Chemotherapeutic agents with low toxicity to normal tissues are a major goal in cancer research. In this regard, the therapeutic activities of cationic dyes, such as rhodamine 6G, toward cancer cells have been studied for decades with observed toxicities toward normal and cancer cells. Herein, we report rhodamine 6G-based organic salts with varying counter-anions that are stable under physiological conditions, display excellent fluorescence photostability, and more importantly have tunable chemotherapeutic properties. Our in-vitro studies indicate that the hydrophobic compounds of this series allow production of nanoparticles which are non-toxic to normal cells and toxic to cancer cells. Furthermore, the anions, in combination with cations such as sodium, were observed to be non-toxic to both normal and cancer cells. To the best of our knowledge, this is the first demonstration that both the cation and anion play an extremely important and cooperative role in the antitumor properties of these compounds.

A novel pH sensitive, colorimetric ionic liquid nanosensor based on phosphonium salts of fluorescein is reported. Herein, fluorescein salts of various stoichiometries were synthesized by use of a trihexyltetradecylphosphonium cation [TTP]+ in combination with dianionic [FL]2− and monoanionic [FL]− fluorescein. Nanomaterials derived from these two compounds yielded contrasting colorimetric responses in neutral and acidic environments. Variations in fluorescence spectra as a function of pH were also observed. Examination of TEM and DLS data revealed significant expansion in the diameter of [TTP]2[FL] nanodroplets in acidic environments of variable pHs. A similar trend was also observed for [TTP][FL] nanoparticles. The pH dependent colorimetric and other optical properties of these nanomaterials are attributed to alterations in molecular orientations and stacking as suggested by measuring the absorption, fluorescence, and zeta potential. Since the pH is an important indicator for many diseases, including cancer, these nanosensors are considered to be potential candidates for biomedical applications.

We report on the synthesis and characterization of a PEGylated IR786 GUMBOS (Group of Uniform Materials Based on Organic Salts). The synthesis of this material was accomplished using a three step protocol: (1) substitution of chloride on the cyclohexenyl ring in the heptamethine chain of IR786 by 6-aminohexanoic acid, (2) grafting of methoxy poly ethyleneglycol (MeOPEG) onto the 6-aminohexanoic acid via an esterification reaction, and (3) anion exchange between [PEG786][I] and lithium bis(trifluoromethylsulfonyl)imide (LiNTf2) or sodium bis(2-ethylhexyl)sulfosuccinate (AOT) in order to obtain PEG786 GUMBOS. Examination of spectroscopic data for this PEG786 GUMBOS indicates a large stokes shift (122 nm). It was observed that this PEG786 GUMBOS associates in aqueous solution to form nano-and meso-scale self-assemblies with sizes ranging from 100 to 220 nm. These nano- and meso-scale GUMBOS are also able to resist nonspecific binding to proteins. PEGylation of the original IR786 leads to reduced cytotoxicity. In addition, it was noted that anions, such as NTf2 and AOT, play a significant role in improving the photostability of PEG786 GUMBOS. Irradiation-induced J aggregation in [PEG786][NTf2] and to some extent in [PEG786][AOT] produced enhanced photostability. This observation was supported by use of both steady state and time-resolved fluorescence measurements.

Herein, we report on the role of endocytosis in the selective chemotherpeutic toxicity of rhodamine 6G (R6G) based nanomaterials, i.e., nanoGUMBOS, that are derived from a group of uniform materials based on organic salts (GUMBOS). Evaluation of cellular uptake in the presence and absence of endocytosis inhibitors suggests nanoGUMBOS internalization via clathrin-mediated endocytosis in cancer cells and reveals lack of endocytic internalization in normal cells. Results from characterization of these nanomaterials suggest that endocytic internalization in cancer cells leads to nanoGUMBOS dissociation within the endosomal environment. This ultimately results in selective cytotoxicity of the nanoGUMBOS for cancer cells with no toxicity toward normal cells under examined conditions. Following examination of the selectivity mechanism, in vivo investigations were performed to examine potential therapeutic properties of these nanoparticles. Remarkably, nanoGUMBOS treatment using a mouse xenograft model reduced the tumor volume by 50% suggesting retention of in vitro therapeutic properties in vivo. These results corroborate the selective behavior of nanoGUMBOS and demonstrate their in vivo therapeutic effects, providing further insight into the possible use of these nanomaterials as potential chemotherapeutic agents.

A rapid liquid phase extraction employing a novel hydrophobic surfactant-based room temperature ionic liquid (RTIL), tetrabutylphosphonium dioctyl sulfosuccinate ([4C4 P][AOT]), coupled with capillary electrophoretic-UV (CE-UV) detection is developed for removal and determination of phenolic compounds. The long-carbon-chain RTIL used is sparingly soluble in most solvents and can be used to replace volatile organic solvents. This fact, in combination with functional-surfactant-anions, is proposed to reduce the interfacial energy of the two immiscible liquid phases, resulting in highly efficient extraction of analytes. Several parameters that influence the extraction efficiencies, such as extraction time, RTIL type, pH value, and ionic strength of aqueous solutions, were investigated. It was found that, under acidic conditions, most of the investigated phenols were extracted from aqueous solution into the RTIL phase within 12 min. Good linearity was observed over the concentration range of 0.1-80.0 μg/mL for all phenols investigated. The precision of this method, expressed as RSD, was determined to be within 3.4-5.3% range. The LODs (S/N = 3) of the method were in the range of 0.047-0.257 μg/mL. The proposed methodology was successfully applied to determination of phenols in real water samples.