Experimental and Computational Approaches for Solubility Measurement of Pyridazinone Derivative in Binary (DMSO + Water) Systems.

Faiyaz Shakeel,Mohd Imran,Abdullah Alanazi,Sultan Alshehri,Nazrul Haq,Md Khalid Anwer

doi:10.3390/molecules25010171

Abstract

The current research work was performed to evaluate the solubilization behavior, solution thermodynamics, and solvation behavior of poorly soluble pyridazinone derivative i.e., 6-phenyl-pyridazin-3(2H)-one (PPD) in various binary solvent systems of dimethyl sulfoxide (DMSO) and water using experimental and various computational approaches. The solubility of PPD in various binary solvent system of DMSO and water was investigated within the temperature range T = 298.2 K to 318.2 K at constant air pressure p = 0.1 MPa, by employing an isothermal technique. The generated solubility data of PPD was computationally represented by five different cosolvency models including van’t Hoff, Apelblat, Yalkowsky–Roseman, Jouyban–Acree, and Jouyban–Acree–van’t Hoff models. The performance of each computational model for correlation studies was illustrated using root mean square deviations (RMSD). The overall RMSD value was obtained <2.0% for each computational model. The maximum solubility of PPD in mole fraction was recorded in neat DMSO (4.67 × 10−1 at T = 318.2 K), whereas the lowest one was obtained in neat water (5.82 × 10−6 at T = 298.2 K). The experimental solubility of PPD in mole fraction in neat DMSO was much higher than its ideal solubility, indicating the potential of DMSO for solubility enhancement of PPD. The computed values of activity coefficients showed maximum molecular interaction in PPD-DMSO compared with PPD-water. Thermodynamic evaluation showed an endothermic and entropy-driven dissolution of PPD in all the mixtures of DMSO and water. Additionally, enthalpy–entropy compensation evaluation indicated an enthalpy-driven mechanism as a driven mechanism for the solvation property of PPD.

Highlights

The solubility of PPD in neat dimethyl sulfoxide (DMSO) and neat water has been reported at T = 298.2 K to 318.2
The results suggested linear increase in the logarithm solubility of PPD with increase in mass fraction of DMSO in binary DMSO + water systems at each temperature point studied
The solubilities of PPD were found to be increasing with raise in temperature and increase in the mass fraction of DMSO in binary DMSO + water systems in all cases

Summary

Introduction

The investigated molecule 6-phenylpyridazin-3(2H)-one (PPD) [chemical structure: Figure 1; chemical name: 6-phenylpyridazin-3(2H)-one; molecular formula: C10H8N2O; molecular weight: 172.18 g mol−1 and CASRN: 2166-31-6] is a pyridazinone derivative which is being used as cardiotonic agent [1,2].Molecules 2020, 25, 171; doi:10.3390/molecules25010171 www.mdpi.com/journal/moleculesSome other biological activities, including insecticidal [3], cardioprotective [4,5], analgesics [6,7], anti-inflammatory [7,8], antinociceptive [1], antiulcer [9], and antimicrobial activity [10], have been reported for different PPD derivatives. The investigated molecule 6-phenylpyridazin-3(2H)-one (PPD) [chemical structure: Figure 1; chemical name: 6-phenylpyridazin-3(2H)-one; molecular formula: C10H8N2O; molecular weight: 172.18 g mol−1 and CASRN: 2166-31-6] is a pyridazinone derivative which is being used as cardiotonic agent [1,2]. The main problem of PPD and related compounds is high toxicity and week solubilization potential in an aqueous media [1,11]. The solubilities and other physicochemical information about these molecules in aqueous-cosolvent binary systems are important for their complete physicochemical characterization [12,13]. The solubility data and other physicochemical properties of PPD have been reported poorly in the literature. The solubility of PPD in neat DMSO and neat water has been reported recently [17]. The solubility and solution thermodynamic properties of PPD in various DMSO + water systems are not reported elsewhere

Methods

Results

Conclusion