*Corresponding author: Zakiyeh Bayat Tel: +98 (915)1811750, Fax: +98 (51) 47233239 Eurasian Chem. Commun., (2020) 374-386 E-mail: z.bayat@ymail.com Page | 374 ECC Eurasian Chemical Communications Evaluation of the 1-octanol/water partition coefficient of quinolones and quinolones compounds via free energy estimated in quantum chemical calculations Meysam Shir Mohammadi a , Zakiyeh Bayat b, *, Esmat Mohammadinasab a a Department of Chemistry, Arak Branch, Islamic Azad University, Arak, Iran b Department of Chemistry, Quchan Branch, Islamic Azad University, Quchan, Iran Received: 25 September 2019, Accepted: 16 November 2019, Published: 02 December 2019 Abstract A rapid screening assay for the measurement of octanol-water partition coefficients (logP) of pharmaceuticals such as quinolines, quinolones and fluoroquinolones compounds were developed using quantum chemical calculations. In this paper, we report the logP of the pharmaceutical derivative compounds determined by the calculation of the difference in the solvation free energies in water-octanol using the thermodynamic integration method. The logP values calculated by this method are closer to the experimental values compared to other ab initio methods. Solvation free energy in water and octanol, free energy of cavity formation in water and Henry’s constants, and some other parameters are determined at the density functional theory (DFT) and Hartree-Fock (HF) level with 6-31++G** basis set. Moreover, surface area, mass, refractivity, volume, and polarizability have been calculated for some of the compounds with the same levels. Keywords: Solvation free energy; partition coefficients; ab initio method; quinolone antibiotics; quinoline. Introduction Quinolone and fluoroquinolones derivatives are broad-spectrum antibiotic pharmaceutics. Almost, all quinolone antibiotics in use are fluoroquinolones, which contain a fluorine atom in their chemical structure and are effective against both Gram-negative and Gram- positive bacteria [1-5]. Fluoroquinolones are often used for genitourinary infections and are widely used in the treatment of hospital-acquired infections associated with urinary catheters [6,7]. Quinolones exert their antibacterial effect preventing bacterial DNA from unwinding and duplicating. Specifically, they inhibit the ligase activity of the type II topoisomerases, gyrase and topoisomerase IV which cut DNA in order to introduce supercoiling and with their ligase activity disrupted release DNA with single and double strand breaks which lead to cell death [8,9]. The majority of quinolones in clinical use are fluoroquinolones, which have a fluorine atom attached to the central ring system, typically, in the 6-position (R6=F) http://echemcom.com Original Research Article