Synthesis of substituted isoquinolines via Pd-catalyzed cross-coupling approaches

Palladium complexes incorporating ligands based on a 1,3,5,7-tetramethyl-2,4,8-trioxa-6-phosphaadamantanyl scaffold were used to catalyze the arylation of ethyl cyanoacetate, malononitrile, and various ketones. The products from these reactions can be elaborated to substituted β-arylethylamines and used in microwave-assisted Pictet-Spengler reactions. The protocol developed is suitable for the synthesis of libraries of substituted isoquinolines.     

Affinity‐Based Drug Delivery

Affinity‐based drug delivery systems utilize interactions between the therapeutic drug and the delivery system to manipulate drug loading and to control drug release. In this paper, affinity‐based drug delivery system syntheses, types of therapeutic factors delivered, and delivery system loading and release are discussed in detail. The paper is divided into three subsections, based on the type of delivery system: molecular imprinting systems, growth‐factor delivery, and cyclodextrin‐based delivery. The objective of this paper is to examine the current state of research, highlight the breakthroughs and challenges, point out potential impacts of this relatively new technology, and explore future developmental areas.

     

Characteristics of microwaves on second generation nitrogen-doped TiO2 nanoparticles and their effect on photoassisted processes

Characteristics of 2.45-GHz microwave radiation were examined on two second generation nitrogen-doped TiO₂ nanomaterials prepared by annealing Degussa P-25 TiO₂ and Ishihara ST-01 TiO₂ at 400 °C and 500 °C, respectively, in air in the presence of urea, and for comparison on the undoped pristine samples. Band gaps of all four samples were determined by diffuse reflectance spectroscopy. Both the sizes and the BET specific surface areas of the TiO₂ particles were determined, together with dielectric constants and dielectric loss factors. Nitrogen doping caused the size to increase and surface area to decrease. Temperature–time profiles showed that the heating efficiency of the N-doped specimens by the microwaves was greater, particularly significant for the N-doped P25 sample, but rather small for the N-ST01 sample. The effect of microwaves on the surface optical phonons of the samples, with and without UV–vis irradiation, was examined by an in situ Raman spectroscopic technique; for the undoped P-25 and nitrogen-doped N-P25 TiO₂ systems the effect was negligible. By contrast, microwave irradiation of Ishihara ST-01 and nitrogen-doped N-ST01 TiO₂ samples showed significant changes in the 144-cm^?1 optical phonons. Results infer a microwave thermal effect on the Ishihara ST-01 and N-ST01 specimens, whereas for the Degussa P-25 samples the microwaves also imparted a specific effect as the microwaves influenced the N-dopant sites in contrast to the ST-01 systems where the dopant sites were unaffected as evidenced by temperature–time profiles. The microwave-/photo-assisted degradation of 4-chlorophenol under various conditions of UV–vis irradiation and conventional heating, as opposed to microwave heating, confirms the specific microwave effect for the P-25 systems.     

Diagnostic NH and OH Vibrations for Oxazolone and Diketopiperazine Structures: b<Subscript>2</Subscript> from Protonated Triglycine

We present infrared multiple photon dissociation (IRMPD) spectra in the hydrogen stretching region of the simplest b fragment, b₂ from protonated triglycine, contrasted to that of protonated cyclo(Gly-Gly). Both spectra confirm the presence of intense, diagnostic vibrations linked to the site of proton attachment. Protonated cyclo(Gly-Gly) serves as a reference spectrum for the diketopiperazine structure, showing a diagnostic O-H⁺ stretch of the protonated carbonyl group at 3585 cm^–1. Conversely, b₂ from protonated triglycine exhibits a strong band at 3345 cm^–1, associated with the N-H stretching mode of the protonated oxazolone ring structure. Other weaker N-H stretches can also be discerned, such as the amino NH₂ and amide NH bands. These results demonstrate the usefulness of the hydrogen stretching region, and hence benchtop optical parametric oscillator/amplifier (OPO/A) set-ups, in making structural assignments of product ions in collision-induced dissociation (CID) of peptides.     

On the dynamics of fragment isomerization in collision-induced dissociation of peptides

The structures of peptide collision-induced dissociation (CID) product ions are investigated using ion mobility/mass spectrometry techniques combined with theoretical methods. The cross-section results are consistent with a mixture of linear and cyclic structures for both b4 and a4 fragment ions. Direct evidence for cyclic structures is essential in rationalizing the appearance of fragments with scrambled (i.e., permutated) primary structures, as the cycle may not open up where it was initially formed. It is demonstrated here that cyclic and linear a4 structures can interconvert freely as a result of collisional activation, implying that isomerization takes place prior to dissociation.     

Nanoscale protein pores modified with PAMAM dendrimers

We describe nanoscale protein pores modified with a single hyperbranched dendrimer molecule inside the channel lumen. Sulfhydryl-reactive polyamido amine (PAMAM) dendrimers of generations 2, 3 and 5 were synthesized, chemically characterized, and reacted with engineered cysteine residues in the transmembrane pore alpha-hemolysin. Successful coupling was monitored using an electrophoretic mobility shift assay. The results indicate that G2 and G3 but not G5 dendrimers permeated through the 2.9 nm cis entrance to couple inside the pore. The defined molecular weight cutoff for the passage of hyperbranched PAMAM polymers is in contrast to the less restricted accessibility of flexible linear poly(ethylene glycol) polymers of comparable hydrodynamic volume. Their higher compactness makes sulfhydryl-reactive PAMAM dendrimers promising research reagents to probe the structure of porous membrane proteins with wide internal diameters. The conductance properties of PAMAM-modified proteins pores were characterized with single-channel current recordings. A G3 dendrimer molecule in the channel lumen reduced the ionic current by 45%, indicating that the hyperbranched and positively charged polymer blocked the passage of ions through the pore. In line with expectations, a smaller and less dense G2 dendrimer led to a less pronounced current reduction of 25%. Comparisons to recordings of PEG-modified pores revealed striking dissimilarities, suggesting that differences in the structural dynamics of flexible linear polymers vs compact dendrimers can be observed at the single-molecule level. Current recordings also revealed that dendrimers functioned as ion-selectivity filters and molecular sieves for the controlled passage of molecules. The alteration of pore properties with charged and hyperbranched dendrimers is a new approach and might be extended to inorganic nanopores with applications in sensing and separation technology.     

Chemical Synthesis and Immunological Evaluation of a Pentasaccharide Bearing Multiple Rare Sugars as a Potential Anti‐pertussis Vaccine

With the infection rate of Bordetella pertussis at a 60‐year high, there is an urgent need for new anti‐pertussis vaccines. The lipopolysaccharide (LPS) of B. pertussis is an attractive antigen for vaccine development. With the presence of multiple rare sugars and unusual glycosyl linkages, the B. pertussis LPS is a highly challenging synthetic target. In this work, aided by molecular dynamics simulation and modeling, a pertussis‐LPS‐like pentasaccharide was chemically synthesized for the first time. The pentasaccharide was conjugated with a powerful carrier, bacteriophage Qβ, as a vaccine candidate. Immunization of mice with the conjugate induced robust anti‐glycan IgG responses with IgG titers reaching several million enzyme‐linked immunosorbent assay (ELISA) units. The antibodies generated were long lasting and boostable and could recognize multiple clinical strains of B. pertussis, highlighting the potential of Qβ‐glycan as a new anti‐pertussis vaccine.     

Products of cytochrome P450(BioI) (CYP107H1)-catalyzed oxidation of fatty acids

[reaction: see text] Oxidation of tetradecanoic and hexadecanoic acids by cytochrome P450(BioI) (CYP107H1) produces mainly the 11-, 12-, and 13-hydroxy C(14) fatty acids and the 11- to 15-hydroxy C(16) fatty acids, respectively. In contrast to previous reports, terminal hydroxylation is not observed. The enantiospecificity of fatty acid hydroxylation by P450(BioI) was also determined, and the enzyme was shown to be moderately selective for production of the (R)-alcohols.