Quantum chemistry molecular modelling for mitochondria targeted chemotherapy: Verification of oxidative stress on mitochondria and anticancer medicines

Abstract

Background: We understand that most diseases which are accompanied with aging must relate to oxidative stress, i.e. oxidative damage of lipid lamellar bimolecular membranes of mitochondria ( mt ). So-called cancer and tumor are groups of such diseases and are diagnosed on the basis of hard spot touch and cell-deformed invasion image obtained by optical microscope, but molecular-level definition of cancer and tumor cells is unclear. The hard spot and/or the cell invasion will be symptoms relating to metabolic dysfunctions of cells, and hydrogen peroxide-derived hydroxyl radical must induce oxidative degradation of lipid lamellar membranes of mt in the cells. Our goal is to gain insights into reactivity of hydrated HOOH and hydroxyl radicals which produce and exist inevitably in mt , and instability of the mt ’s lipid bimolecular membrane. The result allows us to propose candidates for anticancer medicines which may have antioxidative effects on sustainable mt ’s membranes. Materials and methods: Quantum chemistry molecular modeling, i.e., density functional theory-based molecular modeling (DFT/MM) can be regarded as theory- based “experiments”. DFT/MM can be carried out very quickly using high-end supercomputer-like personal computers. The molecular unit consisting bimolecular membranes is glycerin triester of lauric acid [Gly(n-C 11 H 23 COO) 3 ]. DFT/MM are applicable to molecular aggregates which are induced by van der Waals (vdW) force (i.e. hydrogen bonding and Coulomb interactions). medicines, 5-Fluorouracil, Cisplatin, Oxaliplatin, Vitamin C and thyroid hormone, thyroxine (T4) are verified to suppress oxidation power of HOOH and HO . . DFT/MM verifies that the swelling and/or invasion tissues filled with the swollen and dysfunctional mt is an authentic model of cancer.