Composites Containing Fullerenes and Polysaccharides: Green and Facile Synthesis, Biocompatibility, and Antimicrobial Activity Simon Duri, April L. Harkins, Anna J. Frazier, and Chieu D. Tran* Department of Chemistry, Marquette University, 535 N. 14th Street, Milwaukee, Wisconsin 53233, United States * S Supporting Information ABSTRACT: By use of a green and simple ionic liquid, butylmethylimidazolium chloride (BMIm + Cl - ) as a sole solvent, we developed a novel, green, and simple method to synthesize biocompatible composites containing polysaccharides (cellulose (CEL), chitosan (CS), and γ-cyclodextrin (γ-TCD)) and fullerene derivatives (amino-C 60 and hydroxy-C 60 ). The composites obtained (100%CEL, 100%CS, [CEL+γ-TCD] and [CS+γ- TCD]) readily adsorb amino-C 60 and hydroxy-C 60 . Kinetics and adsorption isotherm results indicate that the fullerene derivatives physically adsorbed onto the surface of the CEL-based composites and subsequently desorbed from the composites when they were soaked in water. Conversely, because both fullerene derivatives strongly adsorbed onto the surface and subsequently diffused into the pores within the matrix of the CS-based composites, it was possible to synthesize (CS+amino-C 60 ), (CS+hydroxy-C 60 ), (CS +γ-TCD+amino-C 60 ), and (CS+γ-TCD+hydroxyl-C 60 ) compo- sites. Microbial assay results show that adding γ-TCD, amino-C 60 , and/or hydroxyl-C 60 to CS substantially increases the composite’s ability to reduce the growth of antibiotic-resistant bacteria such as Vancomycin-resistant Enterococcus (VRE). Biocompatibility assays indicate that hydroxy-C 60 and amino-C 60 are not cytotoxic to humans when encapsulated into CS composites. Taken together, the (CS+γ-TCD+fullerene) composites are well suited for various applications ranging from dressing to treat chronically infected wounds to nonlinear optics, biosensors, and therapeutic agents. KEYWORDS: Ionic liquid, Cellulose, Chitosan, Cyclodextrin, Antibiotic-resistant bacteria, Chronic infected wounds ■ INTRODUCTION Fullerenes have been the subject of wide and intense studies in many disciplines including chemistry, physics, and materials science. 1-5 Because of their unique structure, fullerenes have many interesting and unique properties including nonlinear effect, biological activity, optical limiting effect, and super- conductivity. 1-20 For example, C 60 and its derivatives have effectively served as agents and/or materials in thermores- ponsive materials, sensors to detect illicit drugs (e.g., amphet- amine), endocrine disruptors (e.g., bisphenol A), smart optical filters, and photodynamic therapy [i.e., C 60 and C 70 are strong photosynthesizers to generate singlet oxygen (1O2). The efficiencies of generating 1O2 by fullerenes are 2-3 times higher than well-known photosynthesizers such as rose bengal.], magnetic imaging, neuroprotection, anti-apoptosis, antioxidants, and antibacterials to inhibit growth of various bacteria and fungi such as Propionibacterium acnes, Staph- ylococcus epidermidis, Candida albicans, Malassezia furfur, E. coli, vancomycin-resistant Enterococcus faecalis (VRE), and of various cancer cells and HIV virus. 1-20 Efforts have been made, therefore, to use C 60 to prepare novel and high performance materials that have these antimicrobial and antiproliferative properties. Unfortunately, in spite of considerable efforts, advances in this field are rather limited. This may be due to the fact that C 60 has relatively poor solubility, miscibility, and processability. As a consequence, to date, C 60 -based materials were made by covalently binding or grafting C 60 onto manmade polymers. 21-30 The rather complicated, costly, and multistep process is not desirable as it requires not only expertise in synthesis but also may inadvertently alter properties of C 60 , making the C 60 -based materials less biocompatible and diminishing its unique properties. 21-30 A new method which can effectively incorporate C 60 into biopolymers such as polysaccharides (e.g., cellulose and/or chitosan) without any reaction is particularly needed. Such a method would make it possible to prepare [CEL/CS+C 60 ] composite material that is not only biocompatible but also has combined unique properties of C 60 and chitosan. This is because chitosan (CS) which is a linear amino polysaccharide, obtained by N- deacetylation of chitin, is the second most abundant naturally Received: March 7, 2017 Revised: April 18, 2017 Published: April 25, 2017 Research Article pubs.acs.org/journal/ascecg © XXXX American Chemical Society A DOI: 10.1021/acssuschemeng.7b00715 ACS Sustainable Chem. Eng. XXXX, XXX, XXX-XXX