Theoretical Study of Cyanidin-Resveratrol Copigmentation by the Functional Density Theory

Abstract

Anthocyanins are colored water-soluble plant pigments. Upon consumption, anthocyanins are quickly absorbed and can penetrate the blood-brain barrier (BBB). Research based on population studies suggests that including anthocyanin-rich sources in the diet lowers the risk of neurodegenerative diseases. The copigmentation caused by copigments is considered an effective way to stabilize anthocyanins against adverse environmental conditions. This is attributed to the covalent and noncovalent interactions between colored forms of anthocyanins (flavylium ions and quinoidal bases) and colorless or pale-yellow organic molecules (copigments). The present work carried out a theoretical study of the copigmentation process between cyanidin and resveratrol (CINRES). We used three levels of density functional theory: M06-2x/6-31g+(d,p) (d3bj); ωB97X-D/6-31+(d,p); APFD/6-31+(d,p), implemented in the Gaussian16W package. In a vacuum, the CINRES was found at a copigmentation distance of 3.54 Å between cyanidin and resveratrol. In water, a binding free energy ∆G was calculated, rendering -3.31, -1.68, and -6.91 kcal/mol, at M06-2x/6-31g+(d,p) (d3bj), ωB97X-D/6-31+(d,p), and APFD/6-31+(d,p) levels of theory, respectively. A time-dependent density functional theory (TD-DFT) was used to calculate the UV spectra of the complexes and then compared to its parent molecules, resulting in a lower energy gap at forming complexes. Excited states' properties were analyzed with the ωB97X-D functional. Finally, Shannon aromaticity indices were calculated and isosurfaces of non-covalent interactions were evaluated.

Keywords: DFT; copigmentation; cyanidin; isosurfaces; non-covalent interaction; resveratrol.

Scheme 1

Skeleton of the flavylium ion of an anthocyanin.

Figure 1

Structure of the model after applying a theory level M062X/3-21g* (gd3bj).

Figure 2

Initial random structures generated by the Molclus program.

Figure 3

Non-covalent interaction isosurfaces calculated using VDM and MULTIWFN softwares. The colored graph next to it represents all interactions in 2D. Blue spikes (attractions), green spikes (non-covalent), and red spikes (repulsions). (A) Calculations using M06-2X/gd3bj. (B) Calculations using ωB97X-D and (C) calculations using APFD. All under the same basis set 6-31g+(d,p).

Figure 3

Non-covalent interaction isosurfaces calculated using VDM and MULTIWFN softwares. The colored graph next to it represents all interactions in 2D. Blue spikes (attractions), green spikes (non-covalent), and red spikes (repulsions). (A) Calculations using M06-2X/gd3bj. (B) Calculations using ωB97X-D and (C) calculations using APFD. All under the same basis set 6-31g+(d,p).

Figure 4

Cyanidin: UV spectrum with the three strongest transitions calculated at the ωB97X-D/6-31g+(d,p) level of theory.

Figure 5

Calculated UV transitions of cyanidin at the ωB97X-D/6-31g+(d,p) theory level.

Figure 6

Calculated UV transitions of resveratrol at ωB97X-D/6-31g+(d,p) theory level.

Figure 7

Resveratrol: UV spectrum with the three strongest transitions calculated. λ_max 343.56 nm at ωB97X-D/6-31g+(d,p) level of theory.

Figure 8

Complex: resveratrol–cyanidin. UV spectrum with the three strongest transitions calculated. λ_max 468.83 nm at ωB97X-D/6-31g+(d,p) level of theory.

Figure 9

MO and calculated UV transitions of the resveratrol–cyanidin complex at the ωB97X-D/6-31g+(d,p) theory level.

Figure 10

MO and remaining of the calculated UV transitions of the resveratrol–cyanidin complex at the ωB97X-D/6-31g+(d,p) theory level.

Figure 11

MO and calculated UV transitions of the resveratrol–cyanidin–resveratrol complex at the ωB97X-D/6-31g+(d,p) level of theory.

Figure 12

MO and remaining of the calculated UV transitions of the resveratrol–cyanidin–resveratrol complex at the ωB97X-D/6-31g+(d,p) theory level.

Figure 13

Complex: resveratrol–cyanidin–resveratrol. UV spectrum with the three strongest transitions calculated. λ_max 474.91 nm at the ωB97X-D/6-31g+(d,p) level of theory.

Figure 14

Hydrogen bonds analyzed with IGMPLOT software (version 3.08): hydrogen (26) joined to oxygen 46; hydrogen 61 joined to oxygen 31.

Scheme 2

Thermodynamic cycle for the formation of the copigmentation complex in water. The P and CoP symbols stand for pigment and copigment structures, respectively.