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Proceeding Paper

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

by
Andreea Neacsu
1,*,
Carmellina Badiceanu
2,
Cristina Stoicescu
1 and
Viorel Chihaia
1,*
1
Institute of Physical Chemistry “Ilie Murgulescu” of the Romanian Academy, 202 Spl. Independentei, 060021 Bucharest, Romania
2
Faculty of Pharmacy, University of Medicine and Pharmacy “Carol Davila”, Traian Vuia Str., No. 6, Sect. 2, 020956 Bucharest, Romania
*
Authors to whom correspondence should be addressed.
Presented at the 28th International Electronic Conference on Synthetic Organic Chemistry (ECSOC-28), 15–30 November 2024; Available online: https://sciforum.net/event/ecsoc-28.
Chem. Proc. 2024, 16(1), 27; https://doi.org/10.3390/ecsoc-28-20214
Published: 14 November 2024

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 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.
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.

Author Contributions

Conceptualization, A.N. and C.S.; methodology, A.N. and C.S.; software, V.C.; validation, A.N. and C.S.; formal analysis, A.N.; investigation, A.N.; resources, C.B.; data curation, A.N. and C.B.; writing—original draft preparation, A.N.; writing—review and editing, A.N.; visualization, V.C.; supervision, A.N.; project administration, A.N. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

The original contributions presented in the study are included in the present manuscript; further inquiries can be directed to the corresponding authors.

Conflicts of Interest

The authors declare no conflicts of interest.

References

  1. Badiceanu, C.D.; Missir, A.-V. Synthesis and characterization of some new thioureides of 2-thiophenecarboxylic acid with potential pharmacological activity. Rev. Roum. Chim. 2009, 54, 27–31. [Google Scholar]
  2. Badiceanu, C.D.; Nuta, C.D.; Missir, A.-V.; Hrubaru, M.; Delcaru, C.; Ditu, L.M.; Chifiriuc, M.C.; Limban, C. New derivatives of 2-thiophene carboxylic acid: Synthesis, structure and antimicrobial studies. Farmacia 2018, 66, 237–242. [Google Scholar]
  3. Stoicescu, C.S.; Neacsu, A.; Badiceanu, C.D.; Munteanu, G. Inclusion complexes of some thiourea derivatives in cyclodextrins. J. Incl. Phenom. Macrocycl. Chem. 2020, 96, 275–283. [Google Scholar] [CrossRef]
Figure 1. Base chemical structure of 2-thiophene carboxylic acid thiourea derivative with the substitute group marked in blue.
Figure 1. Base chemical structure of 2-thiophene carboxylic acid thiourea derivative with the substitute group marked in blue.
Chemproc 16 00027 g001
Figure 2. The plot of the frontier orbitals HOMO and LUMO (with an isovalue of 0.03) for the studied chemical structures (ae). The surfaces are drawn by yellow/blue and green/red colors for HOMO and LUMO, respectively, where the negative/positive blobs are represented by light and dark colors. The gray, red, blue, yellow, and white spheres represent the carbon, oxygen, nitrogen, sulfur, and hydrogen atoms, respectively. Light-green, brown, and black spheres are chlorine, bromine, and iodine halogen atoms.
Figure 2. The plot of the frontier orbitals HOMO and LUMO (with an isovalue of 0.03) for the studied chemical structures (ae). The surfaces are drawn by yellow/blue and green/red colors for HOMO and LUMO, respectively, where the negative/positive blobs are represented by light and dark colors. The gray, red, blue, yellow, and white spheres represent the carbon, oxygen, nitrogen, sulfur, and hydrogen atoms, respectively. Light-green, brown, and black spheres are chlorine, bromine, and iodine halogen atoms.
Chemproc 16 00027 g002
Figure 3. Experimentally obtained ATR FT-IR spectra for studied chemical structures (a) and corresponding vibration spectra obtained by simulation (bf).
Figure 3. Experimentally obtained ATR FT-IR spectra for studied chemical structures (a) and corresponding vibration spectra obtained by simulation (bf).
Chemproc 16 00027 g003aChemproc 16 00027 g003b
Table 1. The IUPAC name and the corresponding abbreviation used for the chemical structures considered in this work.
Table 1. The IUPAC name and the corresponding abbreviation used for the chemical structures considered in this work.
IUPAC NameAbbreviation
1-(4-chlorophenyl)-3-(thiophene-2-carbonyl) thiourea1-Cl
1-(4-bromophenyl)-3-(thiophene-2-carbonyl) thiourea2-Br
1-(4-iodophenyl)-3-(thiophene-2-carbonyl) thiourea3-I
1-(4-methoxyphenyl)-3-(thiophene-2-carbonyl) thiourea4-OCH3
1-(4-methylphenyl)-3-(thiophene-2-carbonyl) thiourea5-CH3
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.
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.
DescriptorFormula1-Cl2-Br3-I4-OCH35-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 − A0.081290.0813290.0817080.081760.079843
Chemical Potential(I + A)/2 = μ−0.148461−0.1488005−0.151835−0.140293−0.1418415
Electronegativity−(I + A)/2 = χ0.1484610.14880050.1518350.1402930.1418415
Hardness(I − A)/2 = η0.0406450.04066450.0408540.040880.0399215
Softness1/(2*η) = S12.3016361212.2957370712.2387036812.2309197712.52457949
Electrophilicity(μ^2)/(2*η) = ω0.2711362840.2722471540.282149450.2407305020.251982154
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MDPI and ACS Style

Neacsu, A.; Badiceanu, C.; Stoicescu, C.; Chihaia, V. DFT Studies on Physicochemical Properties and Spectral Data of 2-Thiophene Carboxylic Acid Thiourea Derivatives. Chem. Proc. 2024, 16, 27. https://doi.org/10.3390/ecsoc-28-20214

AMA Style

Neacsu A, Badiceanu C, Stoicescu C, Chihaia V. DFT Studies on Physicochemical Properties and Spectral Data of 2-Thiophene Carboxylic Acid Thiourea Derivatives. Chemistry Proceedings. 2024; 16(1):27. https://doi.org/10.3390/ecsoc-28-20214

Chicago/Turabian Style

Neacsu, Andreea, Carmellina Badiceanu, Cristina Stoicescu, and Viorel Chihaia. 2024. "DFT Studies on Physicochemical Properties and Spectral Data of 2-Thiophene Carboxylic Acid Thiourea Derivatives" Chemistry Proceedings 16, no. 1: 27. https://doi.org/10.3390/ecsoc-28-20214

APA Style

Neacsu, A., Badiceanu, C., Stoicescu, C., & Chihaia, V. (2024). DFT Studies on Physicochemical Properties and Spectral Data of 2-Thiophene Carboxylic Acid Thiourea Derivatives. Chemistry Proceedings, 16(1), 27. https://doi.org/10.3390/ecsoc-28-20214

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