Hostname: page-component-78c5997874-t5tsf Total loading time: 0 Render date: 2024-11-10T08:18:03.722Z Has data issue: false hasContentIssue false
  • English
  • Français

Guanidinium-Functionalized Photodynamic Antibacterial Oligo(Thiophene)s

Published online by Cambridge University Press:  20 September 2019

Zhe Zhou ,
Cansu Ergene  and
Edmund F. Palermo Open the ORCID record for Edmund F. Palermo [Opens in a new window]
Zhe Zhou
Affiliation:
Materials Science and Engineering, Rensselaer Polytechnic Institute, 110 8th St., Troy, NY12180
Cansu Ergene
Affiliation:
Materials Science and Engineering, Rensselaer Polytechnic Institute, 110 8th St., Troy, NY12180
Edmund F. Palermo*
Affiliation:
Materials Science and Engineering, Rensselaer Polytechnic Institute, 110 8th St., Troy, NY12180
*
*(Email: palere@rpi.edu)
Get access

Abstract

We synthesized precision oligomers of thiophene with cationic and hydrophobic side chains to mimic the charge, hydrophobicity, and molecular size of antibacterial host defense peptides (HDPs). In this study, the source of cationic charge was a guanidinium salt moiety intended to reflect the structure of arginine-rich HDPs. Due to the pi-conjugated oligo(thiophene) backbone structure, these compounds absorb visible light in aqueous solution and react with dissolved oxygen to produce highly biocidal reactive oxygen species (ROS). Thus, the compounds exert bactericidal activity in the dark with dramatically enhanced potency upon visible light illumination. We find that guanylation of primary amine groups enhanced the activity of the oligomers in the dark but also mitigated their light-induced activity enhancement. In addition, we also quantified their toxicity to mammalian cell membranes using a hemolysis assay with red blood cells, in the light and dark conditions.

Keywords

polymerbiomimeticbiomaterial
Type
Articles
Information
MRS Advances , Volume 4 , Issue 59-60: International Materials Research Congress XXVIII , 2019 , pp. 3223 - 3231
Copyright
Copyright © Materials Research Society 2019 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

References:

Peterson, L. R., Bad Bugs, No Drugs: No ESCAPE Revisited. Clin Infect Dis 2009 , 49 (6), 992-993.CrossRefGoogle ScholarPubMed
Jenssen, H.; Hamill, P.; Hancock, R. E. W., Peptide antimicrobial agents. Clinical Microbiology Reviews 2006 , 19 (3), 491-+.CrossRefGoogle ScholarPubMed
Brogden, K. A., Antimicrobial peptides: Pore formers or metabolic inhibitors in bacteria? Nat Rev Microbiol 2005 , 3 (3), 238-250.CrossRefGoogle ScholarPubMed
Zasloff, M., Antimicrobial peptides of multicellular organisms. Nature 2002 , 415 (6870), 389-395.CrossRefGoogle ScholarPubMed
Zasloff, M., Antimicrobial peptides in health and disease. New Engl J Med 2002 , 347 (15), 1199-1200.CrossRefGoogle ScholarPubMed
Matsuzaki, K.; Sugishita, K.; Fujii, N.; Miyajima, K., Molecular-Basis for Membrane Selectivity of an Antimicrobial Peptide, Magainin-2. Biochemistry 1995 , 34 (10), 3423-3429.CrossRefGoogle ScholarPubMed
Ergene, C.; Yasuhara, K.; Palermo, E. F., Biomimetic antimicrobial polymers: recent advances in molecular design. Polym Chem 2018 , 9 (18), 2407-2427.CrossRefGoogle Scholar
Palermo, E. F.; Kuroda, K., Chemical Structure of Cationic Groups in Amphiphilic Polymethacrylates Modulates the Antimicrobial and Hemolytic Activities. Biomacromolecules 2009 , 10 (6), 1416-1428.CrossRefGoogle ScholarPubMed
Palermo, E. F.; Lee, D.-K.; Ramamoorthy, A.; Kuroda, K., Role of Cationic Group Structure in Membrane Binding and Disruption by Amphiphilic Copolymers. J Phys Chem B 2011 , 115 (2), 366-375.CrossRefGoogle ScholarPubMed
Lewis, K.; Klibanov, A. M., Surpassing nature: rational design of sterile-surface materials. Trends Biotechnol 2005 , 23 (7), 343-348.CrossRefGoogle ScholarPubMed
Locock, K. E. S.; Michl, T. D.; Valentin, J. D. P.; Vasilev, K.; Hayball, J. D.; Qu, Y.; Traven, A.; Griesser, H. J.; Meagher, L.; Haeussler, M., Guanylated Polymethacrylates: A Class of Potent Antimicrobial Polymers with Low Hemolytic Activity. Biomacromolecules 2013 , 14 (11), 4021-4031.CrossRefGoogle ScholarPubMed
Locock, K. E. S.; Michl, T. D.; Griesser, H. J.; Haeussler, M.; Meagher, L., Structure-activity relationships of guanylated antimicrobial polymethacrylates. Pure Appl Chem 2014 , 86 (8), 1281-1291.CrossRefGoogle Scholar
Sarapas, J. M.; Backlund, C. M.; deRonde, B. M.; Minter, L. M.; Tew, G. N., ROMP- and RAFT-Based Guanidinium-Containing Polymers as Scaffolds for Protein Mimic Synthesis. Chem-Eur J 2017 , 23 (28), 6858-6863.CrossRefGoogle ScholarPubMed
Treat, N. J.; Smith, D.; Teng, C. W.; Flores, J. D.; Abel, B. A.; York, A. W.; Huang, F. Q.; McCormick, C. L., Guanidine-Containing Methacrylamide (Co)polymers via aRAFT: Toward a Cell-Penetrating Peptide Mimic. ACS Macro Lett 2012 , 1 (1), 100-104.CrossRefGoogle Scholar
Reuter, M.; Schwieger, C.; Meister, A.; Karlsson, G.; Blume, A., Poly-L-lysines and poly-L-arginines induce leakage of negatively charged phospholipid vesicles and translocate through the lipid bilayer upon electrostatic binding to the membrane. Biophys Chem 2009 , 144 (1-2), 27-37.CrossRefGoogle ScholarPubMed
Deitcher, S. R.; Furie, B.; Furie, B. C., Role of Arginine-9 and Arginine-15 in the Gamma-Carboxyglutamic Acid (Gla) Domain of Human Prothrombin in Mediating Binding to Acidic Phospholipid-Vesicles. Blood 1994 , 84 (10), A532-A532.Google Scholar
Maisch, T.; Baier, J.; Franz, B.; Maier, M.; Landthaler, M.; Szeimies, R. M.; Baumler, W., The role of singlet oxygen and oxygen concentration in photodynamic inactivation of bacteria. P Natl Acad Sci USA 2007 , 104 (17), 7223-7228.CrossRefGoogle ScholarPubMed
Dosselli, R.; Tampieri, C.; Ruiz-Gonzalez, R.; De Munari, S.; Ragas, X.; Sanchez-Garcia, D.; Agut, M.; Nonell, S.; Reddi, E.; Gobbo, M., Synthesis, Characterization, and Photoinduced Antibacterial Activity of Porphyrin-Type Photosensitizers Conjugated to the Antimicrobial Peptide Apidaecin 1b. Journal of Medicinal Chemistry 2013 , 56 (3), 1052-1063.CrossRefGoogle ScholarPubMed
Ding, L. P.; Chi, E. Y.; Chemburu, S.; Ji, E.; Schanze, K. S.; Lopez, G. P.; Whitten, D. G., Insight into the Mechanism of Antimicrobial Poly(phenylene ethynylene) Polyelectrolytes: Interactions with Phosphatidylglycerol Lipid Membranes. Langmuir 2009 , 25 (24), 13742-13751.CrossRefGoogle ScholarPubMed
Zhou, Z. J.; Corbitt, T. S.; Parthasarathy, A.; Tang, Y. L.; Ista, L. F.; Schanze, K. S.; Whitten, D. G., "End-Only" Functionalized Oligo(phenylene ethynylene)s: Synthesis, Photophysical and Biocidal Activity. J Phys Chem Lett 2010 , 1 (21), 3207-3212.CrossRefGoogle Scholar
Wang, Y.; Jones, E. M.; Tang, Y. L.; Ji, E. K.; Lopez, G. P.; Chi, E. Y.; Schanze, K. S.; Whitten, D. G., Effect of Polymer Chain Length on Membrane Perturbation Activity of Cationic Phenylene Ethynylene Oligomers and Polymers. Langmuir 2011 , 27 (17), 10770-10775.CrossRefGoogle ScholarPubMed
Ji, E. K.; Parthasarathy, A.; Corbitt, T. S.; Schanze, K. S.; Whitten, D. G., Antibacterial Activity of Conjugated Polyelectrolytes with Variable Chain Lengths. Langmuir 2011 , 27 (17), 10763-10769.CrossRefGoogle ScholarPubMed
Wang, Y.; Jett, S. D.; Crum, J.; Schanze, K. S.; Chi, E. Y.; Whitten, D. G., Understanding the Dark and Light-Enhanced Bactericidal Action of Cationic Conjugated Polyelectrolytes and Oligomers. Langmuir 2013 , 29 (2), 781-792.CrossRefGoogle ScholarPubMed
Parthasarathy, A.; Pappas, H. C.; Hill, E. H.; Huang, Y.; Whitten, D. G.; Schanze, K. S., Conjugated Polyelectrolytes with Imidazolium Solubilizing Groups. Properties and Application to Photodynamic Inactivation of Bacteria. ACS Appl Mater Inter 2015 , 7 (51), 28027-28034.CrossRefGoogle ScholarPubMed
Huang, Y.; Pappas, H. C.; Zhang, L. Q.; Wang, S. S.; Ca, R.; Tan, W. H.; Wang, S.; Whitten, D. G.; Schanze, K. S., Selective Imaging and Inactivation of Bacteria over Mammalian Cells by Imidazolium-Substituted Polythiophene. Chem Mater 2017 , 29 (15), 6389-6395.CrossRefGoogle Scholar
Zhao, Q.; Li, J. T.; Zhang, X. Q.; Li, Z. P.; Tang, Y. L., Cationic Oligo(thiophene ethynylene) with Broad-Spectrum and High Antibacterial Efficiency under White Light and Specific Biocidal Activity against S. aureus in Dark. ACS Appl Mater Inter 2016 , 8 (1), 1019-1024.CrossRefGoogle ScholarPubMed
Chen, Z.; Yuan, H. X.; Liang, H. Y., Synthesis of Multifunctional Cationic Poly(p-phenylenevinylene) for Selectively Killing Bacteria and Lysosome-Specific Imaging. ACS Appl Mater Inter 2017 , 9 (11), 9260-9264.CrossRefGoogle ScholarPubMed
Zhu, C. L.; Yang, Q. O.; Liu, L. B.; Lv, F. T.; Li, S. Y.; Yang, G. Q.; Wang, S., Multifunctional Cationic Poly(p-phenylene vinylene) Polyelectrolytes for Selective Recognition, Imaging, and Killing of Bacteria Over Mammalian Cells. Adv Mater 2011 , 23 (41), 4805-+.CrossRefGoogle ScholarPubMed
Zhou, Z.; Ergene, C.; Lee, J. Y.; Shirley, D. J.; Carone, B. R.; Caputo, G. A.; Palermo, E. F., Sequence and Dispersity Are Determinants of Photodynamic Antibacterial Activity Exerted by Peptidomimetic Oligo(thiophene)s. ACS Appl Mater Inter 2019 , 11 (2), 1896-1906.CrossRefGoogle ScholarPubMed
Zhou, Z.; Palermo, E. F., Templated Ring-Opening Metathesis (TROM) of Cyclic Olefins Tethered to Unimolecular Oligo(thiophene)s. Macromolecules 2018 , 51 (15), 6127–6137.CrossRefGoogle Scholar
Matsuzaki, K.; Yoneyama, S.; Miyajima, K., Pore formation and translocation of melittin. Biophys J 1997 , 73 (2), 831-838.CrossRefGoogle ScholarPubMed