DFT calculation, molecular docking, and molecular dynamics simulation study on substituted phenylacetamide and...

Area of Science:

• Computational chemistry
• Molecular modeling
• Drug discovery

Background:

• Understanding chemical reactivity and degradation is crucial for predicting compound behavior.
• Assessing the binding affinity and toxicity of degradation products is essential for drug development.

Purpose of the Study:

• To determine the chemical reactivity and electronic properties of title compounds using DFT.
• To predict reactive sites and degradation pathways of compound 15.
• To evaluate the binding affinity and ADMET profile of compound 15's degradation products.

Main Methods:

• Hybrid DFT calculations (B3LYP/6-31G++) for atomic and molecular properties.
• Quantum chemical analyses (HOMO, LUMO, MESP, ALIE) for reactivity.
• Molecular docking, MM-GBSA, and MD simulations for binding and stability.
• ADMET profiling for toxicity assessment.

Main Results:

• Electronic charge transfer identified through conjugated paths.
• Nucleophilic and electrophilic sites mapped using MESP and ALIE.
• Bond dissociation energy calculated for compound 15 to assess degradation.
• Compound 15/4URL complex showed stable binding via MD simulations.
• Degradation products exhibited varying binding affinities and toxicity profiles.

Conclusions:

• Computational methods effectively predict chemical reactivity and degradation.
• Degradation products of compound 15 require careful evaluation for potential toxicity and binding interactions.
• The study provides a framework for assessing the stability and biological impact of chemical compounds and their derivatives.