Ferrocene-Based Aliphatic and Aromatic Poly(azomethine)esters: Synthesis, Physicochemical Studies, and Biological Evaluation Asghari Gul, † Zareen Akhter, †, * Muhammad Siddiq, † Sehrish Sarfraz, ‡ and Bushra Mirza ‡ † Department of Chemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan ‡ Department of Biochemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan * S Supporting Information ABSTRACT: In continuation to our efforts in finding potential therapeutic agents, a series of biologically significant poly- (azomethine)esters (fe-PAME) were synthesized by the reaction of preformed (E)-4-((4-hydroxyphenylimino)methyl)phenol (SB) with 1,1-di(chlorocarboxyl)ferrocene, (PFe). Different aliphatic and aromatic sequences (1,3-propandiol, 1,6-hexandiol, and poly(dimethylsiloxane), hydroxyl-terminated (n = 550), 1,1,1,3,3,3-hexafluorobis(phenol)propane, and bisphenol A) were incorporated in the parent chain to study their effect on biological activity. The overall results led to the identification of some interesting polymers which seem to be potent antioxidants, highly cytotoxic, and more importantly DNA protecting and hence can be studied further for other pharmacological activities to be used as potential drug candidates. FTIR and 1 H NMR spectroscopic studies and elemental analysis were used to establish structural elucidation and structure-property relations. Laser light scattering was used to determine molecular parameters. ■ INTRODUCTION Ferrocene macromolecules have drawn much attention because of their useful applications like chemical modification of electrodes, electrochemical sensors, charge dissipation material and therapeutic applications. The stability of the ferrocenyl group in aqueous, aerobic media and its promising electro- chemical properties make ferrocene and its derivatives ideal for biological applications and conjugation with biomolecules. 1 Assimilation of a ferrocenyl group into an organic material often yields unexpected biological activity. 2 Ferrocene is transformed into the ferrocenium ion (Fc + ) through one- electron reversible oxidation; however, substituents on the ferrocene moiety have the capability to influence this redox behavior by altering the energy level of HOMO, 3 so reversibility may be lowered significantly. 4 The low cytotoxicity of ferrocene in biological system, its lipophillicity, the cytotoxicity of its metabolites toward tumors, the π-conjugated system and the resulting exclusive electron-transfer ability make its polymers good candidates for the investigation of their biological applications. 2-4 An exhaustive literature survey revealed that in addition to these material, poly(azomethine)s have shown significant antifungal, antibacterial, antitumor and antioxidant activities. 7,8 The literature on the synthesis of ferrocene-poly(azomethine)s by polycondensation is very scarce. Although this procedure is straightforward that does not require stringent reaction conditions and also permit to use a large range of functionalized monomers resulting in polymers with internal polar functions (esters, imide etc.) which could influence the properties of material. 5,6 Macromolecular systems based on ferrocenyl units along with flexible aliphatic or more rigid aromatic organic sequences can induce properties like solubility and flexibility. However these types of materials with ferrocene in their core chain, so far have reported show lower molecular weights. 2,9,10 The efficient mean to improve the physical and chemical properties of material is the chemical modification of macro chains by introducing flexible aliphatic spacers in the main chain, pendent alkyl groups along the backbone, by the copolymerization of di fferent soft groups, by forming composites or by dopant engineering. 11-14 We recently addressed the molecular weight limitation and solubility issue encountered with previously investigated poly(azomethine)esters. This led to the variety of high- molecular-weight, soluble organometallic, biologically active poly(azomethine)esters and their terpolymers by using low temperature solution condensation technique. ■ MATERIALS AND METHODS Materials. Ferrocene (mp = 172-174 °C, Fluka), acetyl chloride (bp = 51-52 °C, Fluka), thionyl chloride (bp = 74.6 °C, Fluka), aluminum chloride (mp = 192.4 °C, Fluka), 4-aminophenol (mp = 188-190 °C, Fluka), 4-hydroxybenzaldehyde (mp = 112-114 °C, Fluka), p-toluenesulfonic acid (monohydrated, mp = 98-102 °C, Fluka) 1,3-propandiol (211-217 °C, Sigma-Aldrich), 1,6-hexandiol (250 °C, Sigma-Aldrich), poly(dimethylsiloxane), hydroxyl-terminated (n = 550, Sigma-Aldrich), 1,1,1,3,3,3-hexafluorobis(phenol)propane (160-163 °C, Sigma-Aldrich), and bisphenol A (158-159 °C, Sigma- Aldrich), nutrient broth medium (b.p = 121 °C, dissolved in water, Merck), nutrient agar medium (bp = 121 °C, dissolved in water, Merck), 2,2-diphenyl-1-picrylhydrazyl (mp ∼ 135 °C, Sigma-Aldrich) were used as received. The chemicals from commercial sources were Received: January 29, 2013 Revised: March 19, 2013 Article pubs.acs.org/Macromolecules © XXXX American Chemical Society A dx.doi.org/10.1021/ma400192u | Macromolecules XXXX, XXX, XXX-XXX