In the present study, ciprofloxacin-salicylic acid molecular salt has been synthesized and preliminarily characterized by FT-IR spectroscopy. The single crystal X-ray diffraction (SCXRD) reveals the proton transfer from carboxylic acid group of salicylic acid to piperazine moiety in ciprofloxacin confirming the formation of new molecular salt. The molecular packing of the molecular salt is mainly supported by N+–H？O？, O–H？O, C–H？F, C–H？ , and interactions. The 3D Hirshfeld surfaces and the associated 2D fingerprint plots were investigated for intermolecular hydrogen bonding interactions. 1. Introduction In the pharmaceutical industry salt formation is a widely used method to modulate the physicochemical properties of active pharmaceutical ingredients (APIs) [1]. Salts have been shown to modulate the solubility and bioavailability of APIs [2–4]. An active pharmaceutical salt is a combination of an API with the GRAS (generally regarded as safe by US FDA) listed coformer [5]. A crystal engineering approach in the selection of acid or base for a given drug molecule to make salts or cocrystals is reported in the literature [6, 7]. Hydrochloride salts are the most preferred method to improve the solubility and stability of APIs [1], but hygroscopicity is a drawback for the hydrochloride salts [8]. Ciprofloxacin (CPF) is a synthetic antibacterial fluoroquinolone related to nalidixic acid having a fluorine atom and piperazine ring at the positions 6 and 7 of quinolone-3-carboxylic acid. It is one of the most active fluoroquinolones with a wide spectrum of biological activity, which is active against both Gram-positive [9] and Gram-negative bacteria [10]. In recent years, CPF has drawn great interest from crystal engineers, due to its tendency to form robust supramolecular architectures with compounds having carboxylic acid functional groups, and also various salts of ciprofloxacin are reported in [11–16]. Our endeavours in the present study are synthesis of CPF molecular salt with GRAS listed salicylic acid, determination of crystal structure by SCXRD, and investigation of various intra- and intermolecular hydrogen bonding by Hirshfeld surface analysis. The molecular structures of CPF and SA are shown in Figure 1. Figure 1: Chemical diagrams of ciprofloxacin (a) and salicylic acid (b). 2. Materials and Methods 2.1. Materials Ciprofloxacin (purity 98%) and salicylic acid (purity 99%) were purchased from Alfa Aesar, India. Methanol with HPLC grade purity was obtained from Rankem,, India, and used without further purification. Distilled water was used for
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