Elucidating the therapeutic activity of selective curcumin analogues: DFT-based reactivity analysis

Abstract

Density functional theory (DFT) has been employed to study the structure, stability and reactivity of curcumin and some of its important analogues by computing HOMO-LUMO energy gap (H-L gap), ionization potential (IP), electron affinity (EA), chemical potential (μ), chemical hardness (η), electrophilicity index (ω) and density of states (DOS). In this study, curcumin is found to be more reactive in dimethyl sulfoxide (DMSO) solvent than in the gas phase in both of its enol and keto isomeric forms. Next, reactivities of the keto-based curcumin analogues are found to follow the order of 1,5-bis(3,4-dimethoxyphenyl)penta-1,4-dien-3-one (GO-035) > 1,5-bis(3,4,5-trimethoxyphenyl)penta-1,4-dien-3-one (GO-Y016) > 1,5-bis[3,5-bis(methoxymethoxy)phenyl]penta-1,4-dien-3-one (GO-Y031) > 1,5-bis[3,5-dimethoxy-4-(methoxymethoxy)phenyl]penta-1,4-dien-3-one (GO-Y030) > dibenzalacetone (DBA) in both gas and DMSO solvent phases. However, there is enhancement in reactivities of the complexes in DMSO solvent from those in the gas phase. The reactivity order is observed on the basis of H-L gap, IP, μ, η and DOS analyses. Moreover, GO-Y030, GO-Y031 and DBA possess similar electrophilic behaviours as indicated by their comparable EA and ω values, while GO-Y016 and GO-035 behave as the strongest and the weakest electrophiles. Furthermore, the nature of the reactive sites in the curcumin analogues has been identified via local reactivity descriptors and the molecular electrostatic potential (MEP) maps, results of which are consistent with the molecular orbital analyses.