ORIGINAL PAPER Lignin-derived oak phenolics: a theoretical examination of additional potential health benefits of red wine William N. Setzer Received: 1 October 2010 / Accepted: 31 October 2010 / Published online: 16 November 2010 # Springer-Verlag 2010 Abstract Lignin-derived phenolic compounds can be extracted from oak barrels during the aging of red wine, and it is hypothesized that these compounds may contribute to the health benefits of red wine by their antioxidant, radical-scavenging, or chemopreventive activities. Density functional calculations (B3LYP/6-311++G**) support the radical-scavenging abilities of the oak phenolics. Sinapal- dehyde, syringaldehyde, syringol, and syringylacetone all have bond dissociation energies that are lower than resveratrol and comparable to the flavonoid catechin. Molecular docking studies of the oak phenolics with known resveratrol protein targets also show that these compounds dock favorably to the protein targets. Thus, lignin-derived oak phenolics, although found in small concentrations, may contribute to the beneficial antioxidant, chemopreventive, and cardioprotective effects of red wine. Keywords Antioxidant . Radical-scavenging . Density functional theory . Molecular docking . Coniferaldehyde . Guaiacylacetone . Sinapaldehyde . Syringaldehyde . Syringol . Syringylacetone . Vanillin Introduction The potential health benefits of red wine have been copiously reviewed (see, for example, [1–4]). Many of the health-related benefits of red wine have been attributed to polyphenolics such as gallic acid, catechin, epicatechin, and resveratrol [5–7]. It has been suggested that these com- pounds exert their beneficial effects by way of their antioxidant properties, which reduce free-radical formation and prevent oxidative damage of biologically relevant targets [8–10]. Resveratrol has exhibited cancer chemo- preventive [11], cardioprotective [12, 13], and anti- inflammatory [14, 15] activities. A number of biochemical targets of resveratrol have been identified [16, 17], including estrogen receptor α (ERα) [18], histone deacetylase (HDAC) [19], cyclooxygenases 1 (COX-1) and 2 (COX-2) [11, 20–22], phosphoinositide 3-kinase (PI3K) [23], orni- thine decarboxylase (ODC) [24], transthyretin (TTR) [25], lipoxygenase (LOX) [26], aromatase (CYP 19) [27, 28], inducible nitric oxide synthase (iNOS) [29], ribonucleotide reductase (RNR) [30], quinone reductase 2 (QR2) [31], c-Src tyrosine kinase (CSK) [32], protein kinase C (PKC) [32], leukotriene A4 hydrolase (LTA4H) [33], F 1 -ATPase [34], and human cytosolic sulfotransferases (SULT) [35]. In addition to the polyphenolic compounds from grapes, aging red wine in oak barrels leads to the extraction of additional polyphenolic compounds into the wine that enhance the flavor and aroma [36–38]. In particular, toasted oak leads to a number of extractible guaiacyl and syringyl derivatives, including syringol (2,6-dimethoxyphenol), vanillin (4-hydroxy-3-methoxybenzaldehyde), guaiacylace- tone [1-(4-hydroxy-3-methoxyphenyl)-2-propanone], syringaldehyde (4-hydroxy-3,5-dimethoxybenzaldehyde), coniferaldehyde (4-hydroxy-3-methoxycinnamaldehyde), syringylacetone [1-(4-hydroxy-3,5-dimethoxyphenyl)-2- propanone], and sinapaldehyde (3,5-dimethoxy-4- hydroxycinnamaldehyde) [39–41] (see Fig. 1). These lignin-derived materials have previously shown radical- scavenging and antioxidant activities [42–46]. This work presents a theoretical examination of the potential antiox- idant and health-related benefits of oak-derived phenolics found in red wine. W. N. Setzer (*) Department of Chemistry, University of Alabama in Huntsville, Huntsville, AL 35899, USA e-mail: wsetzer@chemistry.uah.edu J Mol Model (2011) 17:1841–1845 DOI 10.1007/s00894-010-0893-3