Abstract
This study focuses on the structure—response relationship of symmetrically substituted phenothiazinium dyes. Four hydrophilic derivatives with the ability of additional hydrogen bonding (5, 6) or additional electrostatic interaction (3, 4) were synthesized, photophysically characterized and compared to the parent compound methylene blue (MB, 1) and a lipophilic derivative (2) without additional coordination sites. Derivative 5 was most effective against Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli reaching a maximum photodynamic efficacy of >5log10 steps (≥99.999%) of bacteria killing in 10 minutes (5 µM, 30 J cm−2) without inherent dark toxicity after one single treatment with the incoherent light source PDT1200 (λmax = 660 nm, 50 mW cm−2). Interestingly, one derivative with two additional primary positive charges (3) showed selective killing of Escherichia coli (5 µM, 30 J cm−2, 4log10 steps inactivation (≥99.99%)) and no antimicrobial effect on Staphylococcus aureus. This might allow the development of a new generation of photosensitizers with higher antimicrobial efficacy and selectivity for future applications.
Article PDF
Similar content being viewed by others
Abbreviations
- MB:
-
Methylene blue
- PS:
-
Photosensitizer
- PIB:
-
Photodynamic inactivation of bacteria
- CFU:
-
Colony forming unit
- ROS:
-
Reactive oxygen species
- TFA:
-
Trifluoro acetic acid
- TMPyP:
-
5,10,15,20-Tetrakis(1-methyl-4-pyridinio)porphyrin tetra(p-toluenesulfonate)
References
D. Cressey, Nature News Blog, September, 2013.
A. P. Magiorakos, A. Srinivasan, R. B. Carey, Y. Carmeli, M. E. Falagas, C. G. Giske, S. Harbarth, J. F. Hindler, G. Kahlmeter, B. Olsson-Liljequist, D. L. Paterson, L. B. Rice, J. Stelling, M. J. Struelens, A. Vatopoulos, J. T. Weber, D. L. Monnet, Clin. Microbiol. Infect. 2012 18 268–281.
P. J. van Duijn, M. J. Dautzenberg, E. A. Oostdijk, Curr. Opin. Crit. Care 2011 17 658–665.
T. Maisch, S. Hackbarth, J. Regensburger, A. Felgentraeger, W. Baeumler, M. Landthaler, B. Roeder, J. Dtsch. Dermatol. Ges. 2011 9 360–366.
T. Maisch, T. Shimizu, A. Mitra, J. Heinlin, S. Karrer, Y. F. Li, G. Morfill, J. L. Zimmermann, J. Ind. Microbiol. Biotechnol. 2012 39 1367–1375.
T. G. Klampfl, G. Isbary, T. Shimizu, Y. F. Li, J. L. Zimmermann, W. Stolz, J. Schlegel, G. E. Morfill, H. U. Schmidt, Appl. Environ. Microbiol. 2012 78 5077–5082.
T. Maisch, T. Shimizu, Y. F. Li, J. Heinlin, S. Karrer, G. Morfill, J. L. Zimmermann, PLoS One 2012 7 e34610.
S. Matsuzaki, M. Rashel, J. Uchiyama, S. Sakurai, T. Ujihara, M. Kuroda, M. Ikeuchi, T. Tani, M. Fujieda, H. Wakiguchi, S. Imai, J. Infect. Chemother. 2005 11 211–219.
F. Harris, L. K. Chatfield, D. A. Phoenix, Curr. Drug Targets 2005 6 615–627.
M. C. DeRosa, R. J. Crutchley, Coord. Chem. Rev. 2002 233 351–371.
M. Wainwright, Int. J. Antimicrob. Agents 2000 16 381–394.
C. M. Cassidy, R. F. Donnelly, M. M. Tunney, J. Photochem. Photobiol., B 2010 99 62–66.
S. Menezes, M. A. M. Capella, L. R. Caldas, J. Photochem. Photobiol., B 1990 5 505–517.
H. Singh, D. D. Ewing, Photochem. Photobiol. 1978 28 547–552.
P. S. Zolfaghari, S. Packer, M. Singer, S. P. Nair, J. Bennett, C. Street, M. Wilson, BMC Microbiol. 2009 9.
L. M. Giroldo, M. P. Felipe, M. A. de Oliveira, E. Munin, L. P. Alves, M. S. Costa, Lasers Med. Sci. 2009 24 109–112.
G. G. Carvalho, M. P. Felipe, M. S. Costa, J. Microbiol. 2009 47 619–623.
M. S. Baptista, M. Wainwright, Braz. J. Med. Biol. Res. 2011 44 1–10.
S. J. Wagner, A. Skripchenko, D. Robinette, J. W. Foley, L. Cincotta, Photochem. Photobiol. 1998 67 343–349.
X. Ragas, T. Dai, G. P. Tegos, M. Agut, S. Nonell, M. R. Hamblin, Lasers Surg. Med. 2010 42 384–390.
C. Komine, Y. Tsujimoto, J. Endod. 2013 39 411–414.
M. N. Usacheva, M. C. Teichert, M. A. Biel, Lasers Surg. Med. 2001 29 165–173.
M. B. Fonseca, P. O. Junior, R. C. Pallota, H. F. Filho, O. V. Denardin, A. Rapoport, R. A. Dedivitis, J. F. Veronezi, W. J. Genovese, A. L. Ricardo, Photomed. Laser Surg. 2008 26 209–213.
P. V. Araujo, K. I. Teixeira, L. D. Lanza, M. E. Cortes, L. T. Poletto, Acta Odontol. Latinoam. 2009 22 93–97.
J. A. Williams, G. J. Pearson, M. J. Colles, M. Wilson, Caries Res. 2003 37 190–193.
M. Wainwright, R. M. Giddens, Dyes Pigm. 2003 57 245–257.
S. A. Gorman, A. L. Bell, J. Griffiths, D. Roberts, S. B. Brown, Dyes Pigm. 2006 71 153–160.
M. Wainwright, K. Meegan, C. Loughran, R. M. Giddens, Dyes Pigm. 2009 82 387–391.
M. Wainwright, S. D. Brandt, A. Smith, A. Styles, K. Meegan, C. Loughran, J. Photochem. Photobiol., B 2010 99 74–77.
D. Creed, W. C. Burton, N. C. Fawcett, J. Chem. Soc., Chem. Commun. 1983 1521–1523.
O. M. New, D. Dolphin, Eur. J. Org. Chem. 2009 2009 2675–2686.
M. Merchat, G. Bertolini, P. Giacomini, A. Villanueva, G. Jori, J. Photochem. Photobiol., B 1996 32 153–157.
Y. Nitzan, R. Dror, H. Ladan, Z. Malik, S. Kimel, V. Gottfried, Photochem. Photobiol. 1995 62 342–347.
K. J. Mellish, R. D. Cox, D. I. Vernon, J. Griffiths, S. B. Brown, Photochem. Photobiol. 2002 75 392–397.
A. Felgentraeger, T. Maisch, D. Dobler, A. Spaeth, Biomed Res. Int. 2013 482167.
L. Strekowski, D. F. Hou, R. L. Wydra, R. F. Schinazi, J. Heterocycl. Chem. 1993 30 1693–1695.
J. Baier, T. Fuss, C. Poellmann, C. Wiesmann, K. Pindl, R. Engl, D. Baumer, M. Maier, M. Landthaler, W. Baeumler, J. Photochem. Photobiol., B 2007 87 163–173.
P. K. Frederiksen, S. P. McIlroy, C. B. Nielsen, L. Nikolajsen, E. Skovsen, M. Jorgensen, K. V. Mikkelsen, P. R. Ogilby, J. Am. Chem. Soc. 2005 127 255–269.
A. A. Miles, S. S. Misra, J. O. Irwin, The Journal of hygiene 1938 38 732–749.
J. M. Boyce, D. Pittet, Infect. Control. Hosp. Epidemiol. 2002 23 S3–S40.
J. Mosinger, B. Mosinger, Experientia 1995 51 106–109.
S. B. Brown, J. Griffiths, K. J. Mellish, C. C. O’Grady, D. J. H. Roberts, R. G. Tunstall, and D. I. Vernon, Biologically active methylene blue derivatives, US Patent, US 20040147508 A1, 2004.
S. B. Brown, C. C. O’Grady, J. Griffiths, K. J. Mellish, R. G. Tunstall, D. J. H. Roberts, and D. I. Vernon, (Photopharmica Limited, GB), Biologically active methylene blue derivatives, US Patent, 7,732,439, June 8, 2010.
M. N. Usacheva, M. C. Teichert, M. A. Biel, J. Photochem. Photobiol., B 2003 71 87–98.
S. Sabbahi, Z. Alouini, M. Jemli, A. Boudabbous, Water Sci. Technol. 2008 58 1047–1054.
J. Chen, T. C. Cesario, P. M. Rentzepis, J. Phys. Chem. A 2011 115 2702–2707.
J. Chen, T. C. Cesario, P. M. Rentzepis, Chem. Phys. Lett. 2010 498 81–85.
P. A. R. Tafulo, R. B. Queiros, G. Gonzalez-Aguilar, Spectrochim. Acta, Part A 2009 73 295–300.
A. Spath, C. Leibl, F. Cieplik, K. Lehner, J. Regensburger, K. A. Hiller, W. Baumler, G. Schmalz, T. Maisch, J. Med. Chem. 2014 57 5157–5168.
T. Kiesslich, A. Gollmer, T. Maisch, M. Berneburg, K. Plaetzer, Biomed Res. Int. 2013 2013, 840417.
Y. Usui, K. Kamogawa, Photochem. Photobiol. 1974 19 245–247.
I. Walker, S. A. Gorman, R. D. Cox, D. I. Vernon, J. Griffiths, S. B. Brown, Photochem. Photobiol. Sci. 2004 3 653–659.
D. B. Vieira, A. M. Carmona-Ribeiro, J. Antimicrob. Chemother. 2006 58 760–767.
M. R. Hamblin, T. Hasan, Photochem. Photobiol. Sci. 2004 3 436–450.
X. Zhang, L. Shi, G. Xu, C. Chen, J. Inclusion Phenom. Macrocyclic Chem. 2013 75 147–153.
I. Kacem, T. Laurent, N. Blanchemain, C. Neut, F. Chai, S. Haulon, H. Hildebrand, B. Martel, J. Biomed. Mater. Res., Part A 2013 10.1002/jbma.34965.
G. M. Zhang, S. M. Shuang, C. Dong, J. H. Pan, Spectrochim. Acta, Part A 2003 59 2935–2941.
M. N. Usacheva, M. C. Teichert, C. E. Sievert, M. A. Biel, Lasers Surg. Med. 2006 38 946–954.
S. K. Sharma, T. Dai, G. B. Kharkwal, Y. Y. Huang, L. Huang, V. J. de Arce, G. P. Tegos, M. R. Hamblin, Curr. Pharm. Des. 2011 17 1303–1319.
Author information
Authors and Affiliations
Corresponding author
Additional information
Electronic supplementary information (ESI) available: For selected NMR spectra of the compounds, as well as singlet-oxygen measurements, UV-Vis data concerning aggregation and stability. See DOI: 10.1039/c4pp00309h
Rights and permissions
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
About this article
Cite this article
Gollmer, A., Felgenträger, A., Bäumler, W. et al. A novel set of symmetric methylene blue derivatives exhibits effective bacteria photokilling — a structure — response study. Photochem Photobiol Sci 14, 335–351 (2015). https://doi.org/10.1039/c4pp00309h
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1039/c4pp00309h