Published: August 12, 2011 r2011 American Chemical Society 3528 dx.doi.org/10.1021/bm200718s | Biomacromolecules 2011, 12, 3528–3539 ARTICLE pubs.acs.org/Biomac Photobactericidal Porphyrin-Cellulose Nanocrystals: Synthesis, Characterization, and Antimicrobial Properties Elke Feese, † Hasan Sadeghifar, ‡,# Hanna S. Gracz, § Dimitris S. Argyropoulos, †,‡,|| and Reza A. Ghiladi* ,† † Departments of Chemistry, ‡ Forest Biomaterials, and § Molecular and Structural Biochemistry, North Carolina State University, Raleigh, North Carolina, United States ) Department of Chemistry, University of Helsinki, Helsinki, Finland # Department of Wood and Paper Science, Islamic Azad University, Chalous, Iran b S Supporting Information H ospital acquired infections, in particular, highlight the issue of adherence and survival of bacteria on surfaces leading to an increase in the proliferation and transmission of bacteria. Specifically, antibiotic-resistant bacteria are a rising threat to human health. According to the Centers of Disease Control and Prevention, about 1.7 million healthcare associated infections cause upward of 99000 deaths annually in the United States. 1 A total of 510% of all hospitalized patients are adversely affected, which in turn is adding about $3045 billion to health care costs annually. 2 Food processing/packaging, food service, and waste- water treatment industries, as well as personal households, are also areas of concern and can contribute to the spread of disease through contaminated or improperly disinfected surfaces. Con- sequently, more research into effective surface disinfection and alternative materials (fabrics, plastics, or coatings) with antimi- crobial properties is needed. Several classes of antimicrobial agents are currently being investigated or are commercially available, among which are polymeric compounds containing quarternary ammonium, 37 pyridinium 8,9 or phosphonium salts, 5,10 N-halamines, 11,12 biguanides, 13 antibiotics, 14 heavy metals such as Ag, 1416 and phenol derivatives. 14 Disadvantages of currently available materials are the loss of antimicrobial activity by leaching of the biocide in noncovalent systems, consumption of the germicidal ability, environmentally hazardous agents, or dependency on direct contact of the antimicrobial entity with the microorganism. Thus, there is an urgent need for the develop- ment of novel materials with the potential capability of rapid, efficient, and low-cost sterilization of a range of bacteria. During the past few decades, photodynamic inactivation (PDI) has garnered the attention of many researchers as an alternative technique for eradicating microorganisms. Therefore, we see great potential in the development of photobactericidal materials that could satisfy many desired characteristics while overcoming some of the shortcomings of currently available antimicrobial materials. PDI employs a localized, light-activated photosensitizer (PS) that generates cytotoxic species, particu- larly singlet oxygen, upon illumination with visible light. Singlet oxygen, as opposed to some common disinfectants such as chlorine and hypochlorite, can be regarded as an environmentally benign germicide (short lifetime of 10 6 s in water 17 and Received: May 27, 2011 Revised: August 3, 2011 ABSTRACT: Adherence and survival of pathogenic bacteria on surfaces leading to concomitant transmission to new hosts significantly contributes to the proliferation of pathogens, which in turn considerably increases the threat to human health, particularly by antibiotic-resistant bacteria. Consequently, more research into effective surface disinfection and alternative materials (fabrics, plastics, or coatings) with antimicrobial and other bioactive characteristics is desirable. This report describes the synthesis and characterization of cellulose nanocrystals that were surface-modified with a cationic porphyrin. The porphyrin was appended onto the cellulose surface via the Cu(I)-catalyzed HuisgenMeldalSharpless 1,3-dipolar cycloaddition having occurred between azide groups on the cellulosic surface and porphyrinic alkynes. The resulting, generally insoluble, crystalline material, CNC-Por (5), was characterized by infrared and diffusion 1 H NMR spectroscopies, gel permeation chromatography, and thermogravimetric analysis. Although only suspended, and not dissolved, in an aqueous system, CNC-Por (5) showed excellent efficacy toward the photodynamic inactivation of Mycobacterium smegmatis and Staphylococcus aureus, albeit only slight activity against Escherichia coli. The synthesis, properties, and activity of CNC-Por (5) described herein serve as a benchmark toward our overall objectives of developing novel, potent, bioactive, photobactericidal materials that are effective against a range of bacteria, with potential utilization in the health care and food preparation industries.