Research paper
Chelates of 3- and 5-hydroxyflavone: Quantum chemical study

https://doi.org/10.1016/j.cplett.2020.138142Get rights and content

Highlights

  • Aromaticity changes upon metal ions chelation are analyzed.

  • Binding energies for selected metal complexes are investigated.

  • Vertical electronic transitions are predicted in uniform fashion.

  • Various hybrid and long-range separated functionals are compared.

Abstract

The chemical and electronic structure of 3-hydroxyflavone, 5-hydroxyflavone and their metal complexes (Al3+, Ca2+, Cu+/2+, Mg2+, Ni2+, Sc3+ and Zn2+) were studied using Density Functional Theory. The influence of the solvent was estimated by comparing gas phase and solution-based calculations. The metal chelating ability was assessed from the complexation binding energies corrected on Basis Set Superposition Error. Electronic structure was described by vertical optical transitions calculated using TD-DFT with various functionals. The theoretical results were compared and correlated with the available experimental data.

Introduction

Flavonoids are common compounds in fruits and many plants with beneficial antioxidant activities. Wide variety of biological activities are ascribed to their metal ion chelates [1], [2]. Since flavonoids are part of daily diet, it is hypothesized that they might form complexes with harmful metal ion encountered in the human body [3]. The preferred binding site is subject of great discussions as it depends on the flavonoid chemical structure, metal ion and on the pH value of environment [4]. Monohydroxyflavones with only one chelation site are therefore significantly more straightforward and can be utilized as skeletal precursor for other flavonoids and are useful for validations. Also, in order to fulfil their protective function against harmful ions they should form much weaker coordination bonds with vitally important ions. Moreover, chelation might affect the aromaticity of three rings of their structure. In this context HOMED indices can be applied as resonance effect measure for π-electron systems. Since HOMED are based on bond lengths it can be easily experimentally confirmed by utilizing X-ray structure much unlike other indices often lacking the direct experimental validation [5].

Many published works reported the experimental and theoretical studies on the electronic structure and spectroscopic properties for a large variety of flavone and flavonol derivatives and their complexes [6], [7], [8]. The quantum chemical calculations based on the Density Functional Theory (DFT) help to determine the relative stability of metal flavonoid associations, but also interpret spectroscopic measurements. However, majority of these calculations usually pick only one DFT functional and basis sets often missing discussion of chemical accuracy. Also, between multiple works different conditions and methods are employed. Therefore, the results between these works are hardly comparable. Moreover, all types of solvation models come with different shortcomings and often the primary substitution effect is best estimated for the gas phase.

With respect to these facts, we decided to test the applicability of a simple theoretical model for 3-hydroxyflavone and 5-hydroxyflavone molecules and their selected metal complexes (Fig. 1). In the study, basic effects of chemical modification on chemical structure are discussed in gas phase at first. The partial aims of this quantum chemical study are: (1) to optimize and discuss the chemical structure of selected third and fourth row metal complexes (Al3+, Ca2+, Cu+/2+, Mg2+, Ni2+, Sc3+ and Zn2+); (2) to assess the potential partial atomic charges on metal atoms; (3) to compare chelating ability of vitally important and harmful ions based on binding energy; (4) to estimate chemical accuracy of the theoretical electron transitions within two implicit solvation models and five different DFT hybrid as well as long-range corrected functionals. In this context, shapes of relevant frontier molecular orbitals will be depicted.

Section snippets

Theoretical and computational methodology

The quantum chemical calculations were performed using Gaussian 16 program package [9]. The optimal geometries of studied molecules were calculated by DFT method without any constraints. We used common hybrid B3LYP (Becke’s three parameter Lee–Yang–Parr) [10], [11], PBE0 [12], long-range corrected CAM-B3LYP [13], LC-ωPBE [14], and ωB97XD functionals with dispersion and long-range corrections [15]. All calculations of open-shell (ionized) states used the unrestricted formalism and the spin

Results and discussion

HOMED indices as quantitative measure of aromaticity confirmed almost benzene-like conjugation in rings A and B (HOMED over 0.99) for neutral 3-hydroxyflavone (3OH) as well as for 5-hydroxyflavone (5OH). Very similar X-ray structure [31], [32] based indices verified these values (see Table 1). On the other hand, B3LYP predicted less perturbed aromaticity of ring C (HOMED of 0.88 for 3OH, 0.89 for 5OH) compared to the 0.68 calculated from experimental bond lengths.

Numerous works provided

Conclusions

Metal complexes of 3- and 5-hydroxyflavones (Al3+, Ca2+, Cu+/2+, Mg2+, Ni2+, Sc3+ and Zn2+) were explored at density functional level of theory. Changes of local aromaticity analyzed in terms of HOMED indices pointed to the dramatic aromaticity decrease of C ring after hydroxyl group deprotonation. This was witnessed in gas phase as well as in solvent. Moreover, the conjugation of C ring became almost ideal after metal ion chelation. Evidences of charge transfer from metal ion to ligand were

CRediT authorship contribution statement

Martin Michalík: Writing - review & editing. Monika Biela: Visualization and Investigation. Denisa Cagardová: Conceptualization, Methodology, Software. Vladimír Lukeš: . : Supervision.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgement

The work has been supported by Slovak Research and Development Agency (APVV-15-0053, APVV-19-0024), VEGA Grant Agency through project 1/0504/20. The authors would like to thank for financial contribution from the STU Grant scheme for Support of Young Researchers (1848). We are grateful to the HPC centre at the Slovak University of Technology in Bratislava, which is a part of the Slovak Infrastructure of High Performance Computing (SIVVP project, ITMS code 26230120002, funded by the European region

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