Model Studies on the Antioxidant Activity of Common Terpenoid

Article pubs.acs.org/JAFC

Model Studies on the Antioxidant Activity of Common Terpenoid Constituents of Essential Oils by Means of the 2,2-Diphenyl-1picrylhydrazyl Method Karolina A. Wojtunik, Lukasz M. Ciesla,* and Monika Waksmundzka-Hajnos Department of Inorganic Chemistry, Medical University of Lublin, Chodzki 4a, 20-093 Lublin, Poland S Supporting Information *

ABSTRACT: The research aims to indicate which of the structural elements of monoterpenes are responsible for their antioxidant activity. The activity was determined spectrophotometrically with the use of the DPPH• assay. It has been shown that π bonds are responsible for the chain-breaking antioxidant activity of monoterpenes. It has been proved, for the first time, that blocking of conjugated double bonds leads to a decrease of the antioxidant activity of monoterpenes. A probable reaction mechanism between monoterpenes and DPPH• has been proposed. It has been indicated that the antioxidant activity of monoterpenes strongly depends on the polarity of solvent used in the experiments. The presented results may stimulate additional research in the field of terpenoid antioxidants. KEYWORDS: monoterpenes, monoterpenic phenols, essential oils, 2,2-diphenyl-1-picrylhydrazyl, DPPH, antioxidant activity

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and butyrylcholinesterase inhibition, antimicrobial, etc.24−29 These isoprene derivatives have also been associated with plant protection mechanisms against oxidative stress.1,2 In the literature there are no data concerning the influence of structures of monoterpenes on their antioxidant activity. Some assumptions have been made, as, for example, for scavenging of oxygen in the oxygenated media by γterpinene.28,30 γ-Terpinene has also been shown to be an important nonphenolic free radical scavenger in citrus essential oils.27 The first aim of the research was to indicate which of the structural elements of monoterpenes were responsible for their antioxidant activity. The other goal was to check the influence of solvent, used in the experiments, on the monoterpenes’ antioxidant activity. This is the first time that detailed studies have been performed to identify molecular elements responsible for monoterpenes’ antioxidant activity toward free nitrogen radical (DPPH•).

INTRODUCTION All photosynthetic organisms have to cope with the excessive amount of excitation energy harvested by their photosystems.1,2 The excess of the energy may be responsible for the initiation of radical chain reactions and for the development of oxidative stress. In humans, free radicals have been blamed, at least partially, for the development of several chronic ailments, for example, Alzheimer’s disease, atherosclerosis, cancers, and many others.3,4 Organisms have developed different enzymatic and nonenzymatic systems for the safe dissipation of reactive oxygen species. Under optimal conditions, plants easily manage, with most of the energy absorbed by photosystems.1 In oxygenbreathing organisms, antioxidant enzymes, for example, superoxide dismutase or catalase, effectively defend cells from free radicals.5 The situation may change when an organism is under the influence of adverse environmental conditions. In such a case other mechanisms, namely, the participation of chainbreaking antioxidants, increase. Plant polyphenols are considered the most potent chainbreaking antioxidants.6−8 Several structural elements of polyphenol molecules have been identified as enhancing the free radical scavenging activity of these compounds.7−9 Direct antioxidant activity of polyphenols is often estimated with the use of the 2,2-diphenyl-1-picrylhydrazyl (DPPH•) spectrophotometric test.8−15 It has been shown that there is a strong correlation between the DPPH• scavenging activity of compounds and their ability to scavenge peroxyl radicals, generated in living cells.13 Different factors have been found to influence the measured antioxidant activity of polyphenols.13,16−23 Apart from polyphenols, other secondary plant metabolites have also been found to possess chain-breaking antioxidant activity, for example, terpenoids (mono-, di-, and sesquiterpenes, carotenoids, xanthophylls).5,24 Monoterpenes have been shown to possess the following activities: antioxidant, acetyl© XXXX American Chemical Society

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MATERIALS AND METHODS

Chemicals. DPPH• radical was purchased from Sigma-Aldrich Chemical Co. (St. Louis, MO, USA). The following compounds, (−)-isopulegol (≥99%), (+)-α-pinene (≥99%), menthol (≥99%), pcymene (≥99%), eucalyptol (≥99%), (R)-(+)-pulegone (97%), γterpinene (97%), linalool (≥97%), (S)-(+)-carvone (≥96%), αterpinene (≥95%), citronellal (≥95%), (−)-terpinene-4-ol (≥95%), citral (≥95%), ocimene (≥90%), menthone (≥90%), farnesene (mixtures of isomers, ≥90%), α-phellandrene (≥90%), myrcene (≥90%), eugenol (≥90%), and thymol (≥90%), were obtained also from Sigma-Aldrich. Solvents methanol, 2-butanone, ethyl acetate, chloroform, and n-heptane as well as silver nitrate (AgNO3) were Received: February 4, 2014 Revised: August 23, 2014 Accepted: August 24, 2014

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dx.doi.org/10.1021/jf502857s | J. Agric. Food Chem. XXXX, XXX, XXX−XXX

Journal of Agricultural and Food Chemistry

Article

Figure 1. Free radical scavenging activity toward DPPH•, in methanol, for (a) monoterpenes with conjugated π bonds and (b) monoterpenes lacking conjugated double bonds. obtained from Polish Reagents (Gliwice, Poland). All solvents were of analytical purity grade. DPPH• Radical Scavenging Assay. The radical scavenging activity of the analyzed compounds was determined spectrophotometrically by using the DPPH• assay.12−15 Absorbance was measured by a Genesys 20 UV−vis spectrophotometer (Thermo Fisher Scientific, Waltham, MA, USA) in a 1 cm quartz cell. DPPH• solution was prepared by mixing 0.004 g (10−5 mol) of DPPH• with 100 mL of each of the five solvents used in the study: methanol, 2-butanone, ethyl acetate, chloroform, and n-heptane. The concentration of the resulting solution was 0.1 mM. Fresh reagent was always prepared prior to analysis. A reference sample was prepared by mixing 2.5 mL of DPPH• (0.1 mM) with 0.7 mL of appropriate solvent. Afterward, each of the examined compounds was mixed with DPPH• solution. For each sample, the same amount (0.003 mol) of the compound was added to 2.5 mL of 0.1 mM DPPH• solution (the exact volumes of all liquid compounds and the weighed amounts of thymol and menthol are given in all tables in the Supporting Information). To obtain the exact volume for each of the measurements, the samples were made up to 3.2 mL volume, with the use of proper solvent. The samples were prepared with the same molar ratio of DPPH• to terpene. The loss of DPPH• absorbance was measured in the excess of examined compounds. Each measurement was repeated three times at 517 nm at room temperature. The final result is the average of three replicates. Free radical scavenging activity was calculated as a percentage of DPPH• decoloration according to the formula

scavenging % = 100 × (A blank − A sample /A blank )

samples were prepared by mixing the proper volume of monoterpene containing 0.003 mol of the compound, with AgNO3 (0.003 mol) solution in 0.5 mL of 70% aqueous methanol. After 2 min, 2.5 mL of DPPH• in methanol (0.1 mM) was added to the mixture, and the volume was always made up to 3.7 mL with methanol. The activity of tested samples was compared to the activity of samples that contained a proper amount of methanol instead of AgNO3 solution. For each sample, the absorbance was measured at 517 nm directly after mixing. The measurements were repeated three times. Free radical scavenging activity was calculated according to eq 1. Statistical Analysis. All of the experiments were performed in triplicate, and the data are presented as mean values (±standard deviation values are given in the Supporting Information).

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RESULTS AND DISCUSSION In the attempt to develop a pharmacophore model of monoterpene chain-breaking antioxidant, the experiments aimed at identification of structural elements responsible for free radical scavenging activity. The literature broadly covers the problem of polyphenols’ structure−activity relationships; however, in the case of monoterpenes such data are scarce, and no evidence has been delivered at to which part of the molecule is responsible for direct antioxidant activity or for its enhancement. Twenty compounds (17 monoterpnes, 1 sesquiterpene, 1 monoterpenic phenol, and 1 phenyl propanoid) commonly present in essential oils were used in the study. The loss of DPPH• absorbance was read in the presence of an excess of the analyzed compounds. The DPPH•/analyte molar ratio was kept constant for all of the analyzed compounds. Keeping this ratio constant was crucial to give the possibility to properly compare the activity of individual analytes (the amount of moles of all the studied terpenoids, which reacted with DPPH•, was equal). In the literature equal

(1)

where Ablank is the absorbance of the sample except tested substances and Asample is the absorbance of the sample with a tested compound. DPPH• Radical Scavenging Assay in the Presence of Silver Nitrate. To check the influence of double bonds on the DPPH• scavenging activity of terpenes, a test with AgNO3 was performed. Silver ions are known to form stable complexes with dienes. A reference sample was prepared by mixing 2.5 mL of DPPH• (0.1 mM) in methanol with 0.003 mol of AgNO3 dissolved in a 1.2 mL of mixture of 0.4 mL of distilled water and 0.8 mL of methanol. Tested B



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Figure 2. Influence of silver nitrate addition on free radical scavenging activity of selected monoterpenes. For experimental details, please refer to Materials and Methods.

Figure 3. Proposed reaction mechanism between DPPH• and monoterpenes possessing conjugated double bonds.

volumes of liquid terpenes are usually added to DPPH• without taking into account that these volumes refer to different amounts of moles. The radical scavenging activity of terpenoids was expressed as the percentage quenching of DPPH• radical.8 The absorbance was read every 2 min from the beginning of the reaction until a plateau was reached. In the literature the activity of individual compounds is compared, for example, after 5 or 30 min.8,12−15 However, the reaction of each free radical scavenger with DPPH• may be different, even among the compounds characterized with potent free radical scavenging activity, as can be seen for several terpenoids in Figure 1. The following terpenes have been found inactive or of weak activity in methanol (insoluble hydrocarbons are not taken into consideration): α-pinene, p-cymene, eucalyptol, menthol, and terpinene-4-ol (see Figure 1b). Another group of compounds has been found to scavenge DPPH• radical very quickly, reaching plateau values after several minutes: citral, carvone, myrcene, γ-terpinene, and pulegone. α-Terpinene and αphellandrene, although found active in methanol, exerted

lower scavenging activity when compared to the aforementioned five very active monoterpenes (see Figure 1a). All of the analyzed compounds that were found to scavenge DPPH• free radical possessed a double bond in their molecule. Terpenes with conjugated double bonds quickly scavenged DPPH• radical, reaching plateau values within minutes, as seen in Figure 1a. To check the influence of blocking π bonds on monoterpenes’ free radical scavenging activity, another test was performed. The π bonds were blocked with the use of silver ions as the Ag(I)−diene complexes are easily formed.31 As can be seen in Figure 2, addition of silver nitrate leads to the decrease of chain-breaking antioxidant activity of terpenes. The decrease is more significant for terpenoids possessing conjugated double bonds (citral, myrcene, α-phellandrene) than for those without conjugation of double bonds, for example, citronellal. It can be concluded that π bonds are responsible for the chain-breaking antioxidant activity of terpenes. It has been proved, for the first time, that blocking conjugated double bonds leads to inhibition of the chainbreaking antioxidant activity of terpenes, which proves C



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Figure 4. Comparison of free radical scavenging activity of two monoterpenes with very similar structures (citral, with conjugated double bonds; and citronellal, without conjugated double bonds) toward DPPH• in methanol.

Figure 5. Comparison of free radical scavenging activity of α- and γ-terpinene toward DPPH• in methanol.

conjugated π bonds are essential for the free radical scavenging activity of monoterpenes. To explain the influence of conjugated double bonds on terpenes’ chain-breaking antioxidant activity, the possible reaction mechanism with DPPH• is proposed, as seen in Figure 3. Terpenes may lose allylic hydrogen atoms (C−H allylic bond dissociation energy = 364 kJ/mol, compared to those of alkylic C−H bonds = 410 kJ/mol and vinylic C−H bonds = 452 kJ/mol) and neutralize a radical, as also postulated by Ö ztürk.28 In the presence of free radical scavenger DPPH• is reduced to hydrazine, and resulting antioxidant radical is formed. The resulting antioxidant radical may either propagate or terminate radical chain reaction. To be an effective direct antioxidant, a new radical, formed in the reaction with DPPH•, should not propagate the chain reaction. The resulting antioxidant radical should be unreactive to terminate radical chain reaction quickly. The reaction of DPPH• with conjugated double-bond terpenes results in the formation of resonancestabilized structure. The stabilization is associated with the charge delocalization over the whole molecule, possibly due to the presence of conjugation of π bonds (Figure 3). The following terpenes have been characterized with potent chain-breaking antioxidant activity, as they quickly terminated radical chain reaction in methanol (Figure 1a): citral, pulegone, γ-terpinene, carvone, and myrcene. The influence of conjugated double bonds on terpene’s activity can be easily noted when two monoterpenes, with very similar structures, are compared, for example, citral and citronellal (Figure 4). The only

difference between these two structures is the presence of a conjugated double bond (additional π bond) in citral. However, this small difference leads to a substantial change of citral chainbreaking antioxidant activity in comparison to the activity of citronellal. Quite surprising were the results obtained for terpinenes: αterpinene, possessing conjugated π bonds in its structure, was a less potent free radical scavenger than γ-terpinene (Figure 5). In the literature γ-terpinene has been defined as a very effective antioxidant with the possibility to easily lose allylic hydrogen atoms in the 3- and 6-positions (1,4-cyclohexadiene derivative).28 In the case of α-terpinene (1,3-cyclohexadiene derivative) allylic H atoms are at the 5- and 6-positions. Therefore, it may be postulated that in case of cyclic monoterpenes, containing double bonds, the 1,4-cyclohexadiene moiety enhances their free radical scavenging activity. The spare electron of the resulting antioxidant is better delocalized over the whole molecule when double bonds are between the C1−C2 and C4−C5 atoms. This effect can be compared to a similar good resonance stabilization of radicals formed in the reaction between DPPH• and hydroquinone (benzene-1,4-diol) derivatives.6 Further studies with the use of terpenes containing 1,4-cyclohexadiene moiety (of natural and synthetic origin) can be performed to provide additional proof. Generally, terpenes, which quickly lead to stable (plateau) radical scavenging activity values, can be considered as good free radical scavengers, as they terminate radical chain reaction. Those that form non-resonance-stabilized radicals, in the D



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Figure 6. Comparison of free radical scavenging activity of selected monoterpenes and thymol, as influenced by their structures.

Figure 7. Influence of solvent type, used in the DPPH• assay, on free radical scavenging activity of two exemplary monoterpenes: (a) ocimene and (b) α-pinene.

reaction with DPPH•, for example, citronellal (a molecule without π bond conjugation), may propagate radical reactions and may not be regarded as efficient free radical scavengers. To grasp the idea of how the molecular structure influences direct antioxidant activity of common terpenes, the activities of selected terpenes and thymol have been compared (Figure 6). Monoterpenes without a π bond, for example, menthol, do not exert free radical scavenging activity in the DPPH• assay. When one double bond appears in the molecule, DPPH• scavenging ability increases, as, for example, for menthone. Compounds with two double bonds, as already explained, quickly terminate radical chain reaction and can be considered as potent free radical scavengers, for example, pulegone. Direct antioxidant activity disappears when a diene molecule is replaced by an

aromatic ring, as was observed for p-cymene. A molecule regains its activity when a hydroxyl group appears, as, for example, in thymol. In the last part of the experiment, the activity of the analyzed compounds was investigated in a set of five solvents, representing a continuous scale of polarity: n-heptane, chloroform, ethyl acetate, 2-butanone, and methanol (Figure 7). The first stimulus to measure the activity of compounds in the above-mentioned solvents was due to terpenes’ solubility problems in DPPH• methanolic solution. The other one was related to the fact that the reaction environment, for example, the polarity of solvent, was found to influence the antioxidant activity of fragrance phenols.13 Less polar terpenes, for example, myrcene, α-pinene, farnesene, and ocimene, were characterized E



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downstream antioxidant therapeutic options. Curr. Neuropharmacol. 2009, 7, 65−74. (5) Graßmann, J. Terpenoids as plant antioxidants. Vitam. Horm. 2005, 72, 505−535. (6) Kancheva, V. D. Phenolic antioxidants − radical-scavenging and chain-breaking activity: a comparative study. Eur. J. Lipid Sci. 2009, 111, 1072−1089. (7) Rice-Evans, C. A.; Miller, N. J.; Paganga, G. Structure-antioxidant activity relationships of flavonoids and phenolic acids. Free Radical Biol. Med. 1996, 20, 933−956. (8) Burda, S.; Oleszek, W. Antioxidant and antiradical activities of flavonoids. J. Agric. Food Chem. 2001, 49, 2774−2779. (9) Ordoudi, S. A.; Tsimidou, M. Z.; Vafiadis, A. P.; Bakalbassis, E. G. Structure-DPPH· scavenging activity relationships: parallel study of catechol and guaiacol acid derivatives. J. Agric. Food Chem. 2006, 54, 5763−5768. (10) Ciesla, L.; Kowalska, I.; Oleszek, W.; Stochmal, A. Free radical scavenging activities of polyphenolic compounds isolated from Medicago sativa and Medicago truncatula assessed by means of thinlayer chromatography DPPH• rapid test. Phytochem. Anal. 2013, 24, 47−52. (11) Kowalska, I.; Jedrejek, D.; Ciesla, L.; Pecio, L.; Masullo, M.; Piacente, S.; Oleszek, W.; Stochmal, A. Isolation, chemical and free radical scavenging characterization of phenolics from Trifolium scabrum L. aerial parts. J. Agric. Food Chem. 2013, 61, 4417−4423. (12) Mishra, K.; Ojha, H.; Chaudhury, N. K. Estimation of antiradical properties of antioxidants using DPPH• assay: a critical review and results. Food Chem. 2012, 130, 1036−1043. (13) Marteau, C.; Nardello-Rataj, V.; Favier, D.; Aubry, J.-M. Dual role of phenols as fragrances and antioxidants: mechanism, kinetics and drastic solvent effect. Flavour Fragrance J. 2013, 28, 30−38. (14) Kedare, S. B.; Singh, R. P. Genesis and development of DPPH method of antioxidant assay. J. Food Sci. Technol. 2011, 48, 412−422. (15) Sharma, O. P.; Bhat, T. K. DPPH antioxidant assay revisited. Food Chem. 2009, 113, 1202−1205. (16) Foti, M.; Ruberto, G. Kinetic solvent effects on phenolic antioxidants determined by spectrophotometric measurements. J. Agric. Food Chem. 2001, 49, 342−348. (17) Foti, M. C.; Daquino, C.; Mackie, I. D.; DiLabio, G. A.; Ingold, K. U. Reaction of phenols with the 2,2-diphenyl-1-picrylhyrazyl radical. Kinetics and DFT calculations applied to determine ArO-H bond dissociation enthalpies and reaction mechanism. J. Org. Chem. 2008, 73, 9270−9282. (18) Bertalanič, L.; Košmerl, T.; Poklar Ulrih, N.; Cigić, B. Influence of solvent composition on antioxidant potential of model polyphenols and red wines determined with 2,2-diphenyl-1-picrylhydrazyl. J. Agric. Food Chem. 2012, 60, 12282−12288. (19) Bietti, M.; Salamone, M.; DiLabio, G. A.; Jockusch, S.; Turro, N. J. Kinetic solvent effects on hydrogen abstraction from phenol by the cymyloxyl radical. Toward an understanding of the role of protic solvents. J. Org. Chem. 2012, 77, 1267−1272. (20) Prevc, T.; Šegatin, N.; Poklar Ulrih, N.; Cigić, B. DPPH assay of vegetable oils and model antioxidants in protic and aprotic solvents. Talanta 2013, 109, 13−19. (21) Litwinienko, G.; Ingold, K. U. Solvent effects on the rates and mechanism of reaction of phenols with free radicals. Acc. Chem. Res. 2007, 40, 222−230. (22) Dawidowicz, A. L.; Olszowy, M. Mechanism change in estimating of antioxidant activity of phenolic compounds. Talanta 2012, 97, 312−317. (23) Ciesla, L.; Kryszen, J.; Stochmal, A.; Oleszek, W.; Waksmundzka-Hajnos, M. Approach to develop a standardized TLC-DPPH• test for assessing free radical scavenging properties of selected phenolic compounds. J. Pharm. Biomed. Anal. 2012, 70, 126− 135. (24) González-Burgos, E.; Gómez-Serranillos, M. P. Terpene compounds in nature: a review of their potential antioxidant activity. Curr. Med. Chem. 2012, 19, 5319−5341.

with better antioxidant activity in nonpolar solvents than in polar ones, which is the opposite of the results obtained for monoterpenic phenols. Hydrogen bond accepting solvents (HBA) (ketones, esters, ethers) formed hydrogen bonds with phenols’ hydroxyl groups, making them less accessible to DPPH•. For terpenes, another mechanism may be suspected, as hydrogen abstraction from phenols is due to the presence of hydroxyl groups, which may form hydrogen bonds with HBA solvents. As the free radical scavenging activity of terpenes is due to π bonds, therefore HBA solvents will not decrease the activity of terpenes as substantially as in the case of phenols. The results presented in Figure 7 clearly show that the free radical scavenging activity of terpenes depends on the solvent type used in the study. It is well seen with the example of αpinene, which quickly reaches scavenging activity plateau values in n-heptane, although α-pinene possesses only one π bond. This compound is a representative of bicyclic monoterpenes. Further studies are required to study the aforementioned phenomenon. It may be concluded that compounds exerting potent free radical scavenging activity in nonpolar solvents may act as efficient antioxidants in lipophilic end-use products, whereas those active in a polar environment may be efficient in scavenging free radicals in polar end-use products’ media. The presented results should stimulate additional research in the field of terpenoid antioxidants. Further studies may consider the influence of different substituents on the exerted activity, for example, for chemically modified structures. As interesting results have been obtained for α-pinene, in nonpolar solvents, the analysis of a broader group of bicyclic monoterpenes may provide interesting data. In nature, individual terpenes are found in complex mixtures; therefore, synergistic and antagonistic interactions should be considered. Structure−activity relationships for terpenes may also be checked with other antioxidant tests, for example, ABTS•+, βcarotene assays, and other methods measuring antioxidant activity.

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ASSOCIATED CONTENT

S Supporting Information *

Tables presenting scavenging activity results obtained for all of the analyzed compounds in five different solvents. This material is available free of charge via the Internet at http://pubs.acs.org.

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AUTHOR INFORMATION

Corresponding Author

*(L.M.C.) Phone: +48 81756 4837. Fax: +48 81535 7378. Email: [email protected]. Funding

This work was supported by the TEAM research subsidy from the Foundation for Polish Science. Notes

The authors declare no competing financial interest.

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REFERENCES

(1) Peñuelas, J.; Munné-Bosch, S. Isoprenoids: an evolutionary pool for photoprotection. Trends Plant Sci. 2005, 10, 166−169. (2) Peñuelas, J.; Llusiá, J.; Asensio, D.; Munné-Bosch, S. Linking isoprene with plant thermotolerance, antioxidants and monoterpene emissions. Plant Cell Environ. 2005, 28, 278−286. (3) Perwez Hussain, S.; Hofseth, L. J.; Harris, C. C. Radical causes of cancer. Nat. Rev. Cancer 2003, 3, 276−285. (4) Uttara, B.; Singh, A. V.; Zamboni, P.; Mahajan, R. T. Oxidative stress and neurodegenerative diseases: a review of upstream and F



Article

(25) Ciesla, L. Thin-layer chromatography with biodetection for the search of new potential drugs to treat neurodegenerative diseases − state of the art and future perspectives. Med. Chem. 2012, 8, 102−111. (26) Ciesla, L.; Kryszen, J.; Stochmal, A.; Oleszek, W.; Waksmundzka-Hajnos, M. Low-temperature thin-layer chromatography preliminary bioautographic tests for detection of free radical scavengers and acetylcholinesterase inhibitors in volatile samples. J. Planar Chromatogr. − Modern TLC 2012, 25, 225−231. (27) Choi, H.-S.; Song, H. S.; Ukeda, H.; Sawamura, M. Radicalscavenging activities of citrus essential oils and their components: detection using 1,1-diphenyl-2-picrylhydrazyl. J. Agric. Food Chem. 2000, 48, 4156−4161. (28) Ö ztürk, M. Anticholinesterase and antioxidant activities of Savoury (Satureja thymbra L.) with identified major terpenes of the essential oil. Food Chem. 2012, 134, 48−54. (29) Kivrak, I.; Duru, M. E.; Ö ztürk, M.; Mercan, N.; Harmandar, M.; Topçu, G. Antioxidant, anticholinesterase and antimicrobial constituents from the essential oil and ethanol extract of Salvia potentillifolia. Food Chem. 2009, 116, 470−479. (30) Foti, M. C.; Ingold, K. U. Mechanism of inhibition of lipid peroxidation by γ-terpinene, an unusual and potentially useful hydrocarbon antioxidant. J. Agric. Food Chem. 2003, 51, 2758−2765. (31) Bera, M.; Roy, S. Silver(I)-diene complexes as versatile catalysts for the C-arylation of N-tosylaziridines: mechanistic insight from in situ diagnostics. J. Org. Chem. 2010, 13, 4402−4412.

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Model Studies on the Antioxidant Activity of Common Terpenoid

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