ligand as an anchor.…”

Dual Reactive Oxygen Species Generator Independent of Light and Oxygen for Tumor Imaging and Catalytic Therapy

“…To realize the effective loading of trivalent manganese, we first synthesized the salen ligand by an aldimine condensation reaction between ethylenediamine (EDA) and salicylaldehyde. [17][18][19][20] Subsequently, the structure of salen was characterized by 1 H NMR (Figure S1). In the 1 H NMR spectrum, the hydrogen atom peaks at 13.39, 8.59, and 7.51-6.80 ppm were allocated to the exposure of salicylaldehyde.…”

Gallium (III) Complexes in Cancer Chemotherapy

“…Recently, with the in‐depth study of microenvironment, destroying the homeostasis has become a new strategy to treat tumor or inflammation. For example, a mitochondrion‐target rhenium complex ( 12 ) conjugated with iron chelates can destroy cellular iron homeostasis, leading to tumor cell death; [22] a tri‐Mn complex ( 13 ) as a catalase can scavenge hydrogen peroxide accumulated in inflammation sites, which was applied in stroke treatment [23] . An iridium half‐sandwich complex ACC25 ( 14 ), a lipophilic cation, is highly restricted to mitochondria and distorts the mitochondrial membrane, resulting in a net influx of calcium ions into the mitochondrion matrix [24] .…”