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International Journal of Biomedical Imaging
Volume 2013 (2013), Article ID 803579, 11 pages
Review Article

Hydraphiles: A Rigorously Studied Class of Synthetic Channel Compounds with In Vivo Activity

1Departments of Chemistry and Biochemistry and Biology, Center for Nanoscience, University of Missouri-St. Louis, St. Louis, MO 63121, USA
2Department of Chemistry and Biochemistry, 236 Nieuwland Science Hall, University of Notre Dame, Notre Dame, IN 46556, USA
3Notre Dame Integrated Imaging Facility, University of Notre Dame, Notre Dame, IN 46556, USA

Received 31 August 2012; Accepted 26 November 2012

Academic Editor: Anne Clough

Copyright © 2013 Saeedeh Negin et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Hydraphiles are a class of synthetic ion channels that now have a twenty-year history of analysis and success. In early studies, these compounds were rigorously validated in a wide range of in vitro assays including liposomal ion flow detected by NMR or ion-selective electrodes, as well as biophysical experiments in planar bilayers. During the past decade, biological activity was observed for these compounds including toxicity to bacteria, yeast, and mammalian cells due to stress caused by the disruption of ion homeostasis. The channel mechanism was verified in cells using membrane polarity sensitive dyes, as well as patch clamping studies. This body of work has provided a solid foundation with which hydraphiles have recently demonstrated acute biological toxicity in the muscle tissue of living mice, as measured by whole animal fluorescence imaging and histological studies. Here we review the critical structure-activity relationships in the hydraphile family of compounds and the in vitro and in cellulo experiments that have validated their channel behavior. This report culminates with a description of recently reported efforts in which these molecules have demonstrated activity in living mice.