Products And Essential Approach Of Xanthones Family In Antioxidant Action

ObjectiveXanthone is a kind of natural compound with the dibenzo-y-pyrone framework,which is widely found in plants of Gentianaceae,Guttiferae,and other families.It has anti-infection,anti-inflammatory,anti-cancer,anti-platelet aggregation,antioxidation and other pharmacological activities.When xanthones undergo antioxidant reactions,various antioxidant mechanisms are involved.In the radical adduct formation(RAF)mechanism,xanthones can covalently bond with free radicals to form different antioxidant products.This article aims to react a variety of xanthone compounds with oxygen-centered/nitrogen-centered radicals,analyze the mass spectrometry information of the antioxidant products,explore the necessary ways to produce these products,systematically preliminarily summarized the relationship between the structure and antioxidant products of xanthones in RAF reaction with different free radicals,and further enriched the content of the antioxidant field of xanthone compounds.MethodsA series of xanthones with evident structural characteristics are selected,which are combined with oxygen free radicals(16-DOXYL-stearic acid·,16-DSA·)and nitrogen free radicals(1,1-diphenyl-2-picrylhydrazyl,DPPH·).Using ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry(UPLC-ESI-Q-TOF-MS/MS)technically qualitatively detect the RAF antioxidant products in the reaction solution,then analyzes the generated antioxidant products based on the experimental results,and performs mass spectrometry analysis on the products.Results1.After reacting the xanthones with 16-DSA· or DPPH·,two types of RAF products,xanthone-radical adducts and xanthone-xanthone dimers,were detected by UPLC-ESI-Q-TOF-MS/MS.Specifically,in the reaction solution of xanthones and DPPH’,most of xanthones without catechol or hydroquinone produce xanthone-radical adducts,and characteristic fragments of DPPH such as m/z 225,196,180,136,etc.usually appear in the secondary mass spectrum of the adducts.Xanthones with catechol or hydroquinone usually produce xanthone-xanthone dimers,and there are usually monomer characteristic fragments in the secondary mass spectrum of the dimers.In the reaction solution of xanth ones and 16-DSA’,only 2-hydroxyxanthone and 3-isomangostin can form adducts with 16-DSA’,the formation regular of dimerization products are similar to that in the DPPH’ reaction solution.2.In the reaction solution of the two free radicals,most of xanthone-xanthone dimers have Retro Diels-Alder(RDA)fragments,but isomangiferin,mangiferin,garcinone C,y-mangostin,8-desoxygartanin has no RDA fragments.3.In the reaction solution of the two free radicals,1,2,3,7-tetramethoxyxanthone produced neither adduct nor dimerization product.4.In the DPPH radical reaction solution,1,6,7-trihydroxyxanthone has no 1,6,7-trihydroxyxanthone-radical adduct but has dimerization products,and 1,7-dihydroxyxanthone has 1,7-dihydroxyxanthone-radical adducts but no dimerization product.1,3,5,6-tetrahydroxyxanthone and 1,5,6-trihydroxyxanthone produced the same type of RAF antioxidant products;lancerin and its aglycone produced the same type of RAF antioxidant products.Isomangiferin and mangiferin produced the same type of RAF antioxidant products;Garcinone C has no Garcinone C-radical adducts and dimerization product,Garcinone D has Garcinone D-radical adducts but no dimerization product;Garcinone C and γ-mangostin produced the same type of RAF antioxidant products.Conclusions1.Xanthone compounds can produce RAF antioxidant products whether they react with oxygen-centered free radicals or nitrogen-centered free radicals.There are mainly two types of antioxidant products,namely xanthone-radical adduct and xanthone-xanthone dimer;when xanthones react with oxygen-centered free radicals,xanthone-radical adducts are difficult to form.When reacting with nitrogen free radicals,xanthone-radical adducts are easier to form;The formation of xanthone-xanthone dimers are not affected by the type of free radicals.2.The hydrogen extraction reaction is the necessary way for xanthones to form RAF antioxidant products.The xanthone loses a hydrogen atom to form phenoxy radicals,which results in different antioxidant products.When xanthones and free radicals generate xanthone-radical adducts,they usually lose one hydrogen atom,which involves a hydrogen atom transfer site,and the RAF dimerization product will lose two hydrogen atoms,which involves two hydrogen atom transfer sites.3.The new covalent bond forming the xanthone-radical adducts may be C-N linkage.For the dimerization products,the most likely connection method to form the xanthone-xanthone dimers is to connect to the ring C-C.4.Xanthone-xanthone dimers(16-DSA·,DPPH·)usually break new covalent bond to produce monomer fragments,and commonly lose-CO,-CO2.Xanthone-xanthone dimers without isopentenyl substitution have RDA cleavage,and xanthone-xanthone dimers substituted with isopentenyl or sugar groups have no RDA cleavage process.In addition,RDA cleavage will occur after the isopentenyl cyclization,it is speculated that when there are some functional groups in the xanthones structure that are prone to mass spectroscopy cracking,the RDA cracking reaction may not occur easily.5.As mentioned above,the hydrogen extraction reaction is the prerequisite for RAF,xanthones have phenolic hydroxyl group that can be regarded as essential group for the formation of RAF antioxidant products after it reacts with free radicals.Without-OH,RAF antioxidant products cannot be formed.In addition,xanthones with catechol or hydroquinone structure are not easy to produce adduct products,they are easier to produce dimerization products.Therefore,compared with the number of phenolic hydroxyl groups,the relative position of phenolic hydroxyl groups is the main factor affecting the RAF antioxidant products.The number and position of groups other than phenolic hydroxyl groups,such as sugar groups,methoxy groups,isopentenyl groups,cycloisopentyl groups,etc.,have almost no significant impact on the formation of RAF antioxidant products.Destruction of the original catechol or hydroquinone structure will have a greater impact on the formation of xanthone antioxidant products.