QSAR study and theoretical investigation on the lethality of halogenated aliphatic hydrocarbons toward Aspergillus (A.) Nidulans

Jabir H. Al-Fahemi; Faten A. Aljiffrey; Elshafie A. M. Gad; Mahmoud A. A. Ibrahim; Jabir H. Al-Fahemi; Faten A. Aljiffrey; Elshafie A. M. Gad; Mahmoud A. A. Ibrahim

doi:10.3934/environsci.2025019

AIMS Environmental Science

2025, Volume 12, Issue 3: 419-434. doi: 10.3934/environsci.2025019

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Research article

QSAR study and theoretical investigation on the lethality of halogenated aliphatic hydrocarbons toward Aspergillus (A.) Nidulans

1.
Department of Chemistry, Faculty of Science, Umm Al-Qura University, Makkah 21955, Saudi Arabia
2.
Petrochemicals Department, Egyptian Petroleum Research Institute, Cairo, Egypt
3.
Computational Chemistry Laboratory, Chemistry Department, Faculty of Science, Minia University, Minia 61519, Egypt
4.
Department of Engineering, College of Engineering and Technology, University of Technology and Applied Sciences, Nizwa 611, Sultanate of Oman
5.
School of Health Sciences, University of KwaZulu-Natal, Westville Campus, Durban 4000, South Africa

Received: 20 August 2024 Revised: 06 January 2025 Accepted: 08 May 2025 Published: 19 May 2025

The prediction of Aspergillus (A.) nidulans toxicities (log1/D₃₇) for a set of 55 halogenated aliphatic hydrocarbons (HAHs) was thoroughly investigated using density functional theory (DFT) computations. Different multiple linear regression (MLR)methods were employed to assess the reliability of the proposed quantitative structure-activity relationships (QSAR) model. The obtained E_LUMO, E_gap, molecular polarizability (α), and molar refractivity (MR) values offered informative indications in determining the toxicity of the HAHs. A promising three-descriptor linear model was constructed using 41 molecules as a training set; then, the model was validated on the remaining 14 molecules. Statistical comparisons between these models and others quoted from the literature were presented. Furthermore, the potential causes of the outlier molecules in the proposed QSAR models were explored. The most preferable interactions were obviously noticed within the 1-bromo-2-methylpropane…α-glucan complex, followed by 2-bromo-2-methylpropane…α-glucan and 2-chloro-2-methylpropane…α-glucan complexes. Compared to other analogs, the higher number of bond paths and bond critical points within the 1-bromo-2-methylpropane…α-glucan complex highlighted its high preferability.
- QSAR,
- DFT,
- MLR,
- Descriptors,
- QTAIM
Citation: Jabir H. Al-Fahemi, Faten A. Aljiffrey, Elshafie A. M. Gad, Mahmoud A. A. Ibrahim. QSAR study and theoretical investigation on the lethality of halogenated aliphatic hydrocarbons toward Aspergillus (A.) Nidulans[J]. AIMS Environmental Science, 2025, 12(3): 419-434. doi: 10.3934/environsci.2025019

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Abstract

The prediction of Aspergillus (A.) nidulans toxicities (log1/D₃₇) for a set of 55 halogenated aliphatic hydrocarbons (HAHs) was thoroughly investigated using density functional theory (DFT) computations. Different multiple linear regression (MLR)methods were employed to assess the reliability of the proposed quantitative structure-activity relationships (QSAR) model. The obtained E_LUMO, E_gap, molecular polarizability (α), and molar refractivity (MR) values offered informative indications in determining the toxicity of the HAHs. A promising three-descriptor linear model was constructed using 41 molecules as a training set; then, the model was validated on the remaining 14 molecules. Statistical comparisons between these models and others quoted from the literature were presented. Furthermore, the potential causes of the outlier molecules in the proposed QSAR models were explored. The most preferable interactions were obviously noticed within the 1-bromo-2-methylpropane…α-glucan complex, followed by 2-bromo-2-methylpropane…α-glucan and 2-chloro-2-methylpropane…α-glucan complexes. Compared to other analogs, the higher number of bond paths and bond critical points within the 1-bromo-2-methylpropane…α-glucan complex highlighted its high preferability.

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