Fine-tuning pharmacological properties of mirtazapine antidepressant drug: a theoretical study

It has become obvious that fluorinated drugs have a significant role in medicinal applications. In this study, the fluorination of mirtazapine antidepressant drug was investigated using density functional theory calculations. We found that the intramolecular hydrogen bonding and charge transfers of the mirtazapine drug were influenced by fluorine substitution. Our results also reveal that the fluorination altered the stability, solubility, and molecular polarity of the mirtazapine antidepressant drug. Moreover, our results show that the electronic spectra of fluorinated derivatives of the mirtazapine exhibit a red shift toward higher wavelengths compared to the original antidepressant drug. Our calculations show that the difference between G value of the gas and water (Delta G) of fluorinated derivatives of the mirtazapine drug was negative. We also found that the fluorination can increases the first hyperpolarizability of the mirtazapine antidepressant drug. Our results present an efficient strategy to improve the nonlinear optical responses of the antidepressant drugs. Consequently, the results of present study show that the fluorination of mirtazapine could be considered as a promising strategy to design antidepressant drugs with better pharmacological properties. Communicated by Ramaswamy H. Sarma

Automated summary

The study investigates the fluorination of mirtazapine antidepressant drug using density functional theory calculations, finding that fluorine substitution influences intramolecular hydrogen bonding, charge transfers, stability, solubility, molecular polarity, and electronic spectra. The results show a red shift in electronic spectra of fluorinated derivatives and a negative Delta G value. Furthermore, fluorination increases the first hyperpolarizability of the drug, presenting an efficient strategy to enhance the nonlinear optical responses of antidepressant drugs.