Mechanisms of action of (meth)acrylates in hemolytic activity, in vivo toxicity and dipalmitoylphosphatidylcholine (DPPC) liposomes determined using NMR spectroscopy.

We investigated the quantitative structure-activity relationships between hemolytic activity (log 1/H(50)) or in vivo mouse intraperitoneal (ip) LD(50) using reported data for α,ß-unsaturated carbonyl compounds such as (meth)acrylate monomers and their (13)C-NMR ß-carbon chemical shift (δ). The log 1/H(50) value for methacrylates was linearly correlated with the δC(ß) value. That for (meth)acrylates was linearly correlated with log P, an index of lipophilicity. The ipLD(50) for (meth)acrylates was linearly correlated with δC(ß) but not with log P. For (meth)acrylates, the δC(ß) value, which is dependent on the π-electron density on the ß-carbon, was linearly correlated with PM3-based theoretical parameters (chemical hardness, η; electronegativity, χ; electrophilicity, ω), whereas log P was linearly correlated with heat of formation (HF). Also, the interaction between (meth)acrylates and DPPC liposomes in cell membrane molecular models was investigated using (1)H-NMR spectroscopy and differential scanning calorimetry (DSC). The log 1/H(50) value was related to the difference in chemical shift (ΔδHa) (Ha: H (trans) attached to the ß-carbon) between the free monomer and the DPPC liposome-bound monomer. Monomer-induced DSC phase transition properties were related to HF for monomers. NMR chemical shifts may represent a valuable parameter for investigating the biological mechanisms of action of (meth)acrylates.

Relationships between base-catalyzed hydrolysis rates or glutathione reactivity for acrylates and methacrylates and their NMR spectra or heat of formation.

The NMR chemical shift, i.e., the π-electron density of the double bond, of acrylates and methacrylates is related to the reactivity of their monomers. We investigated quantitative structure-property relationships (QSPRs) between the base-catalyzed hydrolysis rate constants (k1) or the rate constant with glutathione (GSH) (log k(GSH)) for acrylates and methacrylates and the (13)C NMR chemical shifts of their α,ß-unsaturated carbonyl groups (δC(α) and δC(ß)) or heat of formation (Hf) calculated by the semi-empirical MO method. Reported data for the independent variables were employed. A significant linear relationship between k1 and δC(ß), but not δC(α), was obtained for methacrylates (r(2) = 0.93), but not for acrylates. Also, a significant relationship between k1 and Hf was obtained for both acrylates and methacrylates (r(2) = 0.89). By contrast, log k(GSH) for acrylates and methacrylates was linearly related to their δC(ß) (r(2) = 0.99), but not to Hf. These findings indicate that the (13)C NMR chemical shifts and calculated Hf values for acrylates and methacrylates could be valuable for estimating the hydrolysis rate constants and GSH reactivity of these compounds. Also, these data for monomers may be an important tool for examining mechanisms of reactivity.

Radical-scavenging activity of dietary phytophenols in combination with co-antioxidants using the induction period method.

The radical-scavenging activity of dietary phytophenols has been investigated by many researches due to their antioxidant, anti-inflammatory and anticancer property but the radical-scavenging effect of 2-phytophenol and the phytophenol:co-antioxidants, vitamin C and thiol combination under nearly anaerobic conditions still remains unknown. The radical-scavenging activity for seventeen phytophenols and for six synthetic phenols (positive controls) was investigated using the induction period method in the polymerization of methyl methacrylates (MMA) initiated by thermal decomposition of benzoyl peroxide (BPO) by monitoring differential scanning calorimetery (DSC). The k(inh) for the phytophenols was likely with the range 0.5 × 10³ M⁻¹s⁻¹-2.2 × 10³ M⁻¹s⁻¹, whereas that for synthetic phenols, hydroquinone and galvinoxyl, was with the range 7 × 10³ M⁻¹s⁻¹-8 × 10³ M⁻¹s⁻¹. Also, the additive scavenging effect of the (-)-epigallocatechin (EGC):(-)-epicatechin (EC) and the (+)-catechin:epicatechin (EC) combination was observed at 1:1 molar ratio, whereas that of the EC:quercetin combination showed the cancel (prooxidative) effect. Furthermore, the EGC:ASDB (L-ascorbyl 2,6-dibutylate) or 2-ME (2-mercaptoethanol) combination showed the prooxidative effect. Such enhancement of prooxidation in the combination may increase their toxic effects due to their cooxidation. Also, the synergic, additive or cancel effects of the flavonoid:vitamins E combination on the induction period in the BPO (a PhCOO* radical) and 2,2'-azobisisobutyronitrile (AIBN, an R* radical) systems are discussed.

Radical-scavenging activity and cytotoxicity of p-methoxyphenol and p-cresol dimers.

Compoundswith two phenolic OH groups like curcumin possess efficient antioxidant and anti-inflammatory activity. We synthesized p-cresol dimer (2,2'-dihydroxy-5,5'-dimethylbiphenol, 2a) and p-methoxyphenol dimer (2,2'-dihydroxy-5,5'-dimethoxybiphenol, 2b) by ortho-ortho coupling reactions of the parent monomers, p-cresol (1a) and p-methoxyphenol (1b), respectively. Their antioxidant activity was determined using the induction period method, and their cytotoxicity towards RAW 264.7 cells was also investigated using a cell counting kit. The stoichiometric factors n (number of free radicals trapped by one mole of antioxidant moiety) for 2a and 2b were 3 and 2.8, respectively, being greater than those for 1a and 1b. The ratio of the rate constant of inhibition to that of propagation (k(inh)/k(p)) for 2a and 2b was similar to that for 2-t-butyl-4-methoxyphenol (BHA), a conventional food antioxidant. The 50% inhibitory dose (ID50) declined in the order 1b > 1a >> 2b > 2a > BHA. The cytotoxicity for 2a and 2b was significantly greater than that for the parent monomers (p < 0.001), but smaller than that for BHA (p < 0.01). Compounds 2a and 2b may be useful as food antioxidants.

Antioxidant and cyclooxygenase-2-inhibiting activity of 4,4'-biphenol, 2,2'-biphenol and phenol.

The anthropogenic substance 4,4'-biphenol and its analogues are estrogenic and cytotoxic. It has been previously found that synthesized ortho-dimers of phenolic compounds possess potent antioxidative and anti-inflammatory activity. To clarify the relationships between radical-scavenging and anti-inflammatory activities, the radical-scavenging activities of 4,4'-biphenol, 2,2'-biphenol and phenol were investigated by using differential scanning calorimetry to measure the induction period for polymerization of methyl methacrylate initiated by thermal decomposition of 2,2'-azobisisobutyronitrile. We also investigated tThe inhibitory effects of these compounds on lipopolysaccharide (LPS)-stimulated cyclooxygenase-2 (COX-2) mRNA and protein expression and on binding of activator-protein-1 (AP-1) and nuclear factor kappa-B (NF-kappaB) to their respective consensus sequences were also investigated in RAW 264.7 cells. Furthermore, theoretical parameters such as phenolic-OH bond dissociation enthalpy (BDE) and ionization potential (IP(koopman)) were calculated at the density functional theory (DFT)/B3LYP levels. Cytotoxicity declined in the order 4,4'-biphenol > 2,2'-biphenol >> phenol. 2,2'-Biphenol, but not 4,4'-biphenol, showed inhibitory effects on LPS-stimulated COX-2 expression and on AP-1 and NF-kappaB binding to their consensus sequences at 1-10 muM. Expression of COX-2 in RAW cells was enhanced by 4,4'-biphenol plus LPS, possibly because of radical-mediated transformation of 4,4'-biphenol to the cytotoxic diphenylquinone, as judged by the stoichiometric factor (n value) of 3.429 and low IP(koopman) value of this biphenol. In contrast, the anti-inflammatory activity of 2,2'-biphenol may be the result of the formation of a dimer derived from oxidation of this compound, as suggested by its n value close to 1. Phenol showed anti-inflammatory activity but did not completely inhibit COX-2 expression, even at higher concentrations.

Construction of a dental caries prediction model by data mining.

Recently, the distribution of dental caries has been shown to be skewed, and precise prediction models cannot be obtained using all the data. We applied a balancing technique to obtain more appropriate and robust models, and compared their accuracy with that of the conventional model. The data were obtained from annual oral check-ups for schoolchildren conducted in Japan. Five hundred children were followed from ages 5 to 8, and the three-year follow-up data were used. The variables used were salivary levels of mutans streptococci and lactobacilli, 3-min stimulated saliva volume, salivary pH, fluoride usage, and frequency of consumption of sweet snacks and beverages. Initially, conventional models were constructed by logistic regression analysis, neural network (a kind of prediction method), and decision analysis. Next, the balancing technique was used. To construct new models, we randomly sampled the same number of subjects with and without new dental caries. By repeated sampling, 10 models were constructed for each method. Application of the balancing technique resulted in the most robust model, with 0.73 sensitivity and 0.77 specificity obtained by C 5.0 analysis. For data with a skewed distribution, the balancing method could be one of the important techniques for obtaining a suitable and robust prediction model for dental caries.

Bonding durability against water of a fluorine-containing resin for precious metal alloys.

In order to clarify the effect of fluorination of an adhesive resin on the durability of the resin bond to precious metal alloys, 2,2,2-trifluoroethyl methacrylate (TFEMA)-poly(2,2,2-trifluoroethyl methacrylate) (PTFEMA)/TBBO adhesive resin was prepared. The tensile bond strength of this resin to precious metal alloys treated with 9,10-epithiodecyl methacrylate (EP8MA) generally increased in the order Ag alloy

Prediction of the reduced glutathione (GSH) reactivity of dental methacrylate monomers using NMR spectra - Relationship between toxicity and GSH reactivity.

It has been established that the toxicity of acrylate and methacrylate monomers is driven by their reactivity towards glutathione (GSH). With this relationship, the objective of this study was to predict the GSH reactivity of dental methacrylate monomers, and hence their toxicity, using the (13)C-NMR chemical shifts of beta-carbon (delta(Cbeta)) and the (1)H-NMR shifts of the protons attached to beta-carbon (delta(Ha), delta(Hb)). The different nucleophiles were chosen to compare the different nucleophilic reactions involving acrylate and methacrylate monomers. In conjunction with the use of literature data for monomer/GSH reactivity, significant linear relationships between GSH reactivity (log K) and delta(Cbeta )or delta(Ha )were observed (p<0.001). As for the oral LD(50 )values of some dental dimethacrylates in mice, they were estimated using linear regression curve fitting of GSH reactivity-toxicity response data. Results revealed an acceptable correlation between the oral LD(50 )values of acrylates and methacrylates and GSH reactivity (p<0.05, outlier: HEMA). In conclusion, the present findings suggested that NMR spectra might be useful for predicting the toxicity of dental methacrylates.

Comparative study of the alkyl and peroxy radical-scavenging activity of 2-t-butyl-4-methoxyphenol (BHA) and its dimer, and their theoretical parameters.

BACKGROUND: 2-t-Butyl-4-methoxyphenol (BHA) has considerable toxicity and undesirable potential tumor-promoting activities. To clarify the free radical mechanism of BHA-induced toxicity, the comparative radical-scavenging activity of BHA and its dimer (bis-BHA, 3,3'-ditert-butyl-5,5'-dimethoxy-1,1'-biphenyl-2,2'-diol) with or without 2-mercapto-1-methylimidazole (MMI) was studied using the induction period method. MATERIALS AND METHODS: The induction period and propagation rate (Rp) were determined by differential scanning calorimetry (DSC) monitoring of polymerization of methyl methacrylate, initiated by the thermal decomposition of benzoyl peroxide (a source of the peroxy radical, PhCOO*) or 2,2'-azobisisobutyronitrile (a source of the alkyl radical, R*) under nearly anaerobic conditions. The anti-1,1'-diphenyl-2-picrylhydrazyl (DPPH) radical- and O2(-)-scavenging activities were also investigated. Furthermore, theoretical parameters were calculated from the DEFT/B3LYP and HF/6-31G*//B3LYP levels. RESULTS: For both PhCOO* and R* the inhibition rate constant (k(inh)) for BHA and bis-BHA was almost identical, but a marked decrease in the Rp(inh)/Rp(con) was found for the former. The BHA/MMI mixture (1:1 molar ratio) oxidized by R* reduced the total radical-scavenging activity by approximately 20% . BHA showed lower anti-DPPH radical- and higher O2(-)-scavenging activity. CONCLUSION: Upon PhCOO* or R* scavenging, BHA with a lower BDE, IP(koopman's), electronegativity, and electrophilicity value, but not bis-BHA with higher corresponding values, highly suppressed propagation. This may be due to the formation of highly reactive free-radical intermediates, which are potentially toxic.

Development of new bone cement utilizing low toxicity monomers.

Acrylic bone cement is self-curing cement comprising of liquid and powder component of methyl methacrylate (MMA). It has been used extensively in orthopedics; however, adverse effects were associated with its use. Hence we investigated in this paper the possibility of new cement utilizing methacrylates with lower toxicity than MMA. LD50s of candidate monomers were determined with administration to the medullary cavity of the rat's femur. 2-Ethylhexyl methacrylate (EHMA) and trimethylolpropane trimethacrylate (TMP) demonstrated greater LD50 values of 187 mg/kg and 380 mg/kg, respectively, than MMA (108 mg/kg); they were selected as the liquid components of the new cement. The copolymer of EHMA and cyclohexyl methacrylate was then selected as the powder component. With this combination, we developed the new cement (EHMA cement).Temperature rise during polymerization of EHMA cement was 9 degrees C-13 degrees C, which was significantly lower than that of conventional cement. The compression strength of the polymerized EHMA cement was 57 MPa without TMP, and 67 MPa with TMP (15 wt%). Thus we concluded that new EHMA cement was slightly inferior in the compression strength than the conventional cement. However, it was characterized by the low toxicity of utilized monomers and the low temperature rise during polymerization.

A comparative study of the radical-scavenging activity of the phenolcarboxylic acids caffeic acid, p-coumaric acid, chlorogenic acid and ferulic acid, with or without 2-mercaptoethanol, a thiol, using the induction period method.

Phenolcarboxylic acid antioxidants do not act in vivo as radical-scavengers in isolation, but rather together with GSH (glutathione), a coantioxidant, they constitute an intricate antioxidant network. Caffeic acid, p-coumaric acid, ferulic acid and chlorogenic acid with or without 2-mercaptoethanol (ME), as a substitute for GSH, was investigated by the induction period (IP) method for polymerization of methyl methacrylate (MMA) initiated by thermal decomposition of 2,2'-azobisisobutyronitrile (AIBN, a source of alkyl radicals, R(.)) and benzoyl peroxide (BPO, a source of peroxy radicals, PhCOO(.)) using differential scanning calorimetry (DSC). Upon PhCOO(. )radical scavenging, the stoichiometric factors (n, number of free radical trapped by one mole of antioxidant) for caffeic acid, ferulic acid, p-coumaric acid and chlorogenic acid were 2.4, 1.8, 1.7 and 0.9, whereas upon R(.) radical scavenging, the corresponding values were 1.3, 1.2, 1.0 and 0.8, respectively. Antioxidants with n values close to 2 suggest the stepwise formation of semiquinone radicals and quinones. By contrast, those with n values close to 1 suggest the formation of dimers after single-electron oxidation, possibly due to recombination of corresponding aryloxy radicals. The ratio of the rate constant of inhibition to that of propagation (k(inh)/k(p)) declined in the order chlorogenic acid > p-coumaric acid > ferulic acid > caffeic acid. The ratio of the observed IP for the phenolcarboxylic acid/2-mercapto-ethanol (ME) mixture (1:1 molar ratio) (A) to the calculated IP (the simple sum of phenol acid antioxidant and ME) (B) was investigated. Upon R(.) scavenging, the caffeic acid or p-coumaric acid/ME mixture was A/B > 1, particularly the former was 1.2, suggesting a synergic effect. By contrast, upon PhCOO(.) scavenging, the corresponding mixture was A/B < 1, particularly the latter was 0.7, suggesting an antagonistic effect. Upon both radicals scavenging, the A/B for the ferulic acid or chlorogenic acid/ME mixture was approximately 1. The reported beneficial antioxidant, anti-inflammatory and anticancer effects of caffeic acid and p-coumaric acid may be related to their prooxidant-antioxidant balance in the presence of GSH.

Comparative radical-scavenging activity of curcumin and tetrahydrocurcumin with thiols as measured by the induction period method.

BACKGROUND: The in vivo radical-scavenging activity of curcumin (CUR) and THC (tetrahydrocurcumin, a metabolite of CUR) does not occur in isolation, but through an intricate antioxidant network together with co-antioxidants such as glutathiones (GSH). In the present investigation, the radical-scavenging activity of CUR and THC with 2-mercapto-1-methylimidazole (MMI, a thiol) was studied using the induction period method. MATERIALS AND METHODS: The induction period (IP) and propagation rate (Rp) for mixtures of MMI with THC or CUR were determined by differential scanning calorimetry (DSC) monitoring of the polymerization of methyl methacrylate (MMA) initiated by thermal decomposition of benzoyl peroxide (BPO, a source of peroxy radical, PhCOO*) or 2,2'-azobisisobutyronitrile (AIBN, a source of alkyl radical, R*) under nearly anaerobic conditions. RESULTS: The stoichiometric number of PhCOO* radicals that could be trapped per molecule (n) was 3.4 and 3.3 for CUR and THC, and that of the R* radical was 3.1 and 2.5, respectively. At a molar ratio of antioxidant:co-antioxidant (MMI) = 1:5, a THC/MMI mixture with PhCOO* enhanced the total radical-scavenging activity, possibly due to partial regeneration of THC, whereas a CUR/MMI mixture with PhCOO* reduced it. Similarly, CUR/MMI and THC/MMI mixtures with R*, particularly the former, reduced the total radical-scavenging activity, possibly due, in part, to destructive interference between the antioxidant and the co-antioxidant. CONCLUSION: THC oxidized by peroxy radicals may be more antioxidative than the corresponding CUR in the interplay with GSH.

Kinetic radical-scavenging activity of colchicine and tropolone.

The kinetics of radical-scavenging activities for colchicine and tropolone remain unknown. Their antioxidant activities were determined by the induction period (IP) method in the polymerization of methyl methacrylate initiated by thermal decomposition of 2,2'-azobisisobutyronitrile (AIBN, R*) or benzoyl peroxide (BPO, PhCOO*) using differential scanning calorimetry (DSC) under nearly anaerobic conditions. The IPs for colchicine and tropolone were very short despite the addition of a high concentration of these compounds relative to initiators; the stoichiometric factor (n, the number of moles of PhCOO* trapped by the antioxidant) was approximately 0.03 and 0.04 for colchicine and tropolone, respectively. The n value of these compounds for R* was less than that for PhCOO*. The rate constant of inhibition to that of propagation (kinh/kp) for both compounds was 23-27, and the difference between them was considerably small. Both compounds had weak antioxidant properties at very high concentrations.

Predicting the biological activities of 2-methoxyphenol antioxidants: effects of dimers.

UNLABELLED: Selective cyclooxygenase (COX)-2 inhibitors have attracted much attention in relation to the design of non-steroidal anti-inflammatory agents (NSAIDs). The relationship between experimentally derived data on the antioxidant capacity, cytotoxicity and COX-2 inhibition for a range of 2-methoxyphenols and their calculated descriptors was investigated. MATERIALS AND METHODS: Quantitative structure-activity relationship (QSAR) studies were performed on a series of 2-methoxyphenols that act as COX-2 inhibitors using electronic descriptors, such as the highest occupied molecular orbital (HOMO), the lowest unoccupied molecular orbital (LUMO), ionization potential (IP), chemical hardness (q), and electronegativity (chi), which were calculated by the CONFLEXIPM3 method. The antioxidant capacity of a range of 2-methoxyphenols was evaluated by 2,2'-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging activity, and the anti-peroxy radical activity (stoichiometric factor, n) was determined by the induction period method in the polymerization of methyl methacrylate (MMA) initiated by thermal decomposition of benzoyl peroxide (BPO). The 50% cytotoxic concentration (CC50) against human submandibular gland tumor cell line (HSG) was determined by the MTT method. RESULTS: Cytotoxicity declined in the order of curcumin > dehydrodiisoeugenol > isoeugenol >bis-MMP > eugenol > ferulic acid > 2-methoxy-4-methylphenol (MMP) > bis-eugenol > bis-ferulic acid. The inhibitory effects on LPS-induced COX-2 gene expression in RAW 264.7 cells were determined by Northern blot assay. The majority of 2-methoxyphenols studied were COX-2 inhibitors. In particular, dehydrodiisoeugenol was a potent inhibitor, followed by bis-ferulic acid and curcumin. A linear relationship between anti-DPPH radical activity (log 1/IC50) and IP for 2-methoxyphenols except for dehydrodiisoeugenol was observed (r2=0.768.) The n for methoxyphenols was less than 2 in most cases. A linear relationship (r(2)=0.713) between the log (1/CC50) and the r1-term except for ferulic acid was observed. COX-2 inhibition, except for hesperetin, was related to the chi-term (r(2)=0.685). CONCLUSION: It may be possible to predict the mechanism responsible for the biological activities of 2-methoxyphenols.

Radical-scavenging activity of the reaction products of isoeugenol with thiol, thiophenol, mercaptothiazoline or mercaptomethylimidazole using the induction period method.

The reaction products in the presence of Lewis acid of isoeugenol (1) with ethanethiol, thiophenol, 2-mercaptothiazoline or 2-mercapto-1-methylimidazole (ISO-S1-ISO-S-4) were obtained. The radical-scavenging activity of these compounds was investigated using the induction period method for polymerization of methyl methacrylate (MMA) initiated by thermal decomposition of 2,2'-azobisisobutyronitrile (AIBN) and benzoyl peroxide (BPO) and monitored by differential scanning calorimetry (DSC). For BPO, the stoichiometric factor (number of free radicals trapped by one mole of antioxidant moiety, n) declined in the order isoeugenol (1.8) > ISO-S-1 (1.6) > ISO-S-2 (1.2) > ISOS- 3 (0.9) > ISO-S-4 (0.3), whereas for AIBN, their n values were about 1, except for ISOS- 3 (0.6). The ratio of the rate constant of inhibition to that of propagation (k(inh)/k(p)) for BPO declined in the order ISO-S-4 (56) > ISO-S-3 (15) > ISO-S-2 (11) >ISO-S-1 (9) > isoeugenol (8). Similarly, for AIBN the k(inh)/k(p) of the reaction products (33-57) was greater than that of isoeugenol (31). The reaction products of isoeugenol with a SH group showed greater inhibition rate constants (kinh) than the parent compound isoeugenol.

Radical-scavenging activity of natural methoxyphenols vs. synthetic ones using the induction period method.

The radical-scavenging activities of the synthetic antioxidants 2-allyl-4-X-phenol (X = NO2, Cl, Br, OCH3, COCH3, CH3, t-(CH3)3, C6H5) and 2,4-dimethoxyphenol, and the natural antioxidants eugenol and isoeugenol, were investigated using differential scanning calorimetry (DSC) by measuring their anti-1,1-diphenyl-2-picrylhydrazyl (DPPH) radical activity and the induction period for polymerization of methyl methacrylate (MMA) initiated by thermal decomposition of 2,2'-azobisisobutyronitrile (AIBN) and benzoyl peroxide (BPO). 2-Allyl-4-methoxyphenol and 2,4-dimethoxy-phenol scavenged not only oxygen-centered radicals (PhCOO*) derived from BPO, but also carbon-centered radicals (R*) derived from the AIBN and DPPH radical much more efficiently, in comparison with eugenol and isoeugenol. 2-Allyl-4-methoxyphenol may be useful for its lower prooxidative activity.

Water durability of resin bond to pure gold treated with various adhesion promoting thiirane monomers.

Adhesion promoting monomers for precious metals, 2,3-epithiopropyl methacrylate (EP1MA), 4,5-epithiopentyl methacrylate (EP3MA), 9,10-epithiodecyl methacrylate (EP8MA), 10,11-epithioundecyl methacrylate (EP9MA), 9,10-epithiodecyl 4-vinylbenzoate (EP8VB), 2,3-epithiocyclohexyl methacrylate (EPCHMA), and 3,4-epithiobutyl 2,2-bis(methacryloyloxymethyl)-propionate (EP2BMA), were used as surface treatment agents for pure gold to improve the durability of resin bonds against water. Treated specimens were butt-jointed together with MMA-PMMA resins, and tensile bond strength was measured after 2,000 thermal cycles in water. Bond strength to precious metal alloys was also determined under the same condition to clarify the influence of metal composition. The adhesion performance of thiirane monomers to pure gold highly depended on their chemical structure. EP3MA, EP8MA, EP9MA, EP8VB, and EP2BMA showed excellent performance, while EP1MA exhibited a moderate one and EPCHMA a poor one. The comparison of pure gold with precious metal alloys revealed the usefulness of pure gold as a standard, common adherend for bond strength evaluations.

Anti- and pro-oxidant effects of oxidized quercetin, curcumin or curcumin-related compounds with thiols or ascorbate as measured by the induction period method.

Phenolic antioxidants, such as quercetin (QUE), curcumin (CUR) and the CUR-related compounds eugenol (EUG) and isoeugenol (IsoEUG), do not act in isolation in vivo but form an intricate antioxidant network together with ascorbate or glutathione (GSH). To clarify the antioxidant/prooxidant activity of these compounds in their interplay with ascorbate or GSH, the induction period (IP) and propagation rate (Rp) for mixtures of 2-mercapto-1-methylimidazole (MMI, a thiol) or L-ascorbyl-2,6-dibutyrate (ASDB, an ascorbate derivative) with QUE, CUR, EUG or IsoEUG were determined from differential scanning calorimetry (DSC) monitoring of the polymerization of methyl methacrylate (MMA), initiated by thermal decomposition of 1.0 mol% benzoyl peroxide (BPO, a PhCOO* radical) under nearly anaerobic conditions. The IP (min) for 0.01 mol% test compounds declined in the order CUR (28.31) > IsoEUG (19.47) > EUG (16.83) > QUE (10.17) > MMI (2.06) > ASDB (0.16). The inhibition rate constant (kin(inh), M(-1)s(-1)) declined in the order ASDB (7.85 x 10(5)) > MMI (5.99 x 10(4)) > QUE (1.21 x 10(4)) > EUG (7.93 x 10(3)) > IsoEUG (7.04 x 10(3)) > CUR (4.50 x 10(3)). The observed IP for MMI/QUE mixtures, particularly at molar ratios of 2:1 and 5:1, was significantly less than that for QUE alone as well as that calculated for MMI/QUE. The decrease in IP was similar to the observed IP in the control, suggesting the occurrence of oxygen uptake, possibly due to the formation of thiol RS radicals which, together with oxygen, produce oxo- and peroxo-sulphur radicals. The observed IPs for MMI/CUR or the MMI/IsoEUG mixtures, particularly the former, were less than the corresponding calculated IPs, suggesting co-oxidation of the MMI without oxygen uptake. In contrast, the observed IP of MMI/EUG mixtures was much greater than the corresponding calculated IP, suggesting the formation of an new antioxidative adduct between EUG-quinonemethide and MMI. The observed IP for the ASDBI/QUE mixtures was greater than the corresponding calculated IP, suggesting the effectiveness of QUE as a co-antioxidant for ascorbate. In contrast, the observed IP for the ASDB/CUR mixtures was significantly less than the corresponding calculated IP, suggesting the catalytic effectiveness of CUR for ascorbate co-oxidation. Cancer cells are anaerobic in their metabolism and they selectively absorb more ascorbate than normal cells do. Thus, the present findings for the ASDB/CUR mixtures could help explain the effectiveness of CUR in chemoprevention by inducing cancer cell apoptosis. In addition, the findings for the MMI/QUE mixtures suggest the production of toxic oxo- and peroxo-sulphur radicals from thiols.

Kinetic radical-scavenging activity of platonin, a cyanine photosensitizing dye.

Platonin is known to possess antioxidant activity. However, the kinetics of the radical-scavenging activities of this compound remain unknown. The aim of this study was to investigate the radical-scavenging activities of platonin by the induction period method in the polymerization of methyl methacrylate (MMA), initiated by thermal decomposition of 2,2'-azobis (isobutyronitrile) (AIBN) (a carbon-centered radical, R*), and benzoyl peroxide (BPO) (an oxygen-centered radical, PhCOO*), under nearly anaerobic conditions. The number of moles of R* or PhCOO* radicals trapped by platonin calculated with respect to 1 mole of inhibitor moiety unit (stoichiometric factor, n) was determined, and this showed that the n of fully oxidized platonin was 4. The inhibition rate constant (k(inh)) of platonin showed a wide range of 0.8 x 10(3) M(-1)s(-1) to 1.6 x 10(4) M(-1)s(-1). To clarify the interaction between platonin and thiols, 2-mercapto-1-methylimidazole (MMI) was used as a representative thiol, because glutathiones were unsuitable due to their limited solubility in MMA. MMI in the presence of platonin showed neither catalytic activities nor synergistic activities. Platonin possesses radical-scavenging activities and acts as an antioxidant. On the basis of our experimental results, the radical-scavenging mechanism is discussed.

A quantitative approach to the free radical interaction between alpha-tocopherol and the coantioxidants eugenol, resveratrol or ascorbate.

The regeneration of alpha-tocopherol (vitamin E; VE) by coantioxidants such as phenolics and ascorbate has been studied in homogeneous hydrocarbon solution and in biological systems. However, VE phenoxyl radicals (VE*) may be sufficiently reactive to cooxidize phenolic compounds and ascorbates. The coantioxidant behavior of some relevant phenols such as eugenol (EUG), isoeugenol (IsoEUG), 2,6-di-tert-butyl-4-methoxyphenol (DTBMP), trans-resveratrol (RES) and L-ascorbyl-2,6-dibutyrate (ASDB; an ascorbate derivative) with the antioxidant VE at a molar ratio of 1:1 was investigated by the induction period (IP) method in the kinetics of polymerization of methyl methacrylate (MMA) initiated by the thermal decomposition of 2,2'-azobis(isobutyronitrile) (AIBN; a source of alkyl radicals, R*) or benzoyl peroxide (BPO; a source of peroxy radicals, PhCOO*) under nearly anaerobic conditions. Synergism, implying regeneration of VE by the coantioxidant, was observed with only two of these combinations, VE/EUG with PhCOO* and VE/DTBMP with R*. For other mixtures of VE with a phenolic coantioxidant, VE was able to cooxidize the phenolic. Regeneration can only be observed if the bond dissociation energy (BDE) of the coantioxidant is lower than, or at least close to, that of VE. The driving force for regeneration of VE by EUG may be removal of the semiquinone radical of EUG by VE, leading to the formation of VE and EUG-quinonemethide, even though the BDE value of EUG is greater by 5.8 kcal/mol than that of VE. Further evidence for this mechanism of regeneration is provided by the value of approximately 2 for the stoichiometric factor (n) of EUG induced by PhCOO*, but not by R*, again implying the formation of EUG-quinonemethide. The regeneration of VE by DTBMP in the R* system may result from their much smaller difference in BDE (0.1-1.3 kcal/mol). Since VE is rapidly oxidized by PhCOO*, regeneration of VE by DTBMP was not found in this system. The observed IP for the VE/ASDB mixture in the R* system was much lower than that for VE alone, whereas the IP for VE/ASDB in the PhCOO* system was similar to that of VE. In the R* system, VE* was sufficiently reactive to cooxidize ASDB and, in addition, the prooxidation of VE may be promoted by the catalytic action of the ascorbate derivative. The present system, under nearly anaerobic conditions, is relatively biomimetic, since oxygen in living cells is sparse. Such studies could help to explain the mechanism of regeneration of VE by coantioxidants such as phenolic compounds and vitamin C in vivo.