Molecular clips with spatially proximal urea residues for efficient transmembrane co-transport of H+/Cl- ions.

We report the design of bis(urea) functionalized amphiphilic molecular clips viz. 1a-1e to achieve efficient transmembrane co-transport of H+/Cl- ions. The most promising molecule 1a demonstrated a low nanomolar EC50 value (6.96 nM) to co-transport H+/Cl- ions via a carrier-mediated pathway and showed selective toxicity against cancerous HeLa cells as a result.

Anion-responsive self-assembled hydrogels of a phenylalanine-TREN conjugate allow sequential release of propranolol and doxorubicin.

Stimuli-responsive self-assembled and supramolecular hydrogels derived from peptide amphiphiles have opened exciting new avenues in biomedicine and drug delivery. Herein, we screened a series of phenylalanine-amphiphiles possessing polyamine and oxyethylene appendages for their self-assembly and anion-responsiveness and found that the tris(aminoethyl)amine (TREN) containing amphiphile NapF-TREN formed injectable hydrogels that could be disrupted upon the addition of stoichiometric amounts of tetrahedral monovalent anions such as H2PO4- and HSO4-, while the addition of other anions such as Cl-, HPO42-, CO32-, HCO3- or SO42- did not affect the gel stability. The anion-gelator interaction was investigated by 1H and 31P NMR spectroscopy as well as by Isothermal Titration Calorimetry (ITC). These studies confirmed a 1 : 1 stoichiometry and revealed negative enthalpy and negative entropy for the binding of H2PO4- with NapF-TREN. Microscopic investigations by TEM, AFM, and SAXS revealed that H2PO4- anions induced a nanofiber-to-nanoglobule morphological change in the aqueous self-assemblies of NapF-TREN. However, upon ageing the samples, slow reformation of the nanofibers was also observed, reflecting the reversibility of the anion-gelator interaction. The anion- and pH-responsive nature of the NapF-TREN hydrogels was exploited to program sequential release of entrapped drugs propranolol and doxorubicin.

Polydopamine and dopamine interfere with tetrazolium-based cytotoxicity assays and produce exaggerated cytocompatibility inferences.

Tetrazolium-based assays such as the MTT assay have been commonly employed in evaluating biocompatibility. Here, we show that PDA (or its precursor dopamine (DA)) spontaneously reduces MTT and produces exaggerated cytocompatibility inferences. The extent of interference depends on the method of DA polymerization. We observed that the trypan blue exclusion assay allowed more accurate determination of cell viability in the presence of DA- and PDA-based nanomaterials.