A fluidic diode, valves, and a sequential-loading circuit fabricated on layered paper

Current microfluidic paper-based devices lack crucial components for fluid manipulation. We created a fluidic diode fabricated entirely on a single layer of paper to control the wicking of fluids. The fluidic diode is a two-terminal component that promotes or stops wicking along a paper channel. We further constructed a trigger and a delay valve based on the fluidic diode. Furthermore, we demonstrated a high-level functional circuit, consisting of a diode and a delay valve, to manipulate two fluids in a sequential manner. Our study provides new, transformative tools to manipulate fluid in microfluidic paper-based devices.     

Direct atomic force microscopy observation of DNA tile crystal growth at the single-molecule level

While the theoretical implications of models of DNA tile self-assembly have been extensively researched and such models have been used to design DNA tile systems for use in experiments, there has been little research testing the fundamental assumptions of those models. In this paper, we use direct observation of individual tile attachments and detachments of two DNA tile systems on a mica surface imaged with an atomic force microscope (AFM) to compile statistics of tile attachments and detachments. We show that these statistics fit the widely used kinetic Tile Assembly Model and demonstrate AFM movies as a viable technique for directly investigating DNA tile systems during growth rather than after assembly.     

First principles study of cobalt hydride, CoH, and its ions CoH+ and CoH-

The electronic structure of the diatomic species CoH, CoH(+), and CoH(-) have been studied mainly by multireference configuration interaction (MRCI) methods and basis sets of quintuple quality. The restricted coupled-cluster with iterative singles + doubles + quasi-perturbative connected triples, RCCSD(T), approach was also employed, limited however to the ground states only. At the MRCI level we have constructed 27 (CoH), 24 (CoH(+)), and 12 (CoH(-)) potential energy curves correlating adiabatically to six, seven, and two energy channels, respectively. For the ground states scalar relativistic and core-subvalence effects have been taken into account. We report energetics, spectroscopic parameters, dipole moments, excitation energies, and spin-orbit coupling constants. Our CoH calculated results are in accord with experiment, but there is an interesting discrepancy between theory and experiment concerning the dipole moment, the former being significantly larger than the latter. Experimental results on CoH(+) and CoH(-) are scarce. The ground state of CoH, CoH(+), and CoH(-) are definitely of (3)Φ, (4)Φ, and (4)Φ symmetries with calculated (experimental) dissociation energies D(0)(0) = 46.4 ± 0.5(45.0 ± 1.2), 49.6(47 ± 2), and 45.6(43.1 ± 1.2) kcal/mol, respectively. In all 24 calculated CoH states, a Co-to-H charge transfer of 0.2-0.3 e(-) is recorded; in CoH(-), however, the negative charge resides almost exclusively on the Co atom.     

Simultaneous quantification of candesartan and irbesartan in rabbit eye tissues by liquid chromatography–tandem mass spectrometry

Diabetic retinopathy is a major cause of vision loss in adults. Novel eye-drop formulations of candesartan and irbesartan are being developed for its cure or treatment. To support a preclinical trial in rabbits, it was critical to develop and validate a new LC–MS/MS method for simultaneous quantification of candesartan and irbesartan in rabbit eye tissues (cornea, aqueous humor, vitreous body and retina/choroid). Eye tissue samples were first homogenized in H₂O-diluted rabbit plasma. The candesartan and irbesartan in the supernatants together with their respective internal standards (candesartan-d₄ and irbesartan-d₄) were extracted by solid-phase extraction. The extracted samples were injected onto a C₁₈ column for gradient separation. The MS detection was in the positive electrospray ionization mode using the multiple reaction monitoring transitions of m/z 441 → 263, 445 → 267, 429 → 207, and 433 → 211 for candesartan, candesartan-d₄, irbesartan and irbesartan-d₄, respectively. For the validated concentration ranges (2–2000 and 5–5000 ng/g for candesartan and irbesartan, respectively), the within-run and between-run accuracies (% bias) were within the range of −8.0–10.0. The percentage CV ranged from 0.6 to 7.3. There was no significant matrix interference nor matrix effect from different eye tissues and different rabbits. The validated method was successfully used in the Good Laboratory Practice (GLP) study of rabbits.     

Phosphorus heterocycle synthesis using phosphenium ions and 1,4-dienes

The stabilized phosphenium ion, [Prⁱ₂NPCl]⁺, reacts readily with 1,4-dienes to afford high yields of bicyclic phosphonium salts, the structure of one of which has been determined by X-ray crystallography.     

Alkyl Ether Analogs of Chlorophyll-a Derivatives: Part 1. Synthesis, Photophysical Properties and Photodynamic Efficacy

The synthesis, preliminary in vivo biological activity, singlet oxygen and fluorescence yields of a series of alkyl ether derivatives of chlorophyll-a analogs are described. For short-chain carbon ethers (1–7carbon units), it was observed that the biological activity increased by increasing the length of the carbon chain, being maximum in compounds with n-hexyl and n-heptyl chains. Related sensitizers prepared by reacting 2-(1-bromoethyl)-2-devinylpyropheophorbide-a with (sec)alcohols were found to be less effective. Under similar treatment conditions, photosensitizers containing cis- and trans- 3-hexenyl side chains were ineffective. Thus, both stereochemical and steric factors caused differences in sensitizing activity. In general, pyropheophorbide-a analogs were found to be more active than related chlorin e₆ derivatives, in which the isocyclic ring (ring “E”) was cleaved. Related photosensitizers in the 9-deoxy- series were found to be as effective as the corresponding pyropheophorbide-a analogs. The photosensitizers prepared from pyropheophorbide-a methyl ester and chlorin e₆ trimethyl ester have long wavelength absorption at 660 nm (ε 45000 to 50000). Reduction of the carbonyl group in the pyropheophorbide-a to methylene (ring E) resulted in a blue shift to 648 nm (ε 38000).     

Conformation and absolute configuration of nocathiacin I determined by NMR spectroscopy and chiral capillary electrophoresis

Nocathiacin I (BMS-249524) is a highly cross-linked thiazolyl peptide that displays potent activity against Gram-positive bacteria, including a number of antibiotic-resistant strains. This natural product contains 10 chiral centers. NMR studies have been performed to characterize the solution structure of nocathiacin I. A uniformly 13C,15N-labeled sample was used to obtain NMR assignments. Restrained simulated annealing calculations were performed by using accurately determined NOE distance restraints. All of the chiral centers were allowed to float during the simulated annealing protocol. Two clusters of structures were obtained that satisfy the NOE restraints very well and that are reasonably consistent with vicinal J-coupling constants. Within each cluster, all 10 chiral centers are uniquely defined. The two clusters are effectively mirror images of each other: all chiral centers that have the R(S) configuration in one cluster have the S(R) configuration in the other. The single threonine residue in nocathiacin I was subsequently determined to be l-threonine by chiral capillary electrophoresis, allowing the absolute configurations of all 10 chiral centers to be defined.     

Single-drop liquid-phase microextraction for the determination of hypericin, pseudohypericin and hyperforin in biological fluids by high performance liquid chromatography

The analysis of hypericin, pseudohypericin (collectively called in this study hypericins) and hyperforin in biological fluids is reported using single-drop liquid-phase microextraction in conjunction with HPLC-UV-fluorescence detection. A new option for analysis of the active principle constituents in biological samples is proposed, reducing the steps required prior to analysis. There are several parameters which determine the mass transfer such as the extraction solvent, drop and sample volumes, extraction time and temperature, pH and ionic strength, stirring rate and depth of needle tip in the bulk solution. These parameters were chosen to optimize the performance in the current study. The method was validated with respect to precision, accuracy and specificity. The intra-day precision values were below 2.3% for the high concentration level of control samples and 6.2% for the low level. The respective inter-day precision values were calculated to be below 4.4 and 7.1%, respectively, for the two concentration levels. Accuracy of the method, calculated as relative error, ranged from -2.6 to 7.0%. It was demonstrated that as long as the extraction procedure is consistently applied, quantitative analysis is performed accurately and reproducibly in human urine and plasma samples. Limits of quantitation (LOQs) in urine were calculated to be 3, 6 and 12 ng/ml for pseudohypericin, hypericin and hyperforin, respectively. Slightly higher limits were measured in plasma, i.e. 5, 12 and 20 ng/ml, for the respective analytes.     

Magnetic ionic liquid in stirring-assisted drop-breakup microextraction: Proof-of-concept extraction of phenolic endocrine disrupters and acidic pharmaceuticals

The use of magnetic ionic liquids (MILs) is in constant growth due to their switchable properties in the presence of an external magnetic field along with the outstanding properties of ionic liquids. In this study, a novel stirring-assisted drop-breakup microextraction (SADBME) approach is put forward, based on the synthesis and utilization of methyltrioctylammonium tetrachloroferrate (N_{8 8,8,1}[FeCl₄]), as a MIL. The proposed procedure complies with the principles of the green chemistry, since it uses low volumes of easily synthesized ILs-based magnetic extracting phases avoiding the use of toxic solvents. To demonstrate its applicability, the proposed microextraction procedure is studied in conjunction with HPLC for the determination of selected phenols and acidic pharmaceuticals in aqueous matrices, taking into account the main experimental variables involved. The results obtained are accurate and highly reproducible, thus making it a good alternative approach for routine analysis of phenols and acidic pharmaceuticals. The low-cost approach is straightforward, environmentally safe and exhibits high enrichment factors and absolute extraction percentages and satisfactory recoveries. To the best of our knowledge, this is the first time that a MIL is used for analytical purposes in a practical, efficient and environmentally friendly drop-breakup microextraction approach for small molecules.