DFT Studies on Physicochemical Properties and Spectral Data of 2-Thiophene Carboxylic Acid Thiourea Derivatives ^†

Abstract

This study focused on examining five synthesized 2-thiophene carboxylic acid thiourea derivatives that have significant pharmaceutical applications. These compounds exhibit antibacterial properties against both bacterial and fungal strains. In this study, density functional theory (DFT) calculations were performed, and the electronic properties of the investigated compounds, such as ionization potential, electron affinity, and electronic excitation energies, were calculated and compared to determine the beneficial features of these potential future medications. A vibrational analysis of the considered structures was performed, and the experimental FT-IR ATR spectra of the solid powders are presented.

1. Introduction

The emergence of drug-resistant microorganisms has become a severe public health problem in the present day. Due to the evolutionary adaptation of bacteria and fungi to actual medication, the treatment of infectious diseases has become inefficient, leading to the use of higher doses of drugs. The urgent need for new antimicrobial compounds has led to interest in thioureides of 2-thiophene carboxylic acid, which are considered some of the most promising drugs for application in future therapeutic schemes. In this work, five synthesized thiourea derivative compounds with important pharmaceutical applications were studied. The general chemical formula of the 2-thiophene carboxylic acid thiourea derivative is presented in Figure 1.

Such compounds have antimicrobial activity against bacterial and fungal strains. Moreover, they offer significant advantages in future treatment strategies [1,2]. In this research, density functional theory (DFT) calculations were used and five molecules were described from the 6-311G(d,p) basis set [3]. The optimized molecular structure and the energy of individual molecular orbitals were predicted for thioureide derivatives. For studied molecules, electronic properties such as ionization potential, electron affinity, and electronic excitation energies were calculated and compared in order to establish the beneficial traits of these possible future pharmaceuticals. Also, using DFT, the vibrational frequencies, thermodynamic properties, and NMR chemical shifts of molecules were obtained. To show how this calculation method matches well with the experimental data, we compared the FT-IR experimental data of the thioureide derivatives with the calculated frequencies of the proposed molecules. We found candidates for which the experimental FT-IR spectra were well matched with the DFT calculations. Based on these computations, we obtained properties and key molecular descriptors related to chemical reactivity and spectral behavior.

2. Materials and Methods

2.1. Materials

In

Table 1. The IUPAC name and the corresponding abbreviation used for the chemical structures considered in this work.

IUPAC Name	Abbreviation
1-(4-chlorophenyl)-3-(thiophene-2-carbonyl) thiourea	1-Cl
1-(4-bromophenyl)-3-(thiophene-2-carbonyl) thiourea	2-Br
1-(4-iodophenyl)-3-(thiophene-2-carbonyl) thiourea	3-I
1-(4-methoxyphenyl)-3-(thiophene-2-carbonyl) thiourea	4-OCH3
1-(4-methylphenyl)-3-(thiophene-2-carbonyl) thiourea	5-CH3

, the name of the chemical structures considered in this study in accordance with IUPAC (International Union of Pure and Applied Chemistry) nomenclature and the corresponding abbreviations used in plots and in the text of the manuscript are presented.

2.2. Methods

Density functional theory (DFT) calculations were used to calculate various properties of the studied chemical structures, including electronic structures, energies, and geometries. For packing analysis, DFT was used to accomplish vibrational analysis and predict IR spectra.

Fourier-transform infrared spectroscopy (FT-IR) spectra were obtained at room temperature using a Nicolet iS10 FT-IR spectrometer in the range from 4000 cm⁻¹ to 600 cm⁻¹. The spectra were acquired by a fast average of 32 scans with a spectral resolution of 4 cm⁻¹ in attenuated total reflectance (ATR) mode.

3. Results

The analysis of the frontier orbitals, the highest occupied molecular orbital (HOMO), and the lowest unoccupied molecular orbital (LUMO) indicates the shapes and distributions of these orbitals, showing where the electron density is concentrated in the considered molecules. This graphical representation is presented in Figure 2. Some reactivity descriptors resulting from HOMO–LUMO analysis are given in

Table 2. The HOMO and LUMO energy, energy gap, chemical potential, chemical hardness, chemical softness, electronegativity, and electrophilicity of the studied chemical structures in vacuum. The presented values are in eV.

Descriptor	Formula	1-Cl	2-Br	3-I	4-OCH3	5-CH3
E(HOMO)	(−I)	−0.189106	−0.189465	−0.192689	−0.181173	−0.181763
E(LUMO)	(−A)	−0.107816	−0.108136	−0.110981	−0.099413	−0.10192
Band Gap	∆E = I − A	0.08129	0.081329	0.081708	0.08176	0.079843
Chemical Potential	(I + A)/2 = μ	−0.148461	−0.1488005	−0.151835	−0.140293	−0.1418415
Electronegativity	−(I + A)/2 = χ	0.148461	0.1488005	0.151835	0.140293	0.1418415
Hardness	(I − A)/2 = η	0.040645	0.0406645	0.040854	0.04088	0.0399215
Softness	1/(2*η) = S	12.30163612	12.29573707	12.23870368	12.23091977	12.52457949
Electrophilicity	(μ^2)/(2*η) = ω	0.271136284	0.272247154	0.28214945	0.240730502	0.251982154

.

Further, for the considered compounds, the ATR FT-IR spectra and the simulated vibration patterns are presented in Figure 3.

4. Conclusions

The energy gap between HOMO and LUMO (referred to as the HOMO–LUMO gap) is significant in predicting a molecule’s stability; thus, a smaller gap typically indicates higher reactivity. The presented results suggest that the gaps decrease in the following order: 5-CH3 < 1-Cl < 2-Br < 3-I < 4-OCH3, indicating a greater stability for 4-OCH3. According to Pearson’s principle, the structure of 4-OCH3 is less reactive, while 5-CH3 is more reactive. Therefore, for the halogenated structures, the reactivity of the molecule is influenced by the electronegativity of the halogen attached.

A higher electrophilicity corresponds to a lower energy of the LUMO, which implies a greater ability to accept electrons, so the electrophilicity index (ω) increases in the following order: 4-OCH3 < 5-CH3 < 1-Cl < 2-Br < 3-I.

As presented, there are similarities but also many differences between the spectra recorded experimentally and the simulated ones. Simulations often assume a single conformation, while experiments may capture multiple conformers or dynamic effects. Simulations typically use harmonic approximations, while real molecular vibrations can exhibit anharmonic behavior, leading to discrepancies in frequency predictions. Also, the method, the basis set, and environment conditions have a strong influence on spectra prediction.