<p>The growing demand for novel compounds with pharmacological and biological activities has led to a variety of experimental and theoretical methods aimed at better understanding the properties of these compounds. This study investigates the structural and electronic properties of a novel chalcone derivative bearing two butyl substituents (BHC), aiming to understand how weak intermolecular interactions influence its supramolecular organization and reactivity. Single-crystal X-ray diffraction revealed a crystal structure stabilized exclusively by weak C–H···O and C–H···N interactions, with estimated interaction energies ranging from 0.8 to 2.0 kcal·mol⁻1. Thermal analyses (TGA/DSC) indicated high thermal stability, with no degradation below 130 °C. Density Functional Theory (DFT) calculations using the ωB97X-D functional suggests that the X-ray-determined geometry closely approximates a gas-phase optimized structure (RMSD < 0.15 Å) and a HOMO–LUMO energy gap of 729.23 kJ·mol⁻1. Molecular Electrostatic Potential (MEP) mapping and Fukui function analysis identified the region near the carbonyl oxygen as the most reactive site toward electrophilic attack. Hirshfeld surface analysis and QTAIM topological parameters (e.g., <InlineEquation ID="IEq1"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="12210_2025_1348_Article_IEq1.gif" Format="GIF" Height="20" Rendition="HTML" Resolution="72" Type="Linedraw" Width="51" /> </InlineMediaObject> <EquationSource Format="TEX">${\nabla }^{2}\rho (r)$</EquationSource> <EquationSource Format="MATHML"><math> <mrow> <msup> <mrow> <mi mathvariant="normal">∇</mi> </mrow> <mn>2</mn> </msup> <mi>ρ</mi> <mrow> <mo stretchy="false">(</mo> <mi>r</mi> <mo stretchy="false">)</mo> </mrow> </mrow> </math></EquationSource> </InlineEquation> = 0.037 a.u. and <InlineEquation ID="IEq2"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="12210_2025_1348_Article_IEq2.gif" Format="GIF" Height="19" Rendition="HTML" Resolution="72" Type="Linedraw" Width="40" /> </InlineMediaObject> <EquationSource Format="TEX">$H\left(r\right)$</EquationSource> <EquationSource Format="MATHML"><math> <mrow> <mi>H</mi> <mfenced close=")" open="("> <mi>r</mi> </mfenced> </mrow> </math></EquationSource> </InlineEquation> ≈ − 0.0004 a.u. for C–H···O) confirmed the presence of weak yet structurally significant interactions. These analyses provide valuable insights into the electronic properties, supporting future studies in this class and aiding the development of new bioactive compounds.</p> Graphical abstract <p></p>

Molecular modeling of a novel butane-substituted chalcone: from synthesis to comprehensive electron density analysis

期刊论文
发表日期：

2025年8月9日

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Aécio V. B. Oliveira,
Vitor S. Duarte,
Renata Layse. G. de Paula,
Jaqueline E. Queiroz,
Gilberto L. B. de Aquino,
Hamilton B. Napolitano,
Ademir J. Camargo

摘要

The growing demand for novel compounds with pharmacological and biological activities has led to a variety of experimental and theoretical methods aimed at better understanding the properties of these compounds. This study investigates the structural and electronic properties of a novel chalcone derivative bearing two butyl substituents (BHC), aiming to understand how weak intermolecular interactions influence its supramolecular organization and reactivity. Single-crystal X-ray diffraction revealed a crystal structure stabilized exclusively by weak C–H···O and C–H···N interactions, with estimated interaction energies ranging from 0.8 to 2.0 kcal·mol⁻1. Thermal analyses (TGA/DSC) indicated high thermal stability, with no degradation below 130 °C. Density Functional Theory (DFT) calculations using the ωB97X-D functional suggests that the X-ray-determined geometry closely approximates a gas-phase optimized structure (RMSD < 0.15 Å) and a HOMO–LUMO energy gap of 729.23 kJ·mol⁻1. Molecular Electrostatic Potential (MEP) mapping and Fukui function analysis identified the region near the carbonyl oxygen as the most reactive site toward electrophilic attack. Hirshfeld surface analysis and QTAIM topological parameters (e.g., ${\nabla }^{2}\rho (r)$ $\nabla^{2} ρ (r)$ = 0.037 a.u. and $H\left(r\right)$ $H (r)$ ≈ − 0.0004 a.u. for C–H···O) confirmed the presence of weak yet structurally significant interactions. These analyses provide valuable insights into the electronic properties, supporting future studies in this class and aiding the development of new bioactive compounds.

Graphical abstract