In this tautomer the distance between the electron deficient carbonyl centers is maximal, which is Chlorpropamide energetically favorable and explains its high abundance. The high abundance of this specific tautomer is corroborated by the formation of adducts in the A ring, i.e. 6-GSH-quercetin and 8GSH-quercetin, in the reaction of GSH with oxidized quercetin. In monoHER a rutinose is attached to the 3-OH group of the C ring and a hydroxyethyl group is attached to the hydroxyl group oxygen at position 7 of the A ring. These substitutions preclude the formation of quinone methide tautomers in oxidized monoHER. Therefore, only the ortho-quinone can be formed. In this ortho-quinone two carbonyls are adjacent, which is energetically unfavorable compared to the larger distance between these groups in the preferential tautomer of oxidized quercetin. The presence of an ortho-quinone in the B ring is corroborated by the formation of an adduct in this ring, i.e. 29-GSH-monoHER, in the reaction of oxidized monoHER with GSH. Apparently, the oxidation products of monoHER and quercetin are energetically different. The LUMO of oxidized monoHER is primarily concentrated in the B ring and therefore relatively high, while that of oxidized quercetin is spread over the whole molecule. This is reflected by a LUMO of oxidized quercetin that is substantially lower than that of oxidized monoHER. Pearson��s HSAB concept assigns the terms ��hard�� or ��soft�� to chemical species to explain or predict the outcome of a chemical reaction. ��Hard�� applies to electrophiles that have LUMO of high energy or nucleophiles with a low HOMO energy. ��Soft��, on the other hand, applies to electrophiles with a low LUMO value or nucleophiles with a high HOMO value. According to the HSAB concept, hard electrophiles react faster and form stronger bonds with hard nucleophiles, whereas soft electrophiles react faster and from stronger bonds with soft nucleophiles. Based on their LUMO values, oxidized quercetin is a softer electrophile than oxidized monoHER. The reaction of GSH with both oxidized monoHER and quercetin is a Michael addition in which GSH acts as a nucleophile. The reaction with ascorbate is a redox reaction in which ascorbate finally donates two electrons to the oxidized products. GSH is a relatively soft nucleophile compared to ascorbate. This can explain the preferential reaction of the soft electrophile, oxidized quercetin, with thiols over ascorbate. Oxidized monoHER, on the other hand, is a Olsalazine Disodium harder electrophile than oxidized quercetin explaining its preference for the harder nucleophile ascorbate over GSH. Moreover, as depicted in Fig. 6A, the active part of ascorbate can approach the active part of oxidized monoHER by a hydrogen bond and a p-p interaction between ascorbate and the ortho-quinone. The reaction between oxidized monoHER and ascorbate is presented step by step in Fig. 6B. Based on our findings, the following concept is proposed.