1 3 J IRAN CHEM SOC DOI 10.1007/s13738-016-0984-x ORIGINAL PAPER A computational study of the electronic structure and the chemical activity of curcumin and some novel curcuminoids by density functional theory Masoumeh Ighaei Bonab 1,2 · Jaber Jahanbin Sardroodi 1,2 · Alireza Rastkar Ebrahimzadeh 1,3 · Faramarz Mehrnejad 4 Received: 31 January 2016 / Accepted: 25 September 2016 © Iranian Chemical Society 2016 Introduction Curcumin, the yellow pigment in the Indian turmeric spice (along with curry powder), has been associated with the sup- pression of inflammation, diabetes, angiogenesis, diseases of the cardiovascular, nervous system, respiratory system, skin and liver, loss of bone and muscle, depression and chronic fatigue [1–6]. The utility of curcumins is limited by its color, lack of water solubility and the relatively low bioavailability in vivo [7, 8]. Because of the numerous therapeutic activi- ties attributed to curcumin, however, there is growing search for some super curcumin whose structure would not have such problems [9]. Several synthetic analogue approaches are being tested to overcome these limitations. The search for super curcumin was pioneered by Anand et al. [10]. They introduced several methods for the discovery of curcumin’s analogues and compared several biological activities of them. The biological activities attributed to curcumin come from its complex molecular structure and chemistry, as well as its ability to influence multiple signaling molecules [11]. In this paper, we selected some analogues of curcumin and then the binding characteristics of curcumin and these analogues were explained by conducting an accurate quan- tum chemical study and employing the density functional theory (DFT). Some of their properties and parameters, such as the HOMO and LUMO energies, HOMO-LUMO gap, global hardness and global softness, were calculated for all studied structures in vacuum and the solution phase. These parameters could justify binding characteristics of them. Methods A full geometric optimization of the electronic ground state of curcumin and its analogues in the vacuum was obtained Abstract Structural modification of curcumin repre- sents a strategy to improve its stability, water solubility, pharmaceutical properties and bioactivity. In this context, numerous structural analogues of curcumin, including curcuminoids, have been developed. In this paper, the pre- cise density functional theory computations were used for investigating the electronic and geometrical structure of curcumin and some of its derivatives. The chemical activity of the considered molecules was investigated with the help of the global softness and hardness concepts. Among the studied molecules, bisdemethoxycurcumin had the most chemical activity and hexahydrocurcumin had the most sta- ble structure. Among two isomers of the curcumin, the enol isomer was found to be active. Keywords Electronic structure · Tautomerism · Curcumin · Density functional theory · Hardness · Softness * Masoumeh Ighaei Bonab ighaei@azaruniv.edu 1 Molecular Simulation Lab, Azarbaijan Shahid Madani University, Tabriz, Iran 2 Computational Nano Physical Chemistry Lab. Department of Chemistry, Azarbaijan Shahid Madani University, Tabriz, Iran 3 Department of Physics, Faculty of Basic Sciences, Azarbaijan Shahid Madani University, Tabriz, Iran 4 Department of Life Science Engineering, Faculty of New Sciences and Technologies, University of Tehran, Tehran, Iran