Stepwise Aggregation of Cholate and Deoxycholate Dictates the Formation and Loss of Surface-Available Chirally Selective Binding Sites.

Bile salts are facially amphiphilic, naturally occurring chemicals that aggregate to perform numerous biochemical processes. Because of their unique intermolecular properties, bile salts have also been employed as functional materials in medicine and separation science (e.g., drug delivery, chiral solubilization, purification of single-walled carbon nanotubes). Bile micelle formation is structurally complex, and it remains a topic of considerable study. Here, the exposed functionalities on the surface of cholate and deoxycholate micelles are shown to vary from one another and with the micelle aggregation state. Collectively, data from NMR and capillary electrophoresis reveal preliminary, primary, and secondary stepwise aggregation of the salts of cholic (CA) and deoxycholic (DC) acid in basic conditions (pH 12, 298 K), and address how the surface availability of chirally selective binding sites is dependent on these sequential stages of aggregation. Prior work has demonstrated sequential CA aggregation (pH 12, 298 K) including a preliminary CMC at ca. 7 mM (no chiral selection), followed by a primary CMC at ca. 14 mM that allows chiral selection of binaphthyl enantiomers. In this work, DC is also shown to form stepwise preliminary and primary aggregates (ca. 3 mM DC and 9 mM DC, respectively, pH 12, 298 K) but the preliminary 3 mM DC aggregate is capable of chirally selective solubilization of the binaphthyl enantiomers. Higher-order, secondary bile aggregates of each of CA and DC show significantly degraded chiral selectivity. Diffusion NMR reveals that secondary micelles of CA exclude the BNDHP guests, while secondary micelles of DC accommodate guests, but with a loss of chiral selectivity. These data lead to the hypothesis that secondary aggregates of DC have an exposed binding site, possibly the 7α-edge of a bile dimeric unit, while secondary CA micelles do not present binding edges to the solution, potentially instead exposing the three alcohol groups on the hydrophilic α-face to the solution.

Rapid Voltammetric Measurements at Conducting Polymer Microelectrodes Using Ultralow-Capacitance Poly(3,4-ethylenedioxythiophene):Tosylate.

UNLABELLED: We use a vapor-phase synthesis to generate conducting polymer films with low apparent capacitance and high conductance enabling rapid electrochemical measurements. Specifically, oxidative chemical vapor deposition was used to create thin films of poly(3,4-ethylenedioxythiophene):tosylate ( PEDOT: tosylate). These films had a conductance of 17.1 ± 1.7 S/cm. Furthermore, they had an apparent capacitance of 197 ± 14 µF/cm(2), which is an order of magnitude lower than current commercially available and previously reported PEDOT. Using a multistage photolithography process, these films were patterned into PEDOT: tosylate microelectrodes and were used to perform fast-scan cyclic voltammetry (FSCV) measurements. Using a scan rate of 100 V/s, we measured ferrocene carboxylic acid and dopamine by FSCV. In contrast to carbon-fiber microelectrodes, the reduction peak showed higher sensitivity when compared to the oxidation peak. The adsorption characteristics of dopamine at the polymer electrode were fit to a Langmuir isotherm. The low apparent capacitance and the microlithographic processes for electrode design make PEDOT: tosylate an attractive material for future applications as an implantable biosensor for FSCV measurements. Additionally, the integration of PEDOT: tosylate electrodes on plastic substrates enables new electrochemical measurements at this polymer using FSCV.

Preferential accumulation within tumors and in vivo imaging by functionalized luminescent dendrimer lanthanide complexes.

We have created a dendrimer complex suitable for preferential accumulation within liver tumors and luminescence imaging by substituting thirty-two naphthalimide fluorophores on the surface of the dendrimer and incorporating eight europium cations within the branches. We demonstrate the utility and performance of this luminescent dendrimer complex to detect hepatic tumors generated via direct subcapsular implantation or via splenic injections of colorectal cancer cells (CC531) into WAG/RijHsd rats. Luminescence imaging of the tumors after injection of the dendrimer complex via hepatic arterial infusion revealed that the dendrimer complex can preferentially accumulate within liver tumors. Further investigation indicated that dendrimer luminescence in hepatic tumors persisted in vivo. Due to the incorporation of lanthanide cations, this luminescence agent presents a strong resistance against photobleaching. These studies show the dendrimer complex has great potential to serve as an innovative accumulation and imaging agent for the detection of metastatic tumors in our rat hepatic model.