A Nanoenzyme Constructed from Manganese and Strandberg-Type Phosphomolybdate with Versatility in Antioxidant and Modulating Conformation of Aβ Protein Misfolding Aggregates In Vitro

Abstract

Amyloid β-peptide (Aβ) misfolding aggregates with β-sheet structures and surplus reactive oxygen species (ROS) are both considered to be the culprit of neuronal toxicity in Alzheimer’s disease (AD). Therefore, modulating the misfolding mode of Aβ and inhibiting ROS simultaneous has become an important method for anti-AD. Herein, a nanoscale manganese-substituted polyphosphomolybdate (H2en)3[Mn(H2O)4][Mn(H2O)3]2[P2Mo5O23]2·14.5H2O (abbreviated as MnPM) (en = ethanediamine) was designed and synthesized by single crystal to single crystal transformation method. MnPM can modulate the β-sheet rich conformation of Aβ aggregates, and thus reduce the formation of toxic species. Moreover, MnPM also possesses the ability to eliminate the free radicals produced by Cu2+-Aβ aggregates. It can inhibit the cytotoxicity of β-sheet-rich species and protect synapses of PC12 cells. MnPM combines the conformation modulating ability of Aβ and anti-oxidation ability, which makes a promising multi-funcational molecular with a composite mechanism for the new conceptual designing in treatment of such protein-misfolding diseases.

A Nanoscale Cobalt Functionalized Strandberg-Type Phosphomolybdate with β-Sheet Conformation Modulation Ability in Anti-Amyloid Protein Misfolding

“…The structural analysis results are shown in Figure 1a, which shows that the CoPM unit cell includes eight K + counter ions, eight crystallized water molecules, and one {Co(H2O)4} 2+ complex sandwiched polyoxoanion [P2Mo5O23] 6− (Figure 1a,b). ) 2 ] (C1) [37] and (H 2 en) 6 {[Co(H 2 O) 4 ](P 2 Mo 5 O 23 )} 3 •11H 2 O (C2) [38]. However, there are some differences among them: First of all, they have different molecular formulas.…”

“…According to a retrieval of the CCDC database, CoPM's molecular structure Hitherto, there are two similar POMs deposited in the CCDC d [H8(H2O)16][Co(H2O)4(HP2Mo5O23)2] (C1) [37] and (H2en)6{[Co(H2O)4](P2Mo5O23)} (C2) [38]. However, there are some differences among them: First of all, they have d molecular formulas.…”

“…POMs have several unique, unmatched characteristics that enable them to serve as substantial polydentate ligands for transition-metal ions with various coordination modes, such as oxygen-rich nucleophilic surfaces, nanoscale sites, and sites that form multiple bonds [24][25][26][27][28][29][30][31][32]. Recently, it was shown that some nanoscale POMs, because of their distinct nanoscale size, high negative charge, and oxygen-rich surface, had a remarkable capacity for modifying misfolded βsheet-rich conformation [33][34][35][36]. As a result, combining cobalt complexes with nanoscale POM clusters to create a single hybrid molecule may not only preserve but also advantageously express the desirable properties of all individual components.…”