<p>Benzocaine (BZC; ethyl 4-aminobenzoate) is an ester local anesthetic, but its spectroscopic signatures, solvent-dependent electronic response, local reactivity, and drug-likeness have rarely been unified in a molecular framework. We optimized BZC using density functional theory at the B3LYP/6-311++G(d,p) level and performed vibrational, Raman, time-dependent density functional theory ultraviolet–visible, frontier-orbital, global/local reactivity, density of states, molecular electrostatic potential, reduced density gradient, electron localization function, localized orbital locator, thermodynamic, and SwissADME analyses. The solvent effects in water, ethanol, and acetonitrile were treated using the polarizable continuum model of the integral equation formalism. Benchmarking calculated Fourier-transform infrared frequencies against reported experimental bands yielded a mean absolute error of 35.21 <InlineEquation ID="IEq1"><EquationSource Format="TEX">\(\hbox {cm}^{-1}\)</EquationSource></InlineEquation>, root mean square error of 53.03 <InlineEquation ID="IEq2"><EquationSource Format="TEX">\(\hbox {cm}^{-1}\)</EquationSource></InlineEquation>, mean absolute percentage error of 1.56%, and coefficient of determination of 0.9992. Diagnostic bands include ester C=O stretching at 1749.55 <InlineEquation ID="IEq3"><EquationSource Format="TEX">\(\hbox {cm}^{-1}\)</EquationSource></InlineEquation>, coupled C–C/C–O stretching at 1284.96 <InlineEquation ID="IEq4"><EquationSource Format="TEX">\(\hbox {cm}^{-1}\)</EquationSource></InlineEquation>, N–H stretching at 3629.10 <InlineEquation ID="IEq5"><EquationSource Format="TEX">\(\hbox {cm}^{-1}\)</EquationSource></InlineEquation>, and C–H stretching at 3160.41 <InlineEquation ID="IEq6"><EquationSource Format="TEX">\(\hbox {cm}^{-1}\)</EquationSource></InlineEquation>. The longest-wavelength gas-phase transition appears at 268.30 nm, with a brighter nearby transition at 267.19 nm; solvent calculations shift the main band to 281.40-−281.53 nm and increase oscillator strength. This indicates solvent-stabilized <InlineEquation ID="IEq7"><EquationSource Format="TEX">\(\pi \rightarrow \pi ^{*}\)</EquationSource></InlineEquation> excitation. Polar media narrow the frontier orbital gap and increase electrophilicity, whereas electrostatic and Fukui analyses identify the carbonyl oxygen, amino group, and aromatic framework as key interaction/reactivity regions. This study provides a consolidated computational reference for interpreting BZC structure–property behavior and guiding derivative, formulation, and spectroscopic studies.</p>

DFT-assisted spectroscopic characterization, reactivity analysis, and drug-likeness evaluation of ethyl 4-aminobenzoate for pharmaceutical applications

期刊论文
出版模式：

开放获取
发表日期：

2026年7月1日

查看全文

Bhijan Neupane,
Jeevan Ghimire,
Khakendra Basnet,
Nabal Khadka,
Prakash Man Shrestha,
Suresh Prasad Gupta,
Krishna Bahadur Rai

摘要

Benzocaine (BZC; ethyl 4-aminobenzoate) is an ester local anesthetic, but its spectroscopic signatures, solvent-dependent electronic response, local reactivity, and drug-likeness have rarely been unified in a molecular framework. We optimized BZC using density functional theory at the B3LYP/6-311++G(d,p) level and performed vibrational, Raman, time-dependent density functional theory ultraviolet–visible, frontier-orbital, global/local reactivity, density of states, molecular electrostatic potential, reduced density gradient, electron localization function, localized orbital locator, thermodynamic, and SwissADME analyses. The solvent effects in water, ethanol, and acetonitrile were treated using the polarizable continuum model of the integral equation formalism. Benchmarking calculated Fourier-transform infrared frequencies against reported experimental bands yielded a mean absolute error of 35.21 \(\hbox {cm}^{-1}\), root mean square error of 53.03 \(\hbox {cm}^{-1}\), mean absolute percentage error of 1.56%, and coefficient of determination of 0.9992. Diagnostic bands include ester C=O stretching at 1749.55 \(\hbox {cm}^{-1}\), coupled C–C/C–O stretching at 1284.96 \(\hbox {cm}^{-1}\), N–H stretching at 3629.10 \(\hbox {cm}^{-1}\), and C–H stretching at 3160.41 \(\hbox {cm}^{-1}\). The longest-wavelength gas-phase transition appears at 268.30 nm, with a brighter nearby transition at 267.19 nm; solvent calculations shift the main band to 281.40-−281.53 nm and increase oscillator strength. This indicates solvent-stabilized \(\pi \rightarrow \pi ^{*}\) excitation. Polar media narrow the frontier orbital gap and increase electrophilicity, whereas electrostatic and Fukui analyses identify the carbonyl oxygen, amino group, and aromatic framework as key interaction/reactivity regions. This study provides a consolidated computational reference for interpreting BZC structure–property behavior and guiding derivative, formulation, and spectroscopic studies.