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QSPR/QSAR-based Perturbation Theory approach and mechanistic electrochemical assays on carbon nanotubes with optimal properties against mitochondrial Fenton reaction experimentally induced by Fe2+-overload

2017; Elsevier BV; Volume: 115; Linguagem: Inglês

10.1016/j.carbon.2017.01.002

1873-3891

Michael González‐Durruthy, Micheli Rosa de Castro, Silvana Manske Nunes, Juliane Ventura‐Lima, Luciane C. Alberici, Zeki Naal, David T. Atique-Sawazaki, Carlos Curti, Caroline Pires Ruas, Marcos A. Gelesky, Kunal Roy, Humberto González‐Díaz, José María Monserrat,

ATP Synthase and ATPases Research

In the present study, different in vitro and electrochemical protocols were employed to determine the mitoprotective properties of carbon nanotubes family (pristine-CNT, oxidized-CNT) based on free radical scavenging ability against the most aggressive reactive oxygen species (ROS) as hydroxyl radical (·OH) formed by Fenton-Haber-Weiss reaction, which was experimentally induced on isolated rat-liver mitochondria through Fe2+ ions overload. The results suggest that the mitochondrial Fenton-inhibition response involves a significant reduction of (·OH) concentration linked to iron-complexing ability of CNT-family, following the order: carboxylated-CNT > pristine-CNT ∼ hydroxylated-CNT, without affecting the electrochemical mitochondrial membrane potential in Fe2+-overloaded mitochondria. Besides, a new in silico dose-response QSPR-model was applied suggesting reliability for the CNT-dose-effect series predictions towards the mitochondrial Fenton ROS-inhibition with excellent linear behavior on the training set (R2 = 0.901; R2(adj.) = 0.901; Q2(LOO-CV) = 0.901) and test set (Q2F1 = 0.9008; Q2F2 = 0.9008; Q2F3 = 0.9009; MAE = 21.213) for internal and external validation respectively, with p < 0.05 for all regression coefficient for > 70,000 data points. Lastly, these experimental and theoretical evidences open a gate to the rational design of novel carbon nanomaterials toward mitochondrial nanomedicine based redox-targeting as an alternative of treatment of several chronic diseases where pathological Fenton-reaction mechanisms have been directly involved.