Green Approach toward Triazole forming Reactions for Developing Anticancer Drugs.

Compounds containing triazole have many significant applications in the dye and ink industry, corrosion inhibitors, polymers, and pharmaceutical industries. These compounds possess many antimicrobial, antioxidant, anticancer, antiviral, anti-HIV, antitubercular, and anticancer activities. Several synthetic methods have been reported for reducing time, minimizing synthetic steps, and utilizing less hazardous and toxic solvents and reagents to improve the yield of triazoles and their analogues synthesis. Among the improvement in methods, green approaches towards triazole forming biologically active compounds, especially anticancer compounds, would be very important for pharmaceutical industries as well as global research community. In this article, we have reviewed the last five years of green chemistry approaches on click reaction between alkyl azide and alkynes to install 1,2,3-triazole moiety in natural products and synthetic drug-like molecules, such as in colchicine, flavanone cardanol, bisphosphonates, thiabendazoles, piperazine, prostanoid, flavonoid, quinoxalines, C-azanucleoside, dibenzylamine, and aryl-azotriazole. The cytotoxicity of triazole hybrid analogues was evaluated against a panel of cancer cell lines, including multidrug-resistant cell lines.

Strain-Dependent Kinetics in the Cis-to-Trans Isomerization of Azobenzene in Bulk Elastomers.

The cis-to-trans isomerization of azobenzene is accelerated in a bulk PDMS elastomer under uniaxial tension. The kinetics are cleanly described by a single-exponential first-order process (k = 2.7 × 10-5 s-1) in the absence of tension but become multiexponential under constant strains of 40-90%. The complex kinetics can be reasonably modeled as a two-component process. The majority (∼92%) process is slower and occurs with a rate constant that is similar to that of the unstrained system (k = 2.3-2.7 × 10-5 s-1), whereas the rate constant of the minority (∼8%) process increases from k = 10.1 × 10-5 s-1 at 40% strain to k = 21.3 × 10-5 s-1 at 90% strain. Simple models of expected force-rate relationships suggest that the average force of tension per strand in the minority component ranges from 28 to 44 pN across strains of 40-90%.

The Surface Science of Microarray Generation-A Critical Inventory.

Microarrays are powerful tools in biomedical research and have become indispensable for high-throughput multiplex analysis, especially for DNA and protein analysis. The basis for all microarray processing and fabrication is surface modification of a chip substrate and many different strategies to couple probe molecules to such substrates have been developed. We present here a critical assessment of typical biochip generation processes from a surface science point of view. While great progress has been made from a molecular biology point of view on the development of qualitative assays and impressive results have been obtained on the detection of rather low concentrations of DNA or proteins, quantitative chip-based assays are still comparably rare. We argue that lack of stable and reliable deposition chemistries has led in many cases to suboptimal quantitative reproducibility, impeded further progress in microarray development and prevented a more significant penetration of microarray technology into the diagnostic market. We suggest that surface-attached hydrogel networks might be a promising strategy to achieve highly sensitive and quantitatively reproducible microarrays.

Substituent Effects and Mechanism in a Mechanochemical Reaction.

We report the effect of substituents on the force-induced reactivity of a spiropyran mechanophore. Using single molecule force spectroscopy, force-rate behavior was determined for a series of spiropyran derivatives substituted with H, Br, or NO2 para to the breaking spirocyclic C-O bond. The force required to achieve the rate constants of ∼10 s-1 necessary to observe transitions in the force spectroscopy experiments depends on the substituent, with the more electron withdrawing substituent requiring less force. Rate constants at 375 pN were determined for all three derivatives, and the force-coupled rate dependence on substituent identity is well explained by a Hammett linear free energy relationship with a value of ρ = 2.9, consistent with a highly polar transition state with heterolytic, dissociative character. The methodology paves the way for further application of linear free energy relationships and physical organic methodologies to mechanochemical reactions, and the characterization of new force probes should enable additional, quantitative studies of force-coupled molecular behavior in polymeric materials.

Enhanced Release of Molecules upon Ultraviolet (UV) Light Irradiation from Photoresponsive Hydrogels Prepared from Bifunctional Azobenzene and Four-Arm Poly(ethylene glycol).

Advances in biosensors and drug delivery are dependent on hydrogels that respond to external stimuli. In this work, we describe the preparation and characterization of photoresponsive hydrogels prepared by cross-linking of di-NHS ester of azobenzoic acid and four-armed, amine-terminated poly(ethylene glycol). The porous structure and composition of the hydrogels were confirmed by scanning electron microscopy (SEM) and Fourier transform infrared (FTIR) spectroscopy. The reversible photoisomerization of the azobenzene-containing hydrogel cross-linkers in the gels was confirmed by absorption spectroscopy. Specifically, the photoisomerization of the cross-linkers between their trans and cis configurations was observed by monitoring the absorbance of the hydrogels at the two characteristic peaks of azobenzene (π-π* at 330 nm and n-π* at 435 nm). The effect of photoisomerization on the hydrogel structure was investigated by microscopy. Ultraviolet (UV) irradiation-induced reduction in hydrogel size was observed, which may be a result of the inherently smaller footprint of the cis azobenzene conformation, as well as dipole-dipole interactions between the polar cis azobenzene and the polymer network. The UV-triggered reduction in hydrogel size was accompanied by enhanced release of the near-infrared fluorescent dye Alexa Fluor 750 (AF750). Enhanced release of AF750 was observed in samples irradiated with UV versus dark control. Together, these data demonstrate the potential of these systems as reversible photoresponsive biomaterials.

Photoresponsive azo-combretastatin A-4 analogues.

Colchicine analogues in which an azo group is incorporated into a molecule containing the key pharmacophore of colchicine, have found particular utility as switchable tubulin binding chemotherapeutics. Combretastatin is a related compound containing a stilbene fragment that shows different bioactivity for the cis and trans isomers. We have performed cell assays on 17 new compounds structurally related to a previously reported azo-analogue of combretastatin. One of these compounds showed enhanced potency against HeLa (IC50 = 0.11 µM) and H157 cells (IC50 = 0.20 µM) for cell studies under 400 nm irradiation and the highest photoactivity (IC50 with irradiation/IC50 in dark = 550). We have performed docking and physicochemical studies of this new compound (7). Kinetic studies in water reveal a longer half-life for the cis isomer of 7 which may be one factor responsible for the better IC50 values in cell assays and the improved photoresponsive behavior.

Through-space (19)F-(19)F spin-spin coupling in ortho-fluoro Z-azobenzene.

We report through-space (TS) (19)F-(19)F coupling for ortho-fluoro-substituted Z-azobenzenes. The magnitude of the TS-coupling constant ((TS) JFF ) ranged from 2.2-5.9 Hz. Using empirical formulas reported in the literature, these coupling constants correspond to non-bonded F-F distances (dFF) of 3.0-3.5 Å. These non-bonded distances are significantly smaller than those determined by X-ray crystallography or density functional theory, which argues that simple models of (19)F-(19)F TS spin-spin coupling solely based dFF are not applicable. (1)H, (13)C and (19)F data are reported for both the E and Z isomers of ten fluorinated azobenzenes. Density functional theory [B3YLP/6-311++G(d,p)] was used to calculate (19) F chemical shifts, and the calculated values deviated 0.3-10.0 ppm compared with experimental values.

A study of the spiropyran-merocyanine system using ion mobility-mass spectrometry: experimental support for the cisoid conformation.

The spiropyran-merocyanine system was studied using ion mobility-mass spectrometry (IM-MS) and three major conformers were identified. Assignment of conformers is based on DFT-B3LYP energy minimized structures and collision cross-sections as light-induced changes in IM-MS. The three conformers were assigned to the spiropyran, cisoid and transoid structures.

Stimuli-responsive surfaces using polyampholyte polymer brushes prepared via atom transfer radical polymerization.

The synthesis of AB diblock copolymer polyampholyte polymer brushes of the type Si/SiO2//poly(acrylic acid-b-vinyl pyridine) prepared using atom transfer radical polymerization is reported. Both 2- and 4-vinyl pyridine have been used. The diblock polyampholyte polymer brushes demonstrate stimuli-responsive behavior with respect to pH, showing both polyelectrolyte and polyampholyte effects. Furthermore, we have quaternized the 4-vinyl pyridine segments to form a mixed weak/strong, or annealed/quenched, polyelectrolyte system. The quaternized polymer brush exhibits different pH-responsive behavior, with decreasing film thickness being observed with increasing pH.

Stimuli-responsive polyelectrolyte polymer brushes prepared via atom-transfer radical polymerization.

We present an account of our research into polyelectrolyte polymer brushes that are capable of acting as stimuli-responsive films. We first detail the synthesis of poly(acrylic acid) polymer brushes using ATRP in a "grafting from" strategy. Significantly, we employed a chemical-free deprotection step that should leave the anchoring ester groups intact. We have demonstrated how these polymer assemblies respond to stimuli such as pH and electrolyte concentration. We have used poly(acrylic acid) polymer brushes for the synthesis of metallic nanoparticles and review this work. We have used XPS, ATR-FTIR, and AFM spectroscopy to show the presence of silver and palladium nanoparticles within polymer brushes. Finally, we report the synthesis of AB diblock polyampholyte polymer brushes that represent an extension of polyelectrolyte polymer brushes.

Surface initiated polymerizations from silica nanoparticles.

Surface initiated polymerizations yield covalently bonded polymer on the substrate. The properties of such nanoparticles are unique finding a wide range of applications. This article reviews the different techniques of synthesis of these hybrid nanoparticles and their mechanistic approach presented in literature.

Mechanism of Amine-Catalyzed Ester Formation from an Acid Chloride and Alcohol.

Stopped-flow FT-IR spectroscopy has been used to study the amine-catalyzed reactions of benzoyl chloride with either butanol or phenol in dichloromethane at 0 degrees C. There is a paucity of detailed rate information available in the literature for this process. Our goal was to determine whether amine catalysis operated by a nucleophilic-, specific-base-, or general-base-catalyzed mechanism. A large isotope effect was observed for butanol versus butanol-O-d which is consistent with a general-base-catalyzed mechanism. Some anomalous rate dependencies on reactant concentration and the relative rate of benzoyl chloride loss versus butyl benzoate formation were observed. The analogous reaction of phenol was studied in more detailed. An overall reaction order of three, and a negligible isotope effect for phenol versus phenol-d(6) are consistent with either a base- or nucleophilic-catalyzed mechanism. The most interesting result with phenol was a large sensitivity of the rate of phenyl benzoate formation on small structural changes in the amine (e.g., diethylmethylamine versus triethylamine). We observed the key intermediate (acylammonium salt) in the nucleophilic process via NMR for solutions of benzoyl chloride and amine in the absence of alcohol; however, we did not observe this intermediate in the IR during ester formation [with the exception of 4-(dimethylamino)pyridine]. While we can rule out specific-base catalysis (no evidence for phenoxide intermediates), it is difficult to completely eliminate nucleophilic catalysis.