Application of the pKa rule to synthesize salts of bezafibrate

ABSTRACT

Co-crystallization frequently employs forces such as hydrogen bonds, halogen bonds, and π-π stacking to assemble molecules in a multi-component crystal. In an effort to increase the strength of the intermolecular interaction between the anti-cholesterol drug bezafibrate (BEZA), a wastewater contaminant, and hydrogen-bond-acceptor molecules, we modified the pK_a values of the acceptors. Here, we describe the first series of salts incorporating BEZA and achieve a variety of supramolecular architectures including discrete assemblies, 1D chains, tapes, and 2D sheets. We discuss exceptions to the pK_a rule, and demonstrate that the presence of hydrogen-bond-donor atoms on the acceptor molecule supports salt formation.     

Amperometric sensor for L-ascorbic acid determination based on MnO2 bulk modified screen printed electrode

A simple biosensor constructed by bulk-modification of carbon ink with manganese dioxide as a mediator was investigated for its ability to serve as amperometric detector for L-ascorbic acid in hydrodynamic mode. The sensor could be operated at pH 5.0 (0.05 M phosphate buffer) and exhibited excellent reproducibility and stability. Optimization of measurement parameters such as applied working potential and pH value were studied in detail. The screen printed electrode exhibited a linear amperometric increase with the concentration of L-ascorbic acid from 50 mg L(-1) to 250 mg L(-1) and gave a (LOD = 3sigma) detection limit of 0.2 mg L(-1) (1.172 micromol L(-1)). The manganese dioxide modified screen printed electrode shows long term stability.     

Harnessing anionic rearrangements on the benzenoid ring of quinoline for the synthesis of 6,6'-disubstituted 7,7'-dihydroxy-8,8'-biquinolyls

7,7'-Bis(((dimethylamino)carbonyl)oxy)-8,8'-biquinolyl (5) was prepared in 71% yield by regioselective directed ortho metalation (DoM) of N,N-dimethyl O-quinol-7-yl carbamate (2) with LDA followed by oxidation with anhydrous ferric chloride. DoM of 5 with excess LDA induced double anionic ortho-Fries rearrangement and gave 6,6'-bis((dimethylamino)carbonyl)-7,7'-dihydroxy-8,8'-biquinolyl (8). Treatment of N,N-diethyl O-(8-iodoquinol-7-yl) carbamate (16) with LDA in THF solvent at -78 degrees C, followed by addition of anhydrous ferric chloride, resulted in an efficient tandem halogen-dance dimerization process which afforded 7,7'-bis(((diethylamino)carbonyl)oxy)-6,6'-diiodo-8,8'-biquinolyl (17) directly in 54% yield.     

Novel Copolymers of Vinyl Acetate and Alkyl Ring‐Substituted 2‐Phenyl‐1,1‐dicyanoethylenes

Electrophilic trisubstituted ethylene monomers, alkyl ring‐substituted 2‐phenyl‐1,1‐dicyanoethylenes, RC₆H₄CH?C(CN)₂ (where R is 2‐methyl, 3‐methyl,4‐methyl, 4‐ethyl, 4‐isopropyl, 4‐butyl, and 4‐t‐butyl), were synthesized by piperidine catalyzed Knoevenagel condensation of ring‐substituted benzaldehydes and malononitrile, and characterized by CHN elemental analysis, IR, ¹H‐ and ¹³C‐NMR. Novel copolymers of the ethylenes and vinyl acetate were prepared at equimolar monomer feed composition by solution copolymerization in the presence of a radical initiator (ABCN) at 70°C. The composition of the copolymers was calculated from nitrogen analysis, and the structures were analyzed by IR, ¹H and ¹³C‐NMR, GPC, DSC, and TGA. High T_g of the copolymers, in comparison with that of polyvinyl acetate, indicates a substantial decrease in chain mobility of the copolymer due to the high dipolar character of the trisubstituted ethylene monomer unit. The gravimetric analysis indicated that the copolymers decompose in the 190–700°C range.     

The influence of gamma radiation on the dielectric relaxation behaviour of isotactic polypropylene: The α relaxation

The high-temperature α relaxation in gamma irradiated isotactic polypropylene (iPP) was studied over the temperature (298-406 K), frequency (10³-10⁶ Hz) and absorbed dose (0-700 kGy) ranges by means of dielectric spectroscopy. The multiple α relaxation was resolved from the β relaxation by curve fitting and its parameters were determined. Its position, intensity and activation energy were found to be strongly dependent on the changes in the structural and morphological parameters attributed to the exposure of the samples to radiation. Wide angle X-ray diffraction (WAXD) was used to investigate radiation-induced changes in the crystalline structure and degree of crystallinity, since this relaxation is connected with the crystal phase. Infrared (IR) spectroscopy and gel measurements were used to determine the changes in the oxidative degradation and the degree of network formation, respectively; the polar (carbonyl and/or hydroperoxide) groups that were introduced by irradiation were considered as tracer groups. Conclusions derived according to different methods were compared. The results reveal uncommon α relaxation behaviour with gamma radiation and confirm the multiple nature of this process, together with high dielectric and/or relaxation sensitivity of iPP to the radiation-induced changes.     

Experimental and statistical analysis methods for peptide detection using surface‐enhanced Raman spectroscopy

Surface‐enhanced Raman spectroscopy (SERS) has the potential to make a significant impact in biology research due to its ability to provide information orthogonal to that obtained by traditional techniques such as mass spectrometry (MS). While SERS has been well studied for its use in chemical applications, detailed investigations with biological molecules are less common. In addition, a clear understanding of how methodology and molecular characteristics impact the intensity, the number of peaks, and the signal‐to‐noise of SERS spectra is largely missing. By varying the concentration and order of addition of the SERS‐enhancer salt (LiCl) with colloidal silver, we were able to evaluate the impact of these variables on peptide spectra using a quantitative measure of spectra quality based on the number of peaks and peak intensity. The LiCl concentration and order of addition that produced the best SERS spectra were applied to a panel of synthetic peptides with a range of charges and isoelectric points (pIs) where the pI was directly correlated with higher spectral quality. Those peptides with moderate to high pIs and spectra quality scores were differentiated from each other using the improved method and a hierarchical clustering algorithm. In addition, the same method and algorithm was applied to a set of highly similar phosphorylated peptides, and it was possible to successfully classify the majority of peptides on the basis of species‐specific peak differences. Copyright © 2008 John Wiley & Sons, Ltd.     

Xanthene-Based Nitric Oxide-Responsive Nanosensor for Photoacoustic Imaging in the SWIR Window

Shortwave infrared (SWIR) dyes are characterized by their ability to absorb light from 900 to 1400 nm, which is ideal for deep tissue imaging owing to minimized light scattering and interference from endogenous pigments. An approach to access such molecules is to tune the photophysical properties of known near-infrared dyes. Herein, we report the development of a series of easily accessible (three steps) SWIR xanthene dyes based on a dibenzazepine donor conjugated to thiophene ( SCR-1 ), thienothiophene ( SCR-2 ), or bithiophene ( SCR-3 ). We leverage the fact that SCR-1 undergoes a bathochromic shift when aggregated for in vivo studies by developing a ratiometric nanoparticle for NO ( rNP-NO ), which we employed to successfully visualize pathological levels of nitric oxide in a drug-induced liver injury model via deep tissue SWIR photoacoustic (PA) imaging. Our work demonstrates how easily this dye series can be utilized as a component in nanosensor designs for imaging studies.     

Resolution, enantiomerization kinetics, and chiroptical properties of 7,7'-dihydroxy-8,8'-biquinolyl

(+/-)-7,7'-Dihydroxy-8,8'-biquinolyl (6) was resolved into its enantiomorphic atropisomers via reverse phase (C18) chromatographic separation of epimeric bismenthyl carbonates, (-)-lk-9 and (+)-ul-9, derived from 6 and (+)-menthyl chloroformate. The faster eluting diastereoisomer, (-)-lk-9, was revealed to possess an (aS)-configurated biaryl axis by X-ray crystallographic analysis. Saponification of the separated bismenthyl carbonates gave enantioenriched samples of biquinolyl 6, and absolute stereochemical configurations were assigned to the two optical isomers as (-)-(aS)-6 and (+)-(aR)-6 by correlation with their respective progenitors, (-)-lk-9 and (+)-ul-9. First-order rate constants for the enantiomerization of 6 in water were obtained over the temperature range 316-366 K, and activation parameters were determined as DeltaH(++) = 34.0 kcal mol(-1) and DeltaS(++) = 18.7 cal mol(-1) K(-1) by Eyring plot analysis. A low level (AM1) computational study of the rotational dynamics of 6 showed excellent agreement with kinetic experimental data and suggested that enantiomerization occurs preferentially via a syn pathway. In common with (-)-(aS)-1,1'-bi-2-naphthol (BINOL), (-)-(aS)-6 showed positive exciton chirality in its electronic circular dichroism (CD) spectrum and gave a characteristic couplet composed of a positive maximum Cotton effect at 250 nm and a negative minimum at 234 nm (Delta Delta epsilon = +40 M(-1) cm(-1) at 64% ee).