Adsorption and micellization behavior of novel gluconamide-type gemini surfactants

The adsorption and micellization behavior of novel sugar-based gemini surfactants (N,N(')-dialkyl-N,N(')-digluconamide ethylenediamine, Glu(n)-2-Glu(n), where n is the hydrocarbon chain length of 8, 10 and 12) has been studied on the basis of static/dynamic surface tension, fluorescence, dynamic light scattering (DLS) and cryogenic transmission electron microscope (cryo-TEM) data. The static surface tension of the aqueous Glu(n)-2-Glu(n) solutions measured at the critical micelle concentration (cmc) is observed to be significantly lower than that of the corresponding monomeric surfactants. This suggests that the gemini surfactants, newly synthesized in the current study, are able to form a closely packed monolayer film at the air/aqueous solution interface. The greater ability in the molecular association is supported by the remarkably (approximately 100-200 times) lower cmc of the gemini surfactants compared with the corresponding monomeric ones. With a combination of the fluorescence and DLS data, a structural transformation of the Glu(n)-2-Glu(n) micelles is suggested to occur with an increase in the concentration. The cryo-TEM measurements clearly confirm the formation of worm-like micelles of Glu(12)-2-Glu(12) at the concentration well above the cmc.     

Anti-Stokes Luminescence in Multi-Resonance-Type Thermally-Activated Delayed Fluorescence Molecules

Photon-upconversion in organic molecular systems is one of the promising technologies for future energy harvesting systems because these systems can generate excitons that possess higher energy than excitation energy. The photon-upconversion caused by absorbing ambient heat as additional energy is particularly interesting because it could ideally provide a light-driving cooling system. However, only a few organic molecular systems have been reported. Here, we report the anti-Stokes photoluminescence (ASPL) derived from hot-band absorption in a series of multi-resonance-type thermally-activated delayed fluorescence (MR-TADF) molecules. The MR-TADF molecules exhibited an anti-Stokes shift of approximately 0.1 eV with a high PL quantum yield in the solution state. The anti-Stokes shift corresponded well to the 1–0 vibration transition from the ground state to the excited singlet state, and we further evaluated a correlation between the activation energy for the ASPL intensity and the TADF process. Our demonstration underlines that MR-TADF molecules have become a novel class of ASPL materials for various future applications, such as light-driving cooling systems.     

Interaction between Divalent Copper Fluoride and Carboxamide Group Enabling Stereoretentive Fluorination of Tertiary Alkyl Halides

Herein, we report a copper-catalyzed stereospecific fluorination involving CsF and α-bromocarboxamides as tertiary alkyl sources that, unlike traditional stereospecific routes involving stereoinversive S_N2 reactions, proceeds with retention of stereochemistry. The developed stereospecific Cu-catalyzed reaction is among the most efficient methods for synthesizing fluorinated molecules that possess highly congested stereogenic carbon centers. Mechanistic studies revealed that the combined reactivity of CuF₂ and Cs salt is essential for completing the catalytic cycle. Our catalytic system underwent fluorination exclusively with tertiary alkyl bromides and did not react with primary alkyl bromides, indicating that this stereospecific fluorination methodology is suitable for synthesizing fluorinated building blocks possessing stereo-defined F-containing tertiary carbon stereogenic center.     

Direct measurement of interactions between stimulation-responsive drug delivery vehicles and artificial mucin layers by colloid probe atomic force microscopy

A novel thermo- and pH-sensitive nanogel particle, which is a core-shell structured particle with a poly(N-isopropylacrylamide) (p(NIPAAm)) hydrogel core and a poly(ethylene glycol) monomethacrylate grafted poly(methacrylic acid) (p(MMA-g-EG)) shell, is of interest as a vehicle for the controlled release of peptide drugs. The interactions between such nanogel particles and artificial mucin layers during both approach and separation were successfully measured by using colloid probe atomic force microscopy (AFM) under various compression forces, scan velocities, and pH values. While the magnitudes of the compression forces and scan velocities did not affect the interactions during the approach process, the adhesive force during the separation process increased with these parameters. The pH values significantly influenced the interactions between the nanogel particles and a mucin layer. A large steric repulsive force and a long-range adhesive force were measured at neutral pH due to the swollen p(MMA-g-EG) shell. On the other hand, at low pH values, the steric repulsive force disappeared and a short-range adhesive force was detected, which resulted from the collapse of the shell layer. The nanogel particles possessed a pH response that was sufficient to protect the incorporated peptide drug under the harsh acidic conditions in the stomach and to effectively adhere to the mucin layer of the small intestine, where the pH is neutral. The relationships among the nanogel particle-mucin layer interactions, pH conditions, scan velocities, and compression forces were systemically investigated and discussed.     

UPLC-MS/MS detection of disaccharides derived from glycosaminoglycans as biomarkers of mucopolysaccharidoses

Mucopolysaccharidoses (MPSs) are a group of disorders resulting from primary defects in lysosomal enzymes involved in the degradation of glycosaminoglycans (GAGs). Depending on the specific enzyme defect, the catabolism of one or more GAGs is blocked leading to accumulation in tissues and biological fluids. GAG measurements are important for high-risk screening, diagnosis, monitoring treatment efficacy, and patient follow up. The dimethylmethylene blue (DMB) spectrophotometric method commonly used in most biochemical genetics laboratories relies on a non-specific total GAG analysis which has led to false positive results, and even false negative results (mainly for MPS III and IV patients). The main objective of our project was to devise and validate a reliable tandem mass spectrometry multiplex analysis for the urine quantitation of four GAGs (dermatan sulfate (DS), heparan sulfate (HS), keratan sulfate (KS), and chondroitin sulfate (CS)) for an eventual technological transfer to the clinic. The developed methodology is rapid (7 min) and our results showed good intraday and interday precision (RSDs ≤ 8.7%) and accuracy (Biases range: −12.0%–18.4%). Linearity was good (r² > 0.995) for DS, HS, CS, and KS calibration curves. In comparison with the DMB spectrophotometric method, this multiplex tandem mass spectrometry method allows GAG fractionation, thus a differentiation of MPS types, except for MPS I and II which are characterized by the same GAG profile. The devised method is a useful and reliable tool for diagnosis of MPS patients, as well as their monitoring and follow up, as shown by longitudinal studies.     

Papain‐Catalyzed Chemoenzymatic Synthesis of Telechelic Polypeptides Using Bis(Leucine Ethyl Ester) Initiator

In order to construct unique polypeptide architectures, a novel telechelic‐type initiator with two leucine ethyl ester units is designed for chemoenzymatic polymerization. Glycine or alanine ethyl ester is chemoenzymatically polymerized using papain in the presence of the initiator, and the propagation occurs at each leucine ethyl ester unit to produce the telechelic polypeptide. The formation of the telechelic polypeptides is confirmed by ¹H NMR and MALDI‐TOF mass spectroscopies. It is revealed by AFM observation that long nanofibrils are formed from the telechelic polyalanine, whereas a conventional linear polyalanine with a similar degree of polymerization shows granule‐like structures. The telechelic polyglycine and polyalanine show the crystalline structures of Polyglycine II and antiparallel β‐sheet, respectively. It is demonstrated that this method to synthesize telechelic‐type polypeptides potentially opens up a pathway to construct novel hierarchical structures by self‐assembly.

     

Analytical method for determination of disaccharides derived from keratan sulfates in human serum and plasma by high-performance liquid chromatography/turbo-ionspray ionization tandem mass spectrometry

We established a highly sensitive LC/MS/MS method for the analysis of the disaccharides produced from keratan sulfates (KS). It was revealed that the disaccharides produced by keratanase II enzymatic digestion of KS could be determined with high sensitivity by negative ion mode of multiple reaction monitoring. Furthermore, monosulfated and disulfated disaccharides can be separated using a Hypercarb (2.0 mm i.d. x 150 mm, 5 microm) with a gradient elution of acetonitrile-0.01 m ammonium bicarbonate (pH 10). This method was applied to the determination of KS in serum and plasma of control subjects. The intra-day precision expressed as %CV was within 6.8% for five replicate analyses with three different control serum. The inter-day (overall, n = 15) precision was within 7.3% for three days. This method is sensitive, reproducible and would be useful for clinical analysis.     

Baxter-Guttmann-Jensen conjecture for power series in directed percolation problem

A probabilistic model of a flow of fluid through a random medium,percolation model, provides a typical example of statistical mechanical problems which are easy to describe but difficult to solve. While the percolation problem on undirected planar lattices is exactly solved as a limit of the Potts models, there still has been no exact solution for the directed lattices. The most reliable method to provide good approximations is a numerical estimation using finite power-series expansion data of the infinite formal power series for percolation probability. In order to calculate higher-order terms in power series, Baxter and Guttmann [6] and Jensen and Guttmann [33] proposed an extrapolation procedure based on an assumption that thecorrection terms, which show the difference between the exact infinite power series and approximate finite series, are expressed as linear combinations of the Catalan numbers.In this paper, starting from a brief review on the directed percolation problem and the observation by Baxter, Guttmann, and Jensen, we state some theorems in which we explain the reason why the combinatorial numbers appear in the correction terms of power series. In the proof of our theorems, we show several useful combinatorial identities for the ballot numbers, which become the Catalan numbers in a special case. These identities ensure that a summation of products of the ballot numbers with polynomial coefficients can be expanded using the ballot numbers. There is still a gap between our theorems and the Baxter-Guttmann-Jensen observation, and we also give some conjectures.As a generalization of the percolation problem on a directed planar lattice, we present two topics at the end of this paper: The friendly walker problem and the stochastic cellular automata in higher dimensions. We hope that these two topics as well as the directed percolation problem will be of much interest to researchers of combinatorics.     

Myrmekiosides a and b, novel mono-o-alkyl-diglycosylglycerols reversing tumor cell morphology of ras-transformed cells from a marine sponge of myrmekioderma sp

Novel mono-O-alkyl-diglycosylglycerols named myrmekiosides A (1) and B (2) were isolated from a marine sponge of Myrmekioderma sp. and their absolute stereostructures were elucidated on the basis of chemical and physicochemical evidence. Myrmekiosides A (1) and B (2) reversed the phenotype of melanoma H-ras transformed NIH3T3 cells at 5 μg/ml.