EFFECTS OF SOLVENT POLARITY ON SOLVATION FREE ENERGY, DIPOLE MOMENT, POLARIZABILITY, HYPERPOLARIZABILITY AND MOLECULAR REACTIVITY OF ASPIRIN Original Article MOHAMMAD FIROZ KHAN 1 , RIDWAN BIN RASHID 1 , MUHAMMED MAHFUZUR RAHMAN 1 , MD. AL FARUK 2 , MD. MUSTAFEZUR RAHMAN 2 , MOHAMMAD A. RASHID 3* 1 Department of Pharmacy, State University of Bangladesh, Dhaka-1205, Bangladesh, 2 Department of Pharmacy, Daffodil International University, Dhaka, Bangladesh, 3 Received: 24 Oct 2016 Revised and Accepted: 21 Dec 2016 Department of Pharmaceutical Chemistry, University of Dhaka, Dhaka 1000, Bangladesh Email: ridwan@sub.edu.bd ABSTRACT Objective: The aim of the study is to explore the effects of solvent polarity on solvation free energy, dipole moment, polarizability, first order hyperpolarizability and different molecular properties like chemical hardness and softness, chemical potential, electronegativity, electrophilicity index of aspirin which may lead to better understand the reactivity and stability of aspirin in different solvent systems. Methods: Becke, 3-parameter, Lee-Yang-Parr (B3LYP) level of theory with 6-31G(d,p) basis set was employed to conduct all type of calculations for both in the gas phase and in solution. The solvation free energy, dipole moment and molecular properties were calculated by applying the Solvation Model on Density (SMD) in four solvent systems namely water, methanol, ethanol and n-octanol. Results: The solvation energies steadily increased as the dielectric constant was decreased i.e. free energy increases with decreasing polarity of the solvent. The dipole moment of aspirin was found to be increased when going from non-polar to polar solvents. The dipole moment of aspirin was higher in different solvents than that of the gas phase. The polarizability and first order hyperpolarizability were also increased with the increasing dielectric constant of the solvent. Moreover, ongoing from non-polar to polar solvent the chemical potential, electronegativity and electrophilicity index were increased except in n-octanol. The chemical potential, electronegativity and electrophilicity index of aspirin in n-octanol was higher than that of ethanol. On the other hand, chemical hardness was increased with decreasing polarity of the solvent and the inverse relation was found in the case of softness. Conclusion: The calculated solvation free energy, dipole moment, polarizability, first order hyperpolarizability and molecular properties found in this study may lead to the understanding of stability and reactivity of aspirin in different solvent systems. Keywords: Aspirin, Solvation free energy, Dipole moment, Solvation model, Polarizibility © 2017 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4. 0/) DOI: http://dx.doi.org/10.22159/ijpps.2017v9i2.15853 INTRODUCTION Non-steroidal anti-inflammatory drugs (NSAIDs) are a class of compounds that block cyclooxygenase (COX) enzyme involved in the first step of the arachidonic acid cascade. COX exists in two isoforms namely COX-1 and COX-2. The first is constitutively expressed in stomach, kidneys and platelets and is considered important in mucosal protection and platelet function. COX-2 is inducible and plays a major role in prostaglandin biosynthesis in inflammatory cells [1]. Aspirin (fig. 1) is a prototype NSAID and is used to treat pain, fever, and inflammation. Aspirin also inhibits the platelets aggregation. It is a non-selective COX-2 inhibitor and inhibits both the isoforms of COX enzyme. The therapeutic effects of aspirin are obtained due to the inhibition of COX-2; on the other hand, inhibition of COX-1 leads to undesirable side effects on the gastrointestinal tract such as ulceration, bleeding and perforation of the gastrointestinal tract. Low dose of aspirin is effective in preventing heart attacks, strokes and blood coagulation [2]. Besides, low doses of aspirin are also administered to a patient having a heart attack to reduce the risk of another heart attack or death of cardiac tissue [3, 4]. Aspirin is also used to prevent certain types of cancer, particularly colorectal cancer [5]. Several attempts were made to synthesise aspirin derivatives in order to get compounds having desired biological activities with reduced toxicities. Zhen et al. 2014 [6] prepared aspirin derivatives having anti-thrombotic and gastric mucosal protection properties. Aspirin derivatives having antioxidant, anticoagulant and anti- platelet activities were also reported [7]. Few computational and theoretical studies of aspirin have been reported earlier. El-Shahawy, 2014 reported the theoretical spectral studies of aspirin [8]. Datt et al., 2012 investigated experimental and computational study of the loading and release of aspirin from zeolite HY [9]. Besides, Marjan et al., 2014 conducted a computational study to find the prospect of aspirin side effects [10]. Khan et al., 2015 reported a theoretical study of geometry, molecular properties and molecular docking study of aspirin [11]. The variation in solvent polarity and the type of solute-solvent interaction(s) can affect the geometry, dipole moment, polarizability, hyperpolarizability and other molecular properties [12-14] due to variable interactions with the highest occupied and lowest unoccupied molecular orbitals (HOMO-LUMO) [12, 14, 15]; and hence, can influence the stability and reactivity of the molecule. A detail of the molecular characteristics and interactions can be obtained from the Density Functional Theory (DFT) calculations which eventually lead to a good understanding of molecular properties [14, 16]. Hence, as part of our ongoing research [11, 17] the present study was undertaken to report the medium effect on solvation free energy, dipole moment, polarizability, first order hyperpolarizability and chemical reactivity of aspirin which would be potentially helpful to better understand the stability of aspirin in different solvent system and for the development of new pharmaceutical and (bio) chemical products derived from aspirin. International Journal of Pharmacy and Pharmaceutical Sciences ISSN- 0975-1491 Vol 9, Issue 2, 2017