Biophysical and structural insights into Azamethiphos-DNA interactions.

Area of Science:

• Environmental Chemistry
• Toxicology
• Molecular Biology

Background:

• Azamethiphos (AZA) is an organophosphate pesticide known for cholinesterase inhibition and risks to non-target organisms.
• Its high water solubility leads to environmental contamination and potential human exposure through bioaccumulation.
• Understanding AZA's interaction with DNA is crucial for assessing its genotoxic potential.

Purpose of the Study:

• To investigate the DNA-binding potential of Azamethiphos (AZA).
• To elucidate the molecular mechanisms underlying AZA's interaction with DNA.
• To assess the thermodynamic parameters and binding affinity of AZA to DNA.

Main Methods:

• In silico computational techniques were employed to analyze AZA-DNA interactions.
• Fluorescence spectroscopy was used to study AZA binding to calf thymus DNA (Ct-DNA) at varying temperatures (288 K, 298 K, 308 K).
• Thermodynamic analysis was performed to determine the binding characteristics.

Main Results:

• In silico analysis revealed that hydrogen bonding is critical for stabilizing the AZA-DNA complex.
• AZA preferentially binds to AT-rich regions of Ct-DNA, acting as a groove binder.
• Fluorescence spectroscopy indicated moderate binding affinity of AZA to Ct-DNA (ranging from 3.868 to 0.0061 x 10^4 LM^-1 across temperatures).
• Thermodynamic analysis confirmed a spontaneous, enthalpy-driven binding process facilitated by hydrogen bonds and van der Waals forces.

Conclusions:

• AZA interacts with DNA through groove binding, primarily at AT-rich sites, stabilized by hydrogen bonds.
• The binding process is thermodynamically favorable, driven by enthalpy changes.
• These findings provide molecular insights into AZA's genotoxic potential and inform risk assessment.