A DFT study of molecular structure and ¹H NMR, IR, and UV‐Vis spectrum of Zn(II)‐kaempferol complexes: A metal‐flavonoid complex showing enhanced anticancer activity

Abstract

The polyphenol compound Kaempferol, a relevant member of the class of flavonoids, is a good example where coordination to Zn(II) ion was found to improve the anticancer effects compared to the free ligand. Determination of the metal‐complex molecular structure (and binding sites on Kaempferol) in the liquid phase is fundamental for an understanding of biological activities. Experimental UV‐Vis and EPR data only provide indirect evidence or limited structural information. Therefore, theoretical study of structural and spectroscopic properties of the metal‐polyphenol complex, using computational quantum chemistry methods, is certainly relevant as starting point for the investigation of mechanism of action at a molecular level. In this article, we used the density functional theory (DFT) methodology to predict the molecular structure of [Zn(Kaempferol)(H2O)n]+ and [Zn(Kaempferol)2(H2O)n] complexes (n = 0, 2, or 4) and B‐ring nonplanar conformation of flavonoid using as strategy the best match between theoretical and experimental 1H NMR, IR, and UV‐Vis spectroscopic data in solution. These are valuable information for further studies involving structure‐activity relationship.

Structural Determination of Antioxidant and Anticancer Flavonoid Rutin in Solution through DFT Calculations of 1H NMR Chemical Shifts

“…The IR spectra simulations shown in Figure S5 (Supporting Information) for rutin structures 27 , 28 , 30 and 32 revealed that it is not possible to distinguish the planar and rotated rutin structures for any of the geometries shown in Figure , different from the 1 H NMR analysis. This result was also observed for the structural analysis of Zn II ‐kaempferol complexes recently published by our group …”

“…Detailed analysis of NMR chemical shifts may provide specific information regarding molecular structure . Molecular modeling associated with density functional theory (DFT) has been widely employed by our group in studies at the molecular level of the action mechanism of potential drugs candidates for the treatment of cancer and other diseases. De Souza et al .…”

“…These new structural data for flavonoids may be relevant in theoretical studies of the formation of metal complexes and antitumor action of these compounds. Recently, our group reported a DFT conformational analysis study involving thermodynamics and spectroscopic characterization of twenty structures of zinc(II) complexes formed by the flavonoid kaempferol in solution. We have shown that theoretical calculations of IR and UV/Vis absorption bands are able to indicate the preferred site for the coordination of the metal by the kaempferol ligand.…”

Conformational Analysis of 5,4′-Dihydroxy-7,5′,3′-trimethoxyisoflavone in Solution Using 1H NMR: A Density Functional Theory Approach

“…This has been successfully done for complexation of flavonoids with Zn(II) ions in DMSO solution. 10,11 Overall, the knowledge about the molecular structure is of paramount importance for rationalizing its physicochemical properties and interaction with biological targets. 12 The purpose of this work is to use computational chemistry in combination with experimental data from 1 in order to determine the most likely structure in solution.…”

“…The high sensitivity of NMR chemical shifts to local chemical environment make them ideal for investigating the molecular structure present in a real macroscopic sample in solution, through comparison between experimental and theoretical chemical shift data. This has been successfully done for complexation of flavonoids with Zn­(II) ions in DMSO solution. , Overall, the knowledge about the molecular structure is of paramount importance for rationalizing its physicochemical properties and interaction with biological targets . The purpose of this work is to use computational chemistry in combination with experimental data from 1 H NMR in order to determine the most likely structure in solution.…”