Investigating the Molecular Structure of 3'-Hydroxy- 5,7-Dimethoxy-4-O-2'-Cycloflavan Molecule for the Risk of Chronic Cardiovascular Diseases

Hacer Gumuş^{* *}Correspondence: Hacer Gumuş, Department of Pharmaceutics, Golcuk Vocational School, Kocaeli University, Umuttepe, Kocaeli, Turkey, Email:

Author info »

Introduction

Flavonoids (Bostan SZ and Karadeniz T, 2006) are naturally occurring and biologically active compounds found in plants. These compounds are typically present in various parts of plants such as flowers, leaves, and fruits, where they serve as pigments responsible for determining the color and taste of plants (Tranfić M, et al., 2011). Additionally, flavonoids are known for their potent antioxidant properties. Antioxidants can help protect cells and tissues from oxidative stress by neutralizing the harmful effects of free radicals. Therefore, regular consumption of foods containing flavonoids may support heart health, reduce inflammation, and even exhibit protective effects against certain types of cancer.

Recent research provides significant insights into the effects of flavonoids on human metabolism and potential benefits for overall health (Dragovich PS, et al., 2002). For instance, due to their antioxidant activities, flavonoids have been shown to potentially play a role in reducing oxidative stress, thereby lowering the risk of chronic diseases such as cardiovascular diseases. Moreover, flavonoids are noted for their anti-inflammatory (Li Q, et al., 2000) properties and their potential regulatory effects on the immune system. This article will comprehensively examine the biological (Dragovich PS, et al., 2002) significance of flavonoids and their effects on health, while discussing studies on the electronic structures and chemical interactions of flavonoid molecules using theoretical calculation methods like DFT/B3LYP.

Description

Details of computational analysis

The molecular simulation of the molecule in its ground state was conducted using the Gaussian 09W program package (Frish MJ, et al., 2009). DFT methods were employed to intricately resolve the complex interactions of molecular forces and electronic structure. The rich data obtained from these calculations were subsequently analyzed and visualized in detail using the powerful visualization tools provided by Gaussian view 5 (Dennington R, et al., 2009), facilitating a comprehensive understanding of molecular dynamics.

All computations were meticulously performed using the B3LYP method, a hybrid functional developed by Becke AD, 1992 incorporating the LYP correlation functional. This methodological choice was further supported by the use of the 6-311++G(d,p) basis set (Lee C, et al., 1988), known for its wide applicability in calculating electronic structures and reaction energies of molecular systems. The 6-311++G(d,p) basis set enables detailed examination of molecular interactions, enhancing the accuracy of our study.

Analysis of molecular geometry structure

The crystal structure of the flavonoid-containing compound 3’-hydroxy-5,7-dimethoxy-4-O-2’-cyclflavan (C₁₇H₁₆O₅) was synthesized by Cui YM, et al., 2011. The synthesized molecule’s X-ray single crystal structure is available in the Cambridge Structural Database (CSD) under the code CCDC 796429. The experimental structure of the flavonoid compound is depicted in Figure 1. The theoretical geometric structure of the compound containing flavan, C₁₇H₁₆O₅ was computed DFT in Gaussian 09, based on crystal structure data obtained from the CSD. The calculations were performed using the B3LYP/6-311++G(d,p) method and the optimized geometry structure is shown in Figure 2. The bond lengths (Å) and bond angles (º) of the compound containing flavan, C₁₇H₁₆O₅ were theoretically calculated in the stable state and vacuum phase using the Gaussian 09 package. The optimized theoretical bond lengths and bond angles were compared with experimental results obtained from single-crystal X-ray diffraction data sourced from the literature, and are listed in Table 1.

Figure 1: Experimental structure of flavan-containing compound

Figure 2: Optimized geometry of the flavan-containing compound calculated using the B3LYP/6-311++G(d,p) method

Table 1: Geometric parameters of the flavan-containing compound, their bond lengths (Å) and bond angles (º)

Electronic properties

Molecular orbitals can be quantitatively calculated using quantum chemical computational methods such as DFT. In this study, Energy of the Highest Occupied Molecular Orbital (EHOMO) and Energy of the Lowest Unoccupied Molecular Orbital (E_LUMO) energy values of the compound containing flavan were computed using the DFT method. The calculated E_HOMO and E_LUMO energies were used to determine energy difference (ΔE), electron Affinity (A), Ionization potential (I), Electronegativity (χ), chemical Softness (S) and hardness (η) parameters based on formulas derived from electron density distributions. The results are listed in Table 2. LUMO and HOMO are critical concepts in determining the electronic structure of a molecule. These terms refer to the energies of the LUMO and HOMO in the molecule, respectively. E_LUMO and E_HOMO specifically denote the energy levels of these orbitals. In the detailed analysis aimed at exploring the electronic structural properties (Francesca M, et al., 2024) of the compound containing flavan, LUMO and HOMO orbitals have been visualized in detail in Figure 3. These analyses not only provide insights into the nature of molecular interactions but also serve as a fundamental source of information for understanding the physical and chemical properties of the molecule. Such insights form an important starting point for advanced pharmacological and therapeutic research. The molecular structure of the compound containing flavan has been thoroughly examined through detailed 3D graphics depicted in Figure 3. These graphics visually represent electron distributions and charge densities in different regions of the molecule. Particularly, regions carrying negative charges are highlighted in green, while those with positive charges are emphasized in red. This color scheme provides a significant visual tool for understanding the electronic structural characteristics of the molecule and offers an in- depth insight into the analysis of molecular interactions.