Developing of a novel antibacterial agent by functionalization of graphene oxide with guanidine polymer with enhanced antibacterial activity
Graphical abstract
Introduction
Infection control is of utmost importance in various fields. As a consequence, antibacterial materials that can effectively inhibit the growth of microorganisms with limited cytotoxicity have aroused considerable research interests. Antimicrobials, for instance quaternary ammonium salts [1], quaternary phosphonium salts [2], N-halamines [3], metal ions [4], and polyguanidine [5] have been underlined by their broad applications in the filed of biomedicine, food packaging and sterilization of hygienic areas. Guanidine polymer synthesized by the polycondensation of guanidinium and diamine has a wide spectrum antimicrobial activity, excellent biocide efficiency and nontoxicity [6]. However, Guanidine polymer-based antibacterial agents also have the undeniable congenital defects, as a result of its well water soluble, it is difficult to recycle, as a result cause secondary contamination. If the water soluble guanidine polymer is used as additives for industrial goods, the final products are deficient in antibacterial fastness [7]. So developing guanidine polymer composite materials with excellent antibacterial properties and strong antibacterial fastness under various conditions is still a critical need.
Graphene, a single-atom-thick 2-dimensional (2D) graphitic carbon material, has already gained great attention since its discovery [8]. Due to their impressive physical and chemical properties, graphene and its derivatives, such as graphene oxide (GO) and reduced graphene oxide (rGO), have been extensively studied for application in diverse fields, including water purification, molecule sensing, composite materials, energy research, catalysis, and even antibacterial activity [9], [10], [11], [12], [13], [14], [15]. Among all graphene derivatives, graphene oxide (GO), which has a graphene sheet with carboxylic groups at its edge and phenol hydroxyl and epoxide groups on its basal plane, is the most popular one [16]. These abundant oxygen functional groups of GO served as active sites have been used to build new composites. GO can be modified through different types of covalent and non-covalent functionalization approaches, which make it a popular target for functional application. Furthermore, GO can be easily synthesized at a large scale and low cost, from graphite flakes according to the modified Hummers’ method [17], [18].
In recent years, it has been reported that graphene and graphene-based composites present powerful antibacterial effect [13], [19], [20], [21], [22], [23], [24], [25], [26]. Antibacterial activity of graphene and graphene-based composites is found to assign to membrane puncture [22]. By direct contact, the sharp edges of graphene nanosheets can induce membrane stress, which may result in physical damage on cell membranes, leading to the loss of bacterial membrane integrity and the leakage of RNA [22]. Several GO-based composites, such as GO-Ag [20], [23], [24], [25] and GO-ZnO [26] are fabricated as antibacterial products. Those GO-based composites demonstrate markedly enhanced antibacterial effects. Although tremendous explorations have been achieved, a facile synthesis of cost-effective and powerful antibacterial agent is still highly desirable.
Therefore, conjugation of guanidine polymer with GO sheets which act as substrates may give new life to a common antibacterial agent. Yet GO will aggregate in saline solution [27]. Guanidine polymer is usually obtained as a salt, which may cause the aggregation of GO. The aggregation of GO sheets makes them have fewer chances to interact with bacteria for membrane puncture than that of disperse GO sheets [19]. Poly(ethylene glycol) is a very useful reagent for its minimal toxicity, biocompatibility and good solubility in water or other common solvents [28]. The combination of GO with poly(ethylene glycol) can effectively improve its colloidal stability in saline solution [29]. In this paper, the as-prepared GO was functionalized with poly-(ethylene glykol) methylether (PEG) to render higher aqueous solubility and stability in saline solution. Then guanidine polymer was bond to PEGylation of GO sheets without any aggregation.
In this work, polyhexamethylene guanidine hydrochloride (PHGC, as guanidine polymer) was prepared by polycondensation of guanidine hydrochloride with hexamethylenediamine. Then GO-PEG-PHGC consisting of GO sheets with covalently conjugated PEG and PHGC was synthesized. PEG was employed as a stabilizer for conjugating PHGC to GO sheets. Escherichia coli (typical Gram negative bacteria) and S. aureus (typical Gram positive bacteria) were used as model in this experiment. The antibacterial activity of the GO-PEG-PHGC composite was evaluated qualitatively by a biocidal kinetic test. For comparison, the antibacterial activity of GO, GO-PEG and GO-PHGC were discussed by the same method.
Section snippets
Material
Nature graphite powder was purchased from Tianjin Guangfu Fine Chemical Research Institute. Poly-(ethylenglykol) methylether (PEG, Mn = 2000) was purchased from Sigma–Aldrich and used without further purification. Guanidine hydrochloride and hexamethylenediamine were provided from Sinopharm Chemical Reagent Co., Ltd. Concentrated H2SO4, sodium nitrate potassium permanganate and H2O2 (30%) were obtained from Beijing Chemical Company. 1-(3-Dimethylaminopropyl)-3-ehylcarbodiimide hydrochloride (EDC)
Synthesis and Characterization of GO-PEG-PHGC
The modified Hummer's method was employed to prepare GO using natural graphite powder as starting material [17], [18]. GO sheet with carboxylic groups at its edge and phenol hydroxyl and epoxide groups on its basal plane [8] is usually applied as the staring functional precursor. These oxygen-containing groups, acting as anchor sites, enable the in situ functionalization and hybridization with other materials, such as the esterification of carboxyls or ring opening reaction of epoxy groups [30]
Conclusions
In this study, the dual-polymer-functionalized GO (GO-PEG-PHGC) was synthesized by covalently conjugating PEG and PHGC to the surface of GO sheets. GO-PEG-PHGC demonstrates superior antibacterial property against both Gram negative bacteria E. coli and Gram positive bacteria S. aureus. The improved antibacterial activity was described to be related to a better dispersion of GO-PEG-PHGC in the presence of PEG. Furthermore, PHGC obtains strong antibacterial fastness under various conditions,
Acknowledgement
This research was supported by the National Nature Science Foundation of Jilin Province (201115011).
References (37)
- et al.
Synthesis and antimicrobial activity of polymeric guanidine and biguanidine salts
Polymer
(1999) - et al.
An integrated sensing system for detection of DNA using new parallel-motif DNA triplex system and graphene e–mesoporous silica–gold nanoparticle hybrids
Biomaterials
(2011) - et al.
Graphene oxide adsorption enhanced by in situ reduction with Sodiumhydrosulfite to remove acridine orange from aqueous solution
J. Hazard. Mater.
(2012) - et al.
Preparation and antibacterial properties of Ag@polydopamine/graphene oxide sheet nanocomposite
Appl. Surf. Sci.
(2013) - et al.
Green synthesis of high conductivity silver nanoparticle-reduced graphene oxide composite films
Appl. Surf. Sci.
(2014) - et al.
Antibacterial activity and reusability of CNT-Ag and GO-Ag nanocomposites
Appl. Surf. Sci.
(2013) - et al.
Properties and biocompatibility of chitosan films modified by blending with PEG
Biomaterials
(2002) - et al.
In vitro and in vivo behaviors of dextran functionalized graphene
Carbon
(2011) - et al.
Role of graphite precursor in the performance of graphite oxides as ammonia adsorbents
Carbon
(2009) - et al.
Layer-by-layer assembly of graphene oxide on polypropylene macroporous membranes via click chemistry to improve antibacterial and antifouling performance
Appl. Surf. Sci.
(2015)
The use of polyethylenemine-modified reduced graphene oxide as a substrate for silver nanoparticles to produce a material with lower cytotoxicity and long-term antibacterial activity
Carbon
Design of contact-active antimicrobial acrylate-based materials using biocidal macromers
Adv. Mater.
Biologically active polymers. V. Synthesis and antimicrobial activity of modified poly (glycidyl methacrylate-co-2-hydroxyethyl methacrylate) derivatives with quaternary ammonium and phosphonium salts
Polym. Sci. A: Polym. Chem.
Fabrication of monodisperse silica–polymer core–shell nanoparticles with excellent antimicrobial efficacy
Chem. Commun.
Synthesis, characterization and in vitro biological activity of cobalt(II), copper(II) and zinc(II) Schiff base complexes derived from salicylaldehyde and D,L-selenomethionine
Appl. Organomet. Chem.
Bactericidal core-shell paramagnetic nanoparticles functionalized with poly(hexamethylene biguanide)
Langmuir
Antimicrobial-modified sulfite pulps prepared by in situ copolymerization
Carbohydr. Polym.
The chemistry of graphene oxide
Chem. Soc. Rev.
Cited by (82)
Enhanced properties of gelatin films incorporated with TiO<inf>2</inf>-loaded reduced graphene oxide aerogel microspheres for active food packaging applications
2024, International Journal of Biological MacromoleculesAntibacterial activity of SnO<inf>2</inf> in visible light enhanced by erbium–cobalt co-doping
2023, Colloids and Surfaces A: Physicochemical and Engineering AspectsPreparation of AlN–Al<inf>2</inf>O<inf>3</inf> composites exhibiting antibacterial and water purification properties
2023, Journal of the European Ceramic SocietyGraphene-based nanomaterials for antibiotics-independent antibacterial applications
2023, Antimicrobial Nanosystems: Fabrication and DevelopmentTexture and rheological features of strain and pH sensitive chitosan-imine graphene-oxide composite hydrogel with fast self-healing nature
2022, International Journal of Biological Macromolecules