π-Stacked polyphenolic dimers: A case study using dispersion-corrected methods

The accuracy of dispersion-corrected calculations (DFT-D2, DFT-D3 and DFT-NL) is assessed here, with large basis sets (def2-QZVP) to avoid incompleteness effects, for the most stable structure of a real-world polyphenol dimer chosen as an appropriate model. Natural polyphenols form such complexes with π-stacking playing a key stabilizing role. Our benchmark calculations predict its existence favored by 22–24 kcal/mol with respect to the isolated monomers, mainly driven by both π–π and H-bonding interactions. The adequate comparison of lower-cost DFT-based methods allowed bracketing their expected accuracy. These results thus pave the way towards reliable studies of challenging aggregation processes of natural products.The work in Alicante is supported by the ‘Ministerio de Educación y Ciencia’ of Spain and the ‘European Regional Development Fund’ through project CTQ2011-27253. The work in Mons is supported by the Belgian National Fund for Scientific Research (FNRS). The work in Limoges is supported by the ‘Conseil Régional du Limousin’ and COST actions FA1003 ‘East–West Collaboration for Grapevine Diversity Exploration and Mobilization of Adaptive Traits for Breeding’ and CM0804 ‘Chemical Biology with Natural Products’. The work in Malaysia is supported by Akademi Sains Malaysia through the SAGA Grant C20 and by the Ministry of Higher Education through the Grant 600-RMI/ST/FRGS 5/3/Fst (4/2011). The authors gratefully acknowledge the support by the Operational Program Research and Development for Innovation–European Regional Development Fund (Project CZ.1.05/2.1.00/03.0058 of the Ministry of Education, Youth and Sports of the Czech Republic). I.B. gratefully thanks the ‘Association Djerbienne de France’ (ADF) for the financial support