Exploring the Solvent Impact on the Quantum Chemical Properties and Interaction of a Triazole Derivative against Chlamydia trachomatis: An Extensive Computational Investigation

This study highlights an extensive computational inquiry of the solvent effect on the chemical properties of a newly synthesized 1-(4-Chlorophenyl)-3-(3,5-dimethylphenyl)-5-(3-fluorophenyl)-4H-1,2,4-triazol-4yl) urea (CDF-TU) . The study aims to examine the effects of solvents on the chemical properties and lead compound potentials of compound CDF-TU against Chlamydia trachomatis . Density functional theory at the B3LYP-D3(BJ)/aug-cc-evqz level of theory was used for the study of the electronic effect of the compound (CDF-TU) in ethanol, water, and gas. This study examined the pharmacokinetic attributes of CDF-TU, confirming its alignment with Lipinski's rule, and other parameters such as molecular weight of 435.88 g/mol. Moreover, the HOMO-LUMO analysis revealed the ionization energies of CDF-TU showed that water had more stabilizing effect on the compound with the highest energy gap of 5.2543 eV. Also, CDF-TU in water had the highest electronegativity of 3.9136eV compared to Ethanol (3.8884eV) and gas (3.2068eV). Molecular docking analysis revealed that, compared with doxycycline, the standard drug, CDF-TU had higher binding affinity (-8.9 Kcal/mol) compared to Doxycycline (-7.8 Kcal/mol) with protein 1RCW when surrounded by water molecules. Hence, CDF-TU records a lower inhibition (0.298µM) constant when compared to Doxycycline (1.876µM). However, in the absence of water, CDF-TU records the same magnitude of binding affinity with Doxycycline (-6.3 Kcal/mol). More hydrogen bonds were formed with CDF-TU and protein 1RCW in water compared to the compound's interaction with protein 1RCW without water. However, these findings demonstrate the biological potential of CDF-TU due to its docking performance amidst the presence of water.