Effects of para-aminobenzoic acid (PABA) form and administration mode on PABA recovery in 24-hour urine collections.

Para-aminobenzoic acid (PABA) has long been used as an objective measure to assess completeness of 24-hour urine collections. However, pharmaceutical-grade PABA for human ingestion is not available in the United States. An alternative, the potassium salt of PABA, aminobenzoate potassium, can be obtained for clinical use, although it has not yet been validated in this role. Both PABA and aminobenzoate potassium can be directly ingested in their tablet or capsule forms or added to food before consumption. Our aim was to investigate the effect of form (PABA vs aminobenzoate potassium) and administration mode (directly ingested as a tablet/capsule vs added to food) on urinary PABA recovery levels. Twenty healthy participants underwent 3 test days separated by two 24-hour wash-out periods. Three test conditions, one on each test day, were investigated in randomized order: PABA tablet, aminobenzoate potassium capsule, and PABA or aminobenzoate potassium in food. Ingestion of each dose was supervised and participants performed the 24-hour urine collections while free-living. The 24-hour urine collections were analyzed for PABA recovery (%R) levels using a colorimetric assay. Recoveries 85% to 110% were deemed complete and those >110% were reanalyzed by high pressure liquid chromatography and mass spectrometry. Only complete collections (>85%R) were included in analyses. The recovery for the PABA tablet, aminobenzoate potassium capsule, and PABA/aminobenzoate potassium in food were similar at 98.8%R±2.0%R, 95.1%R±2.3%R, and 93.2%R±2.1%R, respectively, and did not differ significantly. These results suggest that aminobenzoate potassium may be used as an alternative to PABA for assessing the completeness of 24-hour urine collections and to track compliance with consuming provided diets in community-dwelling studies.

Photolithography of Dithiocarbamate-Anchored Monolayers and Polymers on Gold.

Dithiocarbamate (DTC)-anchored monolayers and polymers were investigated as positive resists for UV photolithography on planar and roughened Au surfaces. DTCs were formed in situ by the condensation of CS(2) with monovalent or polyvalent amines such as linear polyethyleneimine (PEI) under mildly basic aqueous conditions, just prior to surface passivation. The robust adsorption of the polyvalent PEI-DTC to Au surfaces supported high levels of resistance to photoablation, providing opportunities to generate thin films with gradient functionality. Treatment of photopatterned substrates with alkanethiols produced binary coatings, enabling a direct visual comparison of DTC- and thiol-passivated surfaces against chemically induced corrosion using confocal microscopy.

Bishydrazide glycoconjugates for lectin recognition and capture of bacterial pathogens.

Bishydrazides are versatile linkers for attaching glycans to substrates for lectin binding and pathogen detection schemes. The α,ω-bishydrazides of carboxymethylated hexa(ethylene glycol) (4) can be conjugated at one end to unprotected oligosaccharides, then attached onto carrier proteins, tethered onto activated carboxyl-terminated surfaces, or functionalized with a photoactive cross-linking agent for lithographic patterning. Glycoconjugates of bishydrazide 4 can also be converted into dithiocarbamates (DTCs) by treatment with CS(2) under mild conditions, for attachment onto gold substrates. The immobilized glycans serve as recognition elements for cell-surface lectins and enable the detection and capture of bacterial pathogens such as Pseudomonas aeruginosa by their adsorption onto micropatterned substrates. A detection limit of 10³ cfu/mL is demonstrated, using a recently introduced method based on optical pattern recognition.

Gold nanorods: multifunctional agents for cancer imaging and therapy.

Gold nanorods (GNRs) are strongly absorbing at near-infrared (NIR) frequencies and can be employed as multifunctional agents for biological imaging and theragnostics. GNRs can support nonlinear optical microscopies based on two-photon-excited luminescence and can enhance the contrast of biomedical imaging modalities such as optical coherence tomography and photoacoustic tomography. GNRs are also efficient at mediating the conversion of NIR light energy into heat and can generate localized photothermal effects. However, future clinical applications will require the rigorous removal of CTAB, a micellar surfactant used in GNR synthesis, and reliable methods of surface functionalization for cell-selective targeting and for minimizing nonspecific uptake into cells. This can be accomplished by using polystyrenesulfonate (PSS) as a sorbent for removing CTAB, and in situ dithiocarbamate formation for introducing chemisorptive ligands onto GNR surfaces.

Gyromagnetic imaging: dynamic optical contrast using gold nanostars with magnetic cores.

Plasmon-resonant nanoparticles with optical scattering in the near-infrared (NIR) are valuable contrast agents for biophotonic imaging and may be detected at the single-particle limit against a dark background, but their contrast is often limited in environments with high noise. Here we consider gyromagnetic imaging as a dynamic mode of optical contrast, using gold nanostars with superparamagnetic cores. The nanostars exhibit polarization-sensitive NIR scattering and can produce a frequency-modulated signal in response to a rotating magnetic field gradient. This periodic "twinkling" can be converted into Fourier-domain images with a dramatic reduction in background. We demonstrate gyromagnetic imaging of nanostars inside of tumor cells, using broadband excitation: while their time-domain signals are obscured by incoherent scattering, their Fourier-domain signals can be clearly resolved in less than a second. The gyromagnetically active nanostars do not cause a loss in viability, and can even have a mild stimulatory effect on cell growth.

Biocompatible and biodegradable ultrafine fibrillar scaffold materials for tissue engineering by facile grafting of L-lactide onto chitosan.

A chitosan derivative was prepared with good yields using a "one pot" approach by grafting L-lactide oligomers via ring opening polymerization. Side chains are primarily attached to hydroxyl groups located on carbons 3 and 6 of the glucosamine ring, while the amine group remains nonfunctionalized. By increasing the L-lactide to chitosan ratio, side chain length is controlled. This allows the manipulation of the biodegradation rate and hydrophilicity of the tissue engineering scaffold material. This general synthetic route renders functionalized chitosan soluble in a broad range of organic solvents, facilitating formation of ultrafine fibers via electrospinning. Cytotoxicity tests using fibroblasts (L929 cell line) performed on electrospun L-lactide modified chitosan fibers showed that the specimen with the highest molar ratio of L-lactide (1:24) investigated in this study is the most promising material for tissue engineering purposes, while less stable formulations might still find application in drug delivery vehicles.

Detoxification of gold nanorods by treatment with polystyrenesulfonate.

We address an outstanding issue associated with the biocompatibility of gold nanorods (GNRs), a promising agent for biomedical imaging and theragnostics. GNRs are typically prepared in the presence of cetyltrimethylammonium bromide (CTAB), a cationic surfactant whose rigorous removal is necessary due to its cytotoxicity and membrane-compromising properties. CTAB-stabilized GNRs can be partially purified by treatment with polystyrenesulfonate (PSS), an anionic polyelectrolyte often used as a surrogate peptizing agent, followed by chloroform extraction and ultrafiltration with minimal loss of dispersion stability. However, in vitro cytotoxicity assays of PSS-coated GNRs revealed IC(50) values in the low to submicromolar range, with subsequent studies indicating the source of toxicity to be associated with a persistent PSS-CTAB complex. Further exchange of CTAB-laden PSS with fresh polyelectrolyte greatly improves biocompatibility, to the extent that 85 microg/mL of "CTAB-free" GNRs (the highest level evaluated) has comparable toxicity to a standard phosphate buffer solution. Ironically, PSS is not effective by itself at stabilizing GNRs in CTAB-depleted suspensions: while useful as a detergent for GNR detoxification, it should be replaced by more robust coatings for long-term stability under physiological conditions.

Palladium-catalyzed bisdiene carbocyclizations: a facile [3 + 2] cycloaddition reaction mode.

[reaction: see text] In contrast to alkyl-substituted bisdienes, aryl-substituted substrates undergo surprisingly facile palladium-catalyzed carbocyclization via a novel [3 + 2] cycloaddition mode.

Carbon nucleophiles in the Mitsunobu reaction. Mono- and dialkylation of bis(2,2,2-trifluoroethyl) malonates.

[formula: see text] Simple dialkyl malonate esters, for example diethyl malonate, exhibit relatively limited scope as carbon nucleophiles in the Mitsunobu dehydrative alkylation reaction. In contrast, bis(2,2,2-trifluoroethyl) malonate readily undergoes dehydrative alkylation with primary alcohols, and using only a slight excess of malonate gives monoalkylated product in good yield. Some secondary alcohols can also be employed, and bis(2,2,2-trifluoroethyl) malonates can be used in a second dehydrative alkylation to give dialkylated products in good to excellent yield.