Mariko Ishihara

Kinetic evaluation of the reactivity of flavonoids as radical scavengers

The reactivity of flavonoids as radical scavengers was investigated under kinetic considerations using radical polymerization of methyl methacrylates initiated by benzoyl peroxide. The number of radicals which are trapped by each molecule of phenol (the stoichiometric factors, n values) decreased in the order of epigallocatechin-3- O -gallate (ECG) (5.5) > catechin (3.5) > resveratrol (2.4) > quercetin (1.9)> n -propylgallate (1.5) > hesperetin (1.0). The inhibition rate constants ( k inh ) (1-3 ‐ 10 3 l/(mol s)) for the flavonoids were not different from each other, and, therefore, the radical scavenging activity depend on n values. The n values of the fully oxidized flavonoids were estimated from the frontier orbital theory, using PM3 semiempirical molecular orbital calculation. The experimental n values were consistent with the calculated values.

Kinetics of the radical scavenging activity of β-carotene-related compounds

To clarify the non-enzymatic radical-scavenging activity of β-carotene-related compounds and other polyenes, we used differential scanning calorimetry to study the kinetics of radical polymerization of methyl methacrylate (MMA) by 2,2′-azobisisobutyronitrile (AIBN) or benzoyl peroxide (BPO) in the absence or presence of polyenes under nearly anaerobic conditions at 70°C, and analyzed the results with an SAR approach. The polyenes studied were all-trans retinol, retinol palmitate, calciferol, β-carotene and lycopene. Polyenes produced a small induction period. The stoichiometric factor (n) (i.e. the number of radicals trapped by each inhibitor molecule) of polyenes was close to 0. Tetraterpenes (β-carotene, lycopene) suppressed significantly more of the initial rate of polymerization (R inh) than did diterpenes (retinol, retinol palmitate). The inhibition rate constants (k inh) for the reaction of β-carotene with AIBN-or BPO-derived radicals were determined to be 1.2–1.6 × 105  l / mol s, similar to published values. A linear relationship between k inh and the kinetic chain length (KCL) for polyenes was observed; as k inh increased, KCL decreased. KCL also decreased significantly as the number of conjugated double bonds in the polyenes increased. Polyenes, particularly β-carotene and lycopene, acted as interceptors of growing poly-MMA radicals.

Dipalmitoylphosphatidylcholine (DPPC) and DPPC/Cholesterol Liposomes as Predictors of the Cytotoxicity of Bis-GMA Related Compounds

In light of recent development, dental materials such as 2, 2‐ bis [4‐2(‐hydroxy‐3‐methacryloyloxypropoxy)phenyl] propane, (bis‐GMA); 2, 2‐ bis [4‐(1‐hydroxymethyl‐2‐methacryloxy)phenyl] propane, (iso‐ bis‐GMA); and triethyleneglycol dimethacrylate, (TEGDMA) were investigated to determine whether their phase transition properties (phase transition temperature, temperature width, cooperativity) could be induced in samples of DPPC or DPPC/cholesterol (CHOL) liposomes using differential scanning calorimetry (DSC). The changes in phase transition properties of DPPC liposomes caused by addition of TEGDMA were greater than those caused by addition of bis‐GMA or iso‐bis‐GMA, but the extent of changes in the properties of DPPC/CHOL (10:1 or 4:1) liposomes declined in the order of bis‐GMA > iso‐bis‐GMA > TEGDMA. The degree of alteration was related to the cytotoxicity of these compounds. DPPC/CHOL liposomes were found to be better predictors of cytotoxicity than DPPC liposomes. Whether the computational approach to studying the molecular mechanism of alteration is applicable using descriptors such as reactivity of energy of the highest occupied molecular orbital (HOMO) and/or lowest unoccupied molecular orbital (LUMO) was investigated, and the data suggested that these descriptors are useful for studying the interactive roles of dental materials.

Tumor Specificity and the Type of Cell Death Induced by Heterocycles

Considering the presence of multiple types of cell death induced by chemicals, it is important to determine a definitive strategy for the exploration of new highly tumor-selective compounds. The screening of highly selective compounds should be performed before the identification of the type of cell death (either apoptosis, autophagy, or necrosis) and the cell death induction mechanism. The tumor specificities of heterocyclic compounds and the type of cell death induced by them are summarized.